Abstract

CDX2 expression is considered a marker of intestinal adenocarcinomas. However, CDX2 expression may also be present in adenocarcinomas of intestinal-type differentiation, such as the ones in the urinary bladder, lung and mucinous ovarian tumors, among other neoplasms. In Dermatopathology, CDX2 expression has been reported in four main settings: 1) cutaneous metastases from carcinomas of intestinal origin or intestinal differentiation, 2) extramammary Paget’s disease associated with an underlying colorectal or urothelial tumor, 3) pilomatricomas and pilomatrical carcinomas, and 4) anecdotal reports of primary cutaneous (adeno)squamous carcinomas with intestinal immunophenotype. Herein, we report a series of five cases with an unusual morphology and immunophenotype, with the common denominator being convincing CDX2 positivity. Ages of the patients ranged from 64 to 77 years. The locations of the lesions included the neck, subungual region, groin, vaginal introitus, and lower leg. All cases demonstrated a basaloid and primitive morphology with cellular atypia, variable necrosis, and brisk mitotic activity. Additional findings were present, including squamoid, matrical, neuroendocrine, pseudoglandular/pseudopapillary features, and HPV in situ hybridization positivity in one case each. However, none of these cases showed features of indisputable pilomatrical carcinoma. The possibility of cutaneous metastatic carcinoma was excluded in all cases. Despite extensive workup in these cases, a definitive classification was challenging. We speculate that CDX2 positivity might reflect an early primitive immunophenotype of these basaloid cutaneous carcinomas of ambiguous classification. This finding raises a diagnostic pitfall in clinical application of the CDX2 immunostain, which can be observed in primary cutaneous carcinomas with primitive cytomorphology.

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