Cytokeratin-Negative Undifferentiated (Lymphoepithelial) Carcinoma of the Lacrimal Sac

Epstein-Barr virus-associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. Generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. In the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. Only 3 cases arising in the lacrimal sac in association with Epstein-Barr virus have been reported in the English literature, and all showed typical pathologic findings. The authors report a fourth case, unique in that it showed negative immunostaining for all cytokeratins tested. The clue to the nature of the tumor came from identification of Epstein-Barr virus by in-situ hybridization and demonstration of tonofilaments by electron microscopy. This case demonstrates that a multimodal approach may be needed in the diagnosis of Epstein-Barr virus-associated carcinoma, especially when occurring in uncommon locations.