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: ALK is a proto-oncogene highly expressed in a variety of tumor cells, and in particular in ~2-5% of non-small cell 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).)

Organ: Lung

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 and other T cell lymphomas. ALK is a protein overexpressed as a consequence of the (2;5) translocation that is found in anaplastic large cell lymphoma (ALCL). Expression of ALK is also seen in embryonal carcinomas and in a subset of inflammatory myofibroblastic tumors. Subcellular Localization:  Nuclear and cytoplasmic

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 intracytoplasmic globules, in the setting of alpha-1-antitrypsin deficiency. Subcellular Localization:  Cytoplasmic (globular)

Organ: Liver

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 yolk sac tumors that can be employed as part of a panel of markers of germ cell tumors. Not recommended in this setting as there are more sensitive and specific markers (e.g., glypican-3). Subcellular Localization: Cytoplasm

Organ: OB/GYN, Genitourinary, Liver

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 amyloids, the protein nature of which is derived from AA protein. Subcellular Localization: Extracellular (amyloid deposits)

Disease State: Amyloid Type Analysis

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Amyloid beta localizes to the senile plaques characteristic of Altzheimer’s disease. Subcellular Localization: Extracellular (senile plaques)

Organ: Brain/CNS

Disease State: Amyloid Type Analysis

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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

Disease State: Amyloid Type Analysis

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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

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 a subset of carcinomas, including those primary to the breast, salivary gland, and prostate. Subcellular Localization: Nuclear

Organ: Breast, Genitourinary, Prostate, Hormones

Disease State: Breast Cancer

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Arginase-1 is a highly sensitive and specific marker of hepatocytes and hepatocellular carcinoma. Subcellular Localization: Nuclear and cytoplasmic

Organ: Liver

Disease State: Carcinomas of Unknown Primary, Hepatocellular Carcinoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 plasma cell-associated surface antigen expressed by the great majority of benign and neoplastic plasma cells and by a smaller proportion of benign and neoplastic B cells.

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 (negative). 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 Lewis Y blood group related antigen, which has been demonstrated to be a sensitive marker of adenocarcinoma, not expressed, or expressed only at very low levels, in mesothelial cells or mesothelioma. Subcellular Localization: Membranous and cytoplasmic

Organ: Lung

Disease State: Mesothelioma vs. Adenocarcinoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 all epithelial tissues expressing the blood group A. Useful for identification of floaters, i.e., of contaminating tissues derived from patients of different blood group types. Subcellular Localization: Membranous and cytoplasmic

Disease State: Identification of Floaters

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 all epithelial tissues expressing the blood group B. Useful for identification of floaters, i.e., of contaminating tissues derived from patients of different blood group types. Subcellular Localization: Membranous and cytoplasmic

Disease State: Identification of Floaters

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 all normal B 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 chondromatous and myxoid tumors. Subcellular Localization: Nuclear

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 IHC Breast Multiplex assay is intended for the qualitative identification of Keratin 5/14, p63 protein and Keratin 7/18 by two color immunohistochemistry (IHC). This multiplex assay has two diagnostic applications: 1. Invasive carcinoma versus non-invasive lesions: The presence of myoepithelial cells around suspicious cells nests argues against a diagnosis of invasive carcinoma and can aid in identifying a non-invasive entity, such as carcinoma in situ, atypical ductal hyperplasia (ADH), usual ductal hyperplasia (UDH), and sclerosing adenosis. 2. Usual ductal hyperplasia versus atypical ductal hyperplasia and carcinoma in situ: The presence of staining for Keratin 5 among the luminal cells of a hyperplastic breast lesion can aid in distinguishing usual ductal hyperplasia (typically positive for Keratin 5) from atypical ductal hyperplasia/carcinoma in situ (typically negative for Keratin 5).

Organ: Breast

Disease State: Adenocarcinoma, Breast Cancer

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

CPT Code(s): 88344. 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 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 ia a follicular B cell surface marker also known as CALLA. It is also expressed in a subset of non-hematopoietic tumors, including atypical fibroxanthoma.

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 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 plasmacytoid dendritic cell neoplasms, at variable intensity in all classical hairy cell leukemia, most B-ALLs, and in a subset of AMLs. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 neoplasms of monocytic and Langerhans cell origin from other hematolymphoid neoplasms. CD14 is a glycoprotein expressed on mature monocytes, histiocytes/macrophages, Langerhans cells, 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 granulocytes at the promyelocyte and later stages, and is expressed at lower levels on monocytes/histiocytes. CD15 is aberrantly coexpressed by myeloid blasts in a subset of myeloid stem cell neoplasms. In addition, CD15 is expressed in a membrane and/or Golgi pattern in the majority 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 the monocytic/macrophage lineage. It is present on all circulating monocytes and most tissue macrophages except those found in the mantle zone and germinal centers of lymphoid follicles, interdigitating reticulum cells and Langerhan’s cells. Subcellular Localization: Membranous

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 "dual-positive" stage of T cell development, which is the stage at which CD4 and CD8 are coexpressed on immature T cells in the thymus. CD1a is 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. Subcellular Localization: Membranous and cytoplasmic

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 natural killer (NK) cells. CD2 is aberrantly decreased in a subset of T cell and natural killer cell neoplasms. Rare cases of acute myeloid leukemia show aberrant coexpression of CD2 on the leukemic blasts. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 maturation 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 rarely on plasmacytic neoplasms. CD20 is the target of the therapeutic antibody known as Rituxan. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 (almost always CD200-negative). 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 a B cell specific surface antigen expressed in mature B cells, and positive on B-cell neoplasms such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 a large subset of follicular dendritic cells (FDCs). CD23 tends to be strongly coexpressed with CD5 on the neoplastic B cells of chronic lymphocytic leukemia/small lymphocytic lymphoma. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 myeloid progenitors, monocytes, and macrophages. Acute and chronic myelogenous and monocytic leukemias, as well as acute lymphoblastic leukemias, express CD33. Some cases of multiple myeloma also express CD33. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 lymphohematopoietic 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 46 kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic tail (20 amino acids) and a long extracellular domain (256 amino acids). CD38 is expressed by a variety of leukocytes, including plasma cells (which show the highest levels of expression), immature and mature B and T cells, NK cells, monocytes, macrophages, and myeloid progenitors. It has enzymatic activity as a cyclic ADP ribose hydrolase, which contributes to the regulation of intracellular calcium. The ligand of CD38 is CD31. In mature B cells, CD38 expression is induced once naive B lymphocytes are activated, reaches a first peak when B cells enter the germinal center, decreases during centrocyte/centroblast differentiation, is completely absent in 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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.  A subset of cases of Bernard-Soulier syndrome involve congenital deficiency of CD42b. Subcellular Localization: Membranous

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 leukocytes except resting B lymphocytes. Co-expression of CD43 with CD20 is a feature of a subset of low-grade lymphomas. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 beyond the proerythroblasts stage. A variety of hematopoietic neoplasms show aberrant increases or decreases in the level of CD45 expression. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 NK cell neoplasms, and on a subset of T cell neoplasms. 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 a large subset 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: CD57 is a cell surface-associated protein expressed on a subset of activated T cells, including so-called large granular lymphocytes, and neoplasms derived from these cells. CD57 is also expressed on a variety of neural structures. Identification of CD57-positive cells is of value in positively identifying lymphocyte-predominant Hodgkin lymphoma. Subcellular Localization: Membranous

Disease State: Spindle Cell Tumors / Sarcoma Subtyping, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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. It is employed as a marker of megakaryocytes and platelets. Subcellular Localization: Membranous and cytoplasmic

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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/lysozomal-associated protein expressed by normal and neoplastic monocytes/histiocytes, including Langerhans cells. Neoplasms of lymphoid origin are usually negative, although some B cell neoplasms, most frequently small lymphocytic lymphoma and hairy cell leukemia, show weak staining of the cytoplasm, usually in the form of a few scattered granules. Subcellular Localization: Cytoplasmic

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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. In addition, a significant subset of myeloid stem cell neoplasms, including acute myeloid leukemia and myelodysplastic or myeloproliferative syndromes, demonstrates aberrant coexpression of CD7 on the myeloid blasts. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 transferrin receptor (CD71), required for delivery of iron from transferrin to cells. In clinical practice, CD71 displays specificity for erythrocyte precursors in normal and abnormal bone marrow sections. Subcellular Localization: Strong membranous staining with weak cytoplasmic staining in some cases

Organ: Blood/Bone Marrow

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 decreased in most cases of classical Hodgkin lymphoma, and in a subset of non-Hodgkin B cell lymphomas. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: CD99 has historically been used as a marker of PNET/Ewing sarcoma, as well as a subset of spindle cell tumors, including synovial sarcoma and solitary fibrous tumor, although there are other more specific markers now available for these latter tumors. Use of CD99 is not recommended; please contact one of our pathologists for alternative markers. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 "true" CEA, also known as CD66e, expressed by a subset of epithelial cells and carcinomas. Subcellular Localization: Cytoplasmic

Organ: Liver

Disease State: Hepatocellular Carcinoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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

Clinical Significance: A recurrent problem in surgical pathology specimens is specimen mix-up and contamination of a patient's specimen by "floaters." While many of these cases can be resolved histologically or immunophenotypically using blood group antigen immunohistochemistry, a significant number of cases may not be resolved by these modalities and can have serious clinical and medicolegal implications. Use of fluorescence in situ hybridization (FISH) to perform sex genotyping on tissue specimens with potential tissue contaminants is an effective and reliable means of potentially resolving problems of floater contamination. Minute tissue samples provide sufficient target DNA and nuclei for FISH studies. This assay confirms the presence of these sex chromosomes within the cells of interest. Presence of two green X chromosome signals is indicative of an XX female genotype, whereas the presence of a single green X chromosome and single orange Y chromosome signal are indicative of an XY male genotype. Probe type: Dual color enumeration

Disease State: Identification of Floaters

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): 88366. 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)

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: 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, to a lesser extent, other peripheral T cell lymphomas.  Importantly, 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 and medullary thyroid carcinomas. Subcellular Localization: Cytoplasmic

Organ: Thyroid

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 of myoepithelium around suspicious cell nests and, as part of a panel, is helpful in distinguishing in situ vs. invasive lesions. Subcellular Localization: Cytoplasmic

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Antibodies to calretinin have been demonstrated to be 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 5-7 business days; 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. It is expressed in diffuse large B-cell lymphomas (DLBCL), T-cell rich large B-cell lymphoma, Hodgkin lymphoma, as well as various carcinomas. Clusterin has proven to be an effective tool in the differentiation of anaplastic large cell lymphoma (ALCL) from peripheral T cell lymphoma (PTCL), NOS. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 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 1-2 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, can be helpful in the identification of mantle cell lymphomas. Subcellular Localization: Nuclear

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 Keratin 5

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 and angiomatoid fibrous histiocytoma. Subcellular Localization: Cytoplasmic

Organ: Skin & Mucosa

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 the function of which is 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. Subcellular Localization: Membranous

Organ: Breast

Disease State: Breast Cancer

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 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). EBV-LMP is 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: PCR

Clinical Significance: The Roche cobas® EGFR Mutation Test v2 is an FDA-approved assay for identifying EGFR T790M, exon 19 deletions, and exon 21 L858R substitution mutations in circulating tumor DNA obtained from patients with non-small cell lung carcinoma. The identification of other clinically relevant EGFR mutations has been validated by PhenoPath Laboratories. Circulating tumor / “cell-free” DNA is isolated from plasma using the cobas® cfDNA Sample Preparation Kit; followed by amplification and detection of target DNA sequences using the cobas® z 480 analyzer. Please note that tumor samples (such as cytology preparations, biopsies and resection specimens) are the most robust method for determining EGFR mutation status. EGFR mutation testing of circulating tumor DNA in plasma is inherently more likely to produce a false negative result. When detected, EGFR mutations identified in circulating tumor DNA are associated with EGFR mutation-positive tumors; however, testing of tumor samples is recommended whenever possible.

Organ: Lung

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

Turnaround Time: Within 3-5 business days of receipt

Schedule: Once per week

Specimen Requirements: --Minimum of 2 mL of plasma (following collection instructions below) --Recommend 4-6 mL of plasma for testing . Collection Instructions: --Venipuncture into K2-EDTA/plasma separator tube (ideally collect two to three 5 mL tubes; minimum of one 5 mL tube needed) --Within 4 hours of collection; separate plasma by centrifugation --Transfer plasma into transport tube --Immediately ship to PhenoPath frozen on dry ice

CPT Code(s): 81235. 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, and other tumors. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 is used as part of a panel of markers in 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 main clinical indication for FOXP3 IHC is expected to be immunophenotyping of tumor infiltrating lymphocytes (TILs) in human tumors. However, unforeseen clinical indications cannot be excluded. FOXP3 is a relatively specific marker of regulatory T cells (Tregs) which normally function to limit T cell-driven immune responses. Tregs are also involved in the immune evasion mechanisms promoted 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). In addition to FOXP3 expression in the tissues noted below, FOXP3 may be seen in the tumor infiltrating T cells in any type of human tomor. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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. Fascin expression can be employed in the distinction of anaplastic large cell lymphoma (fascin-negative) from Hodgkin lymphoma (fascin-positive). Subcellular Localization: Cytoplasmic

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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).

Organ: Breast, Genitourinary

Disease State: Carcinomas of Unknown Primary, Breast Cancer

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: GCET1, a cytoplasmic protein that is relatively specific for normal germinal center B cells and germinal center-derived B cell neoplasms, including follicular lymphoma, Burkitt lymphoma, a subset of diffuse large B cell lymphoma (DLBCL), and nodular lymphocyte predominant Hodgkin lymphoma. GCET is also used as part of a panel of markers in immunohistochemical distinction of germinal center-derived DLBCL from non-germinal center-derived DLBCL. Subcellular Localization: Cytoplasmic (secretory), granular, with frequent Golgi staining

Organ: Genitourinary, Testis, Ovary

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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

Organ: Brain/CNS

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Glucagon, a hormone expressed in the alpha cells of the pancreatic islet, as well a subset of pancreatic islet cell tumors (glucagonomas). Subcellular Localization: Cytoplasmic

Organ: Pancreas, Hormones

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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, a marker of erythrocytes and erythroid differentiation in myeloid processes. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 a useful biomarker for cytotoxic T-lymphocytes and natural killer cells, and may aid in differentiating between tumors arising from these cell types and tumors arising from other hematolymphoid cell types. Granzyme B is a serine protease that is the main component in granule-mediated targeted cell lysis. Cytotoxic T-lymphocytes (CTL) and Natural-Killer (NK) cells store granzyme B-containing granules in their cytoplasm and release them during CTL-mediated targeted cell lysis (the ‘cell-mediated’ component of the immune response). After release from the CTL, granzyme B binds its receptor on the target cell, is endocytosed, and remains in the endocytic vesicle until released by perforin. Once released into the target cell cytoplasm, granzyme B can affect cell death via two pathways: 1) initiating a caspase cascade that leads to rapid DNA fragmentation of the target cell (apoptosis) or 2) mediating the release of cytochrome c from the mitochondria, which leads to cell death via necrosis.

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: This antibody is 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 1-2 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

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 originally described as a positive marker of mesotheliomas, but other markers are currently employed for that purpose (e.g., calretinin, WT-1, podoplanin, cytokeratin 5, etc.) HMBE-1, however, has been found to be useful as part of a panel of markers in the distinction of thyroid carcinomas from adenomas. Subcellular Localization: Membranous

Organ: Thyroid

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 hormone produced by trophoblasts. It is useful for the identification of cells manifesting trophoblastic differentiation, e.g., in germ cell tumors. Subcellular Localization: Cytoplasmic

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

Disease State: Germ Cell Tumors

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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. As part of a panel of IHC antibodies, the HGAL antibody is useful to distinguish follicle center-derived B cell non-Hodgkin lymphoma (B-NHL) from other B cell proliferations. Subcellular Localization: Cytoplasmic

Organ: Lymph Node / Spleen

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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). Expressed in lymphomas and leukemias, both myeloid and lymphoid. Examples include acute myeloid leukemias (AML), and chronic myelomonocytic leukemias (CMML). Expression varies in each neoplasm, depending on various factors, including cell maturity and differentiation. HLA-DR has been shown to be consistently expressed in most AMLs of non-M3 (Acute promyelocytic or APL) type, and has been shown to be helpful in differentiating myeloblastic from promyelocytic variants. Subcellular Localization: Membranous

Disease State: Blastic Plasmacytoid Dendritic Cell Neoplasm

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 uncharacterized antigen present in >97% of cases of hairy cell leukemia. Other tumors positive include a high fraction of cases of splenic lymphomas with villous lymphocytes, and a smaller fraction of high grade B cell lymphomas (e.g., immunoblastic). The antibody shows strong positive staining of about 35% of cases of high-grade B cell lymphomas, e.g. centroblastic and immunoblastic types. Subcellular Localization: Cytoplasmic

Disease State: Hairy Cell Leukemia

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Hemoglobin A, a protein expressed in progressively greater amounts in erythroid cells after the basophilic erythroblast stage, reaching a maximum level in mature erythrocytes. Subcellular Localization: Membranous

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Hepatitis B infected cells in the liver and other sites. Subcellular Localization: Nuclear

Disease State: Identification of Organisms

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Hepatitis B infected cells in the liver and other sites. Subcellular Localization: Cytoplasm

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 1-2 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: IgA-positive plasma cells and plasma cell neoplasms. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: IgD, or immunoglobulin D 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 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: This clone identifies IgG4 positive plasma cells, which are increased in IgG4-related sclerosing disease. The immunohistochemical evaluation for IgG4-related disease (IRD) is commonly based on the percentage of IgG4-specific plasma cells among the total IgG-positive plasma cells (usually over 40%, or over 50 IgG4+ plasma cells per 400x field, in this disease, see reference). Therefore, PhenoPath's assay employs antibodies to both IgG4 and total IgG. In some cases, antibodies to CD38 or IgA may also be employed, particularly when total IgG+ plasma cells appear to represent a minority of the total plasma cells, as is common in the gastrointestinal tract. Our pathologists are happy to answer questions concerning interpretation of IgG4 or PhenoPath's testing policy. Ref: Mod Pathol 25:1181-92, 2012 Subcellular Localization: Cytoplasmic

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

Disease State: Benign/reactive sclerosing lesion

Turnaround Time: Within 1-2 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 1-2 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. Subcellular Localization: Cytoplasmic

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 and lambda immunoglobulin light chains, expressed by plasma cells and plasmacytoid lymphocytes. Also expressed, but less reliably detected, on B cells with small amounts of 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 clonality 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Kappa and lambda immunoglobulin light chains are expressed by plasma cells and plasmacytoid lymphocytes. They are also expressed, but less reliably detected, on B cells with weak cytoplasmic staining. However, immunoglobulin are also a major component of serum, leading to (in many tissue types) high background/non-specific staining which may obscure the detection/observation of light chain restriction among B lineage cells. This non-specific staining also impedes the assessment of light chain skewing in non-neoplastic populations. As all proteins are translated from mRNA, detection of mRNA transcripts can be a useful surrogate for protein expression and therefore in-situ hybridization for kappa and lambda mRNA transcripts can be used to determine the light chain restriction status for plasma cell and plasmacytoid B cell populations. Subcellular Localization: Cytoplasmic

Organ: Blood/Bone Marrow, Lymph Node / Spleen

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

CPT Code(s): 88365 or 88364. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 "high molecular weight" cytokeratins. It is an excellent marker of squamous differentiation, as well as a marker of the outer cell layer in prostatic glands, which is absent in carcinoma. Subcellular Localization: Cytoplasmic

Organ: Genitourinary, Prostate

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 MIB-1 and is generally employed in the context of decalcified bone marrow specimens. Subcellular Localization: Nuclear

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 mantle cell lymphoma. Subcellular Localization: Nuclear

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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. In the setting of diffuse large B-cell lymphomas (DLBCLs), LMO2 has high sensitivity in differentiating between germinal center B-cell (GCB) DLBCLs and non-GCB DLBCLs. Based on the recently published Tally Method algorithm, LMO2 will be used in a panel, along with CD10, GCET1, MUM1, and FoxP1, to help distinguish between GCB versus non-GCB origin among DLBCLs. Subcellular Localization: Nuclear

Disease State: Diffuse Large B Cell Lymphoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Kappa and lambda immunoglobulin light chains, expressed by plasma cells and plasmacytoid lymphocytes. Also expressed, but less reliably detected, on B cells with small amounts of 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 clonality 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Kappa and lambda immunoglobulin light chains are expressed by plasma cells and plasmacytoid lymphocytes. They are also expressed, but less reliably detected, on B cells with weak cytoplasmic staining. However, immunoglobulin are also a major component of serum, leading to (in many tissue types) high background/non-specific staining which may obscure the detection/observation of light chain restriction among B lineage cells. This non-specific staining also impedes the assessment of light chain skewing in non-neoplastic populations. As all proteins are translated from mRNA, detection of mRNA transcripts can be a useful surrogate for protein expression and therefore in-situ hybridization for kappa and lambda mRNA transcripts can be used to determine the light chain restriction status for plasma cell and plasmacytoid B cell populations. Subcellular Localization: Cytoplasmic

Organ: Blood/Bone Marrow, Lymph Node / Spleen

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

CPT Code(s): 88365 or 88364. 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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

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): 36787 (reference only; CPTs may vary)

Methodology: Send out test

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): 36789 (reference only; CPTs may vary)

Methodology: Send out test

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): 36788 (reference only; CPTs may vary)

Methodology: IHC

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

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 and adrenal cortical tumors. Subcellular Localization: Cytoplasmic

Organ: OB/GYN, Skin & Mucosa

Disease State: Melanoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Identifies: 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Almost entirely 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Identifies: MUM1 gene product, also known as interferon regulatory factor 4. In hematolymphoid neoplasms, MUM1 is positive in multiple myelomas, lymphoplasmacytic lymphomas, Reed-Sternberg cells of Hodgkin lymphoma and in approximately 50% (up to 75% in some studies) of diffuse large B-cell lymphomas (DLBCL). It is expressed at low levels (i.e., in less than 30% of the cells) in marginal zone lymphomas, follicular lymphomas, and B cell CLL/SLL. It is negative on Burkitt’s lymphoma. Subcellular Localization: Nuclear and cytoplasmic

Disease State: Classical Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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.

Organ: Skin & Mucosa

Disease State: Carcinomas of Unknown Primary, Metastatic Carcinoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Mesothelin, a cell surface protein expressed by mesothelial cells and mesothelioma, but also by ovarian carcinoma and pancreatic adenocarcinoma. Displays significantly less specificity for mesotheliomas than other markers such as WT-1, calretinin, and podoplanin. Subcellular Localization: Membranous

Organ: Lung, Pancreas

Disease State: Mesothelioma vs. Adenocarcinoma

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 mitochondrial antigen. The presence of increased numbers of mitochondria, and hence fine granular positivity with this antibody, can assist in the analysis of eosinophilic tumors (e.g., oncocytomas) of the kidney. Subcellular Localization: Cytoplasmic (granular)

Organ: Genitourinary

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 smooth, skeletal, and cardiac isoforms of actin. HHF35 can be employed as a marker of leiomyosarcomas, rhabdomyosarcomas, and tumors showing myoepithelial differentiation. Subcellular Localization: Cytoplasmic

Disease State: Spindle Cell Tumors / Sarcoma Subtyping

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 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 cells showing granulocytic differentiation. Subcellular Localization: Cytoplasmic

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

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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: Antibodies to myoglobin can be employed to identify myoglobin-containing casts within renal tubules, which can be seen following rhabdomyolysis and in cases of myoglobin cast nephropathy. Myoglobin is NOT recommended as a marker of rhabdomyosarcoma, as much more sensitive markers such as myogenin, myoD1, and desmin are best employed in this setting. Clinical Indication(s): This anti-myoglobin antibody will be used to identify the presence of myoglobin-containing tubular casts in the lumina of renal tubules. Subcellular Localization: Cytoplasmic

Organ: Kidney

Disease State: Renal disease

Turnaround Time: Within 1-2 business days of receipt

Schedule: Monday - Friday

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

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: NKX2.2 is 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 (NUT) 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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 highly 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 1-2 business days of receipt

Schedule: Monday - Friday

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

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