Hematopathologic findings in chronic idiopathic myelofibrosis

Until now scant knowledge was available about the dynamics of chronic idiopathic myelofibrosis (CIMF). However, follow-up studies are in keeping with a stepwise evolution starting with a prefibrotic (hypercellular) phase that progressively transforms into the classical fibro-osteosclerotic endstage with myeloid metaplasia. Prefibrotic CIMF is characterized by a granulocytic and megakaryocytic myeloproliferation lacking an increase in reticulin. Most conspicuous are abnormalities of megakaryopoiesis with regard to their histotopography and maturation. There is a more than 65% probability of progression from an early to advanced CIMF accompanied by increasing anemia, splenomegaly, and leuko-erythroblastosis. A significant relationship is recognizable among frequency, tortuosity, and luminal dilation of the microvessels and the extent of myelofibrosis. Quantity of CD34(+) progenitor cells in the bone marrow (BM) reveals a close association with advancement of disease (fibrosis, splenomegaly, anemia, peripheral blasts) and therefore prognosis. Cell kinetic studies show increased proliferation associated with a higher rate of apoptosis in initial (hypercellular) stages, as well as a reduced endoreduplicative activity of megakaryopoiesis and a blocked synthesis phase of the erythroid precursors. It is noteworthy that prefibrotic and early CIMF often present with a marked thrombocytosis mimicking essential thrombocythemia. Regarding prognosis, early CIMF is associated with a significantly more favorable survival than advanced stages.