LCD L37602: MDS FISH

This policy provides coverage for indicated fluorescent in situ hybridization (FISH) probes for patients whose bone marrow examination is suggestive of myelodysplasia (MDS) and who have an inadequate cytogenetic assessment by conventional karyotyping. In general, conventional karyotype analysis is sufficient for confirmation for the diagnosis of MDS. MDS FISH studies should only be performed when there are fewer than 20 metaphases available for analysis, or an unresolved karyotype. Medicare will only cover up to 4 FISH studies -7 or del(7q), -5 or del(5q), +8 and del(20q) on initial evaluation to diagnose MDS. Reflex testing for additional FISH markers to diagnose MDS is only reasonable and necessary when the initial 4 studies are negative or the diagnosis remains uncertain following the initial 4 probes.

Generally, FISH testing is not reasonable and necessary for MDS and provides little if any additional information to conventional karyotyping.

The myelodysplastic syndromes (MDS) represent a spectrum of clonal bone marrow diseases with heterogeneous presentations. The classic triad for MDS includes 1 or more cytopenias, defective differentiation (dysplasia) of 1 or more blood cell lines and marrow hypercellularity. Over time, there is an increased rate of progression to acute myeloid leukemia (AML). These secondary AML cases carry a worse prognosis than de novo AML cases. Furthermore, there are myeloid neoplasms that share overlapping characteristics with both MDS and myeloproliferative neoplasms (MPNs), such as chronic myelomonocytic leukemia (CMML). The World Health Organization (WHO) has designated these diseases separately as MDS/MPNs, distinct from either MDS or MPNs. 1

According to the 2016 National Comprehensive Cancer Network (NCCN) Guidelines, the overall incidence of MDS is approximately 5/100,000 per year, primarily in adults. MDS is rare in patients under the age of 40, but much more common in older patients. The incidence of MDS among patients 70-79 years of age is 30/100,000, and in patients > 80 years the incidence is 60/100,000. 2

MDS has historically been classified by a combination of traditional laboratory techniques, such as demonstration of stable cytopenias by complete blood count, microscopic examination of a bone marrow biopsy, and bone marrow cytogenetic (conventional karyotype) studies. Other than the clinical feature of the number of cytopenias and specific cytogenetic changes found recurrently in MDS, all other diagnostic criteria in MDS rely upon light microscopy findings. These include the number of dysplastic changes on 1 or more cell lineages, of megakaryocytes, erythrocytes and granulocytes; increased myeloblasts; and/or presence ringed sideroblasts. Low-risk MDS is associated with dysplasia affecting only 1 cell lineage, with or without ringed sideroblasts, and isolated deletions involving the long arm of chromosome 5 (5q-). High-risk disease is associated with dysplasia across multiple lineages, increased blast percentages, and complex karyotype.

Neither the 2016 WHO Classification of MDS, the International Prognostic Scoring System (IPSS) nor the Revised IPSS (IPSS-R) require the use of additional MDS-associated mutations to establish a diagnosis of MDS. As noted in NCCN 2017 Guidelines, “Bone marrow or peripheral blood cells may be assayed for MDS-associated gene mutations. These can establish the presence of clonal hematopoesis which can help exclude benign causes of cytopenia with non-diagnostic morphology but do not establish the diagnosis of MDS in the absence of clinical diagnostic criteria.”