Answer: Lymphoepithelial-like carcinoma

Histology: The histologic picture is dominated by a dense lymphoid stroma. At higher power one can
appreciate that the lymphoid cells surround, permeate and obscure nests of atypical cells. The atypical cells have syncytial cytoplasm and vesicular nuclei with conspicuous nucleoli. They lack evidence of specific differentiation such as squamous or glandular differentiation. The atypical
cells are immunoreactive for cytokeratin (see below). An in situ hybridization study for Epstein-Barr virus (EBV) demonstrates a strong nuclear signal in the tumor cells (not shown).

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Discussion: Lymphoepithelial-like carcinoma of the lung is a rare variant of large cell carcinoma that is histologically identical to its nasopharyngeal counterpart. Like nasopharyngeal undifferentiated carcinoma, the lung tumors are histologically characterized by a prominent lymphoid stroma, syncytial cytoplasm, vesicular nuclei with eosinophilic nucleoli, and the absence of squamous or glandular differentiation. EBV can usually be demonstrated in the nuclei of the tumor cells by in situ hybridization. Because of the way that the lymphoid stroma can dominate the histologic picture and obscure the more unassuming neoplastic component, lymphoepithelial-like carcinoma is notorious for being misdiagnosed as an inflammatory process (e.g. inflammatory pseudotumor or pseudolymphoma) or malignant lymphoma. Immunohistochemical studies utilizing cytokeratin markers are conclusive in documenting the epithelial nature of the large atypical cells.