[Clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma]

Objective: To analyze the clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma. Methods: A retrospective case series study was conducted. Data from three patients diagnosed with conjunctival lymphoepithelial carcinoma and treated with tumor resection surgery at Tianjin Eye Hospital from January 2006 to December 2022 were collected. Four paraffin specimens (including one patient undergoing two surgeries) were subjected to immunohistochemical staining for epithelial antigen and lymphocytic antigen. Epstein-Barr virus (EBV)-encoded RNA (EBER) was detected using in situ hybridization, and whole-exome sequencing was performed on three specimens from two patients using next-generation sequencing methods. Results: All three patients were males aged over 65, with a disease duration ranging from 3 to 44 months. The tumors were unilateral, located on the bulbar or limbal conjunctiva, appearing red, with a maximum diameter of 4-20 mm. Imaging examinations revealed anterior location of the tumors with no involvement of the orbital bone, extraocular muscles, optic nerve, or paranasal sinuses. No local lymph node metastasis was observed in any patient. Pathological findings included undifferentiated carcinoma nests with significant reactive lymphocytic and plasma cell infiltration. Tumor cells were positive for pan-cytokeratin (CK-pan), epithelial membrane antigen (EMA), tumor protein 40 (p40), and tumor protein 63 (p63), with a cell proliferation index (Ki67) exceeding 80%. Cluster of differentiation 20 (CD20), CD3, and CD8 were positive for lymphocytes. In situ hybridization showed partial tumor cell expression of EBER in two specimens of one patient. Whole-exome sequencing revealed 58, 50, and 36 mutated genes in the three specimens, with enriched signaling pathways including melanoma signaling pathway, Notch1 signaling pathway, and RHOQ GTP cycle; enriched biochemical processes included amino acid starvation response, programmed cell death, regulation of lipid synthesis, sodium ion transport, and chromosome segregation. The common mutated gene in all three specimens was SZT2, and SZT2 was involved in the amino acid starvation response. One patient underwent a second complete resection surgery 40 months after partial excision, while the other two underwent complete resection surgery without recurrence. Two patients did not undergo radiation or chemotherapy, and one was lost to follow-up. Conclusions: Conjunctival lymphoepithelial carcinoma is associated with prominent lymphocytic and plasma cell infiltration, some cases are associated with EBV infection, and SZT2 mutations are present in conjunctival lymphoepithelial carcinoma.