Answer: Nasopharyngeal carcinoma, undifferentiated

Histology: At low power, the background shows a heavy lymphoid infiltrate. Against this background are cohesive nests of cells that do not elicit a desmoplastic reaction. At high power, the cells forming these nests have round to oval vesicular nuclei, prominent nucleoli, scant cytoplasm and indistinct cell borders. There is no evident pigment deposition or keratinization.

Discussion: Undifferentiated nasopharyngeal carcinonoma (UNC) is an aggressive tumor with a propensity for regional and distant metastases. UNC can be confusing to pathologists. First, they are easily mistaken for other poorly differentiated tumors at the morphologic level. Foremost in the differential diagnosis are lymphoma and malignant mucosal melanoma. Distinction from Hodgkins and non-Hodgkins lymphoma may be particularly problematic when dealing with those tumors dispersed as single cells among a sea of lymphocytes (i.e. the Schmincke pattern). I have seen several examples of UNCs growing as sharply demarcated nests (i.e. the Regaud pattern) that had been initially misdiagnosed as follicular lymphoma or entirely dismissed as reactive germinal centers. Immunohistochemistry can play a crucial role in establishing the diagnosis. Unlike melanomas and lymphomas, UNC are consistently immunoreactive for cytokeratin, and they are not immunoreactive for lymphoid and melanocytic markers.

Second, the nomenclature of nasopharyngeal carcinomas is somewhat oblique. The W.H.O. brought about some much needed clarity by adopting a classification scheme that recognized three forms of carcinoma arising from the surface and crypt epithelium of the nasopharynx: 1) differentiated keratinizing squamous cell carcinoma, 2) differentiated non-keratinizing carcinoma, and 3) undifferentiated carcinoma. These tumor appear to be biologically and clinically distinct, emphasizing the need for accurate subclassification of nasopharyngeal carcinomas. Distinction of UNC from the differentiated non-keratinizing squamous cell carcinoma is made on morphologic grounds. Most importantly, the tumor cells of non-keratinizing squamous cell carcinomas have a distinct cell borders giving rise to a “pavestone” appearance of the cell nests. Many have vehemently objected to usage of the term “lymphoepithelioma”, pointing out that the lymphoid component is not a neoplastic component of the tumor. While this is indeed true, the term remains useful in that it is well understood by most clinicians and minimizes confusion with other undifferentiated tumors such as small cell undifferentiated carcinoma and sinonasal undifferentiated carcinoma.