Cancer Cytogenomic Studies

Bone marrow cytogenetic evaluation is considered appropriate for patients with neoplastic or pre-neoplastic hematological disorders. Supply 1-2 ml of bone marrow aspirate in sodium heparin vacutainer. Average turnaround time is 3-14 days.

Cytogenetic evaluation of lymph node, spleen, or solid tumor samples is appropriate in patients where neoplastic or pre-neoplastic cells are suspected to be present in the biopsied sample. Supply 0.3-1 cubic centimeter sample submerged in sterile culture medium (or a balanced salt solution). Turnaround time varies by specimen from 5-21 days.

Cytogenetic evaluation of unstimulated blood samples is appropriate in patients with acquired hematologic malignancy where sufficient neoplastic or pre-neoplastic cells (blast cells) are detected in peripheral blood. If the neoplasm is of lymphoid origin, then stimulation is needed for B-cells (IL2/IL4/IL2+DSP30) or T-cells (PHA). If the blast count or mitotic index is low in the blood, chromosome analysis may be infeasible, and interphase FISH or microarray could be an alternative. Supply 5-10 ml of peripheral blood in sodium heparin vacutainer. Average turnaround time is 3-14 days.

NOTE: These studies involve culturing of living cells; therefore, turnaround times given represent average times, which are subject to multiple variables.

Chromosome analysis CPT codes:

Leukemic blood/bone marrow/lymph node: 88237, 88264, 88291

Solid tumor: 88239, 88264, 88291

Note: limited study will use CPT code 88261 instead of 88264; additional codes may be used for extended analyses (additional karyotypes 88280; additional cell counts 88285)

Fluorescence in Situ Hybridization (FISH) testing extends routine cytogenetic banding methods by resolving ambiguous diagnoses and providing another tool to diagnose submicroscopic and cryptic abnormalities. FISH is a relatively simple, fast, and reliable procedure. FISH testing can be performed independently or concurrently with other cytogenetics studies.

Applications of FISH for hematologic disorders include delineation of chromosomal numerical abnormalities, detection of recurrent translocations and gene rearrangements, and determination of donor cell engraftment following sex-mismatched bone marrow and stem cell transplants. Disease-specific FISH panels for MDS, AML, B-ALL, CLL, MM/MGUS and lymphoma have been standardized to supplement routine chromosome analysis to screen for recurrent chromosome abnormalities. Average turnaround time is 2-7 days.

FISH CPT codes:

FISH analysis may include 88230-88239, 88271-88275 and 88291. Contact lab for specific codes based on specimen type and exact testing being performed.

ALL, B-cell/pre-B-cell Acute lymphoblastic leukemia/lymphoma

• ALL panel: ABL1-BCR* t(9;22) │ KMT2A* (MLL) 11q23.3 │ ETV6-RUNX1* t(12;21) │ Trisomy 4*, 10*, 17 (CEP4, CEP10, CEP17)
• Ph-like panel: ABL2* 1q25.2 │ PDGFRB* 5q33 │ JAK2 9p24.1 │ ABL1* 9q34.1 │ CRLF2 Xp22.3/Yp11.3
• Available on request/reflex: TCF3-PBX1 (E2A-PBX1) t(1;19) │ MYC 8q24 │ 9p- (CDKN2A (p16) 9p21.3, D9Z3 9q12) │ IGH 14q32

ALL, T-cell Acute Lymphoblastic Leukemia/lymphoma

Lymphoma, T-cell

Lymphoma, B-cell

Lymphoma, Cutaneous T-cell, CTCL

Waldenstrom’s/LPL

Multiple Myeloma (MM), Monoclonal Gammopathy (MGUS), Plasma Cell Neoplasms

CLL, Chronic Lymphocytic Leukemia

T-cell PLL, Prolymphocytic Leukemia

B-cell PLL, Prolymphocytic Leukemia

MDS, Myelodysplastic Syndrome

AML, Acute Myeloid Leukemia

*COG AML required testing

CML, Chronic Myeloid Leukemia

MPN/MPD (unspecified), Myeloproliferative neoplasm/disorder

Polycythemia Vera

Primary Myelofibrosis

Mastocytosis/Mast cell disease

Eosinophilia

Rhabdomyosarcoma

Neuroblastoma

Ewing Sarcoma

Sex mis-match chimerism

Chromosomal microarray analysis (CMA) is used to identify somatic copy number aberrations (CNAs) and unbalanced gene rearrangements in cancer-related abnormal clones. CMA has the advantage in identification of cryptic imbalances and detection of clonal aberrations in populations of non-dividing cancer cells and samples with poor chromosome morphology. Microarray analysis can further define the size, precise breakpoints, and gene content of the clonal abnormalities detected by chromosome analysis; characterize marker chromosomes and unknown chromosome materials involving gene amplification; rule out the presence of cryptic imbalance in apparently balanced rearrangements; detect complex genomic imbalances in chromothripsis; and assess regions of copy-neutral loss of heterozygosity, which is common in neoplasia and often masks homozygous mutations involving oncogenes or tumor suppressor genes.

OncoScan microarray assay (OMA), using molecular Inversion Probe (MIP) technology with enhanced resolution of ~900 cancer genes, offers genome-wide CNAs and CN-LOH detection from either fresh, frozen or paraffin-embedded cancer tissues. Average turnaround time is 10-28 days.

NOTE: Microarray turnaround time assumes insurance prior authorization/approval is in place.

Microarray CPT code:

Neoplasia Microarray (Oncoscan): 81277

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Bewersdorf JP, Siddon A, DiAdamo A, Zeidan AM. A complex karyotype and a genetic mutation in acute myeloid leukaemia. Lancet. 2021 Dec 19;396(10267):2018.