Pembrolizumab-Induced Eruptive Keratoacanthomas Managed With Intralesional Corticosteroids: A Case Report

Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is approved for multiple malignancies, including renal cell carcinoma in combination with axitinib. While highly effective, PD-1 blockade can provoke immune-mediated cutaneous adverse events, including eruptive squamous cell carcinomas and keratoacanthomas. These squamoproliferative lesions may reflect a reactive epidermal proliferation triggered by immune activation, potentially through unmasking of subclinical epidermal dysplasia. Histologically, keratoacanthomas and well-differentiated squamous cell carcinomas can be difficult to distinguish, and clinicopathologic correlation is essential for guiding management. We present a case of a patient receiving pembrolizumab and axitinib for renal cell carcinoma who developed a high burden of eruptive squamoproliferative lesions across multiple anatomic sites. Biopsies were interpreted as either well-differentiated squamous cell carcinoma or keratoacanthoma-type squamous proliferations, underscoring the diagnostic ambiguity inherent to these lesions. Most lesions were successfully managed with intralesional triamcinolone, allowing continuation of immunotherapy without interruption. Two subsequent lesions required surgical excision due to clinical concern for invasive behavior, although no aggressive histologic features were identified. This case adds to the growing literature supporting conservative dermatologic management of pembrolizumab-associated squamoproliferative lesions. Unlike previous reports describing only a small number of lesions, this case involved a high lesion burden treated with intralesional corticosteroids across multiple sites, with clearly documented technique and follow-up. The case reinforces the clinical importance of correlating histopathologic findings with therapeutic response and demonstrates that, with appropriate monitoring, immunotherapy can often be continued safely while managing cutaneous findings locally.