Mutations involving TGFB and MAPK may be associated with malignancy in granular cell tumors

Abstract Granular cell tumors are mesenchymal neoplasms of presumed schwannian differentiation that may present as solitary or multifocal lesions with excision usually being curative. A minority of cases, however, shows histological features associated with an increased risk for metastasis and are highly aggressive leading to death in about a third of cases1. While benign and malignant cases have been shown to harbor mutations in the H + ATPase genes, there is only limited data examining molecular aberrations associated with malignancy. The departmental archives were searched for cases of atypical/malignant granular cell tumor. Clinical and histopathological features were noted. Whole exome sequencing was performed. Three cases of malignant granular cell tumor and on atypical granular cell tumor were included. Three tumors metastasized to distant sites with a median disease-free survival of 16 months and an overall follow-up time of 32.5 months. Whole exome sequencing showed mutations involving TGFβ and MAPK pathways in all four tumors. Mutations involving the TGFβ and MAPK pathways may be associated with tumor progression or malignant transformation in granular cell tumor pathogenesis.