Presumed tumor-infiltrating clonal hematopoiesis unmasking a concomitant systemic mastocytosis with associated myeloid neoplasm in a patient with metastatic melanoma

We report a unique case in a 67-year-old male patient in whom melanoma tumor sequencing identified DNMT3A and SF3B1 mutations suggesting tumor-infiltrating clonal hematopoiesis. Following comprehensive bone marrow evaluation, the patient was discovered to have a well-differentiated (WD) systemic mastocytosis with an associated myeloid neoplasm (SM-AMN) best classified as myelodysplastic syndrome with SF3B1 mutation. Notably, the SM component was negative for KIT D816V mutation, as expected for WD-SM; however, the immunophenotype was atypical with aberrant expression of CD25. This case highlights the potential for solid tumor genomics to expose occult myeloid neoplasms incidentally and underscores the importance of a comprehensive workup, including bone marrow examination, in distinguishing between incidental clonal hematopoiesis and bona fide myeloid neoplasms.