Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne.
Department of Hematology, University Hospital of Clermont-Ferrand, Clermont-Ferrand.
Haematologica. 2023 Jan 1;108(1):181-195. doi: 10.3324/haematol.2022.281226.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.
单一表型上皮样肠道 T 细胞淋巴瘤（MEITL）是一种罕见的侵袭性 T 细胞淋巴瘤，主要见于亚洲。我们对 71 例欧洲 MEITL 患者（36 名男性，35 名女性，中位年龄 67 岁）进行了全面的临床、病理和基因组研究。大多数患者有胃肠道受累，需要紧急手术，40%的患者有 IV 期疾病。肿瘤的形态学分类为两组：典型（58%）和非典型（即非单形性或伴有坏死、血管浸润或星空图案）（42%），具有相同的免疫表型特征（CD3+[98%] CD4- [94%] CD5- [97%] CD7+[97%] CD8+[90%] CD56+[86%] CD103+[80%]细胞毒性标志物+[98%]），TCRgd 的表达更为频繁（50%），而 TCRab 的表达较少（32%）。MYC 表达（30%的病例）部分反映了 MYC 基因座的改变，与非单形性细胞学相关。几乎所有病例（97%）都有有害突变和/或 SETD2 基因缺失，90%的病例存在 H3K36 三甲基化缺陷。其他经常发生突变的基因是 STAT5B（57%）、JAK3（50%）、TP53（35%）、JAK1（12.5%）、BCOR 和 ATM（11%）。TP53 突变和 MYC 表达均与非典型形态相关。63 例患者（43/63 例仅在初始手术后接受化疗）的中位总生存期（OS）为 7.8 个月。多变量分析发现，MYC 表达、TP53 突变、STAT5B 突变和较差的体能状态对预后有强烈的负面影响，而异常 B 细胞标志物表达（20%的病例）与更好的生存相关。总之，MEITL 是一种侵袭性疾病，对常规治疗具有耐药性，主要特征是驱动基因改变，导致组蛋白甲基化和 JAK/STAT 信号通路失调，并包括与极高临床风险相关的遗传和形态学变异。
