In a letter to the editor of Annals of Hematology, researchers described the case study of a patient diagnosed with well-differentiated systemic mastocytosis

A woman in her 20s presented with a large hematoma following a hip injury. Magnetic resonance imaging revealed splenomegaly and abnormal bone marrow signaling throughout her pelvis and her spine. Her past medical history included diffuse cutaneous mastocytosis (diagnosed in infancy) and an appendectomy carried out 6 years prior that showed mast cell infiltration. The patient’s drug history included cromolyn, antihistamines, and intermittent steroids for symptomatic control. 

The patient’s serum tryptase levels were more than 500 ng/mL. A bone marrow core biopsy demonstrated 90% cellularity with marrow replacement by sheets of CD117 and oval mast cells that were tryptase-positive but lacked CD25 or CD34 expression. The karyotype was normal, and next-generation sequencing did not reveal any abnormalities. However, she did have a pathogenic missense KIT mutation p.F522c with a 48.7% variant allele frequency. 

These findings were highly suggestive of well-differentiated systemic mastocytosis. More specifically, the diffuse replacement of the bone marrow by neoplastic mast cells and the presence of less than 10% circulating mast cells were indicative of aleukemic mast cell leukemia. With the absence of C-findings, the neoplasm could be characterized as being chronic. The high variant allele frequency of 48.7% was suggestive of a germline mutation, which could be further investigated with cultured skin fibroblasts. 

Read more about systemic mastocytosis etiology

The patient’s physicians started her on cytoreductive therapy with imatinib; this decision was based on previous studies indicating good receptivity to the drug in patients with systemic mastocytosis harboring the KIT p.F522C mutation. 

“This case demonstrates the importance of incorporating the disease history, lesion morphology and molecular studies in the classification of mast cell diseases,” the authors wrote. 


Chen K, Hendrie PC, Naresh KN. Aleukemic mast cell leukemia, well-differentiated and chronic typeAnn Hematol. Published online April 4, 2023. doi:10.1007/s00277-023-05195-5