Idiopathic myelofibrosis (IMF) is generally characterized by bone marrow (BM)
fibrosis,
anemia,
splenomegaly and a leuko-erythroblastic blood picture. Although, histopathology is in keeping with the assumption of a stepwise evolution of the disease, little hematological data are available for patients with prefibrotic and early stages of disease. Therefore a clinicopathological study was performed that included firstly an exploratory sample of 68 patients with minor supportive
therapy in whom BM biopsies during follow-up (41 +/- 32 months) revealed an evolution of a prefibrotic or very early fibrotic lesion into overt IMF. The validation sample consisted of 556 patients with pretreatment marrow specimens on admission. Diagnostic features and BM lesions were identical compared with the patients of the exploratory sample at their first examination. BM biopsies were processed by routine stainings including
silver impregnation (
reticulin fibers) and frequently also by immunohistochemistry to identify megakaryocytes and erythroid precursor cells more properly. Apart from minor
hemorrhage and peripheral
thrombosis patients with early stage IMF presented with non-specific symptoms including varying degrees of
leukocytosis (51%),
anemia (38%), a platelet count exceeding 600 x 10(9)/
l (86%),
splenomegaly (15%) and increase in leukocyte
alkaline phosphatase (LAP) (24%) and serum
lactate dehydrogenase (LDH) (20%). BM histology confirmed a moderate increase in hematopoiesis with a mixed granulocytic and megakaryocytic myeloproliferation, a reduction of erythroid precursors and significant megakaryocytic abnormalities. In keeping with the first BM examination of the exploratory sample no or only a borderline to slight increase in
reticulin fibers was detectable, however, in 68 of 134 patients follow-up biopsies revealed a transition into overt IMF (intervals about three years). Median survival of this cohort with early-stage IMF was 129 months thus contrasting manifest IMF with an usually more unfavorable prognosis. Recognition of early stage IMF certainly alters the generally applied diagnostic criteria of this disorder. Regarding patients with associated
thrombocytosis, differentiation from
essential thrombocythemia is recommended. Moreover, characterization of early stage IMF probably exerts an impact on survival and may influence the decision to perform a BM
transplantation.