In a recent study, approximately 8% of individuals with unexpected KIT mutations in myeloid neoplasms also met the diagnostic criteria for systemic mastocytosis (SM), according to findings from a study of next-generation sequencing (NGS) published in the journal Clinical Lymphoma, Myeloma & Leukemia.
In patients with SM, mast cells accumulate in one or several organs or body systems—mainly the skin and the bone marrow. The disorder is clinically heterogeneous, with patients’ symptoms ranging from mild to severe. In those with SM, the involvement of at least one extracutaneous organ is observed, either with or without any evidence of skin lesions.
Based on the World Health Organization (WHO) Classification of Hematolymphoid Tumors, the diagnostic criteria for SM comprise the major criterion of “multifocal dense infiltrates of mast cells in affected organs” and the following four minor criteria:
- Atypical mast cell morphology
- Mutations in the KIT gene
- Aberrant expression of CD2, CD25, or CD30 in mast cells
- Baseline serum tryptase levels of >20 ng/mL in the absence of any associated myeloid neoplasms
In fact, an SM diagnosis can be rendered if the major criterion and at least one of the minor criteria have been fulfilled or if at least three of the minor criteria have been met.
Read more about SM treatment and care
Currently, NGS is performed routinely in almost all bone marrow samples, with KIT mutations detected among individuals without any known or suspected SM. Based on these findings, the researchers sought to evaluate whether KIT mutations can be associated with the presence of unsuspected SM. They explored NGS results from The University of Texas MD Anderson Cancer Center, Houston, Texas, to identify patients with positive results for KIT mutations detected by targeted NGS between 2012 and 2021.
Although a total of 94 patients who were assessed exhibited KIT mutations, “only 49 of them had bone marrow core biopsy paraffin blocks available.” Of these 49 individuals, 30 were men and 19 were women. The median participant age was 60 years (range, 20 to 79 years). Among the 49 participants, there was a single KIT mutation in 41 patients and ≥2 KIT mutations in eight patients.
Overall, 38 of the patients had acute myeloid leukemia and six had chronic myelomonocyte leukemia. All of the participants underwent immuno-histochemical stains for CD117 and MST.
Results of the study revealed that 8.2% (4 of 49) of the patients evaluated exhibited mast cell nodules in which spindle-shaped mast cells were observed, thus fulfilling the WHO criteria for SM. All of these 4 participants harbored a single KIT p.816V mutation.
The median variant allelic frequency (VAF) of the KIT mutations was 20.8% (range, 1.0% to 78.4%). Further, in 71.4% (35 of 49) of the patients, the VAF of the KIT mutation was >10%. Among the 8 participants with ≥2 KIT mutations, the difference between the KIT mutation with the greatest VAF and that with the lowest VAF was >10% in 3 individuals.
“Our data support that application of additional immuno-histochemical studies is recommended to identify underrecognized SM when KIT mutations are found by molecular assays,” the authors concluded.
