Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Gastroenterology Department, Hôpital Européen Georges Pompidou Assistance Publique des Hôpitaux de Paris, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France.
Université Paris Descartes-Sorbonne Paris Centre, Paris, France; Inserm U989, Paris, France; Institute Imagine, Paris, France.
Clin Gastroenterol Hepatol. 2014 Apr;12(4):599-608.e1. doi: 10.1016/j.cgh.2013.11.028. Epub 2013 Dec 4.
BACKGROUND & AIMS: Little is known about intestinal CD4+ T-cell lymphoma; this rare malignancy is misdiagnosed frequently. We evaluated diagnostic criteria and factors that might affect its development and outcome.
In a retrospective analysis, we analyzed medical records and intestinal specimens from 10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive patients examined for severe enteropathy with villous atrophy. Samples were analyzed by histology, flow cytometry, and comparative genomic hybridization.
Small-intestine epithelial and lamina propria tissues from patients who presented with chronic diarrhea and malnutrition had variable levels of infiltration of CD3+ CD4+ T cells. Flow cytometry showed a high frequency of CD4+ intraepithelial cells, which frequently expressed a specific Vβ chain. T-cell receptor β clonality was confirmed by DNA sequencing. Two patients had HLA and serology results compatible with celiac disease and autoimmune enteropathy, respectively. Two patients were found to have antibodies against human T-cell leukemia virus and 2 patients had signs of a recent infection with the herpes viruses. Comparative genomic hybridization analyses showed heterogeneous chromosomal abnormalities. Symptoms were reduced in patients treated with steroids (n = 5), but not in patients given purine analogues or chemotherapy. Antibodies against CD52 produced clinical and histologic responses in 2 of 2 patients, whereas severe adverse effects developed in 1 patient. At the latest follow-up evaluation, all patients were alive.
There is much heterogeneity in the onset and genetic features of intestinal CD4+ T-cell lymphomas, despite their common presentation as indolent lymphoproliferations of the intestinal mucosa. Patients should be treated with steroids, and possibly antibodies against CD52 (for the most aggressive forms of this disorder).
人们对肠道 CD4+T 细胞淋巴瘤知之甚少；这种罕见的恶性肿瘤经常被误诊。我们评估了可能影响其发展和结局的诊断标准和因素。
在一项回顾性分析中，我们分析了 115 例连续接受绒毛萎缩性严重肠炎检查的患者中 10 例肠道 CD4+T 细胞淋巴瘤患者的病历和肠道标本。通过组织学、流式细胞术和比较基因组杂交分析进行样本分析。
表现为慢性腹泻和营养不良的患者小肠上皮和固有层组织有不同程度的 CD3+CD4+T 细胞浸润。流式细胞术显示 CD4+上皮内细胞的频率较高，这些细胞经常表达特定的 Vβ链。通过 DNA 测序证实 T 细胞受体β克隆性。两名患者的 HLA 和血清学结果分别与乳糜泻和自身免疫性肠炎相符。两名患者发现有针对人类 T 细胞白血病病毒的抗体，两名患者有近期感染疱疹病毒的迹象。比较基因组杂交分析显示存在异质性染色体异常。接受类固醇治疗的 5 例患者症状减轻，但接受嘌呤类似物或化疗的患者症状无改善。2 例患者的抗 CD52 抗体产生了临床和组织学反应，而 1 例患者出现严重不良反应。在最新的随访评估时，所有患者均存活。
尽管肠道 CD4+T 细胞淋巴瘤的表现为惰性肠黏膜淋巴增生，但在发病和遗传特征方面存在很大的异质性。应使用类固醇，可能还应使用抗 CD52 抗体（针对这种疾病的最具侵袭性形式）治疗患者。
