Squamous Cell Carcinoma In Situ Arising From HPV60 ‐Related Plantar Epidermoid Cyst

Palmoplantar epidermoid cysts are typically benign lesions associated with trauma or eccrine duct hypertrophy, occasionally associated with human papillomavirus (HPV) infection, particularly HPV60. Malignant transformation into squamous cell carcinoma (SCC) within these cysts is extremely rare. A 21-year-old Japanese woman presented with a slowly enlarging 1.0 cm lesion on her left sole. Ultrasonography suggested a benign cystic lesion, and excisional biopsy was performed. Histopathology revealed an epidermoid cyst with koilocytosis, inclusion bodies, and focal SCC in situ characterized by atypical squamous epithelial proliferation. Immunohistochemical staining showed diffuse p16 positivity, partial Rb loss, and a high Ki67 index in the SCC in situ component. Anti-HPV antibody (K1H8) was positive in the cyst wall but negative in the SCC in situ. RNAscope analysis demonstrated HPV60-E6/E7 mRNA expression within the SCC in situ, raising the possibility of HPV-associated oncogenesis. These findings suggest a potential link between low-risk HPV60 and cutaneous oncogenesis, emphasizing the need for thorough histopathological evaluation of plantar epidermoid cysts, even in young patients.