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Case Reports

Abstract

Pseudoepitheliomatous hyperplasia (PEH) is a benign epithelial proliferation that can closely mimic squamous cell carcinoma (SCC), particularly in the presence of coexisting malignancies. We report a diagnostically challenging case of a large ulcerated nodular lesion on the leg of a 76-year-old female. Dermoscopic evaluation revealed a pink lesion with white streaks and red globules, initially suggestive of a non-melanocytic malignancy. Histopathological examination showed prominent acanthosis, keratin pearls, and keratinocyte atypia with invasive-appearing squamous islands in the dermis, supporting the clinical impression of SCC. Separate sections revealed epidermal ulceration with a dense dermal inflammatory infiltrate, raising suspicion for SCC with tumor-associated lymphoid aggregates. However, high-power examination identified subtle atypical epithelioid blue cells admixed within the infiltrate, and immunohistochemical staining confirmed malignant melanoma. SCC-melanoma collision tumors are exceedingly rare, with only 17 cases reported in the literature. The interaction between neoplastic cells and the tumor microenvironment may induce reactive epithelial changes that closely resemble malignancy. Additionally, theories such as field cancerization and paracrine signaling suggest that neoplastic cells may influence adjacent benign tissue, potentially contributing to malignant transformation. These observations raise an important question: Can PEH progress to malignancy? This case underscores the importance of thorough histopathological and immunohistochemical evaluation in ulcerated nodular lesions, particularly when inflammatory infiltrates obscure atypical cells. It also highlights the diagnostic complexity of PEH when it mimics SCC and coexists with melanoma, potentially leading to underdiagnosis of the more aggressive component. Further molecular studies may help clarify PEH’s relationship to malignancy.