Mastocytosis: Imaging Spectrum and Diagnostic Insights

Mastocytosis is a rare clonal disorder marked by the excessive proliferation and accumulation of mast cells in different tissues, with the skin and bone marrow being the most commonly affected sites. Mastocytosis is primarily driven by somatic mutations that most commonly affect the c-KIT proto-oncogene. The World Health Organization classifies mastocytosis into three main categories. Cutaneous mastocytosis involves infiltration limited to the skin and is more prevalent in children than in adults. Systemic mastocytosis involves infiltration of extracutaneous organs, including the liver, spleen, lymph nodes, and gastrointestinal tract, and is the most common form of mastocytosis in adults. Mast cell sarcoma is rare and highly aggressive. Skeletal involvement is the most frequently observed radiologic feature of mastocytosis, ranging from diffuse osteosclerosis to osteolytic lesions, and is best visualized on radiographs and CT images. MRI is essential in evaluating bone marrow infiltration. Advanced disease may manifest with hepatosplenomegaly, lymphadenopathy, and gastrointestinal wall thickening. PET/CT allows functional assessment, helping to differentiate between indolent and aggressive subtypes. The differential diagnosis of mastocytosis includes metastatic disease, myeloproliferative disorders, and metabolic bone conditions. Thus, correlation of imaging findings with clinical and laboratory markers, including serum tryptase levels and findings at bone marrow biopsy, is necessary. While histopathologic confirmation remains the reference standard, characteristic imaging findings can prompt early suspicion and guide appropriate workup. The authors review the pathogenesis, classification, and imaging features of mastocytosis, highlighting multiorgan involvement and potential diagnostic mimics of mastocytosis. ^©RSNA, 2025.