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Case Reports

Abstract

Transcription factor tumor protein 63 (p63) is an epithelial marker and may be used for interpretation of squamous cell carcinoma (SCC) and other epithelial cancers.  Atypical expression in non-epithelial tumors can be a diagnostic pitfall. We report a case of an 86-year-old male presenting with a cutaneous lesion clinically suspicious for SCC or Merkel Cell Carcinoma (MCC).  A large shave biopsy was performed demonstrating a proliferation of epithelioid cells forming large nodules separated by narrow streaks of collagen. The malignant cells demonstrated increased nuclear to cytoplasmic ratio with hyperchromatic chromatin and increased mitotic activity.  Definitive epidermal connection and squamous differentiation was not identified.  Neither dermal pigment nor definitive germinal center formation was present.  Given the clinical concern for a keratinocyte carcinoma, a screening immunohistochemistry panel began with p63, Sox10 and CK 20. Diffuse p63 reactivity was noted within the cells of interest while negative for Sox10 and CK20. The clinical features were concerning for a keratinocyte-derived neoplasm and the initial screening panel would have supported this diagnosis. The histopathological features on H&E however were less convincing for an epithelial neoplasm, despite the p63 reactivity.  Additional studies were performed confirming the diagnosis of an aggressive diffuse large B-cell lymphoma with p63 expression. Expression of p63 has been associated with more aggressive neoplasms to included MCC and diffuse large B-cell lymphomas.  H&E remains the cornerstone for diagnosis and should be supported by the staining profile. This case underscores that reliance on a single immunohistochemical marker can misdirect diagnosis and treatment.