[Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases].
[Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological analysis of twelve cases].
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单形性嗜上皮性肠T细胞淋巴瘤12例临床病理分析
DOI：
10.3760/cma.j.issn.0529-5807.2020.01.004
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Z. Zhang
中科院分区：
文献类型：
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作者：
C. N. Chen;Z. Wang;Y. Jiang;H. Gao;R. Tao;J. Li;Z. Zhang
目的：目的探讨单形性肠嗜上皮性T细胞淋巴瘤（MEITL）的临床病理特征、诊断及鉴别诊断。研究方法：共收集12例标本，均于2012 - 2018年在南京医科大学第一附属医院手术切除，经术后病理、免疫组化染色和基因重排证实为MEITL，均具有完整的临床和病理资料。对MEITL病例进行回顾性分析，比较其临床病理特征，包括形态学和免疫表型特征，并通过电话和门诊随访进行随访。结果：所有病例均诊断为MEITL。男8例，女4例。男女比例为2∶1，中位年龄为54岁。病变部位包括空肠4例，回肠5例，十二指肠1例，回盲部1例，直肠1例。11例肿瘤细胞大小单一，为小至中等细胞，核圆形至稍不规则。免疫表型：CD 3（12/12）、CD 8（11/12）、CD 43（11/12）、CD 56（11/12）、TIA-1（12/12）阳性，CD 5（12/12）、Gran B（9/12）、穿孔素（7/12）阴性。2例异常表达B细胞标志物CD 20。Ki-67免疫组化显示细胞增殖指数高。EBER原位杂交均为阴性（12/12）。MEITL的整个外显子组测序（WES）突变景观是非常同质的，显示组蛋白修饰基因，JAK-STAT和MAPK信号通路之间的显着富集簇。2/4的肿瘤中存在组蛋白赖氨酸N-甲基转移酶SETD 2基因突变。所有分析的患者均在JAK-STAT信号通路中携带至少一个突变，包括STAT 5 B（2/4），JAK 3（3/4）和STAT 5A（2/4）。此外，在3/4的MEITL病例中观察到MAPK通路的频繁改变（TP 53）。来自WES数据的CNV分析确定了频繁收益和损失的多个区域。特别是，观察到1 q，7 q和9 q的增益以及涉及7 p和8 p的经常性损失。结论：MEITL是一种少见的侵袭性淋巴结T细胞淋巴瘤。MEITL的鉴别诊断包括EATL、结节性NT/T细胞淋巴瘤和其他类型的PTCL。诊断应与临床症状相结合，而最终诊断主要基于病理学特征、免疫表型和基因检测。
Objective: 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.