Megakaryocyte dysplasia in primary myelofibrosis

Abstract

In the 2008 WHO classification of tumors of hematopoietic and lymphoid tissues, primary myelofibrosis is classified as a myeloproliferative neoplasm (MPN) rather than as a myelodysplastic/myeloproliferative neoplasm. This is appropriate since it shares molecular abnormalities (mutations in JAK2 and MPL) with polycythaemia vera and essential thrombocythaemia, and since morphologically similar myelofibrosis can occur following these two MPN. Nevertheless, dysplastic features are common in primary myelofibrosis, at presentation as well as during disease progression. This image illustrates megakaryocyte dysplasia during disease progression is a 75-year-old man who had required a splenectomy for progressive splenomegaly and anemia. His full blood count showed: white cell count 3.3 × 109/l, hemoglobin concentration 88 g/l, mean cell volume 110 fl (attributable to hydroxycarbamide therapy) and platelet count 381 × 109/l. His blood film showed megakaryoblasts (top left), micromegakaryocytes (top right and bottom left), and giant fragments of megakaryocyte cytoplasm (bottom right). Circulating megakaryoblasts and micromegakaryocytes in MPN can often be recognized, as in this patient, by their irregular cytoplasmic margins and cytoplasmic blebs. Some micromegakaryocytes have hyperchromatic lobulated nuclei (bottom left). It is to some extent arbitrary whether fragments of megakaryocyte cytoplasm are regarded as megakaryocyte fragments or giant platelets. The fragment shown (bottom right) has a recognizable granulomere and hyalomere so could reasonably be regarded as a giant platelet despite its enormous size. In primary myelofibrosis dysplastic features can occur in all lineages, but megakaryocyte dysplasia is particularly common. Dysplasia at presentation may indicate that the disease has already progressed from a purely myeloproliferative preclinical phase. With disease progression, dysplasia can be very prominent.