[Clinicopathological characteristics of natural killer cell enteropathy: report of two cases and review of literature].

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.目的： 探讨自然杀伤（natural killer，NK）细胞肠病的临床病理学特征及预后，加深对该罕见疾病的了解和认知，避免误诊。 方法： 收集2017年10月至2021年2月郑州大学第一附属医院诊治的NK细胞肠病2例。分析其临床特点、形态学、免疫组织化学、EB病毒编码的RNA（EBER）原位杂交及T细胞受体（TCR）基因重排情况，电话随访患者。 结果： 2例患者均为男性，年龄分别为40岁及28岁，患者均因体检入院，无明显胃肠道症状，内镜示例1胃体部可见黏膜微隆起及少量充血、糜烂，例2直肠黏膜可见充血糜烂。显微镜下观察2例病灶均较局限，表现为黏膜固有层内较多淋巴样细胞浸润，例2可见浸润至黏膜肌层，例1病变区黏膜内腺体减少，腺腔略受挤压变形，2例均未见浸润或破坏腺体现象；淋巴样细胞具有不典型性，胞体中等-偏大，胞质中等-略丰富，嗜酸性或透亮，例2少数细胞胞质内可见特征性的嗜酸性颗粒；2例核均圆形、卵圆形及不规则形，染色质细腻，核仁不明显，未见明确核分裂象；例1可见少量坏死；2例均未见血管中心性生长及破坏现象。免疫表型：不典型淋巴样细胞表达CD56、颗粒酶B及T细胞胞质内抗原1，2例CD3均可见部分细胞胞质阳性，例2 CD4可见部分细胞弱阳性，CD5、CD8、CD30、间变性淋巴瘤激酶及B细胞标志物（CD20、CD79α）均阴性，Ki-67阳性指数约60%及30%。2例EBER原位杂交均阴性，TCR基因重排均呈多克隆性重排。随访：2例患者均未经特殊治疗，生存良好。 结论： NK细胞肠病罕见，生物学行为类似于良性肿瘤，偶可复发；组织学及免疫表型易与NK/T细胞来源的淋巴瘤混淆，结合内镜特点、EBER原位杂交阴性、TCR基因多克隆性重排及良好的预后，可以明确诊断，避免误诊导致过度治疗。.