感染肠道病毒71型婴儿5例尸检组织病理分析

Pathology of enterovirus 71 infection： an autopsy study of 5 cases

目的探讨感染肠道病毒71型（EV71）重症婴幼儿的临床病理特点。方法对5例死亡患者尸体系统解剖，获得脑、肠、心、肝、脾、肺、肾、胰腺和淋巴结等脏器，组织常规HE染色，3例行免疫组织化学EnVision法以标记脑和肺组织细胞，光镜下观察。结果4例中枢神经系统病变明显，即以脑干和颈髓上段为主的多部位脑炎和脊髓炎，表现为神经元变性和坏死、噬神经现象、血管套、脑实质内单核巨噬细胞／小胶质细胞弥漫或结节状增生，伴少量淋巴细胞浸润；脑水肿伴小脑扁桃体疝形成；有脑膜炎和脊膜炎病变；呼吸系统表现为肺淤血和不同程度的神经源性肺水肿及肺出血；消化系统黏膜上皮未见病变，回肠末端黏膜固有层和黏膜下层内淋巴组织增生显著，淋巴滤泡内细胞凋亡严重。另1例中枢神经系统仅见脑水肿伴轻度脑膜炎；呼吸系统见肺泡间隔增宽伴淋巴、单核细胞浸润，部分肺泡上皮增生，广泛肺透明膜形成；消化系统肠黏膜未见明显病变，肠黏膜固有层内淋巴组织增生。5例淋巴造血系统表现为肺门淋巴结和肠系膜淋巴结肿大，其内淋巴滤泡扩大，但生发中心凋亡明显，伴有不同程度的中性粒细胞浸润。脾脏脾小结内各类细胞减少。5例心脏、肝脏和肾脏组织学上均无明显病变。结论感染EV71重症病例的病变主要累及中枢神经系统，呼吸系统为继发性病变，此类患儿主要因脑水肿致脑疝形成或肺水肿致呼吸循环衰竭死亡。个别病例主要表现为呼吸系统病变，中枢神经系统病变不典型。

Objective To study the clinicopathologic features of fatal enterovirns 71 （ EV71 ） infection. Methods Autopsy was performed in 5 neonates died of EV71 infection. Tissue samples from major organs were collected, formalin-fixed and examined under light microscopy. Immunohistochemical study was carried out in selected examples. Results Four of the 5 cases showed predominant changes in central nervous system, with encephalitis and encephalomyelitis identified mainly in brainstem and upper cervical spinal cord. Histologic findings included neuronal degeneration and necrosis, neuronophagia, perivascular cuffing and diffuse or nodular hyperplasia of macrophages/microglia. Cerebral edema, brain herniation and aseptic meningitis were also noted. The lungs showed mainly pulmonary congestion, neurogenic pulmonary edema and focal hemorrhage. There were minimal changes in the intestinal epithelium. The intestinal lymphoid tissue however was hyperplastic and associated with apoptosis of follicular center cells. The remaining case had cerebral edema and mild meningitis. The lung alveolar septa were thickened with lymphocytic infiltrates. Some alveolar cells were hyperplastic and associated with diffuse hyaline membrane formation. No specific abnormalities were identified in gastrointestinal tract. In all the 5 cases studied, there was enlargement of lung hilar and mesenteric lymph nodes, coupled with apoptosis of follicular center cells. In general, no significant pathologic changes were demonstrated in heart, liver and kidneys. Conclusions In fatal EV71 infection, the major pathologic changes lie in the central nervous system. The pulmonary lesions are mainly secondary in nature. The usual cause of death is cerebral edema complicated by brain herniation and pulmonary edema. It is also noteworthy that some cases show only lung damages, without classic neurologic changes.