Granular Cell Dermatofibroma Demonstrates Loss-of-Function Mutations in V-ATPase Component Genes

Granular cell dermatofibroma (GCDF) is a unique histopathological variant of dermatofibroma, characterized by a portion of the lesion composed of cells with abundant granular cytoplasm, resembling granular cell tumors (GCT). GCTs are associated with mutations in V-ATPase component genes; however, the pathogenesis and molecular alterations in GCDF remain uncharacterized. We performed whole exome sequencing on six GCDF cases. Comparative whole exome sequencing analysis of lesional and paired control tissues was conducted to identify genetic mutations in GCDF. Three of the six cases (50%) of GCDF harbored mutations in V-ATPase component genes, including ATP6AP1, ATP6V0C, and ATP6AP2. These findings expand the spectrum of tumors associated with V-ATPase mutations. It is important for dermatopathologists to be aware of clinical, histopathological, and molecular findings in GCDF, and to differentiate these from atypical or malignant GCT, as GCDF are benign and do not need aggressive surgical management.