Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up

Controversy continues whether acute panmyelosis with myelofibrosis (APMF) exists as a well-defined clinicopathological entity. Following exclusion of overt acute myeloid leukemia (AML), especially the megakaryoblastic subtype, a retrospective study was performed on 46 patients with clinical and morphological features suggesting the diagnosis of APMF. All patients had a bone marrow (BM) biopsy performed at onset, and 13 had follow-up examinations. Enzyme histochemical and immunohistochemical techniques were applied and BM features evaluated by a semiquantitative scoring system. Clinical findings consisted of pancytopenia associated with a left-shifted differential count of the peripheral blood (less than 5% blasts) and no or minor splenomegaly. During follow-up (median survival 9 months) 35 patients developed severe BM insufficiency and 10 transformed into overt AML. Although myelofibrosis was a characteristic finding, other BM features proved to be heterogeneous. Cellularity was reduced in 13 and increased in 25 specimens. Most prominent was a left-shifted, often macrocytic erythropoiesis and a maturation defect of the neutrophil series. In 15 patients an increase (less than 20%) in CD34(+) progenitors, immature myelomonocytic cells, and megakaryoblasts was noted. Abnormalities of megakaryocytes (atypical microforms, clustering, dysplasia) were regularly present. The stroma showed an inflammatory reaction (perivascular plasmacytosis, lymphoid nodules, many macrophages, iron deposits) in about 50% of the samples. Sequential BM biopsies revealed an accumulation of lysozyme-expressing myelomonocytic and CD34(+) progenitor cells suggesting an increase in blasts. In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy.