A Case of Systemic Mastocytosis Presenting Initially with Weight Loss and Elevated Alkaline Phosphatase

Abstract

Systemic mastocytosis (SM) is a myeloproliferative disorder characterized by increased numbers of abnormal mast cells that form aggregates in various tissues. Symptoms are related to dysregulated mast cell activation and organ dysfunction. We report a case of SM where the initial single complaint was weight loss with increased alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT). A 64 year-old-man presented for evaluation of weight loss and increased ALP and GGT (Table 1). CT revealed mesenteric and retroperitoneal lymphadenopathy and PET showed mildly increased activity in the nodes. Endoscopic ultrasound demonstrated hypoechoic lymph nodes up to 32 mm in size. Fine needle aspiration revealed lymphocytes, histiocytes, mixed inflammatory cells, but no evidence of lymphoma. The patient developed abdominal pain and palpable hepatomegaly with rising ALP and GGT which prompted a liver biopsy. Biopsy showed portal and lobular aggregates of spindle cells with admixed histiocytes, eosinophils and lymphocytes. The spindled cells stained strongly positive for CD117 indicating mast cells. An elevated serum tryptase and bone marrow biopsy showing multifocal mast cell aggregates with D816V mutated KIT confirmed the diagnosis of SM; specifically, aggressive SM (ASM), due to his liver dysfunction and weight loss, likely secondary to malabsorption from gastrointestinal involvement. Midostaurin was selected as first line treatment. The patient developed significant toxicity on midostaurin, including neutropenic fever and persistent QTc prolongation, and treatment was discontinued. Second-line therapy with cladribine was declined due to risks outweighing potential benefits. The patient expired one month after treatment cessation. ASM is associated with various organopathies and therefore a wide range of clinical manifestations. Malabsorption and lymphadenopathy are both uncommon presentations of ASM1, but were the only presenting symptoms in this patient. Since there were no other indications of SM, no clear direction was provided for workup which increased the time to diagnosis. The delay in treatment initiation in this case demonstrates the implications of the broad clinical spectrum of SM and the potential for rapid progression despite a limited clinical presentation.