Answer: Lymphoepithelial carcinoma

Histology: There is a discrete lymphoid nodule with scattered germinal centers. A lymph node capsule is not identified. Instead, the lymphoid tissue spills into the adjacent salivary gland parenchyma at its periphery. Scattered throughout this lymphoid stroma and only appreciated at high power are nests of epithelioid cells that are heavily permeated by infiltrating lymphocytes. The cells have a syncitial cytoplasm, vesicular nuclei, and prominent eosinophilic central nuclei. Mitotic figures are easily identified. These cell nests are immunoreactive for cytokeratin, and they are EBV positive by in-situ hybridization (EBER).

Discussion: Lymphoepithelial carcinoma (LEC) of the salivary glands is an undifferentiated carcinoma that is morphologically characterized by infiltrating nests and cords of cells separated by zones of lymphoid stroma. The tumor cells consistently exhibit syncitial cytoplasm, open vesicular nuclei, and conspicuous nucleoli. A desmoplastic stromal reaction is notably absent.

The diagnosis of LEC can be very difficult. Because of the prominent and obscuring lymphoid background and absence of a desmoplastic reaction, the underwhelming epithelial component may go unrecognized and the process may be misinterpreted as a benign reactive lymph node. One should have a low threshold for performing cytokeratin immunohistochemical carcinoma from the nasopharynx. Indeed, these tumors are virtually indistinguishable at the morphologic level. EBV in-situ hybridization is of no help. Both tumors represent an EBV-driven process. One can establish a definite diagnose a LEC of primary parotid origin only when the presence of an undifferentiated nasopharyngeal carcinoma has been excluded on clinical grounds. The prognosis for patients with parotid LECs is largely dependent on tumor stage.