C-KIT and PDGFR testing for systemic mastocytosis – pro
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. 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 andPDGFR mutations (e.g. FIP1L1-PDGFRA, PRKG2-PDGFRB).
The major diagnostic criterion for systemic mastocytosis is the presence of dense infiltrates of mast cells in bone marrow or other extracutaneous tissues. Mast cells should be seen in aggregates of 15 or more.
Major criteria may be absent in early disease. In this situation, the minor criteria are used to make the pathologic diagnosis. Three of the following 4 minor criteria are required to make the diagnosis:
- Atypical mast cell morphology in 25% or more of the mast cells
- Expression of CD2 and/or CD25 in addition to normal mast cell markers
- Serum/plasma tryptase levels greater than 20 ng/mL
- A codon-816 c-kit mutation in peripheral blood, bone marrow, or involved tissue
Pettigrew HD, Teuber SS, Kong JS, Gershwin ME. Contemporary challenges in mastocytosis. Clin Rev Allergy Immunol. Apr 2010;38(2-3):125-34.
Ayalew Tefferi, Srdan Verstovsek, Animesh Pardanani, How We Diagnose And Treat WHO-Defined Systemic Mastocytosis In Adults. Haematologica January 2008 93: 6-9
Peter Valent, Wolfgang R. Sperr, and Cem Akin, How I treat patients with advanced systemic mastocytosis (Blood. 2010;116(26):5812-5817)