Diagnosing myelodysplastic/myeloproliferative neoplasms: laboratory testing strategies to exclude other disorders

The 2008 World Health Organization classification of myeloid neoplasms includes the diagnostic category, myelodysplastic/myeloproliferative neoplasms (MDS/MPN), which encompasses those rare clonal myeloid proliferations that at initial presentation, show overlapping myeloproliferative and myelodysplastic features, making classification as either a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) problematic. There are four main subcategories, chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML), juvenile myelomonocytic leukemia (JMML), and myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U), which also includes the provisional entity, refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T). Notably, the morphological features typical of MDS/MPNs are not specific and can be seen in other myeloid neoplasms at presentation or as part of disease progression or transformation.

This review presents a laboratory approach to diagnosing MDS/MPNs in adults that allows for the exclusion of other disorders that may be otherwise indistinguishable. Ancillary studies including cytochemistry, immunohistochemistry, flow cytometry, and genetic testing are discussed.

The most appropriate classification of myeloid neoplasms presenting with hybrid myelodysplastic/myeloproliferative features requires a comprehensive clinical and laboratory assessment with careful integration of the morphological, immunophenotypic, genetic, and clinical characteristics.