Abstract
INTRODUCTION: Granular cell tumors (GCT) are predominantly benign neoplasms composed by cells with abundant eosinophilic granular cytoplasm. Although the majority of GCTs exhibit a benign clinical course, a minority display cytological atypia and may exhibit aggressive, cancer-like behavior. Definitive evidence of malignancy in GCTs is reliably established only through the presence of metastasis. Addi- tionally, a subset of GCTs demonstrates a high rate of recurrence, underscoring the need for better prog- nostic markers. Therefore, it is crucial to identify molecular markers associated with aggressive behavior in GCTs. Molecular analysis may be particularly beneficial in cases exhibiting cytological atypia to in- form clinical outcome prognostication and guide therapeutic strategies. OBSERVATION: In this case report, a 45-year-old female with multiple gastrointestinal GCTs is pre- sented. The patient did not have any genetic syndromes commonly associated with GCT, such as neu- rofibromatosis type 1, Noonan syndrome or LEOPARD syndrome. The tumors not only demonstrated nuclear atypia, but also harbored a unique FLT3 Y842C somatic alteration identified by next-genera- tion sequencing. The patient remains asymptomatic and under endoscopic surveillance two years after diagnosis and complete resection of the neoplasms. CONCLUSION: We presented an exceedingly rare case of multifocal atypical GCT in an adult without any previously known genetic syndrome. A tumoral FLT3 Y842C point mutation not previously reported in GCT was discovered. Although the precise significance of this finding is uncertain, FLT3 Y842C has been cataloged as likely pathogenic in ClinVar. This report underscores the potential predictive utility of next-generation sequencing in the characterization and management of rare neoplasms.