Mast cells are primarily found in tissues throughout the body and are a normal cellular component of the bone marrow. The neoplastic proliferation of mast cells leads to mastocytosis. The activation of KIT signaling plays a major role in the tumorigenesis of mastocytosis. The most common activation mutation of KIT is D816V in the phosphotransferase domain, which accounts for over 80% of adult cases and 42% of childhood cases,^1,2 but additional mutations are found in the extracellular domain (such as deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), transmembrane domain (such as KIT p.F522C), or juxtamembrane region (such as KIT p.V560G).³ These mutations result in ligand-independent kinase activation and uncontrolled mast cell proliferation.

In some cases of pediatric mastocytosis, concurrent ovarian germ cell tumors can be present, with identical KIT mutations found in both conditions, suggesting that these tumors may originate from a common progenitor cancer cell. This association of germ cell tumors with hematopoietic neoplasms suggests that some hematopoietic stem cells may originate from primordial germ cells.⁴