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Acute megakaryocytic leukaemia (AML‐M7) with myelofibrosis terminating in AML‐MO with concurrent liver fibrosis

To the Editor: Acute myelofibrosis is distinct from classical idiopathic myelofibrosis (IMF) and is associated with haematopoietic disorders including myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). In particular, acute megakaryocytic leukaemia (AMgKL), M7, is closely linked to bone marrow fibrosis (1). We present a case of AMLM7 with acute myelofibrosis progressing to AMLMO and with massive ascites resulting from obscure hepatic fibrosis. A 55-yr-old man was referred to our hospital because of pancytopenia. Physical examination revealed scattered petechiae on his legs in addition to anaemic palpebrae. Neither hepatomegaly nor splenomegaly were found, and there were no enlarged surface lymph nodes. His peripheral blood showed leucoerythroblastic anaemia including a haemoglobin of 3.4g/dl, a platelet count of 28x109/l, and a leucocyte count of 2.9x109/1 with a differential of 1 YO promyelocytes, 0.5% myelocytes, 0.5% metamyelocytes, 55% neutrophils, 7.5% monocytes, 0.5 YO eosinophils, 0.5% basophils and 33.5% lymphocytes, in addition to erythroblasts with a ratio of 4 erythroblasts per 100 leucocytes. Neutrophi1 alkaline phosphatase (NAP) activity was comparable to that of a normal control. Serum concentrations of transaminases, bilirubin, lactate dehydrogenase (LDH) and haptoglobin were all in the normal range, and there were no chemical findings suggesting haemolytic anaemia or hepatic disease. Serum concentrations of platelet factor 4 (PF4) and P thromboglobulin (PTG) were both elevated despite a decreased platelet count (PF4 76 ng/ml (normal value: less than 20), PTG 200 ng/ml (normal value: less than 50)). An attempted bone marrow aspiration resulted in a dry tap, and a trephine biopsy specimen displayed intense collagen fibrosis and increased numbers of megakaryocytes together with proliferation of large blastic cells (Fig. 1). Blastic cells had large nuclei with dense chromatin and were immunohistochemically positive for PLTl monoclonal antibodies against GPIIb/IIIa (CD41, Coulter Immunology, Hialeah, FL, USA). A diagnosis of AMgKL with myelofibrosis was made; steroid pulse therapy in addition to frequent platelet and red cell transfusions did not produce haematologic improvement. Two months later, he noted increased abdominal girth due to ascites. The ascitic fluid was found to be transudative and contain erythroblasts, granulocytes and megakaryocyte-like large cells (Fig. 2). One month before death, the leucocyte count rose suddenly to 28.8x109/1 with 88.0% leukaemic cells; these were both cytochemically and immunophenotypically consistent with AML-MO at this time. Chromosome analysis using peripheral blood leukaemic cells did not demonstrate Philadelphia chromosome (Ph’). Ascites progressed despite frequent drainage; the patient died 7 months following his initial presentation. Postmortem examination revealed massive infiltration of leukaemic cells into the bone marrow, liver, spleen, kidneys, adrenals and diaphragm. There was massive bloody ascites (12,000 ml), but extramedullary haematopoietic foci were not found in the peritoneal cavity. In addition to intense bone marrow fibrosis, sinusoidal fibrosis of the liver was noted in the areas between Glisson’s capsules (Fig. 3), and this was associated with oesophageal and gastric varices. Of interest, liver fibrosis was not accompanied by nodular regeneration of hepatic cells, which is commonly seen in liver cirrhosis. IMF is a myeloproliferative disorder characterized by extramedullary haematopoiesis and intense bone marrow fibrosis. Similar conditions are known to occur in MDS and AML, and these are designated “acute myelodysplasia with myelofibrosis (AMMF)”, “acute myelosclerosis” or “acute megakaryoblastic leukaemia with myelofibrosis”. These disorders are characterized by acute onset, older age, severe pancytopenia reflecting bone marrow insufficiency, no associated organomegaly, and rapid progression to acute leukaemia; the incidence of fibrosis is reported to vary from 30 to 72% in AML and MDS (1). Although classical IMF is known to transform into acute leukaemia (2, 3), our patient initially presented with severe pancytopenia without