Methodology: FISH

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Translocations involving the MLL gene on chromosome 11q23 are noted in a subset of acute myeloid leukemias (AML) as well as acute lymphoblastic leukemias/lymphomas (ALL). In addition, treatment-related leukemias (5-10% of all leukemias), particularly those following treatment with anti-topoisomerase II or intercolating topoisomerase II inhibitors, but even those after more conventional alkylating or radiotherapy, often have translocations involving 11q23. The detection of translocations involving MLL is important in the diagnosis of patients with AML and ALL as they predict a poor overall prognosis. On the molecular level, the MLL gene on 11q23 is often juxtaposed with a variety of partner genes; the most frequent are listed below, although variant translocations involving other partners have been widely described in the literature. t(4;11)(q23;q23): Represents ~1/3 of cases and found mainly (95%) in precursor B acute lymphoblastic leukemia/lymphoma (CD19+ in 75%, CD10+ in 15%) as well as treatment-related ALL (5%). Children represent ~1/2 of cases with infants <1 year of age accounting for 1/3 of all cases. The gene involved on 4q21 is AF4, a transcription activator. t(6;11)(q27;q23): Represents 5% of cases, mostly in children and young adults, with a male predominance. The gene involved on 6q27 is AF6, which plays a role in signal transduction. t(9;11)(p23;q23): Represents 25% of cases and found mainly in AML, of which 70% show M5A morphology and 10% show M4, but 10% of cases represent ALL. In both de novo and therapy-related ALL, children represent half of cases (infants <1 year accounting for 15% of all cases). The gene involved in 9p22 is AF9, a transcription activator. t(10;11)(p12;q23): Represents 5% of cases, most of which present with M4 and M5 morphology. The gene involved on 10p12 is AF10, a transcription activator. t(11;19)(q23;p13.1): Represents 5% of cases, most of which present with AML M4 or M5 morphology. The gene involved on 19p13.3 is ELL, a transcription activator. t(11;19)(q23;p13.3): Represents 5% of cases. Acute lymphoblastic leukemia, biphenotypic acute leukemias and AML M4, M5. Mostly found in infants (roughly 50% of cases) and other children or young adults. The gene involved in 19p13.3 is ENL, a transcription activator. Probe type: Dual color breakapart

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Gliomas are the most common primary neoplasm of the central nervous system and can have strikingly different clinical behaviors and responses to therapy. Distinguishing between different subtypes is often less than perfect with significant inter-observer variability. Although attempts have been made to define clinical and histologic features that correlate with a favorable prognosis, none have been sufficiently reliable at predicting response to adjuvant chemotherapy. However, recent studies have shown that loss of 1p36 and 19q13 are associated with an oligodendroglial phenotype, favorable response to chemotherapy and overall prolonged survival. Fluorescence in-situ hybridization (FISH) studies provide a direct method for identifying loss of 1p36 and 19q13 in formalin-fixed, paraffin-embedded tissue sections. Loss of 1p36 and 19q13 is detected by assessing the ratio of 1p36 and 19q13 to their corresponding reference genes, 1q25 and 19p13, respectively, and by assessing the number of nuclei showing clear 1p36 and 19q13 deletion, according to guidelines defined by the International Society of Pediatric Oncology (ISPO). Probe type: Dual color enumeration (x2)

Organ: Brain/CNS

Disease State: Oligodendroglioma, Astrocytoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday, Tuesday, Wednesday, Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374x2. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Organ: Blood/Bone Marrow, Body Fluids

Disease State: Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH test detects deletion of 20q12, which is a chromosomal abnormality seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This FISH test is frequently utilized in the workup of MDS, which is a heterogeneous group of clonal myeloid stem cell disorders. Deletion of 20q12 as a sole abnormality is associated with a favorable prognosis. When seen with other chromosomal abnormalities, deletion 20q12 is associated with a poor prognosis. Probe type: Single Color Enumeration

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88367 or 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH probe set detects deletion of 7q31 and monosomy 7, which are chromosomal abnormalities seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This FISH test is frequently utilized in the workup of MDS, which is a heterogeneous group of clonal myeloid stem cell disorders. Deletion of 7q31 is associated with an intermediate prognosis while monosomy 7 is associated with a poor prognosis. Probe type: Dual color enumeration

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Organ: Lung

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies anaplastic lymphoma kinase (ALK) overexpression. A small subset of lung carcinomas owing to the presence of a chromosomal 2 EML4-ALK rearrangement. Cytoplasmic localization of ALK can be used to distinguish cancers containing the ALK translocation, with results between IHC and FISH highly concordant. Published data suggest that ALK rearrangement in NSCLC is a strong predictive marker for response to crizotinib. In our validation studies the cutoff for IHC positivity is ≥ 10%. (References: Kwak EL et al., N Engl J Med 363:1693-703, 2010; von Laffert M et al., J Thorac Oncol 9:1685-92, 2014). Subcelluar Localization: Membranous

Organ: Lung

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies anaplastic large cell lymphoma (ALCL), ALK-positive, and a rare form of diffuse large B cell non-Hodgkin lymphoma, ALK-positive large B cell lymphoma. ALK is overexpressed as a consequence of the t(2;5) in the great majority of cases of ALCL, ALK+ (ALK is on chromosome 2), but only rarely as a consequence of the t(2;5) in ALK+ large B cell lymphoma. ALK expression in non-hematopoietic tumors outside of the lung occurs most commonly in a subset of inflammatory myofibroblastic tumors. Subcellular Localization:  Nuclear and cytoplasmic, or only cytoplasmic, depending on the associated chromosomal translocation.

Disease State: Large Cell Undifferentiated Malignant Neoplams, Anaplastic Large Cell Lymphoma (Systemic or Cutaneous)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Clinical Significance: Two recurrent genetic abnormalities that occur in acute lymphoblastic leukemia (ALL) include the t(9;22) BCR/ABL and MLL gene rearrangements. “Ph+” ALL cases are more common in adults than children, but when present in either group portend a worse prognosis. Such cases that are Ph+ have been shown to be responsive to BCR/ABL targeted therapies such as imatinib. The t(v;11q23); MLL rearranged group refer to ALL cases which harbor an MLL translocation with one of a large group of partners. Such cases are best detected by an MLL breakapart FISH probe that detects any MLL rearrangement but does not distinguish between any specific type. MLL translocations may occur in utero and these types of ALL cases are the most common in infants less than 1 year of age. The presence of an MLL rearrangement generally portends a worse prognosis and higher risk of treatment failure.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL)

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: AMACR (alpha-methylacyl-CoA racemase, or p504s) is a highly sensitive positive marker of prostatic adenocarcinoma, and is generally negative on normal or atrophic prostatic glandular epithelium. Generally employed in the context of a panel of antibodies including those to p63 and high MW cytokeratins (antibody 34ßE12). Subcellular Localization: Granular cytoplasmic

Organ: Genitourinary, Prostate

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH panel is useful in the identification of a diverse set of specific chromosome alterations associated with various acute myelogenous leukemia (AML) subtypes that are part of the WHO Classification system for hematopoietic tumors. The t(8;21) is found in ~5% of AML and is associated with younger patient age and favorable response to chemotherapy with a high complete remission rate. The inv16/t(16;16)(p13;q22) group of leukemias occur in younger patients and this genetic alteration results in fusion of the CBFB gene to the MYH1 gene. This form of AML exhibits monocytic and granulocytic differentiation and a prominent eosinophilic component in the marrow. Monosomy 7/del 7q is found in ~40% of childhood myelodysplastic syndrome (MDS) and ~5% of pediatric AML and is associated with an adverse prognosis in the later. The 11q23 (MLL) rearranged cases of AML is associated with monocytic differentiation and a worse prognosis. Trisomy 8 is one of the most common numerical chromosomal alterations in AML, occurring in ~40% of cases and may portend a worse outcome.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374x6, 88367. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This panel is designed to detect residual AML after therapy, and includes 26 unique antibodies to CD117, CD11b, CD123, CD13, CD133, CD14, CD15, CD16, CD19, CD2, CD3, CD33, CD34, CD36, CD38, CD4, CD45, CD5, CD56, CD64, CD7, CD71, CD8, CD9, CD90, HLA-DR.

Disease State: Acute Myeloid Leukemia (AML)

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88184 x 1, 88185 x 25, 88189 x 1. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This panel detects the more commonly seen t(15;17) in acute promyelocytic leukemia (APL) as well as variant translocations detected by the RARA breakapart probe.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374x2. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: The absence of expression of ATRX will be used to assist in the subclassification of gliomas. Studies in the published literature have demonsrtrated that loss of expression of ATRX (Alpha Thalassemia/Mental Retardation Syndrome X-Linked) in grade II/III astrocytomas as determined by immunohistochemistry corresponds to the presence of ATRX mutations. Most ATRX-loss gliomas also have IDH1 mutations, and show overexpression of p53 with the presence of corresponding p53 mutations. Gliomas with ATRX loss almost never show 1p/19q co-deletion. The vast majority of grade II/III gliomas can be categorized into 3 molecular subtypes based on status of IDH1 mutation, ATRX immunohistochemistry, and 1p/19q co-deletion. Subcellular Localization: nuclear

Organ: Brain/CNS

Disease State: Oligodendroglioma, Astrocytoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88312. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies adenovirus infected cells. This antibody reacts with all 41 serotypes of Adenovirus in formalin-fixed, paraffin embedded tissues. Subcellular Localization: Nuclear

Disease State: Identification of Organisms

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies yolk sac tumors and some hepatocellular carcinomas. It can be employed as part of a panel of markers of germ cell tumors. Subcellular Localization: Cytoplasmic

Organ: OB/GYN, Genitourinary, Liver

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a subset of amyloid deposits, the protein nature of which is derived from AA protein. Subcellular Localization: Extracellular (amyloid deposits)

Disease State: Amyloid Type Analysis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies amyloid deposits. The 'plasma' or 'P' component of amyloid is derived from a normal circulating glycoprotein that is present in all amyloid subtypes. Identifies amyloid deposits in tissues. Subcellular Localization: Extracellular (amyloid deposits)

Disease State: Amyloid Type Analysis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: This panel of antibodies can be employed to subclassify amyloid deposits based on their protein composition.

Disease State: Amyloid Type Analysis

Turnaround Time: Within 2-4 business days of receipt

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block or 1 unstained slide for each test requested plus 3-4 additional unstained slides cut at 4µm, plus 2 unstained slides cut at 8-10µm or a Congo Red-stained slide

CPT Code(s): 88342; 88341x4; 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies tumors expressing androgen receptor including a subset of carcinomas from prostate, skin adnexa, salivary gland, and breast. Subcellular Localization: Nuclear

Organ: Breast, Genitourinary, Prostate, Hormones

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies hepatocytes and hepatocellular carcinoma. Subcellular Localization: Nuclear and cytoplasmic

Organ: Liver

Disease State: Carcinomas of Unknown Primary, Hepatocellular Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88312. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This tube is designed to assess surface CD22 and nuclear TdT expression among presumed abnormal B-lymphoblastic cell populations. It includes antibodies to surface CD45, CD11b, CD22, CD19, CD34, CD33, CD79b, CD56, and HLA-DR, as well as a cytoplasmic TdT antibody.

Organ: Blood/Bone Marrow, Thymus (Mediastinal Mass)

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL)

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x10. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This panel is designed to detect residual B-ALL after therapy, and includes antibodies to CD45, kappa, lambda, CD5, CD34, CD20, CD10, CD19, and CD38.

Organ: Blood/Bone Marrow

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL)

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88184 x 1, 88185 x 8, 88188 x 1. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: BAP1 is a ubiquitin hydrolase and has been shown to enhance BRCA1-mediated cell growth suppression, and functions as a tumor suppressor gene. Loss of expression of BAP1 by immunohistochemistry correlates well with the presence of either BAP1 mutations or deletions at the DNA level. In a 2015 study, we have demonstrated that in the context of mesothelial lesions, BAP1 loss is 100% specific for mesothelioma, albeit with low (27%) sensitivity. However, when combined with p16 FISH a sensitivity of 58% for mesothelioma can be attained (Sheffield BS et al., Am J Surg Pathol 39:977-82, 2015). This IHC test is clinically indicated for diagnostic purposes. Specifically, it will be used in conjunction with P16 FISH probe to separate benign from malignant mesothelial proliferations, and is particularly useful when tissue invasion by mesothelial cells cannot be demonstrated. However, combined BAP1/p16 FISH testing is not highly sensitive, and negative results do not rule out a mesothelioma. Subcellular Localization: nuclear

Organ: Lung, Ovary

Disease State: Mesothelioma vs. Adenocarcinoma, Benign vs. Malignant Mesothelial Proliferations

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This sensitive breakapart FISH assay detects any translocation inolving the BCL6 gene but does not specifically distinguish between any of the many different BCL6 translocation partners (e.g., immunoglobulin heavy and light chain genes, the PIM1 gene, and the transferrin receptor gene). Chromosomal translocations involving bcl-6 on 3q27 are one of the most common genetic alterations in B cell non-Hodgkin lymphomas and have been described in up to 35% of diffuse large B cell lymphomas (DLBCLs), follicular lymphomas, and so-called "double-hit" aggressive B cell lymphomas. Detection of translocations involving the bcl-6 gene on 3q27 can be helpful in sub-classifying B cell lymphomas including where folliciluar lymphoma is in the differential and in the evaluation of aggressive B cell lymphomas where Burkitt' lymphoma, atypical Burkitt's, DLBCL, and B cell lymphomas that are intermediate between DLBCL and BL are being considered. Probe type: Dual color breakapart

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Burkitt's Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: BCMA, or B cell maturation antigen, is a post-germinal center B-lymphoid antigen expressed by the great majority of benign and neoplastic plasma cells and by a smaller proportion of benign and neoplastic post-germinal center B cells. Subcelluar Localization: Membranous and/or cytoplasmic with golgi accentuation

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: This real time quantitative (RQ) PCR assay is performed on RNA extracted from fresh bone marrow or peripheral blood specimens. Results are reported using the International Scale, allowing for ready assessment of major molecular response (MMR). This test is indicated in the following settings: • To confirm the diagnosis of CML and ALL in new patients whose blood count suggests the diagnosis of a chronic myeloproliferative disorder or ALL. • To monitor response to therapy in ALL. • To monitor response to therapy in CML: In Chronic myelogenous leukemia (CML), RQ-BCR-ABL Mbcr PCR is recommended to be performed on a peripheral blood specimen in every new patient prior to therapy and then afterwards at 3 month intervals to monitor patient responsiveness to anti-tyrosine kinase therapy. Once complete cytogenetic remission is achieved BCR-ABL Mbcr transcript monitoring can be reduced to every 12 months. Type: Reverse Transcription PCR, Quantitative

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML)

Turnaround Time: Within 4-8 business days of receipt

Schedule: Started Monday, out for analysis on Tuesday

Specimen Requirements: • Specimen MUST be received within 48 hrs of collection • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top)

CPT Code(s): 81206. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: This real time quantitative (RQ) PCR assay is performed on RNA extracted from fresh bone marrow or peripheral blood specimens. Results are reported as a ratio of p190 transcript to ABL1 transcript. This test is indicated in the following settings: • To confirm the diagnosis of CML and ALL in new patients whose blood count suggests the diagnosis of a chronic myeloproliferative disorder or ALL. • To monitor response to therapy in ALL. • To monitor response to therapy in CML: In Chronic myelogenous leukemia (CML), RQ-BCR-ABL mbcr PCR is recommended to be performed on a peripheral blood specimen in every new patient prior to therapy and then afterwards at 3 month intervals to monitor patient responsiveness to anti-tyrosine kinase therapy. Once complete cytogenetic remission is achieved BCR-ABL mbcr transcript monitoring can be reduced to every 12 months. Type: Reverse Transcription PCR, Quantitative

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML)

Turnaround Time: Within 4-8 business days of receipt

Schedule: Started Monday, out for analysis on Tuesday

Specimen Requirements: • Specimen MUST be received within 48 hrs of collection • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top)

CPT Code(s): 81207. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: PhenoPath’s real-time PCR assay utilizes allele-specific PCR to detect BRAF V600 mutations, including the V600E BRAF mutation (c.1799T>A) as well as a subset of other less common activating BRAF V600 mutations (such as V600K, V600D, etc); however, these mutations cannot be distinguished by this assay. BRAF V600 mutations occur in a variety of human malignancies, including (but not limited to) subsets of colorectal carcinomas, papillary thyroid carcinomas, melanomas*, gastrointestinal stromal tumors (GIST) that are negative for KIT and PDGFRA mutations, CNS neoplasms, malignant peripheral nerve sheath tumors, Langerhans cell histiocytoses, and Erdheim-Chester disease; and in virtually all cases of hairy cell leukemia. In colorectal carcinomas, the V600E mutation has been associated with a lack of response to epidermal growth factor receptor (EGFR) targeted therapies (cetuximab or panitumumab). When evaluated in conjunction with KRAS/NRAS mutation testing, BRAF V600 mutation analysis may predict response to these therapies. Determination of BRAF mutation status can also be useful in the work-up hereditary non-polyposis colorectal carcinomas (HNPCC), as BRAF V600 mutations are found in non-hereditary/sporadic CRC cases exhibiting microsatellite instability, but not in HNPCC. *For BRAF V600 testing in melanomas, please see BRAF IVD cobas v600.

Organ: Lung, Brain/CNS, Skin & Mucosa, Blood/Bone Marrow, Colon & Other GI, Thyroid, Lymph Node / Spleen

Disease State: Hairy Cell Leukemia, Langerhans Cell Histiocytosis, Oligodendroglioma, Astrocytoma, Adenocarcinoma, Lynch Syndrome / HNPCC

Turnaround Time: Within 3-6 business days of receipt

Schedule: Tuesday and Friday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block, 10 FFPE tissue slides, or peripheral blood or bone marrow in EDTA or heparin.

CPT Code(s): 81210; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: The FDA-approved cobas 4800 BRAF V600 mutation test (IVD) is a real-time PCR assay designed to detect the presence of activating BRAF V600 mutations in melanoma and is the companion diagnostic test for the vemurafenib, a BRAF inhibitor. This assay will detect the V600E BRAF mutation (T1799A) as well as a subset of other less common activating BRAF V600 mutations (including some V600K BRAF mutations). BRAF mutations have been identified in 40% - 60% of malignant melanomas as well as other human cancers including colorectal cancer, ovarian cancer, and thyroid cancer. BRAF is part of a highly regulated signaling pathway that mediates the effects of growth factor receptors (such as EGFR) through RAS, RAF, MEK and ERK. Oncogenic mutations in BRAF result in a gain of kinase function, rendering the RAF-MEK-ERK pathway constitutively active in the absence of typical growth factors.

Organ: Skin & Mucosa

Disease State: Melanoma

Turnaround Time: Within 4-8 business days of receipt

Schedule: Wednesday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): 81210; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Loss of expression characterizes SMARCA4 deficient neoplasms. Subcellular Localization: Nuclear

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Sensitive but not highly specific marker of MALT lymphoma and pancreatic acinar cell carcinoma. Subcellular Localization: Cytoplasmic

Organ: Pancreas

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a cytoplasmic/mitochondrial protein that can promote tumorigenesis by inhibiting apoptosis, and represents a therapeutic target in several tumors. In the majority of follicular lymphomas, and in a significant subset of diffuse large B cell lymphomas (DLBCL) of germinal center phenotype, Bcl-2 is overexpressed as a result of the t(14;18). Non-t(14;18)-associated Bcl-2 expression occurs in other a variety of other lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and T cell lymphomas, and in other hematolymphoid neoplasms including acute myeloid leukemia. Importantly, bcl-2 is negative in Burkitt lymphoma. Among the non-hematopoietic neoplasms, synovial sarcomas and some muscle-derived tumors also have been shown to express Bcl-2. Subcellular Localization: Cytoplasmic

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, T Cell Non-Hodgkin Lymphoma (not otherwise classified)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Anti-bcl-2 rabbit monoclonal antibody clone SP66 replaces mouse monoclonal antibody clone C2 as Phenopath's alternative bcl-2 antibody, particularly for situations in which there is concern for a false negative result with our first-line anti-bcl-2 mouse monoclonal antibody clone 124. There are several published reports that SP66 is more sensitive than 124, presumably because SP66 recognizes a 36 amino acid epitope, while the 124 epitope is only 14 amino acids long. Clone 124 remains our first-line antibody because it provides stronger staining than SP66 for most of the tissues evaluated in our validation set, but for situations in which there is only a single recut section available for bcl-2 IHC, clone SP66 is recommended over 124. Subcellular Localiztion: Cytoplasmic

Turnaround Time: Within 3-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A nuclear protein expressed by both normal and neoplastic germinal center-derived B cells, with the neoplasms including the great majority of follicular lymphomas, the majority of diffuse large B cell lymphomas (including virtually all of germinal center origin), all Burkitt lymphomas, and all of the neoplastic “L&H” or "LP" cells of nodular lymphocyte predominant Hodgkin lymphoma. Bcl-6 is also expressed by the large majority of normal and neoplastic CD4+ T cells of follicular helper origin, including angioimmunoblastic lymphoma, and in normal and neoplastic squamous epithelium. Subcellular Localization: Nuclear

Organ: Pancreas

Disease State: Angioimmunoblastic T Cell Lymphoma, Burkitt's Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies pCAM, a glycoprotein expressed in the vast majority of adenocarcinoma. and almost always negative in mesothelioma. Best used as part of a panel including antibodies to other glycoproteins such as the MOC-31 antibody to epithelial glycoprotein-2 and the Bg8-defined Lewis Y antigen. Subcellular Localization: Membranous and cytoplasmic

Organ: Lung

Disease State: Mesothelioma vs. Adenocarcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Abnormal nuclear localization of beta catenin generally indicates the presence of a mutation in WNT/APC pathway. Such mutations are characteristic of abdominal fibromatoses. High levels of nuclear beta catenin expression can also be seen in endometrial stromal tumors, synovial sarcomas, solitary fibrous tumors, and a subset of colorectal and endometrial adenocarcinoma. Subcellular Localization: Cytoplasmic and membranous (normal); nuclear (abnormal)

Organ: OB/GYN, Pancreas

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A nuclear protein expressed by normal B-lymphoid cells throughout maturation, from immature forms to plasma cells. Bob-1 and Oct-2 are co-expressed in almost all non-Hodgkin lymphomas, plasma cell neoplasms, and nodular lymphocyte predominance lymphomas, but one or both is aberrantly lost in nearly all cases of classical Hodgkin lymphoma. Subcellular Localization: Nuclear

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Classical Hodgkin Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies chordomas. Negative in chondroid and myxoid tumors. Subcellular Localization: Nuclear (normal)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the protein product of the proto-oncogene first discovered in Burkitt’s lymphoma, overexpressed as a consequence of chromosomal translocation involving chromosome 8. Used to screen aggressive B cell non-Hodgkin lymphomas to identify those with high-level expression, corresponding to those tumors with a relatively high likelihood of harboring a c-MYC gene rearrangement by FISH. Subcellular Localization: Nuclear

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CAM5.2 is an antibody to "low molecular weight" cytokeratins, i.e., cytokeratin 8, which is expressed in a wide range of epithelial tumors.

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342

Methodology: FISH

Clinical Significance: FISH studies for inv(16) / t(16;16)(p13;q22) are clinically indicated in new diagnoses of acute myeloid leukemia (AML) for proper diagnostic classification, as the inv16/t(16;16) is a recurrent chromosomal abnormality in AML. FISH testing for this abnormality may also be indicated for follow-up studies to monitor disease progression and response to therapy. Translocations/inversions of chromosome 16 are found in about 10% of AML, with approximately half of these cases being AML M4 subtype with abnormal eosinophilia. The CBFB-MYH11 fusion gene is formed due to a pericentric inversion on chromosome 16, inv(16)(p13q22), or in rare instances, is due to a translocation: t(16;16)(p13;q22). Probe type: Dual color breakapart

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD10 is normally expressed by a variety of cell types, including normal and neoplastic immature B cells (B-lymphoblasts, in which CD10 is sometimes referred to as CALLA, or "Common Acute Lymphoblastic Leukemia Antigen), normal and neoplastic mature B cells of germinal center origin, normal and neoplastic mature neutrophils, normal and neoplastic gastrointestinal epithelium (brush border), and some other non-hematopoietic tumors including atypical fibroxanthoma. Subcellular Localization: membranous

Organ: Breast, Skin & Mucosa

Disease State: Spindle Cell Tumors / Sarcoma Subtyping, Angioimmunoblastic T Cell Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD103, or integrin αE, is preferentially expressed in human intestinal intraepithelial lymphocytes (IELs) and in specific types of lymphoid tumors. The main areas of diagnostic interest are the identification of hairy cell leukemia (HCL, almost always CD103+), and the distinction from marginal zone lymphomas and other potential HCL mimics (usually, but not always, CD103-negative). One other potential use of this antibody is the identification of intraepithelial gastrointestinal T cells (usually CD103+) and enteropathy-associated T cell lymphoma (EATL), a malignancy derived from these T cells, often in the setting of underlying celiac disease. Due to the the fact that CD103 is not a lineage-specific antigen, PhenoPath's policy is to run the B cell marker PAX-5 in conjunction with all CD103 test orders. Ref: AJCP 139:220-230, 2013 Subcellular Localization: Cytoplasmic and membranous with membranous accentuation

Organ: Blood/Bone Marrow, Colon & Other GI, Lymph Node / Spleen

Disease State: Hairy Cell Leukemia, Marginal Zone/MALT Lymphoma, T Cell Non-Hodgkin Lymphoma (not otherwise classified)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • Minimum of 4 unstained slides cut at 4µm

CPT Code(s): 88342 and 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the interleukin-3 receptor. CD123 is strongly expressed in normal and neoplastic plasmacytoid dendritic cells, moderately expressed in normal and neoplastic basophils, at variable intensity in classical hairy cell leukemia, in most B-ALLs (but not normal immature B cells), and in a subset of AMLs. Subcellular Localization: Membranous

Disease State: Hairy Cell Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies syndecan-1, a cell surface-associated protein expressed in plasma cells and plasmacytoid B cells, and on neoplasms derived from these cells, including almost all plasmacytic/plasmablastic neoplasms. CD138 is also expressed by a significant subset of normal and neoplastic epithelia. Subcellular Localization: Membranous

Disease State: B Cell NHL with Plasmacytoid Differentiation

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: The expression of CD14 by IHC is a useful biomarker for distinguishing normal and neoplastic mature monocytes from both immature monocytes and other hematolymphoid cell types. CD14 is a glycoprotein expressed on mature monocytes and histiocytes/macrophages, and to a lesser degree on neutrophils, and is a receptor for bacterial lipopolysaccharide (LPS), thus functioning as an opsonic receptor to facilitate phagocytic uptake. Subcellular Localization: Membranous and cytoplasmic

Organ: Lung, Skin & Mucosa, Blood/Bone Marrow, Lymph Node / Spleen, Soft Tissue

Disease State: Spindle Cell Tumors / Sarcoma Subtyping, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML), Langerhans Cell Histiocytosis, Myelodysplastic Syndromes

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A cytoplasmic- and cell surface-associated protein that is strongly expressed by normal granulocytes at the promyelocyte and later stages, and is expressed at lower levels on monocytes/histiocytes; marked CD15 downregulation in the neoplastic cells of acute promyelocytic leukemia, compared to the high-level expression in normal promyelocytes, can be a helpful diagnostic finding. CD15 is aberrantly coexpressed by myeloblasts in a subset of myeloid stem cell neoplasms. In addition, CD15 is expressed in a membrane and/or Golgi pattern in most of cases of classical Hodgkin lymphoma. Finally, CD15 is expressed by a subset of normal and neoplastic epithelia. Subcellular Localization: Membranous

Disease State: Classical Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD163 is a transmembrane protein that acts as a scavenger receptor, and is restricted in its expression to monocytes/macrophages in the M2 activation stage, as opposed to CD68 expression, which is expressed by monocytes/ macrophages in both the M1 and M2 activation states. Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD19, like the CD79 complex and cytoplasmic CD22, is a pan-B-lineage antigen that is first expressed in very early B-lymphoid progenitors, and continues to be expressed at variable levels through terminal B-lymphoid differentiation in plasma cells. With the exception of true plasma cell neoplasms and classical Hodgkin lymphoma, the great majority of mature and immature B-lymphoid neoplasms express CD19. Some neoplasms such as hairy cell leukemia overexpress CD19, while others such as follicular lymphoma typically underexpress CD19. Rare non-B-lymphoid neoplasms express CD19, most notably acute myeloid leukemia (AML) bearing the t(8;21). Subcellular Localization: Mainly membranous; partially cytoplasmic

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), B Cell NHL with Plasmacytoid Differentiation, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Hairy Cell Leukemia, HIV-Associated Lymphoma, Mantle Cell Lymphoma, Marginal Zone/MALT Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma, Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Plasma Cell Myeloma/Neoplasm, Lymphoplasmacytic Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD1a is a cell surface-associated protein expressed at the common thymocyte (dual CD4+ and CD8+) stage of T cell development in the thymus, and is therefore expressed on a subset of precursor T lymphoblastic leukemias/lymphomas corresponding to this stage of T cell development. CD1a is also expressed on the great majority of normal and neoplastic Langerhans cells, and is a good marker to assess the extent of dermatopathic change in the interfollicular zone of lymph nodes. Subcellular Localization: Membranous and cytoplasmic

Disease State: Precursor T-Lymphoblastic Lymphoma/Leukemia (T-ALL), Langerhans Cell Histiocytosis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD2 is a cell surface-associated protein expressed in both mature and immature T cells, as well as most natural killer (NK) cells. CD2 is aberrantly decreased in a subset of T cell and natural killer cell neoplasms. Many cases of systemic mastocytosis, and some cases of acute myeloid leukemia and chronic myelomonocytic leukemia, show aberrant coexpression of CD2 on the neoplastic cells. Subcellular Localization: Membranous

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Angioimmunoblastic T Cell Lymphoma, NK/T Cell Lymphoma, Nasal Type, Mastocytosis, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD20 is a cell surface-associated protein expressed during the middle to later stages of B cell development in the bone marrow, and on all normal mature B cells. CD20 ceases to be expressed at the terminal differentiation of B cells to plasma cells. CD20 is expressed on the great majority of mature B cell neoplasms, and on a significant subset of immature B cell neoplasms, but only on a minority of plasmacytic neoplasms, particularly those bearing the t(11;14). CD20 is the target of a number of therapeutic antibodies used to treat B cell malignancies. Subcellular Localization: Membranous

Organ: Blood/Bone Marrow

Disease State: Large Cell Undifferentiated Malignant Neoplams, B Cell Non-Hodgkin Lymphoma (not otherwise classified), Classical Hodgkin Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD200, a cell surface antigen expressed in a variety of benign and neoplastic tissues, is thought to promote immune evasion by tumors. CD200 evaluation can help distinguish chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL, usually CD200-positive) from mantle cell lymphoma (usually CD200-negative). CD200 is also expressed by hairy cell leukemia, and most neuroendocrine carcinomas. Among the large B cell non-Hodgkin lymphomas, CD200 expression has been associated with the primary mediastinal subtype. Subcellular Localization: Membranous and cytoplasmic

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Angioimmunoblastic T Cell Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD21 is a cell surface-associated protein expressed in the follicular dendritic cells (FDCs) of lymphoid tissues, and in tumors derived from FDCs. Disruption of CD21-positive FDC meshworks can be seen in a variety of B cell lymphomas, and in angioimmunoblastic T cell lymphomas. CD21 is also expressed by a significant subset of B cells, and is the receptor for Epstein-Barr virus. Subcellular Localization: Membranous

Disease State: Angioimmunoblastic T Cell Lymphoma, Follicular Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma, Follicular Dendritic Cell Sarcoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD22 is expressed in the cytoplasm of virtually all normal and neoplastic B cells, including both mature and immature forms, and on the surface of the large majority of these B cells. In contrast, normal and neoplastic plasma cells are usually CD22-negative. Subcellular Localization: Membranous

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD23 is a cell surface-associated protein expressed on a subset of activated B cells, and on the subset of follicular dendritic cells (FDCs) that envelopes the germinal center, but typically not the mantle zone. CD23 is usually coexpressed with CD5 on the neoplastic B cells of CLL/SLL, but is only rare coexpressed with CD5 in mantle cell lymphoma. Among the large B cell non-Hodgkin lymphomas, CD23 expression has been associated with the primary mediastinal subtype. Subcellular Localization: Membranous

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Follicular Lymphoma, Follicular Dendritic Cell Sarcoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD25 (IL-2Rα) is a cell surface-associated protein that is the receptor for interleukin-2. CD25 is expressed on a significant subset of activated T cells, and tends to be strongly expressed on the neoplastic T cells of adult T cell leukemia/lymphoma and anaplastic large cell lymphoma. CD25 is also coexpressed on a subset of B cell neoplasms, most notably hairy cell leukemia. Aberrant CD25 expression on mast cells is an important immunophenotypic clue to the diagnosis of systemic mastocytosis. Subcellular Localization: Membranous

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Hairy Cell Leukemia, Mastocytosis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD3 is a multimeric cell surface-associated protein expressed in T cells in association with the T cell antigen receptor. Cell surface CD3 begins to be expressed during T cell development in the thymus, and is expressed throughout later T cell maturation. CD3 is aberrantly decreased in a subset of T cell neoplasms. NK cells do not express surface CD3, but do express the epsilon chain of CD3 in the cytoplasm. Subcellular Localization: Membranous

Disease State: Angioimmunoblastic T Cell Lymphoma, NK/T Cell Lymphoma, Nasal Type, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD30 is a cytoplasmic- and cell surface-associated protein expressed by a significant subset of activated B cells and T cells. CD30 is expressed at variable levels by Reed-Sternberg cells and variants in the majority of cases of classical Hodgkin lymphoma. Among the non-Hodgkin lymphomas, CD30 is strongly and uniformly expressed in anaplastic large cell lymphoma, and at variable levels in a significant subset of other non-Hodgkin lymphomas, particularly those of large cell type. CD30 is also expressed by embryonal carcinomas. Subcellular Localization: Membranous and cytoplasmic

Organ: OB/GYN, Genitourinary, Testis, Ovary

Disease State: Large Cell Undifferentiated Malignant Neoplams, Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Classical Hodgkin Lymphoma, Mastocytosis, Germ Cell Tumors

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies PECAM-1, a cell surface adhesion molecule expressed on the surface of endothelial cells and is an excellent marker of vascular neoplasms, e.g., angiosarcoma. CD31 can also be expressed by platelets, macrophages, and plasma cells. Subcellular Localization: Membranous Subcellular Localization: Membranous

Disease State: Large Cell Undifferentiated Malignant Neoplams, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Expressed at varying levels on virtually all normal and neoplastic myeloid and monocytic cells, with the highest levels of expression on monocytes/macrophages and mast cells. Some cases of B-ALL and multiple myeloma also express CD33. Subcellular Localization: Membranous Subcellular Localization: Membranous

Disease State: Plasma Cell Myeloma/Neoplasm, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD34 is a transmembrane sialomucin expressed in hematolymphoid stem and progenitor cells, as well as endothelial cells. It is also a marker of a unique subset of mesenchymal tumors (e.g., solitary fibrous tumor, dermatofibrosarcoma protuberans, epithelioid sarcoma, gastrointestinal stromal tumor, etc.). Subcellular Localization: Membranous

Organ: Skin & Mucosa, Liver, Colon & Other GI

Disease State: Large Cell Undifferentiated Malignant Neoplams, Spindle Cell Tumors / Sarcoma Subtyping, Hepatocellular Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A marker of both benign and malignant follicular dendritic cells (FDC), that can be used in addition to CD21, CD23, and podoplanin to identify these cells. Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD38 is a transmembrane glycoprotein expressed by a variety of leukocytes, including plasma cells (which show the highest levels of expression, such that targeted anti-CD38 therapy is common in multiple myeloma), immature and mature B and T cells, NK cells, monocytes/macrophages, and myeloid progenitors. In mature B cells, CD38 expression is induced when naive B lymphocytes are activated by antigen, reaches a first peak when B cells enter the germinal center, decreases during the transition to memory B cells, and reaches its maximum levels as B cells terminally differentiate to plasma cells. In HIV, increased T-cell CD38 expression is associated with disease progression. CD38 expression has been described in some non-hematopoietic tissues. Subcellular Localization: Membranous

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: B Cell NHL with Plasmacytoid Differentiation, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), HIV-Associated Lymphoma, Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Plasma Cell Myeloma/Neoplasm, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Lymphoplasmacytic Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD4 is a cell surface-associated protein expressed at relatively high levels in helper T cells, and at lower levels in monocytes/macrophages and plasmacytoid dendritic cells. CD4 is also the receptor for HIV. CD4 is aberrantly decreased in a subset of T cell neoplasms, and is commonly expressed in monocytic/histiocytic neoplasms. Subcellular Localization: Membranous

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Angioimmunoblastic T Cell Lymphoma, Blastic Plasmacytoid Dendritic Cell Neoplasm, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD42b, also known as platelet glycoprotein Ib, is a cell surface and transmembrane glycoprotein, expression of which commences somewhat later in megakaryocytic development compared to CD61. CD42b is also expressed by platelets.  Some cases of Bernard-Soulier syndrome involve congenital deficiency of CD42b. Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies leukosialin, expressed on all normal leukocytes except most mature B cells. CD43 coexpression on normal B cells in the terminal ileum has been described, but outside of this location, significant mature B cell co-expression of CD43 is often a neoplastic feature, as in CLL/SLL and mantle cell lymphoma. Subcellular Localization: Membranous

Disease State: Small, Blue, Round Cell Tumors, Large Cell Undifferentiated Malignant Neoplams, Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Angioimmunoblastic T Cell Lymphoma, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma, Marginal Zone/MALT Lymphoma, NK/T Cell Lymphoma, Nasal Type, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Blastic Plasmacytoid Dendritic Cell Neoplasm, Langerhans Cell Histiocytosis, Lymphoplasmacytic Lymphoma, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies leukocyte common antigen (LCA), a family of cell surface proteins expressed at variable levels in all normal hematopoietic cells, with the exception of erythroid cells that have matured past proerythroblasts. A variety of hematopoietic neoplasms show aberrant increases or decreases in the level of CD45 expression. Some degree of aberrant loss of CD45 is seen in a subset of precursor B-lymphoblastic leukemias, in the majority of multiple myelomas, and in nearly all cases of classical Hodgkin's lymphoma (on Reed-Sternberg cells and variants). Subcellular Localization: Membranous

Disease State: Large Cell Undifferentiated Malignant Neoplams, Angioimmunoblastic T Cell Lymphoma, Classical Hodgkin Lymphoma, NK/T Cell Lymphoma, Nasal Type, Nodular Lymphocyte-Predominant Hodgkin Lymphoma, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD5 is a cell surface-associated protein expressed in mature and immature T cells, but not in NK cells. CD5 is aberrantly decreased in a subset of T cell neoplasms. CD5 shows characteristic aberrant expression by two B cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma, although a small number of other B cell neoplasms can show low-level coexpression of CD5. Subcellular Localization: Membranous

Disease State: Angioimmunoblastic T Cell Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This tube assesses CD52 and CD22 on CD5+ B cell neoplasms (i.e., CLL/SLL and MCL). In addition to these two antibodies, this tube includes antibodies to CD45, CD19, CD5, CD49d, and CD79b; the latter two antibodies can aid in the distinction of CLL/SLL from MCL.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x7. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies neural cell adhesion molecule (NCAM), a cell surface-associated protein expressed by NK cells and a subset of activated T cells, in addition to a variety of neuroectodermally-derived structures. CD56 is expressed on the majority of neoplasms of NK cell and plasmacytoid dendritic cell origin, and on a subset of T cell neoplasms, particularly those of cytotoxic origin. CD56 is aberrantly expressed by myeloid blasts, granulocytes, and/or monocytes in a subset of acute myeloid leukemias and myelodysplastic/myeloproliferative syndromes, and by the neoplastic plasma cells in the majority of multiple myelomas. Finally, CD56 is strongly expressed by small blue round cell tumors of neuroectodermal origin, and by neuroendocrine carcinomas. Subcellular Localization: Membranous

Organ: Brain/CNS

Disease State: Small, Blue, Round Cell Tumors, NK/T Cell Lymphoma, Nasal Type, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the ITGB3 gene product, also known as integrin beta chain beta 3 or glycoprotein 3a. It is employed as a marker of megakaryocytes and platelets. Subcellular Localization: Membranous and cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a cytoplasmic/lysosome-associated protein expressed by virtually all normal and neoplastic monocytes/histiocytes, including Langerhans cells, as well as normal and neoplastic plasmacytoid dendritic cells. Subcellular Localization: Cytoplasmic

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Langerhans Cell Histiocytosis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD7 is a cell surface-associated protein expressed in both mature and immature T cells, as well as NK cells. CD7 is aberrantly decreased in a subset of T cell and natural killer cell neoplasms, and aberrantly increased on the blasts in a significant subset of myeloid neoplasms, including acute myeloid leukemia and myelodysplastic or myeloproliferative syndromes. Subcellular Localization: Membranous

Disease State: Angioimmunoblastic T Cell Lymphoma, Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the transferrin receptor, which is required for the delivery of iron to cells, particularly erythroid precursors, such that CD71 is expressed at high level in both normal and abnormal erythroid precursors. Subcellular Localization: Strong membranous staining with weak cytoplasmic staining in some cases

Organ: Blood/Bone Marrow

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CD79a is a cytoplasmic antigen expressed at all stages of B cell maturation, from lymphoblasts through plasma cells. CD79a expression is very low to absent in most cases of classical Hodgkin lymphoma (as opposed to higher level expression in other B-lymphoid neoplasms of large cell size), and in a subset of non-Hodgkin B cell lymphomas. Subcellular Localization: Cytoplasmic (inner membrane)

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Classical Hodgkin Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a cell surface-associated protein expressed at relatively high levels by cytotoxic/suppressor T cells (which express the alpha-beta heterodimer of CD8), and at lower levels by gamma-delta T cells and natural killer cells (both of which express the alpha-alpha homodimer of CD8). CD8 is aberrantly decreased in a subset of T cell and NK cell neoplasms. Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Cadherin 17 is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption. Cadherin 17 is expressed in the epithelial cells of embryonic and adult small intestine, colon, and pancreatic ducts. It has also been reported to be frequently expressed in adenocarcinomas arising in the gastrointestinal tract and pancreas. Owing to its restricted expression in these groups of tumors, cadherin 17 can be a useful immunohistochemical marker for assisting in distinguishing these neoplasms from other malignancies. The performance characteristics of this antibody have been established within the context of carcinomas arising at different primary sites. This anti-cadherin 17 antibody displays a sensitivity of 95% and a specificity of 95% for colorectal adenocarcinoma. Subcellular Localization: predominantly membranous with a smaller cytoplasmic component

Organ: Colon & Other GI

Disease State: Carcinomas of Unknown Primary, Adenocarcinoma, Metastatic Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CDX2 is an intestinal-specific transcription factor, highly expressed in colorectal adenocarcinomas, with a sensitivity > 95%, and also expressed, at lower levels, and with a lower sensitivty, in the vast majority of non-colorectal GI carcinomas, i.e., those primary to the pancreatobiliary tract and stomach. CDX2 is also expressed in neuroendocrine carcinomas of the GI tract. Subcellular Localization: Nuclear

Organ: Liver, Colon & Other GI, Pancreas

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: FISH

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL)

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88367 or 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Partial hydatidiform moles have defined histologic abnormalities including dual discrete populations of villi, circumferential mild trophoblastic hyperplasia, trophoblastic inclusions, scalloping of villi, and cistern formation. Nonetheless, morphologic features alone may not be sufficient to confirm the diagnosis of partial hydatidiform mole in some cases, particularly those in the early first trimester. Furthermore, there is significant inter- and intra-observer variability in the diagnosis of hydatidiform mole, with significant problems in differentiating partial hydatidiform moles from hydropic spontaneous abortions. In this assay, the CEP17 probe is used for analysis and interpretation of ploidy status. Identification of triploidy by CEP17 FISH helps to confirm the diagnosis of partial hydatidiform mole and can be used to separate partial hydatidiform moles from complete hydatidiform moles and hydropic products of conception. Probe type: Enumeration (single-color)

Organ: OB/GYN

Disease State: Molar Pregnancy

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested plus 2 unstained slides cut at 6µm

CPT Code(s): 88367 or 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH test detects Trisomy 8, which is a chromosomal abnormality seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This FISH test is frequently utilized in the workup of MDS, which is a heterogeneous group of clonal myeloid stem cell disorders. Trisomy 8 as a sole abnormality is associated with an intermediate prognosis. Probe type: Single color enumeration

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88367 or 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies squamous and transitional cell epithelia, mesothelium, ductal epithelium and their corresponding carcinomas. In complex epithelia such as normal prostate glands, the basal cells in most cases express CK5. CK5 expression can also be seen in some nonsquamous carcinomas, e.g., pancreatic adenocarcinoma. Subcellular Localization: Cytoplasmic

Organ: Lung, Breast, Genitourinary, Prostate

Disease State: Carcinomas of Unknown Primary, Mesothelioma vs. Adenocarcinoma, Spindle Cell Tumors / Sarcoma Subtyping, Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC), Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: This assay is indicated as an aid in identifying patients with gastric or GEJ adenocarcinoma who may be eligble for treatment with VYLOY (zolbetuximab), that are HER2 negative, in accordance with the approved theraputic product labeling.

Turnaround Time: Within 2-3 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: In combination with CD5+ B cell therapy tube, this tube helps distinguish CLL/SLL from mantle cell lymphoma. This tube includes antibodies to CD45, FMC7, CD19, CD22, CD5, CD23, CD200, and CD43.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x10. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has several recurrent and prognostic genetic alterations that have been characterized and are useful in the management of patients. Loss of 13q14.3 is the most common molecular alteration in CLL/SLL (~36% of all CLL/SLL cases) and as a sole abnormality often portends a favorable clinical course. Loss of 17p13.1(P53) or 11q22.3(ATM) are less common and are adverse prognostic markers in CLL/SLL. Trisomy 12, as detected by CEP12 FISH is a marker of intermediate prognosis. This panel includes IGH and t(11;14) FISH probes to aid in the differentiation of CLL/SLL cases from mantle cell lymphoma.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL)

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374x5, 88367. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: The hallmark of chronic myelogenous leukemia (CML) is the presence of the BCR-ABL fusion gene associated with the Philadelphia chromosome (Ph). All cases of CML have a t(9;22) or variant and detection of this genetic abnormality is important in the diagnosis of CML. The BCR/ABL fusion gene resulting from the t(9;22) is the target for the tyrosine kinase inhibitor drug imatinib.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML)

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: CXCL13 is a chemokine that is a relatively specific marker of follicular helper T cells (TFH cells), the presumed cell of origin in angioimmunblastic T cell lymphoma and other related lymphomas.  CXCL13 is a less sensitive but more specific marker of TFH cells than CD10, bcl-6, or PD-1.  By immunohistochemistry, CXCL13 shows granular cytoplasmic reactivity in well-fixed FFPE, but may yield false negative results in suboptimally fixed FFPE. Subcellular Localization: Cytoplasmic (typically granular)

Organ: Blood/Bone Marrow, Lymph Node / Spleen, Soft Tissue

Disease State: Angioimmunoblastic T Cell Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Identifies C cells of the thyroid gland and medullary thyroid carcinomas. Subcellular Localization: Cytoplasmic

Organ: Thyroid

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Smooth muscle marker that is useful in the identification of leiomyosarcoma. Generally negative in endometrial stromal tumors. Subcellular Localization: Cytoplasmic

Organ: OB/GYN

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Calponin is a smooth muscle specific cytoskeletal protein useful in the identification of smooth muscle tumors and myoepithelium. Calponin is useful as a tool to demonstrate the presence or absence of myoepithelium in breast lesions. Subcellular Localization: Cytoplasmic

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: Length-affecting mutations (insertions or deletions) within exon 9 of the Calreticulin (CALR) gene have been described in approximately 70% of essential thrombocythemia (ET) and approximately 60-80% of primary myelofibrosis (PMF) patients without JAK2 or MPL mutations. CALR exon 9 insertion/deletion mutations have not been identified in polycythemia vera (PV) patients.

Organ: Blood/Bone Marrow

Disease State: Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML)

Turnaround Time: Within 4-8 business days of receipt

Schedule: Friday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block, 10 FFPE tissue slides, or peripheral blood or bone marrow in EDTA or heparin.

CPT Code(s): 81219. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A sensitive and relatively specific marker of mesothelial cells and mesothelioma, helping to distinguish the latter from adenocarcinoma. Also identifies ovarian stromal tumors. Subcellular Localization: Nuclear and cytoplasmic

Organ: Lung, OB/GYN, Ovary

Disease State: Mesothelioma vs. Adenocarcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies renal cell carcinoma, as well as other clear cell carcinomas, e.g., from urothelium and adrenal cortex. May also provide prognostic information in CRCC, with low CA-IX expression correlating with poor survival. Subcellular Localization: Cytoplasmic and membranous

Organ: Genitourinary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Cathepsin K is a protease that is involved in bone resorption, and is highly expressed in osteoclast. Its expression has also been demonstrated in normal skin and lung fibroblasts. In neoplastic tissue, Cathepsin K has been reported to be expressed in most mesenchymal tumors, but only rarely in carcinomas. Cathepsin K is positive in the majority of translocation renal cell carcinomas (seven of the Alpha-TFEB gene fusion translocation), and in all 5 of the most common TFE3-positive renal cell carcinomas bearing the t(X;1)(p11.2;q21) translocation. This assay is intended for the identification of these renal cell carcinomas. Published data suggest that TFE3 expression leads to cathepsin K expression. While less sensitive than TFE3, cathepsin K has also been demonstrated in a subset of renal cell carcinomas showing a different translocation, t(6;11). While these latter translocations cannot be identified with antibodies to TFE3, they may account for the apparent reduced specificity of cathepsin K in our study, as the TFE3-negative, Cathepsin K-positive renal cell carcinomas may well correspond to these t(6;11) translocation renal cell carcinomas. Final determination of translocation status in renal cell carcinomas may require FISH or PCR studies. Subcellular Localization: Cytoplasmic

Organ: Genitourinary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a protein unique to the dense core granules of neuroendocrine cells and tumors. It is an excellent marker for carcinoid tumors, pheochromocytomas, paragangliomas, but not as good a marker of high-grade neurendocrine carcinomas as synaptophysin. Subcellular Localization: Cytoplasmic, often with a granular pattern

Organ: Colon & Other GI, Pancreas

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Cytogenetics

Clinical Significance: Chromosomal analysis studies are available on the following specimen types: Bone marrow, peripheral blood, lymph node or other neoplastic tissues with suspect hematologic abnormalities.

Turnaround Time: Blood, bone marrow aspirates and lymph nodes: 7-8 business days (up to 10 days for complex cases) Solid Tumor: 10-14 business days

Schedule: Monday-Saturday

Specimen Requirements: • Bone Marrow Aspirate: In sodium heparin (Green Top vacutainer), 1-2 ml - OR - • Peripheral Blood: In sodium heparin (Green top vacutainer), 5 ml; patient should have WBC of 15,000 or higher, with 10% circulating immature myeloid or lymphoid blast cells - OR - • Solid Tumor Tissue/ Lymph Node: In sterile RPMI or tissue culture media • STORAGE TEMP: Room temperature • NOTE: EDTA is NOT acceptable for cytogenetics studies

CPT Code(s): 88237, 88264, 88280, 88291 (may include 88285 or additional units of 88280; 88239 used in lieu of 88237 for solid tumor). The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a heterodimeric protein associated with clearance of cell debris and apoptosis. Clusterin IHC can aid in differenting anaplastic large cell lymphoma (ALCL, usually clusterin-positive) from peripheral T cell lymphoma (PTCL), NOS, which is usually clusterin-negative, but otherwise lacks sufficient lineage specificity to be very useful diagnostically. Subcellular Localization: Cytoplasmic, in a granular diffuse and/or a Golgi pattern

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Diffuse Large B Cell Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Immunofluorescence

Clinical Significance: Identifies: C3 localization by direct immunofluorescence is useful in the subclassification of bullous and other skin disorders, particularly when employed as part of a panel of FITC-conjugated antibodies, including those to IgG, IgM and IgA. Subcellular Localization: Extracellular

Organ: Skin & Mucosa

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: Skin biopsy in Michel's (aka Zeuss) fixative, with or without patient serum

CPT Code(s): 88346 or 88350. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Disease State: Amyloid Type Analysis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 1 unstained slide cut at 8µm plus 2 unstained slide cut at 8-10µm

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Plasma cell myeloma (or multiple myeloma) is a malignant disorder in which clonal plasma cells accumulate in the bone marrow. This incurable disease is heterogeneous, with survival range varied from a few weeks of diagnosis to more than ten years. Other groups have published numerous studies demonstrating the presence of hyperdiploidy is associated with a favorable prognosis as these patients showed less aggressive clinical features, prolonged remission and higher survival. Hyperdiploidy is characterized by trisomy or tetrasomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and/or 21. Probe type: Enumeration

Organ: Blood/Bone Marrow, Body Fluids

Disease State: Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88367 or 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies cyclin D1, one of the more frequently altered cell cycle regulators in cancers. Uniform overexpression of cyclin D1 is very helpful in the identification of both mantle cell lymphomas and myelomas bearing the t(11;14). Subcellular Localization: Nuclear

Disease State: Hairy Cell Leukemia, Mantle Cell Lymphoma, Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Please see Keratin 17

Methodology: IHC

Clinical Significance: Please see Keratin 19

Methodology: IHC

Clinical Significance: Please see Keratin 20

Methodology: IHC

Clinical Significance: Please see CK5/6

Methodology: IHC

Clinical Significance: Please see Keratin 7

Methodology: IHC

Clinical Significance: Please see Keratins (AE1/AE3)

Methodology: IHC

Clinical Significance: Please see Keratins (OSCAR)

Methodology: IHC

Clinical Significance: Please see Keratins, high molecular weight (34βE12)

Methodology: IHC

Clinical Significance: This clone identifies CMV infected cells in tissue sections. No cross-reactivity with other herpes viruses or adenoviruses. Subcellular Localization: Nuclear and cytoplasmic

Disease State: Identification of Organisms

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This two-tube assay is designed to confirm blast lineage in the setting of acute leukemia. These tubes include surface antibodies to CD45, CD34, CD117, CD19, and CD38; one tube contains antibodies to cytoplasmic myeloperoxidase, cytoplasmic CD79a, and cytoplasmic CD3, while the other tube contains isotype controls for the cytoplasmic antibodies.

Organ: Brain/CNS, Blood/Bone Marrow, Lymph Node / Spleen, Thymus (Mediastinal Mass)

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Precursor T-Lymphoblastic Lymphoma/Leukemia (T-ALL), Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x8. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies DOG1, a novel marker of gastrointestinal stromal tumors (GISTs), and complements other markers such as c-kit (CD117). DOG1 is expressed in a significant subset of c-kit-negative GISTs. Subcellular Localization: Cytoplasmic and membranous

Organ: Colon & Other GI

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Desmin is an intermediate filament protein, expression of which is largely restricted to skeletal, smooth and cardiac muscle cells and tumors (e.g., leiomyosarcoma, rhabdomyosarcoma). Also expressed in reactive mesothelium, angiomatoid fibrous histiocytoma, and a subset of carcinomas. Subcellular Localization: Cytoplasmic

Organ: Skin & Mucosa

Disease State: Small, Blue, Round Cell Tumors, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies E-cadherin, a transmembrane protein that functions in cell-cell adhesion. Lobular carcinomas of the breast can be distinguished from ductal carcinomas by the presence in the former of genetic or epigenetic changes affecting the E-cadherin gene resulting in loss, or profound reduction, of expression of E-cadherin protein. Among the hematolymphoid cells, E-cadherin expression is relatively specific to the earliest stages of erythroid maturation, particularly the proerythroblast and basophilic erythroblast stages. Subcellular Localization: Membranous

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: CISH

Clinical Significance: Identifies: EBER-1, one of the Epstein-Barr virus (EBV)-encoded small non-polyadenylated RNAs (EBERs) that represent the most abundant viral transcripts in latently EBV-infected cells. Subcellular Localization: Nuclear

Disease State: Identification of Organisms, Angioimmunoblastic T Cell Lymphoma, Burkitt's Lymphoma, Classical Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, HIV-Associated Lymphoma, Post-Transplant Lymphoproliferative Disorders

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 3-4 additional unstained slides cut at 4µm

CPT Code(s): 88365. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies EBV LMP-1 (latent membrane protein-1), a cell surface-associated protein encoded by the EBV genome and expressed by a subset of EBV-infected B cells, more commonly in tonsils than in lymph nodes of EBV-infected individuals. LMP-1 is a much less sensitive marker of EBV infection than EBER1 mRNA; the latter is detected by in situ hybridization. Subcellular Localization: Membranous

Disease State: Identification of Organisms, Post-Transplant Lymphoproliferative Disorders

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies epidermal growth factor receptor (EGFR), a transmembrane protein expressed by a subset of carcinomas and other tumors. EGFR is the target of small molecules such as gefitinib and erolitinib, as well as humanized monoclonal antibodies such as cetuximab. Alterations in copy numbers of EGFR can be detected by FISH and mutations of EGFR gene can be detected by PCR. Subcellular Localization: Membranous

Organ: Lung, Colon & Other GI

Disease State: Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: EGFR gene amplification has been reported in a subset of colorectal adenocarcinomas, lung non-small cell carcinomas, and glioblastoma multiforme. Amplification the EGFR gene can often result in overexpression of epidermal growth factor and may contribute to tumorigenesis. With the availability of anti-EGFR monoclonal antibody therapy and small molecular EGFR inhibitors, assessment of EGFR gene amplification may be warranted in some tumors to predict those that may respond to anti-EGFR therapy. This FISH assay uses the established method described by Capuzzo et al., to evaluate tumors for EGFR high polysomy and amplification. Probe type: Dual color enumeration

Organ: Lung

Disease State: Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: The Roche cobas® EGFR Mutation Test v2 is an FDA-approved companion diagnostic for both first and second line therapy decisions for patients with non-small cell lung carcinoma (NSCLC). This assay is FDA approved for identifying NSCLC patients with EGFR exon 19 deletions and exon 21 (L858R) substitution mutations for whom treatment with Tarceva® (erlotinib) may be effective as a first line therapy; and for identifying NSCLC patients who harbor a T790M mutation, indicating eligibility for treatment with Tagrisso® (osimertinib) as second line therapy. Per the FDA news release of November 13, 2015, Tagrisso® (AZD9291) is the only approved medicine indicated for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after EGFR tyrosine kinase inhibitor therapy. Effective Tuesday, November 17, 2015, the Roche cobas® EGFR Mutation Test v2 replaced PhenoPath’s prior EGFR mutation assay. The Roche cobas® assay similarly uses qualitative real-time PCR to detect clinically relevant mutations in exons 18, 19, 20, and 21 of the EGFR gene and provides improved sensitivity as only 5% mutant allele is needed for reliable mutation detection in a background of wild-type DNA. In addition, the cobas® EGFR assay covers a greater number of mutations, identifying 42 mutations in exons 18-21, as compared to the 21 mutations covered by PhenoPath’s prior assay.

Organ: Lung

Disease State: Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 3-5 business days of receipt

Schedule: Tu, W, F

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): 81235; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH probe set detects deletion 5q31 and monosomy 5, which are chromosomal abnormalities seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This FISH test is frequently utilized in the workup of MDS, which is a heterogeneous group of clonal myeloid stem cell disorders. Deletion of 5q31 is associated with a favorable prognosis while monosomy 5 is associated with a poor prognosis. Patients with deletion 5q31 are eligible for Revlimid® (lenalidomide) therapy. Probe type: Dual color enumeration

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Epithelial membrane protein (EMA), a transmembrane glycoprotein encoded by the MUC1 gene. Expression of EMA can assist in the identification of metastatic v. primary cancers in the liver, nerve sheath tumors, meningioma, anaplastic large cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and plasma cell neoplasms. Subcellular Localization: Membranous

Disease State: Large Cell Undifferentiated Malignant Neoplams, Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: ERG is a member of the ETS transcription factor gene family, whose members also include FLI1 and ETS1. It is strongly  expressed in endothelial cells and is a highly sensitive and specific marker of vascular neoplasms. Amongst carcinomas, expression of ERG is highly restricted to a subset (40-50%) of prostatic adenocarcinomas. (Miettinen M et al., Am J Surg Pathol. 35:432-41, 2011; Yaskiv O et al., Am J Clin Pathol 138:803-10, 2012). Subcellular Localization: Nuclear

Organ: Prostate, Soft Tissue

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This FISH assay detects most rearrangements involving the EWSR1 gene irrespective of translocation partner. Genetic approaches to identify rearrangements of the EWSR gene on chromosome 22q12, characteristic of over 90% of PNET/Ewing sarcomas, have become the method of choice for confirming this diagnosis. EWSR1 gene translocation can be identified in a number of different tumors including: 1) primitive neuroectodermal tumor (PNET/Ewing sarcoma) with t(11;22)(q24;q12) involving the EWSR1/Fli-1 as well as other EWSR1 variant translocations, 2) desmoplastic small round cell tumors (DSRCT) with t(11;22)(p13;q12) involving EWSR1/WT-1, 3) clear cell sarcoma (CCS), detecting t(12;22)(q13;q12) involving EWSR1/ATF1, and 4) extraskeletal myxoid chondrosarcomas (EMCs with t(9;22)(q22;q11-12) involving EWSR1/CHN. This assay is therefore of use when these tumors are being considered in a tumor differential. Probe type: Dual color breakapart

Organ: Soft Tissue

Disease State: Small, Blue, Round Cell Tumors, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Idiopathic hypereosinophilic syndrome (HES), or primary eosinophilia, is a chronic and typically slowly progressive disease that eventually results in organ damage. Several molecular mechanisms have been identified, including FIP1L1-PDGFRα and rearrangements of PDGFRβ and FGFR1. The presence of any of these abnormalities is associated with positive response to imatinib mesylate (Gleevec) therapy. While molecularly defined eosinophilias are relatively rare, up to one-quarter of HES patients have been shown to harbor one of these mutations. In these patients, imatinib therapy improves 5-year survival rates to from ~75% to 90-95% and reduces rates of progression from 50% down to less than 1%.

Organ: Blood/Bone Marrow

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374 x3. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Estrogen receptor alpha, a prognostic and predictive marker in breast cancer. Antibodies to ER can also be employed as part of a panel of antibodies in the identification of the primary site of carcinomas presenting as metastases. Subcellular Localization: Nuclear

Organ: Breast, OB/GYN, Pituitary, Hormones

Disease State: Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360 or 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: This assay uses pyrosequencing technology to detect clinically relevant mutations in KRAS codons 59, 61, 117 and 146; and in NRAS codons 12, 13, 59, 61, 117, and 146. See KRAS cobas® IVD (the Roche cobas® KRAS Mutation Test) for testing to detect the most common missense point mutations in codon 12 and 13 of KRAS exon 2. RAS proteins are involved in the EGFR signal transduction pathway. Mutated RAS protein is constitutively activated and tumors carrying these activating mutations have been shown to be resistant to anti-EGFR directed therapy. According to joint guidelines recently issued by ASCP, CAP, AMP and ASCO (see reference below), all patients with colorectal carcinoma being considered for anti-EGFR therapy must undergo RAS mutation testing to determine eligibility. RAS mutation analysis should include KRAS codons 12 and 13 (evaluated by the FDA-approved cobas assay; see KRAS cobas IVD) as well as “extended” RAS testing targeting KRAS codons 59, 61, 117, and 146; and NRAS codons 12, 13, 59, 61, 117, and 146. For colorectal carcinoma patients, PhenoPath recommends ordering RAS mutation testing in a reflexive manner, starting with this FDA-approved cobas® KRAS Mutation Test to test for KRAS exon 2 mutations, followed by extended RAS mutation testing if a KRAS exon 2 mutation is not detected (see Extended RAS Panel). REFERENCE: Sepulveda AR, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Mol Diagn 2017 19(2):187225.

Organ: Colon & Other GI

Turnaround Time: Within 5-8 business days of receipt

Schedule: Thursday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): 81275, 81276; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Translocations that disrupt the fibroblast growth factor receptor-1 (FGFR1) gene are associated with a disease known as 8p11 myeloproliferative syndrome (EMS)/stem cell leukemia-lymphoma syndrome. This syndrome is characterized by myeloid hyperplasia that rapidly transforms to acute myelogenous leukemia and/or lymphoma within a year of the original diagnosis. In the “stem cell” myeloproliferative disorders, a mutation in the pluripotent hematopoietic progenitor results in a spectrum of diseases including T- or B-cell lymphoblastic lymphoma, bone marrow myeloid hyperplasia, and eosinophilia. These poor prognostic disorders are related to recurrent breakpoints on chromosome 8p11 that involve translocation of the FGFR1 gene. Tyrosine kinase fusions involving FGFR1 exhibit an aggressive and more variable sensitivity to current tyrosine kinase inhibitors, like imatinib, so in most cases long-term disease-free survival may only be obtainable with allogeneic hematopoietic stem cell transplantation.

Organ: Blood/Bone Marrow

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Predictive biomarker used as a companion diagnostic to assess patient eligibility for Elahere (mirvetuximab). Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a non-lineage-specific nuclear transcription factor expressed in normal mature B cells at several stages of development, and in a variety of non-Hodgkin lymphomas, but not in Hodgkin lymphomas.  FOXP1 IHC can used to aid in the immunohistochemical distinction of germinal center-derived diffuse large B cell lymphoma (DLBCL) from non-germinal center-derived DLBCL. Subcellular Localization: Nuclear

Organ: Genitourinary, Testis, Ovary

Disease State: Diffuse Large B Cell Lymphoma, Germ Cell Tumors

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: FOXP3 is a relatively specific marker of regulatory T cells (Tregs), which normally function to limit T cell-driven immune responses such as autoimmunity, but can also aid immune evasion by cancer. Studies on several types of cancer suggested that high levels of Treg infiltration of the tumor bed are associated with poor clinical outcome (Martin F et al. 2010. Oncogene). Subcellular Localization: Nuclear

Organ: Blood/Bone Marrow, Lymph Node / Spleen, Thymus (Mediastinal Mass)

Disease State: T Cell Non-Hodgkin Lymphoma (not otherwise classified)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either benign or more malignant tumor types. Rearrangement of the FUS gene has been seen in these tumors, and can be used to aid in diagnosis. The FUS (fused in sarcoma) Breakapart probe is designed to detect rearrangement of the FUS gene on the short arm of chromosome 16 (16p11). The FUS gene encodes a multi-functional protein involved in, among other things, transcriptional activation and RNA binding. It is a member of the TET family of proteins that also includes EWS.

Organ: Soft Tissue

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Fascin, a 55 kD actin-bundling protein. Uniform, relatively strong fascin expression can support the diagnosis of classic Hodgkin lymphoma, but is not specific for this diagnosis. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This assay includes one tube with a cytoplasmic bcl-2 antibody and a second with an isotype control, and is added on to the workup virtually all CD10+ mature B cell lymphomas. Assessment of cytoplasmic bcl-2 allows distinction of BL (bcl-2 negative, and usually strongly CD38+) from other follicle center-derived B cell lymphomas usually bcl-2-positive, with highly variable CD38). Since CD11c is almost never expressed in FL or BL, if one detects a CD10+/CD11c+ B cell neoplasm, one should strongly consider CD10+ hairy cell leukemia, which is reported to represent ~15% of classic hairy cell leukemia. This tube includes antibodies to CD45, bcl-2, CD10, CD19, CD5, CD20, CD11c, and CD38.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Burkitt's Lymphoma, Follicular Lymphoma, Follicular Dendritic Cell Sarcoma

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x8. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This four-tube assay is designed to detect virtually any hematolymphoid neoplasm in the blood or bone marrow and includes all 24 of the consensus antigens recommended for this purpose at the 2006 Bethesda Consensus Meeting on Clinical Flow Cytometry (Cytometry B Clin Cytom 72B: S14-S22, 2007). This panel includes the previously mentioned mature B cell and mature T cell tubes, and also includes two tubes targeted at myeloid blasts and maturing granulocytes and monocytes. In addition to the 15 antigens present in the B and T cell tubes, the two myeloid tubes enable evaluation of 12 additional antigens: CD11b, CD15, CD33, CD117, HLA-DR, CD71, CD36, CD64, CD13, CD14, CD123, and CD16. Potential add-on tubes include: • Myeloid 4 add-on tube • Myeloid 5 add-on tube • Cytoplasmic lineage add-on tubes • Paroxysmal nocturnal hemoglobinuria (PNH) tubes • Rule out mastocytosis tubes • B-ALL add-on tube • T-ALL add-on tube

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Precursor B-Lymphoblastic Lymphoma/Leukemia (B-ALL), Precursor T-Lymphoblastic Lymphoma/Leukemia (T-ALL), Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML), Paroxysmal Nocturnal Hemoglobinuria (PNH), Blastic Plasmacytoid Dendritic Cell Neoplasm, Langerhans Cell Histiocytosis, Mastocytosis, Myelodysplastic Syndromes

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88184 x 1, 88185 x 26, 88189 x 1. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: GATA-3 is a zinc finger nuclear transcription factor that is a highly sensitive marker of carcinomas primary to the bladder and breast. GATA-3 is also expressed in a subset of squamous cell carcinomas, skin adnexal tumors, mesotheliomas, and salivary gland tumors, among others (Miettinen M et al. AJSP 38:13-22, 2014). Subcellular Localization: Nuclear

Organ: Breast, Genitourinary

Disease State: Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Breast carcinoma, sweat gland carcinoma, and a subset of salivary gland carcinoma. Can also be present in 10% of primary lung adenocarcinoma. Subcellular Localization: Cytoplasmic, granular

Organ: Breast

Disease State: Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed almost exclusively in glial cells and tumors of the central nervous system. GFAP is also expressed, however, in a restricted subset of epithelial tumors, including salivary gland pleomorphic adenomas. Subcellular Localization: Cytoplasmic Subcellular Localization: Cytoplasmic

Organ: Brain/CNS

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Galectin-3, a member of the lectin family, is upregulated in thyroid carcinoma, and can be employed as part of a panel of markers to assist in the distinction of thyroid carcinomas from adenomas. In the latter setting, galectin-3 has been demonstrated to be strongly and diffusely positive in papillary thyroid carcinomas, but weakly and focally positive in adenomas. Subcellular Localization: Nuclear and cytoplasmic

Organ: Thyroid

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Gastrin is a hormone expressed by G-cells of the stomach antrum, but also expressed in a subset of pancreatic islet cell tumors (gastrinomas). Subcellular Localization: Cytoplasmic

Organ: Pancreas, Hormones

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Primary use of Glut-1 will be for classification of peripheral nerve sheath tumors, specifically perineuroma and perineurial sarcoma. Subcellular Localization: Membranous

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Glycophorin A, or CD235a, a marker of erythrocytes and later erythroblasts. Glycophorin A and the early erythroid antigen E-cadherin span the entirety of erythroid maturation. Subcellular Localization: Membranous

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Glypican-3, a heparan sulfate proteoglycan that is a reliable marker for hepatocellular carcinoma, with a sensitivity and specificity exceeding both alpha-fetoprotein and HepPar1. Glypican-3 is also a marker of yolk sac tumors in the context of other germ cell neoplasms. Subcellular Localization: Cytoplasmic, granular

Organ: OB/GYN, Genitourinary, Liver, Testis, Ovary

Disease State: Germ Cell Tumors, Hepatocellular Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Granzyme B is expressed by normal and neoplastic cytotoxic T-lymphocytes and natural killer cells, and may aid in identifying tumors arising from these cell types. Subcellular Localization: Cytoplasmic (granular)

Organ: Skin & Mucosa, Blood/Bone Marrow, Lymph Node / Spleen, Soft Tissue

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), NK/T Cell Lymphoma, Nasal Type, T Cell Non-Hodgkin Lymphoma (not otherwise classified), Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88312. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Used for the identification of malignant peripheral nerve sheet tumors (MPNST), approximately 50% of which show complete loss of expression of this nuclear protein. This loss of expression is highly specific to MPNST, and can help distinguish it from other sarcomas and spindle cell melanomas. Subcellular Localization: Nuclear (loss of expression)

Organ: Soft Tissue

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Used for the identification of malignant peripheral nerve sheet tumors (MPNST), approximately 50% of which show complete loss of expression of this nuclear protein. This loss of expression is highly specific to MPNST, and can help distinguish it from other sarcomas and spindle cell melanomas. Subcellular Localization: Nuclear (loss of expression)

Organ: Thyroid

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies HER2 gene product, which is overexpressed, almost always as a consequence of HER2 gene amplification, in a subset of breast cancers, gastric adenocarcinomas, and other tumors. It is a prognostic and predictive marker, and the target of trastuzumab and other HER2 targeted therapies. Subcellular Localization: Membranous

Organ: Breast, Colon & Other GI

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: The Abbott Molecular PathVysion HER2 (ERBB2) DNA Probe Kit is an FDA-approved kit used for evaluation of HER2 (ERBB2) gene amplification in breast cancer. The HER2 (ERBB2) oncogene is a member of the epidermal growth factor receptor family and has been found to be altered in approximately 20% of breast cancers. The PathVysion HER2 (ERBB2) DNA Probe Kit is a dual color probe kit that contains one probe (SpectrumOrange) specific for the HER2 (ERBB2) gene, and a second probe (SpectrumGreen) specific for chromosome 17. The underlying alteration is an amplification of the gene, resulting in more than the usual 2 copies of HER2 (ERBB2) (one on each copy of chromosome 17) typically present in normal breast epithelium and the majority of breast cancers without HER2 (ERBB2) alterations. Gene amplification is defined as a ratio of HER2 (ERBB2) to chromosome 17 signals of >2.2. Amplification of the HER2 (ERBB2) gene is almost always associated with overexpression of the HER2 (ERBB2) protein, as assessed by immunohistochemistry (IHC). PhenoPath Laboratories has accumulated HER2 (ERBB2) protein IHC and FISH data in over 4,000 breast cancer patients over the past several years. These studies demonstrate the positive predictive value of a 3+ IHC study for HER2 (ERBB2) amplification by FISH is 94%, and the negative predictive value for a negative IHC study (i.e., a score of 0 or 1+) for non-amplification by FISH is 96%. A disproportionate fraction of the cases with discordant IHC and FISH results are cases of aneuploid tumors showing excess copies of chromosome 17, which may lead to overexpression of the protein, but without concomitant gene amplification (as the number of copies of the HER2 (ERBB2) gene might not be more than two-fold that of chromosome 17). We recommend the use of IHC as an initial screen for HER2 (ERBB2) status, with FISH studies performed on cases that show 2+ levels of immunostaining: i.e., cases indicated as showing an "indeterminate" HER2 (ERBB2) status by IHC. HER2 (ERBB2) overexpression/gene amplification is an independent prognostic marker of adverse clinical outcome in breast cancer, and can predict response to doxorubicin (Adriamycin)-based adjuvant chemotherapy, as well as resistance to tamoxifen, even in the setting of ER/PR expression. Furthermore, HER2 (ERBB2) status also predicts response to immunotherapy with a "humanized" monoclonal antibody, trastuzumab (Herceptin) directed at the HER2 (ERBB2) protein. Probe type: Dual color enumeration

Organ: Lung, Breast, Liver, Colon & Other GI, Lymph Node / Spleen

Disease State: Adenocarcinoma, Breast Cancer, Metastatic Carcinoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested AND HER2 IHC slide (if no HER2 IHC slide is available, PhenoPath will perform and bill for the IHC, as needed, to interpret the HER2 FISH)

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: HGAL - also known as GCET2, GCAT2, and GCSAM – is a cytoplasmic protein expressed by benign and neoplastic follicle center (germinal center)-derived B cells. Subcellular Localization: Cytoplasmic

Organ: Lymph Node / Spleen

Disease State: Burkitt's Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies HHV8 latent nuclear antigen, or LANA, a nuclear protein expressed by cells infected with HHV8. It is expressed in both Kaposi's sarcoma as well as HHV8-associated lymphoproliferative disorders, including primary effusion lymphomas and multicentric Castleman's disease. Subcellular Localization: Nuclear positivity with speckled staining pattern

Disease State: Identification of Organisms, HIV-Associated Lymphoma, Post-Transplant Lymphoproliferative Disorders

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies HLA-DR (class II histocompatibility antigen), which is expressed by almost all normal and neoplastic B-lymphoid cells at any point in B cell maturation (with the important exception of primary mediastinal large B cell lymphoma, which is typically HLA-DR-negative), in activated normal and neoplastic mature T-lymphoid cells (but rarely in normal or neoplastic immature T-lymphoid cells), in the blasts and blast equivalent of most acute myeloid leukemias with the importantant exceptions of acute promyelocytic leukemia and the much rarer acute megakaryoblastic leukemia, and in the more differentiated monocytes, but not granulocytes, of both the acute and chronic myeloid neoplasms. Subcellular Localization: Membranous

Disease State: Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the gp100 protein, found in premelanosomes.  As such, HMB-45 is a highly sensitive and specific marker of melanoma, particularly in the metastatic setting.  The epitope targeted by HMB-45 behaves as an ‘oncofetal’ antigen that is not expressed in normal, resting melanocytes but is present in reactive and neoplastic melanocytic processes. Furthermore, as a marker of a premelanosomal protein, it is also an excellent marker of clear cell sarcoma as well as PEComas. Subcellular Localization: Cytoplasmic, granular

Organ: Skin & Mucosa

Disease State: Large Cell Undifferentiated Malignant Neoplams, Spindle Cell Tumors / Sarcoma Subtyping, Melanoma, Clear Cell Sarcoma, PEComas

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Herpes simplex viruses I and II-infected cells. Subcellular Localization: Nuclear and cytoplasmic

Disease State: Identification of Organisms

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This tube is particularly useful to look for hairy cell leukemia, and to distinguish this entity from marginal zone lymphoma and other lymphomas that can have some overlapping immunophenotypes. The tube contains antibodies to CD45, CD103, CD22, CD25, CD5, CD11c, CD19, and CD38.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: B Cell NHL with Plasmacytoid Differentiation, Hairy Cell Leukemia, Marginal Zone/MALT Lymphoma, Lymphoplasmacytic Lymphoma

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x8. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Helicobacter pylori organisms in gastric mucosa. Subcellular Localization: N/A

Disease State: Identification of Organisms

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Carbamoyl phosphate synthetase 1, a mitochondrial protein present in hepatocytes and hepatocellular carcinoma. When used as part of a panel of other markers, HepPar1 is useful in distinguishing hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinomas to the liver. However, carbamoyl phosphate synthetase 1 is also expressed in a subset of gastric carcinomas as well as ‘hepatoid’ carcinomas of various organs. Subcellular Localization: Cytoplasmic, granular

Organ: Liver

Disease State: Carcinomas of Unknown Primary, Hepatocellular Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: p57kip2 is a paternally imprinted, maternally expressed gene that is not expressed in the cytotrophoblasts of complete moles (which are of paternal origin only). It is positive in both partial moles and normal hydropic villi. In addition, complete moles are characterized by high Ki-67-defined proliferative index in the cytotrophoblasts.  Further distinction of partial moles from hydropic normal villi can be made by identifying the triploid nature of incomplete moles. This can be accomplished by fluorescence in situ hybridization studies using a chromosome 17 probe to ascertain ploidy. It should be noted that these mole ploidy studies are best interpreted in conjunction with morphology for the evaluation of both complete and partial moles.

Organ: OB/GYN

Disease State: Molar Pregnancy

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested plus 2 unstained slides cut at 6µm

CPT Code(s): 88342; 88360; 88367; 88323. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88367; 88373/88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Identifies isocitrate dehydrogenase 1, an enzyme that participates in the citric acid cycle, and is mutated in a high fraction of gliomas and oligodendrogliomas, particularly in grade II and grade III neoplasms. In these tumors, the overwhelming majority show a point mutation on codon 132 (R132H). The availability of a monoclonal antibody specific for the mutated IDH1, which does not cross react with the native protein, has provided an immunohistochemical tool that can be used to positively identify these tumors. Furthermore, because IDH mutations do not occur in reactive gliosis, the latter can often be separated from diffuse gliomas, which are usually positive for the mutation (and hence positive by IHC). Subcellular Localization: Nuclear and cytoplasmic

Organ: Brain/CNS

Disease State: Oligodendroglioma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This sensitive breakapart FISH assay detects any translocation involving the IGH gene, although it does not identify the gene with which it is partnered. Many different translocation partners for the IGH gene have been identified in human B cell lymphoma including BCL2 in follicular lymphomas resulting in the t(14;18), CCND1 in mantle cell lymphoma resulting in the t(11;14), MYC in Burkitt's lymphoma resulting in the t(8;14), MALT1 in malt lymphoma resulting in the t(14;18), and CMAF and FGFR3 in myeloma reulting in the t(14;16) and t(4;14), respectively. IGH translocations are also frequently seen in diffuse large B cell lymphoma (DLBCL). Probe type: Dual color breakapart

Organ: Skin & Mucosa, Blood/Bone Marrow, Colon & Other GI, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Burkitt's Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone/MALT Lymphoma, Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: This is an oncofetal RNA binding protein normally expressed in embryonal tissues and re-expressed in a significant fraction of neoplastic cells, but generally not expressed in normal adult tissues. IMP3 may be helpful in the identification of malignant tumors. Subcellular localization: Cytoplasmic

Organ: Lung, OB/GYN, Skin & Mucosa, Colon & Other GI

Disease State: Melanoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: The gene product of the INI-1 gene, also referred to as BAF47. This is a tumor suppressor gene, inactivation through mutation or other mechanism characterizes a unique subset of tumors that includes renal and extrarenal rhabdoid tumors, atypical teratoid/rhabdoid tumors of the central nervous system, distal and proximal variants of epithelioid sarcoma, as well as a subset of mesenchymal chondrosarcomas, epithelioid malignant peripheral nerve sheath tumors, and soft tissue myoepitheliomas. Loss of immunostaining is the characteristic feature of these tumors. Subcellular Localization: Nuclear

Organ: Brain/CNS

Disease State: Small, Blue, Round Cell Tumors, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: INPP4B encodes the inositol polyphosphate 4-phosatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This antibody is useful as a diagnostic aid for basal like breast carcinomas, as the absence of expression of INPP4B, has been shown in our hands to have a 90% sensitivity and 80% specificity for basal-like breast carcinomas, which closely reflects the reported literature. INPP4B will be run in a panel with other antibodies used in the diagnosis of basal-like breast carcinomas, such as, Nestin, Keratin 5, and c-kit. Subcellular Localization: membranous and cytoplasmic

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies neuroendocrine tumors with high specificity, but less sensitive than synaptophysin. No aberrant staining in other tumors, i.e., adenocarcinomas, melanomas etc. with the exception of some focal positivity on breast carcinomas, which is expected. Subcellular Localization: Nuclear

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: The Kappa Clonality Assay is a multiplex fluorescent PCR assay based on the pan-European collaborative study (BIOMED-2). It is particularly useful when IgH clonality testing fails to identify a clonal rearrangement which can occur due to somatic hypermutation. Importantly, this test should be interpreted in the context of clinical, histologic, and immunophenotypic information and should not be used in isolation in the evaluation of possible B cell lymphoproliferative disorders. Clinical indications for the test include: • Any suspect B cell proliferation when morphology and immunophenotyping are not conclusive • Lymphoproliferations in immunodeficient patients • Evaluation of the clonal relationship between two B lymphoid malignancies in one patient or discrimination between a relapse and a second malignancy • Occasionally, staging of B cell lymphomas • Aid in minimum residual disease detection Type: PCR/Capillary Electrophoresis, Qualitative

Organ: Skin & Mucosa, Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified)

Turnaround Time: Within 3-5 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 81264; 88381 may apply; G0452 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Immunofluorescence

Clinical Significance: Identifies: IgA localization by direct immunofluorescence is useful in the subclassification of bullous and other skin disorders, particularly when employed as part of a panel of FITC-conjugated antibodies, including those to IgG, IgM and C3. IgA deposits in the skin are particularly important in the identification of dermatitis herpetiformis and Henoch Schoenlein purpura. Subcellular Localization: Extracellular

Organ: Skin & Mucosa

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: Skin biopsy in Michel's (aka Zeuss) fixative, with or without patient serum

CPT Code(s): 88346 or 88350. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Immunoglobulin A (IgA)-positive normal plasma cells and plasma cell neoplasms. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Immunoglobulin D (IgD) heavy chain, a cytoplasmic protein strongly expressed by naive/mantle zone B cells and a small subset of plasma cells, and weakly expressed by germinal center B cells. A subset of B cell non-Hodgkin lymphomas, generally of germinal center or pre-germinal center origin, express IgD. Subcellular Localization: Membranous

Disease State: Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Immunofluorescence

Clinical Significance: Identifies: IgG localization by direct immunofluorescence is useful in the subclassification of bullous and other skin disorders, particularly when employed as part of a panel of FITC-conjugated antibodies, including those to C3, IgM and IgA. IgG deposits in the skin, with unique distributions, characterize a number of dermatologic disorders, including bullous pemphigoid, pemphigus, lupus, etc. Subcellular Localization: Extracellular

Organ: Skin & Mucosa

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: Skin biopsy in Michel's (aka Zeuss) fixative, with or without patient serum

CPT Code(s): 88346 or 88350. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: IgG positive plasma cells and plasma cell neoplasms. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: This clone identifies IgG4 positive plasma cells, which are increased to over 40% of all IgG+ plasma cells in IgG4-related sclerosing disease (IRD), such that PhenoPath's assay for IRD employs antibodies to both IgG4 and total IgG, in order to estimate this percentage reliably. Subcellular Localization: Cytoplasmic

Organ: Colon & Other GI, Thyroid, Soft Tissue, Salivary gland

Disease State: Benign/reactive sclerosing lesion

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • Minimum of 5 unstained slides cut at 4µm

CPT Code(s): 88360 and 88342 and/or 88341 x number of additional antibodies performed. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: The IgH Clonality Assay is a multiplex fluorescent PCR assay based on the pan-European collaborative study (BIOMED-2). This assay uses the framework 1, 2, and 3 primer sets (FR1, FR2, and FR3) utilized by BIOMED-2 for the analysis of IgH gene rearrangements. Importantly, this test should be interpreted in the context of clinical, histologic, and immunophenotypic information and should not be used in isolation in the evaluation of possible B cell lymphoproliferative disorders. Clinical indications for the test include: • Any suspect B cell proliferation when morphology and immunophenotyping are not conclusive • Lymphoproliferations in immunodeficient patients • Evaluation of the clonal relationship between two B lymphoid malignancies in one patient or discrimination between a relapse and a second malignancy • Occasionally, staging of B cell lymphomas • Aid in minimum residual disease detection Type: PCR/Capillary Electrophoresis, Qualitative

Organ: Skin & Mucosa, Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), B Cell NHL with Plasmacytoid Differentiation, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone/MALT Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma, Post-Transplant Lymphoproliferative Disorders, Plasma Cell Myeloma/Neoplasm, Lymphoplasmacytic Lymphoma

Turnaround Time: Within 3-5 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 81261; 88381 may apply; G0452 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Immunofluorescence

Clinical Significance: Identifies: IgM localization by direct immunofluorescence is useful in the subclassification of bullous and other skin disorders, particularly when employed as part of a panel of FITC-conjugated antibodies, including those to C3, IgG and IgA. IgM deposits in the skin, with unique patterns, are characteristic of specific dermatologic disorders, including vasculitis, lupus, and others. Subcellular Localization: Extracellular

Organ: Skin & Mucosa

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: Skin biopsy in Michel's (aka Zeuss) fixative, with or without patient serum

CPT Code(s): 88346 or 88350 . The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: IgM positive plasma cells and plasma cell neoplasms, and is very helpful in assessing the likelihood of lymphoplasmacytic lymphoma, which is almost always strongly IgM-positive Subcellular Localization: Cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Identifies inhibin-alpha, a hormone component that joins either the beta A or beta B subunit to form a pituitary FSH secretion inhibitor. It is expressed by, and can be used as a marker of, granulosa cells and granulosa cell and other sex cord stromal tumors, as well as adrenal cortical cells and tumors. Subcellular Localization: Cytoplasmic

Organ: OB/GYN, Genitourinary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Specimen MUST be received within 48 hrs of collection • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: PCR

Clinical Significance: This real time PCR test detects the exon 14 JAK2 V617F mutation, which is identified in the great majority of polycythemia vera (PV) cases as well as in other non-CML myeoloproliferative disorders. The JAK2 V617F mutation causes a constitutive activation of the JAK2 tyrosine kinase, which is believed to confer erythropoietin hypersensitivity and erythropoietin-independent survival of the myeloid stem cell. Additionally, these diseases may also transform into acute myeloid leukemia. Thus, detection of the JAK2 (V617F) mutation provides important confirmation of non-CML MPD. Type: Real-Time PCR, Qualitative

Organ: Skin & Mucosa, Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML)

Turnaround Time: Within 4-8 business days of receipt

Schedule: Wednesday

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 81270; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood: 5 ml in EDTA (purple top) • Bone marrow aspirate: 2 ml in EDTA (purple top Specimen must arrive within 5 days of collection

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or H&E and 5 unstained slides cut at 5 micron

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: PCR

Clinical Significance: This PCR assay uses the FDA-approved, Roche cobas® KRAS Mutation Test kit to detect the most common missense point mutations in codons 12 and 13 of KRAS exon 2. KRAS is a G-protein that is a key component of the EGFR signal transduction pathway. Mutated KRAS protein is constitutively activated and tumors carrying these activating mutations have been shown to be resistant to anti-EGFR directed therapy. Please note that current guidelines for colorectal carcinoma molecular testing recommend that patients being considered for anti-EGFR therapy must undergo RAS mutation testing to determine eligibility. According to joint guidelines recently issued by ASCP, CAP, AMP and ASCO (see reference below), all patients with colorectal carcinoma being considered for anti-EGFR therapy must undergo “extended” RAS mutation testing that includes the following mutations: KRAS codons 12 and 13 (exon 2), KRAS codons 59 and 61 (exon 3), KRAS codons 117 and 146 (exon 4), NRAS codons 12 and 13 (exon 2) NRAS codons 59 and 61 (exon 3), and NRAS codons 117 and 146 (exon 4). PhenoPath recommends ordering RAS mutation testing in a reflexive manner, starting with this FDA-approved cobas® KRAS Mutation Test to test for KRAS exon 2 mutations, followed by extended RAS mutation testing if a KRAS exon 2 mutation is not detected (see Extended RAS Panel). REFERENCE: Sepulveda AR, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Mol Diagn 2017 19(2):187225.

Organ: Colon & Other GI

Turnaround Time: Within 3-6 business days of receipt

Schedule: Tuesday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): 81275; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Kappa light chains, which can be effectively detected by IHC assessment of true plasma cells, plasmacytoid B cells, and occasional non-plasmacytoid B cells with relatively abundant cytoplasm. The ratio of kappa-positive to lambda-positive cells in normal/polyclonal B cell and plasma cell populations typically ranges from 1:1 to 2:1. Marked increases in this ratio suggest kappa light chain-restriction, while marked decreases in the ratio (significantly < 1) suggest lambda light chain-restriction. Light chain restriction is conventionally used as a surrogate for monoclonality among B cell neoplasms. Subcellular Localization: Cytoplasmic

Disease State: Amyloid Type Analysis, B Cell NHL with Plasmacytoid Differentiation, HIV-Associated Lymphoma, Post-Transplant Lymphoproliferative Disorders

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a subset of epithelia and carcinomas. CK17 expression can help identify primary carcinomas of the pancreatobiliary tract, distinguishing them from ovarian mucinous adenocarcinomas and carcinomas of the stomach, among others. Subcellular Localization: Cytoplasmic

Organ: Pancreas, Ovary

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a subset of epithelia and carcinomas. Published studies suggest that CK19 expression, along with expression of galectin-3 and HBME-1, is useful in differentiating papillary carcinomas of the thyroid from benign thyroid lesions. Subcellular Localization: Cytoplasmic

Organ: Thyroid

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a subset of carcinomas. Co-analysis of expression of cytokeratin 7 can be helpful in the identification of the primary site of carcinomas presenting at metastatic sites. CK20 is also a marker of Merkel cell tumors, usually displaying a dot-like perinuclear pattern of expression. Subcellular Localization: Cytoplasmic

Organ: Colon & Other GI

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a subset of carcinomas. Co-analysis with expression of cytokeratin 20 can be helpful in the identification of the primary site of carcinomas presenting at metastatic sites. Subcellular Localization: Cytoplasmic

Organ: Lung, Genitourinary, Colon & Other GI

Disease State: Carcinomas of Unknown Primary, Mesothelioma vs. Adenocarcinoma, Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies many members of the cytokeratin group of cytoskeletal proteins. AE1/AE3 is a cocktail of two monoclonal antibodies to non-overlapping groups of cytokeratins that are expressed in a wide range of epithelial tumors. Cytokeratin expression can identify carcinomas in the context of undifferentiated malignancies, although cytokeratins (generally at lower levels) can be expressed in a restricted subset of non-epithelial tumors (e.g., melanoma, smooth muscle tumors, etc.) Subcellular Localization: Cytoplasmic

Disease State: Large Cell Undifferentiated Malignant Neoplams

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies many members of the cytokeratin group of cytoskeletal proteins. Very similar pattern of reactivity compared with the AE1/AE3 antibody cocktail. However, as a single monoclonal antibody, it has advantages over the AE1/AE3 antibody cocktail. It can thus be employed to identify carcinomas in the context of undifferentiated malignancies. Cytokeratin expression can identify carcinomas in the context of undifferentiated malignancies, although cytokeratins (generally at lower levels) can be expressed in a restricted subset of non-epithelial tumors (e.g., melanoma, smooth muscle tumors, etc.). Subcellular Localization: Cytoplasmic

Organ: Lung, Genitourinary, Testis, Ovary

Disease State: Small, Blue, Round Cell Tumors, Large Cell Undifferentiated Malignant Neoplams, Carcinomas of Unknown Primary, Mesothelioma vs. Adenocarcinoma, Spindle Cell Tumors / Sarcoma Subtyping, Germ Cell Tumors

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: This IVD IHC assay has been FDA approved for the assessment of claudin 18 (CLDN18) protein. This assay is to be used on formalin-fixed, paraffin-embedded tissue as an aid in identifying adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma who are being considered for treatment with zolbetuximab (VYLOY, Astellas Pharma, LLC) in accordance with the FDA-approved therapeutic product labeling. The CLDN18 clinical cut-off for treatment eligibility is ≥75% viable tumor cells (%TC) exhibiting moderate to strong membrane CLDN18 staining and such cases are considered CLDN18 positive. Cases that have <75% viable tumor cells (%TC) exhibiting moderate to strong membrane CLDN18 staining are considered CLDN18 negative. Subcellular Localization: Cytoplasmic

Organ: Genitourinary, Prostate

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: The Ki-67 defined antigen a nuclear protein expressed in proliferating (i.e., non-G0) cells. Used as a quantitative marker of cell proliferation in tumors. The SP6 clone is more robust than clone MIB-1, and is often employed for IHC on decalcified bone marrow specimens. Subcellular Localization: Nuclear

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360 (reference. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: The Ki-67 defined antigen a nuclear protein expressed in proliferating (i.e., non-G0) cells. Used as a quantitative marker of cell proliferation in tumors. Subcellular Localization: Nuclear

Organ: Lung, Breast, OB/GYN

Disease State: Molar Pregnancy, Non Small Cell Lung Carcinoma (NSCLC), Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88360. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Lymphoid enhancer-binding factor 1, a nuclear transcription factor in the WNT/beta-catenin signaling pathway that is normally expressed in T cells and immature pro-B cells, but not in normal mature B cells.  LEF-1 is aberrantly expressed in virtually all cases of CLL/SLL, but is almost always negative in mantle cell lymphoma, marginal zone lymphoma, and low-grade follicular lymphoma, and therefore may be helpful in distinguishing CLL/SLL from these other lymphomas Subcellular Localization: Nuclear

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: A cysteine-rich protein that also plays a central and crucial role in hematopoietic development. Among both benign and neoplastic B-cell proliferations, LMO2 expression is associated with germinal center origin. Subcellular Localization: Nuclear

Disease State: Diffuse Large B Cell Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Lambda light chains, which can be effectively detected by IHC assessment of true plasma cells, plasmacytoid B cells, and occasional non-plasmacytoid B cells with relatively abundant cytoplasm. The ratio of kappa-positive to lambda-positive cells in normal/polyclonal B cell and plasma cell populations typically ranges from 1:1 to 2:1. Marked increases in this ratio suggest kappa light chain-restriction, while marked decreases in the ratio (significantly < 1) suggest lambda light chain-restriction. Light chain restriction is conventionally used as a surrogate for monoclonality among B cell neoplasms. Subcellular Localization: Cytoplasmic

Disease State: Amyloid Type Analysis, B Cell NHL with Plasmacytoid Differentiation, HIV-Associated Lymphoma, Post-Transplant Lymphoproliferative Disorders

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: Langerin, a protein encoded by the CD207 gene, which is a transmembrane cell surface receptor produced by Langerhans cells and Langerhans cell neoplasms. Subcellular Localization: Cytoplasmic

Disease State: Langerhans Cell Histiocytosis

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This two-tube add-on is used when the population of interest shows large cell size by morphology and/or forward light scatter, and when evaluation of CD30 and CD25 expression is of interest. The base antibodies for these add-on tubes include CD45, CD52, CD30, CD3, CD25, and HLA-DR; additional T cell-associated antigens, such as CD5, CD4, and CD8, may be evaluated in this tube to aid in identification of the abnormal population.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Anaplastic Large Cell Lymphoma (Systemic or Cutaneous), Angioimmunoblastic T Cell Lymphoma, Peripheral T Cell Lymphoma, NOS (of Large Cell Type)

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x6. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Clinical Significance: This test is designed to aid in diagnosis and/or treatment strategy for patients with AML (42 genes: ASXL1, ATF2, ATM, BCOR, BCORL1, CBL, CDKN2B,  CEBPA, CSF3R,  DDX41,  DNMT3A,  ETV6,  EZH2,  FLT3 (internal tandem duplications and tyrosine kinase codon 835/836 mutations only),  GATA1,  GATA2,  IDH1,  IDH2,  IKZF1,  JAK2,  KDM6A,  KIT,  KRAS,  MLL (partial tandem duplication only),  MPL,  NF1,  NPM1,  NRAS,  PHF6,  PTEN,  PTPN11,  RUNX1,  SETBP1,  SF3B1,  SRSF2,  STAG2,  STK11,  TET2,  TP53,  U2AF1,  WT1,  ZRSR2)

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Schedule: Tuesday and Thursday

Specimen Requirements: Preferred Specimen(s): 5mL whole blood or bone marrow collected in an EDTA (lavender-top) tube Minimum Volume: 2 mL Transport at room temperature Specimen Stability: Room temperature: 14 days Refrigerated: 14 days Frozen: Unacceptable Reject Criteria: Gross hemolysis, frozen, clotted

CPT Code(s): 81450 (reference only; CPTs may vary)

Methodology: Send out test

Clinical Significance: LeukoVantage MDS:   This test is designed to aid in diagnosis, prognosis and/or treatment strategy for patients with MDS (36 genes:  ASXL1,  ATM,  BCOR,  CBL,  CEBPA,  CSF3R,  CUX1,  DNMT3A,  ETNK1,  ETV6,  EZH2,  FLT3,  GATA2,  IDH1,  IDH2,  IKZF1,  JAK2,  KRAS,  NF1,  NPM1,  NRAS,  PHF6,  PTEN,  PTPN11,  RUNX1,  SETBP1,  SF3B1,  SRSF2,  STAG2,  STAT3,  STK11,  TET2,  TP53,  U2AF1,  WT1,  ZRSR2)

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Schedule: Tuesday and Thursday

Specimen Requirements: Preferred Specimen(s): 5mL whole blood or bone marrow collected in an EDTA (lavender-top) tube Minimum Volume: 2 mL Transport at room temperature Specimen Stability: Room temperature: 14 days Refrigerated: 14 days Frozen: Unacceptable Reject Criteria: Gross hemolysis, frozen, clotted

CPT Code(s): 81450 (reference only; CPTs may vary)

Methodology: Send out test

Clinical Significance: LeukoVantage MPN:   This test is designed to aid in diagnosis, prognosis and/or treatment strategy for patients with MPN (26 genes:  ASXL1,  BRAF,  CALR,  CBL,  CSF3R,  ETNK1,  ETV6,  EZH2,  HRAS,  IDH1,  IDH2,  IKZF1, JAK2,  KIT,  KRAS,  MPL,  NF1,  NRAS,  PTEN,  PTPN11,  SETBP1,  SF3B1,  SRSF2,  TET2,  TP53,  U2AF1)

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Schedule: Tuesday and Thursday

Specimen Requirements: Preferred Specimen(s): 5mL whole blood or bone marrow collected in an EDTA (lavender-top) tube Minimum Volume: 2 mL Transport at room temperature Specimen Stability: Room temperature: 14 days Refrigerated: 14 days Frozen: Unacceptable Reject Criteria: Gross hemolysis, frozen, clotted

CPT Code(s): 81450 (reference only; CPTs may vary)

Methodology: Send out test

Clinical Significance: This test is designed to aid in diagnosis, prognosis and/or treatment strategy for patients with AML, MPN and MDS (47 genes:  ASXL1,  ATF2,  ATM,  BCOR,  BCORL1,  BRAF, CALR,  CBL,  CDKN2B,  CEBPA,  CSF3R,  CUX1,  DDX41,  DNMT3A,  ETNK1,  ETV6,  EZH2,  FLT3,  GATA1,  GATA2,  HRAS,  IDH1,  IDH2,  IKZF1,  JAK2,  KDM6A,  KIT,  KRAS,  MPL,  NF1,  NPM1,  NRAS,  PHF6,  PTEN,  PTPN11,  RUNX1,  SETBP1,  SF3B1,  SRSF2,  STAG2, STAT3, STK11, TET2, TP53, U2AF1, WT1, ZRSR2)

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Schedule: Tuesday and Thursday

Specimen Requirements: Preferred Specimen(s): 5mL whole blood or bone marrow collected in an EDTA (lavender-top) tube Minimum Volume: 2 mL Transport at room temperature Specimen Stability: Room temperature: 14 days Refrigerated: 14 days Frozen: Unacceptable Reject Criteria: Gross hemolysis, frozen, clotted

CPT Code(s): 81450 (reference only, CPTs may vary)

Methodology: IHC

Clinical Significance: Identifies: A glycoside hydrolase also known as muraminidase that is a marker of granulocytes and monocytes, and therefore of granulocytic and monocytic neoplasms. Subcellular Localization: Cytoplasmic

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This sensitive breakapart FISH assay detects any MALT gene rearrangement including the t(11;18) and the t(14;18). MALT1 gene rearrangements occur in a subset of extra-nodal marginal zone B cell lymphomas (MZBCL) and can aid in this diagnosis.

Organ: Blood/Bone Marrow, Colon & Other GI, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Marginal Zone/MALT Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: The MALT1 beakapart FISH assay is a sensitive test that detects gene rearrangements involving the MALT1 gene but does distinguish between the different MALT1 translocation partners that have been described. The main MALT1 translocations that occur in human MALT lymphomas include the t(11;18)(q21;q21)/API-2-MALT and t(14;18)(q32;q21)/IgH-MALT. Identification of a MALT1 rearrangement is of diagnostic use in atypical B cell proliferations when the diagnosis of MALT lymphoma is being considered. Probe type: Dual color breakapart

Organ: Skin & Mucosa, Blood/Bone Marrow, Colon & Other GI, Body Fluids, Lymph Node / Spleen

Disease State: B Cell NHL with Plasmacytoid Differentiation, Marginal Zone/MALT Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: In this reflexive panel a MALT1 breakapart FISH assay is performed. If negative, no more testing is performed. If positive, one additional FISH assay is performed to positively identify and confirm the presence of t(11;18), which is the most common MALT1 gene translocation that occurs in MZBCL.

Organ: Blood/Bone Marrow, Colon & Other GI, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Marginal Zone/MALT Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374x2. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies MART1 (Melan A), a sensitive and specific marker of melanoma. While its sensitivity is comparable to that of HMB45, MART1, in contrast, is also a marker of sex cord-stromal, adrenal cortical tumors, among others. Subcellular Localization: Cytoplasmic

Organ: OB/GYN, Skin & Mucosa

Disease State: Melanoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: FISH evaluation for MDM2 amplification has been shown to be a useful tool in the diagnosis of lipomatous neoplasms; specifically, well-differentiated liposarcomas, atypical lipomatous tumors, and dedifferentiated liposarcomas containing cytogenetic alterations of the 12q13-15 region. MDM2 is a gene in this genomic region that is frequently amplified in these tumor types. In contrast, benign lipomas and lipocytic tumors as well as most other non-lipomatous sarcomas and mesenchymal neoplasms have been shown to be negative for MDM2 amplification. Testing for MDM2 amplification by FISH therefore aids in the pathologic differential diagnosis of lipomatous/dedifferentiated liposarcomas versus nonlipocytic sarcomas and mesenchymal neoplasms; specifically, when the histologic differential diagnosis is lipoma versus well-differentiated liposarcoma, the presence of MDM2 amplification would be in keeping with liposarcoma. Additionally, when the differential includes dedifferentiated liposarcoma versus sarcoma, NOS, as well as other sarcoma types, the presence of MDM2 amplification also suggests a lipocytic origin. Finally, non-amplified, but polysomic MDM2 and SE12 can be seen in cases of pleomorphic lipoma. Probe type: Dual color enumeration

Organ: Soft Tissue

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: MDS represents a heterogeneous group of clonal myeloid stem cell disorders which are characterized not only by specific histologic changes typically seen in the bone marrow and peripheral blood, but also by specific chromosome abnormalities. The MDS FISH Panel offered at PhenoPath covers the most common MDS-associated chromosomal abnormalities and specifically detects the following: EGR1/5q31 deletion (5q-), monosomy 5, deletion 7q31, monosomy 7, deletion 20q12, and trisomy 8. The different chromosomal abnormalities have prognostic significance and generally can be divided into three prognostic groups: favorable, intermediate, and poor. Tumors manifesting deletion of 5q31, 20q12, and lacking any other genetic abnormalities constitute the favorable group; furthermore, patients with tumors manifesting 5q loss are eligible for Revlimid® (lenalidomide) therapy. Tumors with trisomy 8 and deletion 7q31 constitute the intermediate prognosis group and those with monosomy 5 or 7 represent the poor prognostic group.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Myeloproliferative Neoplasms, Including Chronic Myelogenous Leukemia (CML), Myelodysplastic Syndromes

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374x2, 88367; 88373. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: MET is a 125k bp proto-oncogene receptor tyrosine kinase, known also as c-MET or hepatocyte growth factor receptor (HGFR). It has embryonic activity in epithelial cells, playing a role in the development of a variety of tissues and organs. In adults, MET expression is seen only in stem and progenitor cells. Mutation of MET is associated with a poor prognosis as it can trigger tumor growth, angiogenesis and metastasis. MET amplification has been observed in both non-small cell lung carcinomas (NSCLCs) and esophageal adenocarcinomas. The presence of MET amplification is associated with acquired resistance to certain tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib and sensitivity to other TKIs such as crizotinib. This FISH assay has been validated in both specimen types for detection of MET amplification.

Organ: Lung, Colon & Other GI

Disease State: Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Identified one of the mismatch repair gene products. Loss of expression can help define 'MSI' type colonic and other carcinomas. In general, loss of MLH1 is accompanied by simultaneous loss of PMS2. Subcellular Localization: Nuclear

Organ: OB/GYN, Skin & Mucosa, Colon & Other GI

Disease State: Mismatch Repair Genes - Correlates with MSI, Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) / Lynch Syndrome, Microsatellite Instability (MSI), Lynch Syndrome / HNPCC

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block (preferred) or unstained slides (10 slides are usually sufficient)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Panel of the mismatch repair (MMR) gene products. Loss of expression can help define 'MSI' type colonic and other carcinomas, i.e., tumors deficient in expression of one or more of the MMR gene products.

Organ: OB/GYN, Skin & Mucosa, Colon & Other GI

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342; 88341x3. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Although the expression of MNDA was initially thought to be restricted to the myelomonocytic lineage, several studies have shown the expression of this protein by normal and neoplastic B lymphocytes. MNDA has been shown to be expressed in splenic marginal zone lymphomas, mantle cell lymphomas, nodal marginal zone lymphomas and hairy cell leukemia. MNDA (clone 253A) will be used as part of a larger IHC panel to help distinguish marginal zone B cell lymphoma (MZL) from follicle center-derived B cell lymphoma, particularly CD10-negative FL. Subcellular Localization: Nuclear

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL), Hairy Cell Leukemia, Mantle Cell Lymphoma, Marginal Zone/MALT Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies epithelial glycoprotein 2, a cell surface protein, expression of which has been demonstrated to help in the distinction of adenocarcinoma (positive) from mesothelioma (negative). As mesotheliomas can express low levels of this protein, this marker is best employed as part of a panel of markers. Subcellular Localization: Membranous

Organ: Lung, Genitourinary, Liver

Disease State: Mesothelioma vs. Adenocarcinoma, Hepatocellular Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: This real time PCR assay detects somatic mutations in codon 515 of the “myeloproliferative leukemia virus oncogene” (“MPL”). These mutations occur in chronic myeloproliferative neoplasms, including primary myelofibrosis (PMF) and essential thrombocythemia (ET). MPL codon 515 (W515) mutations are found in ~3-4% of patients with ET and ~7-8% of patients with PMF; the identification of an MPL mutation fulfills one of the WHO major diagnostic criteria for these diseases. MPL mutations are usually found in chronic myeloproliferative neoplasm cases that are negative for the JAK2 V617F mutation and Calreticulin exon 9 mutations.

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Myeloproliferative Neoplasms (non-CML)

Turnaround Time: Within 5-8 business days of receipt

Schedule: Monday (run and analyzed same day)

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE) block or 10 unstained FFPE slides.

CPT Code(s): 81338; 88381 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies one of the mismatch repair gene products. Loss of expression can help identify tumors in Lynch Syndrome patients, as well as identify 'MSI' type sporadic colonic and other carcinomas. In general, loss of MSH2 is accompanied by simultaneous loss of MSH6. Subcellular Localization: Nuclear

Organ: OB/GYN, Skin & Mucosa, Colon & Other GI

Disease State: Mismatch Repair Genes - Correlates with MSI, Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) / Lynch Syndrome, Microsatellite Instability (MSI), Lynch Syndrome / HNPCC

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies one of the mismatch repair gene products. Loss of expression can help identify tumors in Lynch Syndrome patients, as well as identify 'MSI' type sporadic colonic and other carcinomas. In general, loss of MSH6 is accompanied by simultaneous loss of MSH2, although selective loss of MSH6 alone can also be seen. Subcellular Localization: Nuclear

Organ: OB/GYN, Skin & Mucosa, Colon & Other GI

Disease State: Mismatch Repair Genes - Correlates with MSI, Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) / Lynch Syndrome, Microsatellite Instability (MSI), Lynch Syndrome / HNPCC

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: Microsatellite instability (MSI) is the end result of a defective mismatch repair (MMR) system and generally occurs as a result of a germline mutation in one of the MMR genes (hereditary) or as a result of methylation of the MLH1 promoter (sporadic). Microsatellites are repetitive sequences distributed throughout the genome that consist of nucleotide repeats (mono-, di- or higher order nucleotide repeats) that are often copied incorrectly by DNA polymerase. In tumors with mismatch repair defects, these expansions or contractions of the number of nucleotide repeats are not repaired, leading to the phenomenon of MSI. PCR is used to amplify specific microsatellite repeats within the genome and MSI is detected by comparing the length of nucleotide repeats in tumor cells versus normal cells. If the length of the repeat sequences from tumor versus normal differs in 2 or more of the 5 regions tested, microsatellite instability is present, and the specimen is characterized as MSI-high (MSI-H). Specimens showing differing lengths in 1 of the regions tested is characterized as MSI-low (MSI-L). If no differences are seen between the normal and tumor, the sample is considered microsatellite stable (MSS). Cases of hereditary non-polyposis colorectal carcinoma (HNPCC) or Lynch Syndrome and approximately 15% of sporadic colorectal carcinomas (CRC) exhibit defective MMR. In sporadic CRC, MSI is the result of acquired hypermethylation silencing of MLH1. In individuals/families in which HNPCC/Lynch syndrome is suspected, the presence of MSI in a tumor suggests a germline mutation in one of the MMR genes and further mutational testing should be considered. Colorectal carcinomas with defective DNA mismatch repair (MSI-high), have a better prognosis compared to those with intact mismatch repair (microsatellite stable or MSI-low).

Organ: OB/GYN, Skin & Mucosa, Colon & Other GI

Disease State: Mismatch Repair Genes - Correlates with MSI, Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) / Lynch Syndrome, Microsatellite Instability (MSI), Lynch Syndrome / HNPCC

Turnaround Time: Within 5-8 business days of receipt

Schedule: Wednesday

Specimen Requirements: Both Tumor and Normal Required. 1) Formalin-fixed, paraffin-embedded (FFPE) tissue containing greater than 10% tumor - AND - 2) Formalin-fixed, paraffin-embedded (FFPE) tissue containing normal tissue OR normal peripheral blood (Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top); transport with frozen ice pack)

CPT Code(s): 81301; 88381 may apply; G0452 may apply. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: MUC4 is an immunohistochemical marker for low grade fibromyxoid sarcoma and is useful in determining if performing FISH evaluation for a FUS rearrangement, characteristic of such tumors, should be considered. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: MUM1 gene product, also known as interferon regulatory factor 4. In hematolymphoid neoplasms, MUM1 is uniformly positive in multiple myeloma, the plasma cell components of both lymphoplasmacytic and marginal zone lymphomas, the Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma, and in the majority of diffuse large B-cell lymphomas of non-germinal center origin. It can be expressed at low levels (i.e., in less than 30% of the cells) in marginal zone lymphomas, follicular lymphomas, and CLL/SLL. It is negative on Burkitt lymphoma. Subcellular Localization: Nuclear and cytoplasmic

Disease State: Classical Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: This sensitive breakapart FISH assay detects any rearrangement involving the MYC gene. Translocations involving the MYC gene on chromosome 8 are characteristic chromosomal aberrations of Burkitt's-type lymphomas/leukemias (BLs). On the molecular level, the MYC gene on 8q24 is juxtaposed to the heavy chain locus on 14q32 in most cases or less commonly to light chain loci on 2q11 and 22q11, resulting in constitutive overexpression of the transcription factor, MYC. The detection of translocations involving MYC is a major aim in the diagnosis of patients with high-grade B cell lymphomas because treatment strategies differ between BL and other high-grade B cell neoplasms. Probe type: Dual color breakapart

Organ: Brain/CNS, Blood/Bone Marrow, Colon & Other GI, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Burkitt's Lymphoma, Diffuse Large B Cell Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: PCR

Clinical Significance: The MYD88 L265P mutation is detected in ~90% of lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM) cases, ~30% of activated/non-germinal center type diffuse large B cell lymphomas, ~40% of central nervous system lymphomas, and ~50% of IgM monoclonal gammopathies of undetermined significance (IgM-MGUS). Of note, the presence of an MYD88 L265P mutation has been associated with a higher risk progression in patients with IgM-MGUS. However, the MYD88 L265P mutation is not exclusively identified in these neoplasms and has been reported in other diagnostic entitites.

Organ: Blood/Bone Marrow, Lymph Node / Spleen

Disease State: Diffuse Large B Cell Lymphoma, Lymphoplasmacytic Lymphoma

Turnaround Time: Within 4-8 business days of receipt

Schedule: Thursday

Specimen Requirements: Formalin-fixed, paraffin-embedded (FFPE) tissue block, 10 FFPE tissue slides, or peripheral blood or bone marrow in EDTA or heparin.

CPT Code(s): 81305. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a protein that is a sensitive and specific marker of carcinomas primary to the breast. Can also be expressed in a subset of salivary gland tumors as well as ovarian carcinomas. Subcellular Localization: Cytoplasmic

Organ: Breast

Disease State: Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: MCPV is suspected to be an etiological agent in the majority of cases of Merkel cell carcinoma, and has been reported to be identified by immunohistochemistry in up to 80% of these tumors. MCPV is not detected in non-Merkel cell neuroendocrine tumors. Subcellular Localization: Nuclear

Organ: Skin & Mucosa

Disease State: Carcinomas of Unknown Primary, Metastatic Carcinoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This tube is added whenever >20% myeloid blasts are identified by flow cytometry (often when >10% blasts are identified), in order to provide additional characterization of the blasts. This tube can also be helpful in distinguishing benign regenerating myeloid blasts from leukemic myeloid blasts in the setting of post therapy bone marrows. This tube includes antibodies to CD45, CD9, CD133, CD34, CD90, HLA-DR, CD117, CD19, and CD38. Because of recent reports suggesting the prognostic significance of CD25 in AML, we are considering swapping the CD25 for the CD90.

Organ: Blood/Bone Marrow

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x9. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FLOW

Clinical Significance: This tube is designed to help identify erythroid and megakaryocytic differentiation in the setting of AML, and also to help distinguish AML from blastic plasmacytoid dendritic cell neoplasms. The tube includes antibodies to CD45, CD235a (glycophorin A), CD41, CD34, CD117, CD61, and CD11c.

Organ: Blood/Bone Marrow

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma, Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Physician will be contacted by 9:00 PM PST the day of receipt for acute/life threatening conditions; next business day for routine flow cases.

Schedule: Monday-Saturday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Tissue: Finely minced tissue in RPMI transport media - OR - • Body fluids: In RPMI transport media

CPT Code(s): 88185x7. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Several recurrent and prognostic chromosome alterations have been identified in myeloma and their identification is useful in the management of these patients. These include translocations involving the FGFR3, MAF, MAFB and CCND1 genes with the IGH gene, loss of 17p13.1(P53), loss of 13q14.3, rearrangement of MYC, and hyperdiploidy. The t(14;16), t(4;14), and t(14;20) translocations involving the MAF, FGFR3, and MAFB genes, respectively, each independently identify poor prognostic groups. Deletion of 13q14.3, rearrangement of MYC, or 17p13.1(P53) are two additional poor prognostic indicators in myeloma. Hyperdiploidy is associated with a favorable prognosis and the t(11;14) portends an intermediate prognosis.

Organ: Blood/Bone Marrow, Body Fluids

Disease State: Plasma Cell Myeloma/Neoplasm

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI

CPT Code(s): 88374x6, 88367; 88373x5. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: A peroxidase enzyme expressed at high levels in normal and neoplastic cells showing granulocytic differentiation, but not monocytic differentiation. Subcellular Localization: Cytoplasmic

Disease State: Acute Myeloid Leukemia (AML) / Myeloid Sarcoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Special Stains

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Cytocentrifuge preparations of cell suspensions

CPT Code(s): 88313. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a nuclear transcription factor that plays a key role in the regulation of skeletal muscle differentiation, and can be employed as a highly sensitive and specific marker of rhabdomyosarcoma. Subcellular Localization: Nuclear

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a nuclear transcription factor that plays a key role in the regulation of skeletal muscle differentiation, and can be employed as a highly sensitive and specific marker of rhabdomyosarcoma. Subcellular Localization: Nuclear

Disease State: Small, Blue, Round Cell Tumors, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A nuclear transcription factor to the NK2 homeobox 2 gene. This transcription factor is involved in neural morphogenesis as well as the development of neuroendocrine cells, such as those of pancreatic islet cells. The expression of NKX2.2 by IHC is a useful biomarker for distinguishing primitive neuroectodermal tumor/ Ewing sarcoma (PNET/ES) from other small blue round cell tumors, when used as a component of a panel of other tests. Subcellular localization: Nuclear

Organ: Soft Tissue

Disease State: Small, Blue, Round Cell Tumors

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: A putative tumor suppressor protein that is expressed almost exclusively in the prostate and prostatic adenocarcinoma. It can supplement other markers such as PSA. Subcellular Localization: Nuclear

Organ: Prostate

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top)

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: Send out test

Turnaround Time: Variable, depending on where specimen is sent; contact Client Services for additional information

Specimen Requirements: • Peripheral blood, Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in EDTA (purple top) / Acceptable: 1-2 ml in sodium heparin (green top) - OR - • FFPE solid tumor tissue, Preferred: Paraffin block / Acceptable: 1 H&E plus 5-10 unstained slides cut at 5 or more microns

CPT Code(s): Variable, depending on where specimen is sent; contact Client Services for additional information

Methodology: IHC

Clinical Significance: Identifies a nuclear protein expressed normally in germ cells of the testis and ovary. NUT midline carcinoma (NMC) is defined by the presence of chromosomal rearrangement involving the NUT gene on chromosome 15q14 and immunohistochemically detectable expression of the NUT protein. Subcellular Localization: Nuclear (speckled)

Disease State: Carcinomas of Unknown Primary

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies an aspartic protease expressed at high levels by type II pneumocytes of the lung. NapsinA is a realtively sensitive and specific marker of pulmonary adenocarcinoma, although it can also be expressed in a subset of renal cell carcinomas and ovarian carcinomas (i.e., clear cell carcinomas). Subcellular Localization: Granular cytoplasmic

Organ: Lung, OB/GYN

Disease State: Carcinomas of Unknown Primary, Mesothelioma vs. Adenocarcinoma, Adenocarcinoma, Non Small Cell Lung Carcinoma (NSCLC)

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Expression of Nestin, a common marker of neural progenitor cells, is associated with the triple-negative/basal-like phenotype and poor prognosis. Nestin, in a survey of 46 biomarkers, ranked second highest, as well as having 54% sensitivity and 96% specificity for basal-like breast carcinomas (Won, et al, Modern Pathology 2013;26:1438-1450). A 2-marker panel for identification of basal-like breast carcinomas comprised of INPP4B negativity and/or Nestin positivity was observed to have 83% sensitivity and 96% specificity according to published literature (Parry, et al J Clin Pathol 2008;61:1045-1050). Basal-like and/or triple negative breast cancers account for approximately 15% of all breast carcinomas. They are predominately high grade and are associated with early onset, as well as a poor prognosis. The triple negative immunophenotype is known to be an imperfect correlate of the basal-like genotype as determined by molecular studies. Studies have suggested that Nestin might serve as a useful marker of basal-like breast cancers. Using the 10c2 mouse monoclonal antibody to Nestin, we demonstrated 70% sensitivity and 100% specificity, which is higher than the reported literature. Nestin will be run in a panel with other antibodies, including INPP4B, to identify basal-like breast cancers. Subcellular Localization: cytoplasmic

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies the intermediate filament protein comprising neurofilaments, which are expressed exclusively within neurons and tumors showing neuronal differentiation. Subcellular Localization: Cytoplasmic

Organ: Brain/CNS

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Proper WHO classification of aggressive B cell lymphomas is greatly aided by the identification of specific chromosomal alterations involving the MYC, BCL2, BCL6 and IGH genes. The main differential for this class of tumors typically includes Burkitt’s lymphoma, DLBCL, and tumors with morphologic and genetic features intermediate between these two entities. Identification of a “double-hit” (i.e. a MYC rearrangement with either a BCL6 or BCL2 rearrangement) argues against the diagnosis of Burkitt’s and can provide support for the intermediate category, although such double hits can also occur in DLBCL. The findings of this panel of FISH studies should be correlated with the clinical features and the histologic and immunophenotypic findings.

Organ: Blood/Bone Marrow, Body Fluids, Lymph Node / Spleen

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Burkitt's Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Peripheral blood, Preferred: 3 ml in sodium heparin (green top) / Acceptable: 3 ml in EDTA (purple top) - OR - • Bone marrow aspirate, Preferred: 1-2 ml in sodium heparin (green top) / Acceptable: 1-2 ml in EDTA (purple top) - OR - • Fresh tissue in RPMI - OR - • Formalin-fixed, paraffin-embedded tissue (FFPE)

CPT Code(s): 88374x4. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies Octamer transcription factor 2, expressed by all normal B cells throughout maturation (from immature forms to plasma cells). Co-expressed with Bob-1 in almost all non-Hodgkin lymphomas, plasma cell neoplasms, and nodular lymphocyte predominance lymphomas (Oct-2 expression is particularly strong among the L&H/LP cells in the latter), but Oct-, Bob-1, or both is aberrantly lost in nearly all cases of classical Hodgkin lymphoma. Subcellular Localization: Nuclear

Disease State: B Cell Non-Hodgkin Lymphoma (not otherwise classified), Classical Hodgkin Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a nuclear transcription factor expressed at high levels in embryonal carcinoma and seminoma, and used as part of a panel in the subclassification of germ cell tumors. Subcellular Localization: Nuclear

Organ: OB/GYN, Genitourinary, Testis, Ovary

Disease State: Germ Cell Tumors

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: FISH

Clinical Significance: Deletion involving the cyclin-dependent kinase inhibitor 2A/p16 gene at the 9p21 locus on chromosome 9 is frequently observed in mesothelioma. Homozygous deletion of this gene has been reported in 22-74% of mesotheliomas. This characteristic of mesotheliomas can be employed in the often-difficult differential diagnoses of spindle cell mesothelial proliferations where immunohistochemical markers cannot distinguish between benign and malignant mesothelial proliferations. While a negative result for homozygous p16 deletion cannot rule out the possibility of a mesothelioma, a positive result is highly specific for mesothelioma in the appropriate clinical setting.

Organ: Lung

Disease State: Mesothelioma vs. Adenocarcinoma, Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 4-6 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded tissue block or cell block - OR - • Minimum of 5 unstained slide cut at 4µm for each test requested

CPT Code(s): 88374. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies p16-INK4A, a tumor suppressor gene that plays an important role in cell cycle regulation. High-risk types of human papillomavirus (HPV) have been associated with increased expression of viral oncogenes E6 and E7, both of which impact various cell cycle regulating proteins. The retinoblastoma gene product is inactivated by E7, resulting in unregulated transcription of p16. In certain diseases, overexpression of the p16 protein can serve as a surrogate for the presence of high risk HPV types. In the context of head and neck squamous cell carcinomas, p16 overexpression can also serve as a prognostic marker. Subcellular Localization: Nuclear and cytoplasmic

Organ: OB/GYN

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: p63 consists of at least two isoforms, TAp63 and ΔNp63. The ΔNp63 isoform (p40) is predominant in basal and myoepithelial cells, as well as squamous cell carcinomas of lung and other sites. The 4A4 anti-p63 clone that has been in use for many years is actually a “pan-p63” antibody, identifying both the ΔNp63 and the TAp63 isoforms. As the TAp63 isoform has a much wider tissue distribution than p40, antibodies to p40 can serve as a more squamous-specific marker, e.g., in the context of lung carcinomas, than the 4A4 "pan p63" antibody. Subcellular Localization: Nuclear

Organ: Lung, Breast, Skin & Mucosa, Prostate

Disease State: Large Cell Undifferentiated Malignant Neoplams, Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies: The p53 gene product, a tumor suppressor gene product which has been referred to as the “guardian of the genome” owing to its role in preventing genome mutation. Overexpression of p53 correlates with the presence of p53 mutations and can serve as a marker of malignancy. Subcellular Localization: Nuclear

Organ: Breast, OB/GYN

Disease State: Diffuse Large B Cell Lymphoma, Breast Cancer

Turnaround Time: Within 2-4 business days of receipt

Schedule: Monday - Friday

Specimen Requirements: • Formalin-fixed, paraffin-embedded (FFPE) tissue block or cell block - OR - • 3 unstained slides for each test requested plus 1-2 additional unstained slides cut at 4µm

CPT Code(s): 88342 or 88341. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Methodology: IHC

Clinical Significance: Identifies a paternally imprinted protein, expression of which is lost in cytotrophoblasts of molar pregnancy, i.e., complete mole. The combination of analysis of p57 expression and ploidy (e.g., by FISH) can help define complete moles, incomplete moles, and hydropic normal villi. Subcellular Localization: Nuclear

Organ: OB/GYN

Disease State: Molar Pregnancy