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Primary cutaneous anaplastic large‐cell lymphoma with aberrant cytokeratin expression: An unusual mimicker of poorly differentiated carcinomas

An 81‐year‐old male presented with a rapidly growing cheek nodule. Biopsy revealed a dermal infiltrate of large atypical cells, some exhibiting a horseshoe‐shaped nucleus. Immunohistochemistry revealed positivity for CD4, CD3, CD45, and CD30 (>95%). Melanocytic markers, cytotoxic markers, CD20, CD56, ALK1, synaptophysin, CD1a, and ETS‐related gene (ERG) were negative. Notably, there was weak but diffuse expression of pan‐cytokeratin (AE1/AE3) and Oscar keratin. There was also a weak expression of epithelial membrane antigen (EMA). CAM 5.2, p40, and IRF4/DUSP22 rearrangement were negative. Further staging revealed skin‐limited disease. A diagnosis of primary cutaneous anaplastic large‐cell lymphoma (PC‐ALCL) was rendered. We present a rare case of cytokeratin positive PC‐ALCL, a finding never reported in the literature. Both PC‐ALCL and systemic ALCL (S‐ALCL) evoke a broad differential. CD45, EMA, and cytokeratin stains help differentiate from metastatic carcinomas. There have been rare prior reports of cytokeratin expression in S‐ALCL, which tend to stain with an unusual cytoplasmic and membranous pattern like our case, have variable co‐expression of EMA, and null T‐cell phenotypes. These show the significant diagnostic challenges that can arise in differentiating ALCL from metastatic or primary skin carcinomas. Awareness, careful attention to morphology (e.g., hallmark cells), and considering routine CD30 can help lead the pathologist to the correct diagnosis.