Benign Keratoses With Inverted Follicular Keratosis-Like Features in a Patient Receiving Ripretinib: A Case Report

Inverted follicular keratosis (IFK) is a rare benign neoplasm of the follicular infundibulum and typically presents as a solitary, nonpigmented verrucous papule on the head and neck of older males and can mimic viral warts, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC). We report a case of multiple benign keratoses with IFK-like features in an 82-year-old woman undergoing ripretinib therapy for metastatic gastrointestinal stromal tumor (GIST). Eight weeks into therapy, the patient developed multiple darkly pigmented, scaly, raised papules, primarily on the bilateral lower extremities. Histopathologic examination revealed a well-circumscribed endophytic keratinocytic proliferation with a broad, smooth base and numerous squamous eddies. No significant cytologic atypia or brisk mitotic activity was observed. These findings supported a diagnosis of benign keratoses with IFK-like features. The patient remains alive with stable disease 10 months after initiating ripretinib. No specific treatment was required for the benign keratoses with IFK-like features, and ripretinib therapy was continued. Ripretinib, a switch control tyrosine kinase inhibitor that targets KIT and PDGFRA kinases, is associated with an increased risk of cutaneous neoplasms, including actinic keratosis, seborrheic keratosis, SCC, keratoacanthoma, and melanoma. Patients treated with small-molecule inhibitors that target MAPK pathway may develop various keratinocytic dermatologic toxicities. To the best of our knowledge, this represents the first reported association between repretinib treatment and benign keratoses with IFK-like features. Further studies are needed to clarify the clinical significance and biological implications of this observation.