Case Report: aleukemic mast cell leukemia with KIT p.V559G mutation, CD25-negative immunophenotype, and complex...

Mast cell leukemia (MCL), the most aggressive and often fatal subtype of systemic mastocytosis, is predominantly driven by KIT mutations, with the KIT p.D816V mutation being the most prevalent. Rare noncanonical KIT mutations remain poorly characterized, particularly when combined with a CD25-negative immunophenotype and high-risk cytogenetics. Through this case report, we aimed to enrich the molecular spectrum of MCL, emphasize the value of integrated diagnosis, and provide a reference for individualized treatment of older patients with high-risk MCL. This case involves an 81-year-old woman, with aleukemic MCL, who presented with dizziness and back pain. Severe pancytopenia was present, with 3% of atypical mast cells in the peripheral blood and 69.5% of abnormal mast cells in the bone marrow. Flow cytometry revealed a unique CD117^bri, CD9^bri, CD203c⁺, CD2⁺, CD25^-, and HLA-DR^- immunophenotypes. Karyotyping revealed complex clonal abnormalities, including monosomy 7. Next-generation sequencing identified a rare activating KIT p.V559G mutation (variant allele frequency, 42%), which is uncommon in MCL. Despite advanced age, life-threatening complications (sepsis, gastrointestinal bleeding, and myocardial infarction), and dismal prognostic features, the patient achieved clinical improvement with partial hematologic recovery on low-dose imatinib plus intensive supportive care and remained stable without evidence of disease progression during a four month follow-up period. This case represents a rare instance of aleukemic MCL cases with a KIT p.V559G mutation, CD25 negativity, and a complex karyotype, underscoring the importance of a comprehensive diagnostic workup and expands the clinical and molecular spectrum of MCL. Individualized low-intensity targeted therapy may offer short-term disease control in older patients with high-risk MCL, though long-term survival benefit remains unproven.