摘要目的:探讨肠道单形性亲上皮性T细胞淋巴瘤的临床病理学特征以及诊断、鉴别诊断。方法:收集2012至2018年间南京医科大学第一附属医院行外科手术切除后，病理HE切片、免疫组织化学及基因重排证实为单形性亲上皮性T细胞淋巴瘤，并有完整临床病理资料的病例12例，分析其临床及病理特征，完善补充相关检查并获得随访资料。结果:12例患者均为单形性亲上皮性T细胞淋巴瘤，男性8例，女性4例（男女比2∶1），中位年龄54岁；发病部位：空肠4例，回肠5例（其中1例侵及乙状结肠），十二指肠、回盲部和直肠各1例；镜下观察：11例肿瘤细胞形态单一，中等大小，核圆形，深染；1例肿瘤细胞呈多形性，核大，深染，可见多核及巨核，异型性大，核仁明显，核分裂象及核碎裂易见；淋巴结转移1例。免疫组织化学：CD3（12/12）、CD8（11/12）、CD43（11/12）、CD56（11/12）、T细胞胞质内抗原（TIA）1（12/12）均阳性，CD5（12/12）、颗粒酶B（9/12）、穿孔素（7/12）均阴性，Ki-67阳性指数约60%~90%，2例患者出现了CD20（B细胞标志物）反常阳性表达，EB病毒编码的小RNA（EBER）阴性（12/12）。全外显子测序：高频的突变基因为JAK3（3/4）、TP53（3/4）、SETD2（2/4）、STAT5A（2/4）、STAT5B（2/4）；基因拷贝数变异主要有：3例患者均出现1q、7q、9q获得，以及7p、8p缺失。KEGG富集信号通路主要有：PI3K-Akt信号通路，MAPK信号通路，JAK-STAT信号通路及细胞凋亡信号通路。结论:单形性亲上皮性T细胞淋巴瘤是一种罕见的高度侵袭性结外肠道淋巴瘤，临床表现及组织形态学多样，难与NK/T细胞淋巴瘤、肠病相关T、惰性T等肠道T细胞淋巴瘤鉴别，诊断时需结合临床病理、免疫组织化学、基因检测等。

abstractsObjective:To investigate the clinicopathological features, diagnosis and differential diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:A total of 12 specimens were collected, which were surgically resected and verified as MEITL by postoperative pathology, immumohistochemical staining and gene rearrangement at the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018, and all of these had complete clinical and pathological data. The MEITL cases were reviewed to compare the clinicopathological characteristics, including morphologic and immunophenotypic features and followed up by telephone and clinic visit.Results:All the cases were diagnosed with MEITL. There were 8 males and 4 females. Male to female ratio was 2∶1, at a median age of 54 years. The sites of involvement included jejunum (4 cases), ileum (5 cases), duodenum (1 case), ileocecal junction (1 case) and rectum (1 case). The neoplastic cells were monotonous of small to intermediate cells in size with round to slightly irregular nuclei in 11 cases. The immunophenotyping showed that CD3 (12/12), CD8 (11/12), CD43 (11/12), CD56 (11/12), TIA-1 (12/12) were positive; CD5 (12/12), Gran B (9/12), and perforin (7/12) were negative. Two cases aberrantly expressed the B-cell marker CD20. A high proliferation index was demonstrated by Ki-67 immunostaining. In situ hybridization for EBER was all negative(12/12). The whole exome sequencing(WES) mutational landscape of MEITL was remarkably homogeneous, showing significantly enriched clusters among histone modifier genes, JAK-STAT and MAPK-signal pathways. Histonelysine N-methytransferase SETD2 gene was mutated in 2/4 tumors. All the patients analyzed harbored at least one mutation in the JAK-STAT signal pathway, including STAT5B (2/4), JAK3 (3/4) and STAT5A (2/4). Furthermore, frequent alterations (TP53) were observed in the MAPK pathway in 3/4 of MEITL cases. The CNV analysis derived from WES data identified multiple regions of frequent gains and losses. In particular, gains in 1q, 7q and 9q, and recurrent losses involving 7p and 8p were observed.Conclusions:MEITL is a rare and aggressive type of extranodal T-cell lymphoma. The differential diagnosis of MEITL includes EATL, extranodal NT/T-cell lymphoma and other types of PTCL. Diagnosis should be correlated to clinical symptoms while the final diagnosis is mainly based on the pathological features, immunophenotypes and genetic testing.