Epstein-Barr virus associated lymphoepithelial carcinoma of the esophagus

Lymphoepithelial carcinoma (LEC), also called lymphoepithelioma-like carcinoma, is defined as an undifferentiated carcinoma or poorly differentiated squamous cell carcinoma, accompanied by a prominent reactive lymphoplasmacytic infiltrate. LEC can occur in many organs, but is most common in head and neck regions including pharynx. LEC may be associated with Epstein-Barr virus (EBV) infection. LEC of the esophagus is extremely rare; only nine cases have been reported. A 79-year-old man presented epigastralgia and dysphagia. A blood laboratory test showed no significant findings. He was a hepatitis C virus healthy carrier. Tumor markers of CEA and SCC were normal. Upper gastrointestinal endoscopy showed a tumor in the lower esophagus. Biopsies were taken, and they identified malignant epithelioid cells and heavy infiltration of mature lymphocytes. The epithelioid cells showed large size, nuclear atypia, mitotic figure, hyperchromasia, and increased nucleo-cytoplasmic ratio. The lymphocytes were free from atypia. Immunohistochemically, the epithelioid cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK WSS, CK MNF16, CK KL1, CK5/6, CK7, CK8, CK14, CK18, CK19, p53, and Ki-67 (labeling=27%). They were negative for CK34BE12, CK20, p63, CEA, CA19-9, NSE, synaptophysin, CD56, chromogranin, KIT (CD117), desmin, vimentin, MUC apomucins, and several leukocytic markers. The epithelioid cells were positive for EBV associated molecules including EBV-encoded nuclear antigen2 (EBNA2), EBV latent membrane protein-1 (LMP-1), and EBV early RNAs (EBER). The lymphocytes were positive for CD45 and vimentin, and were composed of B-cells positive for CD20, CD79 alpha, bcl-2, and CD10, T-cells positive for CD3 and CD45RO, NK-cells positive for CD56, and plasma cells positive for CD38, CD138, CD79 alpha, kappa-chain, and lambda-chain. No light chain restriction was seen. Most of the lymphocytes were B and T-cells, and NK-cells and plasma cells were very scant. The lymphoplasma cells were reactive cells, because of no atypia and also because no p53 and very low Ki-67 labeling (3%). The lymphocytes were negative for CD21 and other antigens such as CKs and EMA. The pathological diagnosis was primary LEC of the esophagus. Imaging techniques revealed lymph nodes metastasis of the perigastric and periaortic regions, but identified no other tumors in the body. The patient was inoperative, and was treated by chemoradiation. The esophageal LEC and lymph nodes metastases were markedly reduced in size.