Diagnostic criteria of the myeloproliferative disorders (MPD): essential thrombocythaemia, polycythaemia vera and chronic megakaryocytic granulocytic metaplasia

Abstract

Philadelphia chromosome-positive essential thrombocythaemia (Ph(+)-ET) and chronic granulocytic leukaemia (Ph(+)-CGL) constitute a separate malignant disease entity, whereas essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic megakaryocytic granulocytic metaplasia (CMGM) belong to the Philadelphia chromosome-negative (Ph-) myeloproliferative disorders. The megakaryocytes in Ph(+)-ET and Ph(+)-CGL are abnormal and small with round nuclei, showing little lobulation. Both the number and size of megakaryocytes in Ph-ET, -PV and -CMGM are typically increased. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or slightly increased cellular bone marrow represent the hallmark of ET. In reactive thrombocytosis the size and morphology of increased megakaryocytes are normal. The characteristic increase and clustering of enlarged mature and pleomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic hallmark of untreated PV. In secondary polycythaemia, in which increased cellularity of the erythroid cell line may be present, the number, size and morphology of megakaryocytes remain small and normal. CMGM, including early stages without myelofibrosis and advanced myelofibrotic stages of agnogenic myeloid metaplasia, appears to be a distinct neoplastic proliferation of neutrophilic granulopoiesis and megakaryopoiesis. The histopathology of the bone marrow in CMGM is dominated by atypical, enlarged and immature megakaryocytes with cloud-like nuclei which are not seen in ET and PV. Myelofibrosis in ET, PV and CMGM is graded in no reticulin fibrosis (MFO), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor collagen fibrosis (MF2) and advanced collagen fibrosis with or without osteosclerosis (MF3). Myelofibrosis is not a feature of ET, may occur in PV, and constitutes a prominent feature of CMGM during the natural history of the disease.