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Systemic mastocytosis emerging after azacitidine treatment of refractory anaemia with excess blasts type 2
A 73-year-old man was investigated for a pancytopenia of recent onset. He had no skin lesions, lymphadenopathy or splenomegaly. A full blood count showed a haemoglobin concentration of 94 g/l, neutrophil count of 076 9 109/l and platelet count of 40 9 109/l. A bone marrow aspirate showed a hypercelluar marrow with left shifted granulopoiesis and an increased proportion of promyelocytes and myelocytes; a subset of myeloid precursors and mature neutrophils had dysplastic features with hypogranular cytoplasm. There were 17% blast cells, which were intermediate to large in size, with scanty blue agranular cytoplasm and round nuclei that had open reticular chromatin and prominent nucleoli (left); the blast cells were CD34 positive. A diagnosis of refractory anaemia with excess of blasts type 2 (RAEB-2) was made. The patient was treated with azacitidine using a standard protocol for high risk myelodysplastic syndrome (MDS). He responded initially with improved blood counts but clinically became worse. Another bone marrow aspirate performed 5 months later, when neutropenia had resolved, remained hypercellular with a moderate reduction in blast cells (to 9%); new findings were increased mast cells (9%) and eosinophils (18%). Computerized tomography of the abdomen and pelvis demonstrated ascites and splenomegaly that had not been present at diagnosis. Azacitidine treatment was withheld. Another bone marrow apirate 1 month later showed increased abnormal, spindle-shaped mast cells (13%) (right), blasts (3%) and eosinophils (5%). Trephine biopsy demonstrated aggregates of spindle-shaped mast cells in a
ยช 2014 John Wiley & Sons Ltd British Journal of Haematology, 2014, 167, 147
paratrabecular/multi-focal distribution. Immunohistochemistry showed expression of CD117, tryptase and CD25, while CD34 was negative, confirming these as neoplastic mast cells. Investigation was positive for both the rare KIT D816H mutation, previously reported in a case of systemic mastocytosis (SM) with acute myeloid leukaemia, and KIT K818R, not previously reported in SM. Serum tryptase was elevated to >200 ng/ml. Thus, our patient met the major criteria and all four minor criteria for a diagnosis of SM. CD117, CD25 and tryptase applied to the original biopsy specimen showed no evidence of SM. A diagnosis of systemic mastocytosis with associated clonal haematological non-mast cell disease (SM-AHNMD) was made. The patient deteriorated and died within weeks. SM-AHNMD is the second most common variant of SM, accounting for 40% of all cases of SM. SM-MDS is uncommon and our case is very unusual as SM emerged only after the patient showed a response to azacitidine treatment for high risk MDS. Clonal identity of the two neoplasms was not investigated, and one can only speculate that the pressure of medication could have altered the direction of differentiation of a pluripotent haemopoietic stem cell. Zhaodong Xu1, Luke Shier1, Mitchell Sabloff2, Arleigh McCurdy2, Dawn Sheppard2 and Christopher Bredeson2 1
Division of Haematopathology and Transfusion Medicine, Department
of Pathology and Laboratory Medicine, The Ottawa Hospital, and 2
Division of Haematology, Department of Medicine, The Ottawa
Hospital, Ottawa, ON, Canada. E-mail:
[email protected]
First published online 9 July 2014 doi:10.1111/bjh.13024
