A 75-year-old woman presented with an explosive onset of widespread, densely distributed, and uniform papules and nodules on the face and neck over a rapid 2-month period (Fig. 1). She had a history of sigmoid colon cancer with bone metastases and was receiving oral capecitabine. Genetic testing revealed missense mutations in the mechanistic target of rapamycin kinase (MTOR). Histopathology showed well‑differentiated squamous epithelial proliferation in the dermis with keratin pearls, mild atypia, and pushing borders, rather than infiltrative borders (Fig. 2). Ki-67 positivity was confined to the basal layer of the squamous nests (Fig. 3). The diagnosis was capecitabine‑induced eruptive keratoacanthoma (KA). The patient had not received any immunosuppressive therapy because of advanced cancer with bone metastases. Without clinical correlation, the lesion could easily be misdiagnosed as squamous cell carcinoma on histopathology alone. While 5-fluorouracil (5-FU) is commonly used to treat KA, capecitabine is not typically considered a trigger for eruptive KA. Nevertheless, in patients with advanced cancer and poor performance status, capecitabine-induced eruptive KA should be considered when sudden, widespread squamoproliferative eruptions occur.
The etiology of eruptive KA remains unclear, although contributing factors may include ultraviolet exposure, immune dysfunction, viral infection, trauma, and immunomodulatory medications[
1]. No standardized treatment protocol has been established. Various modalities have been attempted with variable success, including topical corticosteroids, 5-FU, methotrexate, and triamcinolone acetonide, intralesional injections of these agents, and oral acitretin[
2]. Given the histopathological overlap with cutaneous squamous cell carcinoma, accurate diagnosis requires integration of clinical and pathological findings[
3].
Teaching points
(1) Diagnostic pitfall of histopathological examination: isolated histopathological features of eruptive KA, including squamous proliferation and keratin pearls, overlap with squamous cell carcinoma. Without clinical correlation, the lesion is highly prone to misdiagnosis as squamous cell carcinoma.
(2) Atypical pathogenic trigger of KA: 5-FU is conventionally used for the treatment of KA, while its oral prodrug capecitabine is rarely recognized as an inducing factor for eruptive KA, leading to underrecognition of this drug-related adverse skin reaction in clinical practice.
(3) Attention to special patient populations: for advanced cancer patients with bone metastases and poor performance status receiving capecitabine monotherapy, drug-induced eruptive KA should be included in the differential diagnosis of new-onset multiple cutaneous papules and nodules, even in the absence of immunosuppressive treatment.
The Author(s) 2026. This article is published by Higher Education Press on behalf of People’s Medical Publishing House.
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