A 45-year-old man from southern China is diagnosed with a nasopharyngeal tumor. Histologically, this neoplasm is composed of anaplastic cells immunoreactive for cytokeratin admixed with abundant lymphocytes. Which of the following factors is MOST likely implicated in the pathogenesis of this neoplasm?

The neoplasm described here is known as lymphoepithelioma, an inappropriate designation that emphasizes the histologic features of a lymphocyte-rich squamous cell carcinoma. This tumor, AKA nasopharyngeal carcinoma, is the most frequent childhood malignancy in ceain African regions and one of the most frequent adult tumors in southern China. Epstein-Barr virus genome has been identified in most of these neoplasms. Cigarette smoking is a risk factor for a number of malignant neoplasms, such as lung cancer. In the upper respiratory tract, cigarette smoking is a strong predisposing factor for laryngeal carcinoma, but it has not been linked to the pathogenesis of nasopharyngeal carcinoma. Radiation injury is a well-known risk factor for many human neoplasms, such as leukemia and thyroid cancer, but not for nasopharyngeal carcinoma. Although any cell type is susceptible to neoplastic transformation by radiation, there is a so of hierarchy of vulnerability. The most frequent radiation-induced cancers are leukemias and thyroid carcinoma, followed by breast, lung, and salivary gland tumors. Skin, bone, and the gastrointestinal tract are least vulnerable to radiation carcinogenesis. Overexpression of the bcl-2 gene is found in most B-cell follicular lymphomas. bcl-2 is a member of a large family of genes that regulate apoptosis. bcl-2 inhibits apoptosis, so that its overexpression allows neoplastic lymphocytes to survive for long periods and accumulate progressively in lymph nodes and bone marrow. Ref: Lustig L.R., Schindler J.S. (2013). Chapter 8. Ear, Nose, & Throat Disorders. In M.A. Papadakis, S.J. McPhee, M.W. Rabow (Eds), CURRENT Medical Diagnosis & Treatment 2013.