Proposal for Revised Diagnostic Criteria of Essential Thrombocythemia and Polycythemia Vera by the Thrombocythemia Vera Study Group

Abstract

The present study revises the criteria of the Polycythemia Vera Study Group (PVSG) for the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in view of accumulating data on in vitro cultures of hematopoietic progenitors and by adding histopathology from bone marrow biopsies. The majority of ET patients show spontaneous megakaryocyte or erythroid growth or both, but in about 35% the growth pattern is normal. So far none of the patients with reactive thrombocytosis have shown either spontaneous megakaryocyte or erythroid colony growth. Virtually all PV patients show spontaneous or endogenous erythroid colony (EEC) formation, whereas patients with secondary erythrocytosis and healthy controls do not show any erythroid colony growth in the absence of erythropoietin (EPO). Some rare patients with a disorder other than a myeloproliferative disease (MPD) may show spontaneous growth of erythroid colonies caused by a mutation in the EPO receptor. Megakaryocytes in bone marrow smears and biopsy material from ET and PV patients are typically increased in number and size. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and the tendency of these megakaryocytes to cluster in a normal or slightly increased cellular bone marrow represent the diagnostic hallmark of ET. Increase and clustering of enlarged, mature, and pleiomorphic megakaryocytes in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic feature of untreated PV. In reactive thrombocytosis and secondary erythrocytosis the size and morphology of megakaryocytes remain normal and there is no tendency of the megakaryocytes to cluster. Both spontaneous EEC and histopathology of bone marrow biopsies appear to offer specific clues to the diagnosis of overt and latent ET or PV and have the potential to differentiate ET from reactive thrombocytosis and PV from secondary erythrocytosis. Moreover, bone marrow histopathology has the diagnostic power to distinguish and to stage the various MPDs without regard to clinical and laboratory data.