An 83-year-old man presented with hematuria and bone pain. Computed tomography–scan imaging demonstrated multiple osteolytic lesions and vertebral collapse. A complete blood count showed anemia with hemoglobin of 9.1 g/dL and normal white blood count and platelets, 4.95 × 10⁹/L and 198 × 10⁹/L, respectively. Total protein was at 105 g/L, with electrophoresis revealing a monoclonal band, identified as immunoglobulin G ĸ at 50 g/L. Bone marrow smear examination found plasma cells comprising 38% of total nucleated cells (TNCs) and an unexpected infiltration (3%) of abnormal mast cells (MCs) with a spindle-shaped morphology (panels A-B; May-Grünwald Giemsa staining, original magnification ×1000). Serum tryptase was elevated at 161 µg/L, and next-generation sequencing revealed D816Y mutation at the exon 17 of the kit gene, found in the MCs, confirming a diagnosis of systemic mastocytosis with an associated hematological neoplasm (SM-AHN). Flow cytometry analysis showed aberrant expression of CD2 and CD25 on the MCs.

After 3 months of lenalidomide and dexamethasone, bone marrow plasma cells were at 2% of TNCs, but the infiltrate of abnormal MCs remained unchanged, and serum tryptase was still elevated at 182 µg/L. This case of SM-AHN involving D816Y mutation and myeloma demonstrates the benefit of microscopic examination as relatively common diseases can hide even the rarest hematologic malignancies.