PB2238 AGGRESSIVE SYSTEMIC MASTOCYTOSIS: A DIAGNOSTIC CHALLENGE IN A PATIENT WITH MYOTONIC DYSTROPHY TYPE 2
Authors: Tran C. , Bauer M. , Jaekel N. , Emmer A. , Wickenhauser C. , Al‐Ali H. K. 
Published: June 2019

Background:Systemic mastocytosis (SM) is a clonal neoplastic disease of mast cells (MCs) with heterogeneous clinical presentations, different organ infiltration, and is often overlooked. The spectrum ranges from indolent to aggressive forms. SM could also be associated with myeloid and lymphoid hematologic diseases.Aims:We present a case where SM was misdiagnosed as a progression of myotonic dystrophy.Methods:A 55‐year‐old caucasian woman with known familial myotonic dystrophy type 2 (DM2) proven by CCTG‐repeat expansion in the ZNF9 gene was referred with a diagnosis of unclassified myeloproliferative neoplasm with 10% bone marrow (BM) blasts and mutations in KRAS, ASXL1 and RUNX1. In the last two months, she complained of weight loss, muscle weakness, and fever. Because of progressive dysphagia, enteral nutrition by percutaneous endoscopic gastrostomy tube (PEG) was initiated. Clinically, a body mass index (BMI) of 13.6 kg/m2, normal skin, and hepatosplenomegaly were seen. Hilar lymphadenopathy and pulmonary infiltrates were detected by CT‐scan. Laboratory analysis showed a WBC count of 39.80x109/L with left shift, Hb of 4.4 g/dl, platelets of 78x109/L, hypoalbuminemia, and an elevated lactate dehydrogenase. Rapid neurological deterioration is typical in myotonic dystrophy type 1, which is associated with a worse prognosis and is unusual for DM2 (Schoser B, Timchenko L.; Current Genomics; 2010). Curiously, DM2 was genetically proven.Results:Assessment of serum tryptase is part of our routine diagnostic work‐up for hematologic diseases and was 46.9 μg/L (reference range <11 μg/l) in the patient. A repeat BM biopsy revealed a hypercellular marrow with delayed myelopoietic maturation and a normal blast count. There were peritrabecular conspicuous nodular areas with minimal reticular fibrosis. Therein, multifocal clustering of MCs (at least 15/cluster) co‐expressing CD2, CD25, CD117, and mast cell tryptase were detected. Cytogenetics were normal but the activating mutation KITD816 V was present.Thus, a diagnosis of SM could be made based on the major criterion (≥ 15 MC in clusters) and three minor criteria (the KIT mutation, CD25/CD2 co‐expression, serum tryptase > 20 μg/l). Due to the presence of C‐findings (transfusion dependent anemia, splenomegaly with thrombocytopenia, and malabsorption with weight loss), the criteria for aggressive SM (ASM) were fulfilled. A hilar lymph node biopsy revealed several small lymphocytes next to dense blastoid cell infiltrates of myeloid lineage without MCs consistent with extramedullary hematopoiesis.Together with the neurologist, we hypothesized that ASM and not the natural course of DM2 was causative for the rapid neurological deterioration. Treatment with the KIT‐tyrosine kinase inhibitor midostaurin was initiated. Within three months, the patient gained weight, regained muscle power, dysphagia disappeared, and the PEG could be removed. The blood count normalized, and hilar lymphadenopathy disappeared. Currently, allogeneic hematopoietic cell transplantation is planned because of the poor prognosis of ASM, particularly if KIT‐independent oncogenic driver mutations such as KRAS, ASXL1 and RUNX1 were found.Summary/Conclusion:In summary, awareness of physicians to SM as a possibility in the differential diagnosis of unclear clinical scenarios is the first step to make the diagnosis and offer adequate therapy. Serum tryptase is a simple tool that could draw the attention of physicians to SM.