Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm that is caused by accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin. The KIT D816V mutation encodes a constitutively activated receptor tyrosine kinase that drives disease pathogenesis. We present a case of systemic mastocytosis with associated clonal hematological non-mast cell disease (SM-AHNMD).
Background: A 71-year-old man presented with anemia, thrombocytopenia, absolute monocyte count of 2,000-4,000 and weight loss in August 2016. A CT showed splenomegaly and lymphadenopathy. Bone marrow biopsy revealed positive CD117 mast cells, CD34 myeloblasts and reticulin fibrosis consistent with SM. Immunohistochemistry confirmed the neoplastic cells were positive for CD25, but negative for CD2. PCR analysis revealed KIT D816V point mutation. Serum tryptase was 295 ug/L (normal 2.2-13.2). He was started on imatinib mesylate. However, his anemia, thrombocytopenia and splenomegaly worsened. He developed bilateral femoral neck fractures in April 2017. Imatinib was discontinued. He underwent bilateral hip hemiarthroplasty. Histology was consistent with SM (positive CD25 and CD117) with dysplastic megakaryocytes and increased monocytosis. By WHO classification he has SM-AHNMD with chronic myelomonocytic leukemia. He was started on cladribine for 4 cycles with good response in splenomegaly, anemia and thrombocytopenia, but he developed leukocytosis. Serum tryptase initially decreased to 141 but then rose to 243. Midostaurin 100 mg orally twice a day was initiated in December 2017. His cytopenia and splenomegaly improved. In March 2018 he was admitted for sigmoid colon obstruction due to inflammation or mass and underwent diverting loop ileostomy. Biopsy could not be performed. His serum tryptase decreased to 178 but increased to 275 in June 2018. He continues on midostaurin.
Discussion: SM-AHNMD constitutes approximately 40% of all SM with poor prognosis. SM is resistance to imatinib because of KIT D816V mutation. Cladribine has some activity. Midostaurin inhibits non-mutant and mutant KIT D816V with 58% response rate and median overall survival of 20 months. Our patient has a good response to both drugs.
Conclusions: Clinicians should be able to diagnose and treat SM. Cladribine and midostaurin are active drugs for SM.
