How we diagnose and treat WHO-defined systemic mastocytosis in adults.

| 6 | haematologica | 2008; 93(1) Current classification and diagnosis of systemic mastocytosis, and its distinction from other myeloid malignancies associated with bone marrow mastocytosis, remain challenging for both clinicians and hematopathologists. In its upcoming revision, due out in 2008, the World Health Organization (WHO) classification system for myeloid malignancies considers mast cell disease as a myeloproliferative neoplasm and systemic mastocytosis as a subcategory of mast cell disease with bone marrow involvement. At the same time, the WHO document distinguishes the usually KIT-mutated systemic mastocytosis from myeloid neoplasms associated with bone marrow mastocytosis and PDGFR mutations (e.g. FIP1L1-PDGFRA, PRKG2-PDGFRB). The latter are often associated with eosinophilia or basophilia and sensitive to treatment with imatinib. WHO-defined systemic mastocytosis is sometimes associated with a clonally-related second myeloid neoplasm, which is not surprising considering its origin as a stem cell disease with multilineage clonal involvement. Conversely, an otherwise welldefined myeloid malignancy, such as myelodysplastic syndrome or a non-mast cell disease myeloproliferative neoplasm, might harbor neoplastic mast cells. Our approach to diagnosis in systemic mastocytosis starts with bone marrow examination with tryptase staining and mast cell CD25 immunophenotyping. The former enhances morphologic and the latter immunophenotypic distinction between normal (round and CD25-negative) How we diagnose and treat WHO-defined systemic mastocytosis in adults