Wang Y C, Li J, Guo Y T, Li J, Lin J Y
Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology of Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin 300020, China.
Zhonghua Yan Ke Za Zhi. 2024 Jan 11;60(1):64-71. doi: 10.3760/cma.j.cn112142-20231013-00136.
To analyze the clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma. 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. 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. 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. 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.
分析结膜淋巴上皮癌的临床病理及基因突变特征。进行了一项回顾性病例系列研究。收集了2006年1月至2022年12月在天津眼科医院诊断为结膜淋巴上皮癌并接受肿瘤切除手术的3例患者的数据。对4份石蜡标本（包括1例接受两次手术的患者）进行上皮抗原和淋巴细胞抗原免疫组化染色。采用原位杂交检测爱泼斯坦-巴尔病毒（EBV）编码RNA（EBER），并对2例患者的3份标本采用二代测序方法进行全外显子组测序。所有3例患者均为65岁以上男性，病程3至44个月。肿瘤均为单侧，位于球结膜或角膜缘结膜，呈红色，最大直径4至20毫米。影像学检查显示肿瘤位于前部，未累及眶骨、眼外肌、视神经或鼻窦。所有患者均未观察到局部淋巴结转移。病理结果包括未分化癌巢，伴有明显的反应性淋巴细胞和浆细胞浸润。肿瘤细胞全细胞角蛋白（CK-pan）、上皮膜抗原（EMA）、肿瘤蛋白40（p40）和肿瘤蛋白63（p63）呈阳性，细胞增殖指数（Ki67）超过80%。淋巴细胞分化抗原20（CD20）、CD3和CD8呈阳性。原位杂交显示1例患者的2份标本中部分肿瘤细胞表达EBER。全外显子组测序显示3份标本中分别有58、50和36个突变基因，富集的信号通路包括黑色素瘤信号通路、Notch1信号通路和RHOQ GTP循环；富集的生化过程包括氨基酸饥饿反应、程序性细胞死亡、脂质合成调节、钠离子转运和染色体分离。所有3份标本中共同的突变基因是SZT2，且SZT2参与氨基酸饥饿反应。1例患者在部分切除术后40个月接受了第二次完整切除手术，另外2例接受了完整切除手术且未复发。2例患者未接受放疗或化疗，1例失访。结膜淋巴上皮癌伴有显著的淋巴细胞和浆细胞浸润，部分病例与EBV感染有关，且结膜淋巴上皮癌存在SZT2突变。
