Cytopathologic features and differential diagnostic considerations of primary lymphoepithelioma‐like carcinoma of the lung

Primary lymphoepithelioma-like carcinoma (LELC) of the lung is an extremely rare disease that occurs more commonly in Asians, and is composed of undifferentiated carcinoma with prominent lymphoid stroma. LELC is reported to be closely associated with Epstein-Barr virus (EBV) infection. A case is presented here in which bronchial brushing smears in a 70-year-old man, revealed large clusters of neoplastic cells with scant cytoplasm. The nuclei were large, hyperchromatic, of irregular contour and with prominent nucleoli. Also identified were prominent intratumoral lymphoid infiltration and brisk mitotic figures. We detected EBV-coded small RNA in situ hybridization in smears. A cytologic diagnosis of a LELC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of large neoplastic cells with enlarged nuclei and prominent nucleoli with marked lymphoid infiltration and lymphoid stroma were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK5/6, CK34βE12, Napsin A and Bcl-2 but were negative for CK7, CK14, CK20, EMA, TTF-1, chromogranin A, synaptophysin and CD56. The proliferative index with MIB-1 was around 60%, and the p53 positive cells around 20%. The diagnosis of primary LELC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical and EBER results, and a detailed systemic examination to exclude possible extrapulmonary (nasopharyngeal) origin. We report the cytopathological features of LELC of the lung and demonstrate here for the first time the positivity of the EBER with RNA-ISH method in smears with emphasis on differential diagnostic considerations.