Practical Issues in the Diagnosis of Myelodysplastic/ Myeloproliferative Overlap Syndromes

The World Health Organization (WHO) classification of hematopoietic neoplasms, published in 2001, included the new category of “Myelodysplastic/ Myeloproliferative Diseases,” intended to accommodate those myeloid neoplasms that simultaneously showed features of chronic myeloproliferative disorders and myelodysplastic syndromes. Typically, myelodysplastic syndromes (MDS) are clonal neoplastic disorders characterized by accelerated apoptosis of the abnormal clone, resulting in a pattern of ineffective hematopoiesis, usually manifest by increased bone marrow cellularity in the presence of decreased peripheral blood counts (cytopenias) and absence of organomegaly. MDS also generally harbor some degree of morphologic dysplasia within one or more hematopoietic lineages. Conversely, the chronic myeloproliferative disorders (MPD) are myeloid neoplasms generally characterized by evidence of effective hematopoiesis, generally in the form of increased peripheral blood counts (“cytoses”), organomegaly, or both. Typically, MPD do not show prominent morphologic dysplasia of hematopoietic elements. The WHO category of MDS/MPD overlap syndromes includes diseases that either have a proliferative component (increased peripheral blood counts, organomegaly) combined with significant morphologic dysplasia, or diseases that may vary in their degree of proliferative characteristics and morphologic dysplasia. The WHO classification lists four disease categories under the heading of MDS/MPD: 1) Chronic myelomonocytic leukemia (CMML), 2) Juvenile myelomonocytic leukemia (JMML), 3) Atypical chronic myeloid leukemia (aCML), and 4) Myelodysplastic/ myeloproliferative diseases, unclassifiable. There are many pitfalls that practicing hematopathologists may face in the diagnosis of MDS/MPD overlap syndromes. This session will focus on the following points: 1) Guidelines for morphologic recognition of the distinct categories of MDS/MPD outlined by the WHO, including recognition of clinical and morphologic heterogeneity in CMML 2) A discussion of the “unclassifiable” category, including the provisional entity “Refractory anemia with ringed sideroblasts associated with marked thrombocytosis.” 3) The distinction between CMML and acute myelomonocytic leukemia, which may be deceptively difficult 4) An illustration of mimickers of morphologic dysplasia in bone marrow that could lead to overdiagnosis of MDS/MPD.