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Case Reports

Abstract

Inverted follicular keratosis (IFK) is a rare benign neoplasm of the follicular infundibulum, first described by Helwig in 1954. It typically presents as a solitary, non-pigmented 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 IFKs in an 81-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 IFK.

The patient remains alive with stable disease 10 months after initiating ripretinib. No specific treatment was required for the IFK lesions, 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 is the first reported case suggesting IFK association adverse reaction from ripretinib therapy. Further studies are needed to clarify the clinical significance and biological implications of this observation.