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

Abstract

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.

Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma

“…A strong correlation between EBV infection and LELC has been reported in Asian patients as is the case of the patients included in the study, but may not be the case in Western populations (4,9,20). The presence of EBV (6,7,21) was tested in Asian patients as necessary because the EBV infection rate in Asian pulmonary LELC was as high as 94-100% (22,23). A large number of tumor cells were revealed by HE staining with the cellular proliferation rate of 80% accompanied by abundant plasma cells.…”

“…Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma (EBER) was found in tumor cells (6,7) and EBV DNA was detectable in the serum of LELC patients (8), suggesting that the EBV infection was closely associated with the pathogenesis of LELC (9). The mutations of driver oncogenes were usually observed in lung cancers, whereas, rare or no mutations were found in the common oncogenes such as EGFR, KRAS, ALK, BRAF, ROS1, and p53 (7,(10)(11)(12)(13), implying that the mutagenesis of these genes was not involved in the tumorigenesis of LELC.…”

Primary pulmonary lymphoepithelioma-like carcinoma initially diagnosed as squamous metaplasia: A case report and literature review

“…The cytological features of the specimens are commonly analyzed by needle aspiration or fibrobronchoscopic brushing, which reveal abnormal cell morphology that usually appears as large clusters of neoplastic cells with scant cytoplasm. The nuclei are normally large and hyperchromatic, with irregular contour and prominent nucleoli (20). Histologically, the tumors appear solid and off-white in color, with a clear demarcation between the surrounding normal pulmonary tissues, while occasionally pleural invasion is observed.…”

“…Histologically, the tumors appear solid and off-white in color, with a clear demarcation between the surrounding normal pulmonary tissues, while occasionally pleural invasion is observed. Immunohistochemical analysis of pulmonary LELCs usually detects positive staining of membrane tumor markers, including latent membrane protein-1, viral capsid antigen and CKs (20). In addition, EBER detection is significant in the diagnosis of pulmonary LELCs, since EBER is absent in other lung carcinomas, such as non-small-cell lung carcinomas.…”

Primary Lymphoepithelioma-Like Carcinoma of the Lung

“…EBER (EBV early RNA) directed to Ebstein Barr virus RNA is typical for LELC. [5] Treatment consists of surgical resection. There is no sufficient data supporting the role of adjuvant treatment.…”