To confirm a diagnosis of systemic mastocytosis in adults, the recommended diagnostic tests include a combination of clinical evaluation, laboratory investigations, and histopathological analysis. First, a bone marrow biopsy and aspirate are essential to identify multifocal dense infiltrates of mast cells, which is a major diagnostic criterion NICE NG12. Immunohistochemical staining for mast cell markers such as CD117 (c-KIT) and tryptase is performed on biopsy samples to confirm mast cell proliferation NICE NG12. Serum tryptase level measurement is also recommended, as persistently elevated baseline serum tryptase (>20 ng/mL) supports the diagnosis NICE NG12. Molecular testing for the KIT D816V mutation in peripheral blood or bone marrow cells is a key minor diagnostic criterion and helps confirm clonal mast cell disease NICE NG12. Additional tests may include flow cytometry to detect aberrant mast cell surface markers (e.g., CD25, CD2) and imaging studies to assess organ involvement NICE NG12.
While the UK guidelines emphasize these criteria, recent literature, including case reports and reviews, supports the importance of integrating clinical features such as subcutaneous hemorrhage and edema with these diagnostic tests to improve diagnostic accuracy Aceino et al. 2021. This literature also highlights the utility of comprehensive histopathological and molecular analyses to differentiate systemic mastocytosis from other mast cell disorders Aceino et al. 2021.