Abstract

We present an interesting case of a 65-year-old with a history of anal squamous cell carcinoma with visceral metastasis status post resection and diverting ostomy, radiation therapy, and chemotherapy. She presented with erythema and pain at her ostomy site which was recalcitrant to ointment and topical steroids. At presentation, she was undergoing treatment follicular lymphoma with Bendamustine and Rituximab. Punch biopsy of skin adjacent to the ostomy site showed full thickness epidermal dysmaturation, including atypical mitotic figures scattered throughout the dermis. The granular cell layer was intact throughout the majority of the specimen and there was overlying compact orthokeratosis. Immohistochemical staining for p16 showed aberrant block positive expression throughout the epidermis. However, send-out in situ hybridization testing was negative for high and low risk HPV.  Immunohistochemical staining for p53 showed scattered expression throughout the epidermis, most consistent with a reactive pattern. A diagnosis of chemotherapy-induced epidermal dysmaturation was rendered based on the history of ongoing treatment with Bendamustine, histologic findings, immunophenotypic profile, and clinical presentation of a diffuse erythematous lesion. Therapy with bendamustine has been shown to induce destabilized mitoses, known as mitotic catastrophe, along a non-apoptotic cell death pathway. This mechanism can lead to histologic features similar to those seen in this case, and may induce cellular expression of p16. This case highlights a potential diagnostic pitfall as there is significant histologic overlap between chemotherapy-related epidermal dysmaturation and HPV-driven squamous dysplasia. Thorough analysis of clinical history, histologic findings, and presentation is critical for avoiding this diagnostic pitfall.