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FISH, Myeloma, 17p-, rea 14q32 with ReflexesTest code(s) 92497
Question 1. What are the components of this test code?
This test includes FISH probes for genomic changes in plasma cell myeloma, including:
- TP53 locus at 17p13 (ie, del 17p13, 17p-)
- Rearrangements of the IGH locus at 14q32
- If a 14q32 rearrangement is detected and there is adequate specimen, additional probes are automatically added (at additional charge) for the four most common IGH translocations: CCND1/t(11;14), FGFR3/t(4;14), MAF/t(14;16) and MAFB/t(14;20)
- Prognostic subpanel including probes for 13q/RB1 (ie, del13), 1q gain, and hyperdiploidy (centromeric probes for chromosomes 9, 11 and 15)
Question 2. Which sample types are acceptable and how is testing performed?
This test is performed only on bone marrow aspirates. Specimens containing ≥10% plasma cells are optimal. However, plasma cell enrichment is performed to improve sensitivity if there is sufficient specimen volume (2 – 3 mL). CD138 antibodies are used for this purpose.
If specimen volume is limited and chromosome analysis/karyotyping is also ordered, plasma cells from the cell culture can be used for this test. In this situation, plasma cell enrichment cannot be done.
When specimen volume is limited, testing is prioritized in the following order:
- Probes for 17p- and 14q32
- The four most common 14q32 IGH translocations if a 14q32 rearrangement was detected
- Prognostic subpanel
Question 3. What are some common limitations of this test?
- Plasma cells can rapidly lose viability following aspiration; therefore, delayed receipt in the laboratory may compromise plasma cell enrichment and/or culture.
- Plasma cell cultures require cytokine stimulation and can take up to 5 days to harvest; this increases the turnaround time.
- If there is limitedaspirate volume or few plasma cells present, some tests in the panel may need to be canceled. Whenever possible, the probes associated with high-risk myeloma subgroups (17p and 14q32) are tested first.
Question 4. Are peripheral blood and bone marrow core biposies acceptable specimen types for this test?
No. Except for rare cases of plasma cell leukemia, the number of plasma cells in a peripheral blood specimen is inadequate for FISH analysis. Bone marrow core biopsy and other fixed tissues are not reliable for all the tests included in this panel. Only bone marrow aspirate should be submitted for this test.
However, tests for individual components of this panel may be validated for other specimen types. Please consult the Quest Diagnostics Test Center (http://www.QuestDiagnostics.com/testcenter/TestCenterHome.action) or contact your local Quest Diagnostics business unit for further information.
Question 5. How does this FISH panel compare to guideline-recommended panels?
FISH testing is recommended for both clinical staging and risk stratification of plasma cell neoplasms (PCN), since distinct cytogenetic aberrations are associated with different outcomes in patients treated with standard therapies.1,3,4 These publications and guidelines have been summarized in the National Cancer Institute National Institutes of Health treatment guidelines5:
This panel detects all of the above cytogenetic aberrations except for the uncommon t(6;14), which in this panel would display 14q32 rearrangement without involvement of any of the 4 tested IGH translocation markers. Some cases may have more than one of the above FISH aberrations. In such cases, a more complex risk stratification strategy would need to be employed.
Given the recommendations for comprehensive genomic risk assessment, other PCN diagnostic panels previously offered by Quest Diagnostics have been discontinued.
This panel may also have a role in the workup of monoclonal gammopathy of unknown significance (MGUS), localized plasmacytoma, asymptomatic/smoldering myeloma, or active myeloma.
Question 6. Why is FISH testing recommended over conventional chromosome analysis?
FISH testing is more accurate because most metaphase cells derived from plasma cell cultures, even with mitogen stimulation, are derived from normal cells. Thus, the majority of the newly diagnosed plasma cell myeloma cases yield a normal karyotype.2 FISH, on the other hand, can use interphase cells to detect common cytogenetic abnormalities seen in PCNs. Furthermore, specific FISH signal patterns are helpful in accurate identification of the cryptic and/or complex rearrangements observed during chromosome analysis.
Question 7. Should this test be used for follow-up testing?
No. This test is designed as an initial prognostic assessment of plasma cell myeloma. For follow-up testing, use the appropriate single analyte test. For example, if the panel identifies t(11;14) (IGH/CCND1), order FISH, Mantle Cell Lymphoma, IGH/CCND1, t(11;14) (test code 17346). Test codes for other individual components may be found by searching the Quest Diagnostics Test Center (http://www.QuestDiagnostics.com/testcenter/TestCenterHome.action).
- Chng WJ, Dispenzieri A, Chim CS, et al and the International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28:269-277.
- Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet. 2011;204:3-12.
- Rajkumar, SV. Multiple myeloma: 2013 update on diagnosis, risk-stratification and management. Am J Hematol. 2013:88:226-235.
- Anderson KC, Bensinger W. NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma. Version 2.2014. https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed November 24, 2014.
- Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®).National Cancer Institute at the National Institutes of Health Web site. http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional/page1. Accessed November 24, 2014.
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