Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare type of myeloproliferative neoplasm characterized by abnormal proliferation and infiltration of different tissue by clonal mast cells. The uncontrolled proliferation and activation of mast cells trigger the release of vasoactive and inflammatory mediators, resulting in a cascade of systemic symptoms. Around 95% of SM arise from a gain-of-function mutation at the gene, specifically at codon 816, which highlights its essential role in SM and makes it an attractive target for therapy. Although -negative SM is exceptionally rare, the increased number of cases documented in the literature makes it an intriguing dimension of this disorder. The reported clinical manifestations of -negative SM are widely variable, but many are similar to -positive SM. KIT-targeted therapeutic options have been a game-changer in -positive SM, however their role in -negative SM remains controversial. This report aimed to further understand -negative SM by presenting two cases of -negative SM, one of which was responsive to KIT-targeted therapy, and analyzing reported cases in the existing literature.