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 variable tissue by clonal mast cells. This uncontrolled proliferation and activation of mast cells triggers the release of vasoactive and inflammatory mediators, resulting in a cascade of systemic symptoms. Around 95% of systemic mastocytosis arise from a gain-of-function mutation at the KIT gene, specifically at codon 816, which highlights its essential role in systemic mastocytosis and makes it an attractive target for therapy. Although KIT -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 KIT -negative SM are widely variable, but many are similar to KIT -positive SM. Therapeutic interventions are tailored based on the severity of the presentation. This report aims to further understand KIT -negative systemic mastocytosis by presenting two cases of KIT -negative SM and analyzing reported cases in the existing literature.