Systemic mastocytosis with associated BCRABL1-negative atypical chronic myeloid leukemia

Abstract

Dear Editor, An 81-year-old man, complaining fatigue and weight loss, was referred to our center due to leukocytosis and mild anemia with thrombocytopenia (WBC, 40100/mm, Hb, 10.1 g/dL, PLT, 103000/mm). Physical examination revealed mild splenomegaly. A peripheral blood smear showed immature granulocytes, dysplastic neutrophils with hypogranularity, and pseudo-Pelger–Huet anomaly (Fig. 1a). A bone marrow (BM) aspirate revealed hypercellularity for age, left shifted myeloid hyperplasia without increased blasts (Fig. 1b). Dysplastic megakaryocytes, including hypolobated forms and micromegakaryocytes, were present. In addition, diffuse spindle-shaped mast cell with an eccentric oval nucleus was detected (Fig. 1c, d). Bone marrow biopsy specimens confirmed cellularity > 95% with increased myelopoiesis, reduced erythropoiesis , and no fibrosis (Fig. 1e) . Paratrabecular round to spindled CD117-positive mast cells were organized in nodular aggregates of 15 to 20 elements (Fig. 1f). Additional studies on the BM showed a normal karyotype (46, XY). Polymerase chain reaction for BCRABL1 was negative, as well JAK2V617F, CAL-R, and MPL. Amplicon-based next-generation sequencing (NGS) targeting entire coding or hotspot regions of a 38-multigene panel associated with myeloid malignancies was performed on whole bone marrow DNA using a Ion Torrent platform (Thermo Fisher Scientific, Inc.). AKITc.2447A > T p.D816Vmutation at a variant allelic frequency (VAF) of 45% and a U2AF1 c.101C > T p.S34F (VAF 47%), a spliceosome machinery gene, were identified. Basal tryptase value was 55.6 ng/mL (reference range < 11.4 ng/mL). Flow cytometry showed aberrant CD2–CD25 expression in 8.7% of MS. A diagnosis of systemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) was made, according to the recent WHO 2016 classification. (1) To our best knowledge, this is the first described case of SM with associated BCRABL1-negative aCML. SM is a myeloid neoplasm and only a rare percentage is associated with hematological neoplasm. The diagnosis of SM is established when a major plus one minor criterion or three minor SM criteria are present.Major criteria are the presence of a multifocal clustering of mast cells in one or more visceral organs; minor criteria are represented by an abnormal morphology of mast cells, an activating mutation of KIT D816V, and levels of serum tryptase > 20 ng /ml (the last does not represent a valid criterion if the patient has another non-mast cell hematologic malignancy). aCML is a rare BCR-ABL1 negative disease with left-shifted granulocytosis and with an estimated frequency of 1 to 2 cases for every 100 CML cases. aCML is defined by peripheral blood leukocytosis due to increased numbers of neutrophils and their precursors comprising ≥ 10% of leukocytes, dysgranulopoiesis, basophils usually < 2% of leukocytes, monocytes < 10% of leukocytes, hypercellular BM with granulocytic proliferation with or without dysplasia in the erythroid and megakaryocytic lineages, < 20% blasts in the blood and BM, and not meeting WHO criteria for myeloproliferative neoplasms (MPNs). (1) The * Giovanni Caocci [email protected]