AIDS合并CMV感染的临床病理特征及其鉴别诊断

摘要/Abstract

摘要：

目的：探讨艾滋病（acquired immune deficiency syndrome，AIDS）合并巨细胞病毒（cytomegalovirus，CMV）感染患者的临床病理特征，及其与其他常见病毒感染及非感染性疾病间的鉴别诊断。方法：2013年至2023年期间，收集上海市公共卫生临床中心病理科经CMV免疫组化染色确诊阳性、人类免疫缺陷病毒（human immunodeficiency virus，HIV）阳性、临床资料完整、符合纳入标准的38例患者，结合组织学形态、特殊染色、原位杂交检查结果及临床资料进行综合分析。结果：患者以发热、恶心呕吐、胃部不适、腹疼腹泻为主，少数病例呕血、便血、咳嗽、咳血。胃肠镜活检获取组织32例，其中送检2个部位以上的10例；淋巴结2例，皮肤、颌下腺、肺、肛周活检各1例。病理形态学显示，胃肠道黏膜糜烂伴急慢性炎为主，3例溃疡形成；淋巴结活检均为淋巴滤泡反应性增生；皮肤、肛周、颌下腺肺穿刺标本均见急慢性炎细胞浸润，局灶凝固性坏死。本研究中有35例患者的上皮细胞、内皮细胞、巨噬细胞、成纤维细胞等体积增大，核内见嗜酸性病毒包涵体，周围有空晕，似“鹰眼”样；另3例患者活检标本（消化道黏膜组织）中未见明确的包涵体结构。免疫组化检测提示，38例CMV均阳性、单纯疱疹病毒（herpes simplex virus，HSV）阴性、潜伏膜蛋白（latent membrane protein，LMP）阴性。特殊染色示，抗酸染色分枝杆菌阳性3例，过碘酸希夫RNA（periodic acid Schiff，PAS）染色和六胺银染色横结肠内查见马尔尼菲篮状菌、胃部白色念珠菌及肺部曲霉菌各1例。EB病毒编码的RNA（Epstein-Barr encoded RNA，EBER）原位杂交检测结果38例均阴性。结论：AIDS合并CMV感染的独特病理学特征是受感染细胞的体积增大，核内出现嗜酸性病毒包涵体，呈“鹰眼”样，结合免疫组化可精准定位CMV在细胞内的表达，同时结合特殊染色和原位杂交技术能为EB病毒、HSV、呼吸道病毒和霍奇金淋巴瘤等病变的鉴别诊断提供有力的证据。

关键词:艾滋病,巨细胞病毒,免疫组化,临床病理

Abstract:

ObjectiveThis study aims to explore the clinicopathologic features of patients with acquired immune deficiency syndrome (AIDS) with cytomegalovirus (CMV) infection, and to analyze the differential diagnosis with other common viral infections and non-infectious diseases.MethodsA total of 38 patients confirmed CMV-positive by immunohistochemical staining, HIV-positive, with complete clinical data and meeting the inclusion criteria were collected from the Department of Pathology, Shanghai Public Health Clinical Center from 2013 to 2023. A comprehensive analysis was conducted based on histological morphology, special staining, in situ hybridization, and clinical data.ResultThe main symptoms of the patients were fever, nausea and vomiting, gastric discomfort, abdominal pain and diarrhea, while a few cases presented with hematemesis, hematochezia, cough, and hemoptysis. Tissue samples from 32 cases were obtained via gastrointestinal endoscopic biopsies, including 10 cases with biopsies from more than 2 sites. 2 cases were from lymph nodes, and 1 case each from skin, submandibular gland, lung, and perianal biopsies. Pathological results showed gastrointestinal mucosal erosion with acute and chronic inflammation, with ulceration forming in 3 cases. Lymph node biopsies showed reactive lymphoid follicle hyperplasia. Acute and chronic inflammatory cell infiltration with focal coagulative necrosis was observed in skin, perianal tissue, submandibular gland, and lung specimens. In this study, 35 patients showed enlargement of epithelial cells, endothelial cells, macrophages, and fibroblasts, with eosinophilic viral inclusions in the nuclei surrounded by a clear halo, resembling an "owl's eye". In the other 3 patients, no definite inclusion bodies were observed in their biopsy specimens (gastrointestinal mucosal tissue). Immunohistochemical testing showed that all 38 cases were positive for CMV and negative for herpes simplex virus (HSV) and latent membrane protein (LMP). Special staining revealed that acid-fast staining was positive forMycobacteriumin 3 cases, while periodic acid Schiff stain and methenamine silver staining detected one case each ofTalaromyces marneffeiin the transverse colon,Candida albicansin the stomach, andAspergillusin the lungs. The results of in situ hybridization for Epstein-Barr encoded RNA (RNAEBER) were negative in all 38 cases.ConclusionThe distinctive pathological feature of AIDS patients with CMV infection is the enlargement of infected cells, with eosinophilic viral inclusions in the nuclei resembling an "owl's eye". Combined with immunohistochemistry, precise locali-zation of CMV expression within the cells can be achieved. Additionally, special staining and in situ hybridization provide robust evidence for the differential diagnosis of lesions caused by EBV, HSV, respiratory viruses, and Hodgkin's lymphoma.

Key words:Acquired immune deficiency syndrome,Cytomegalovirus,Immunohistochemistry,Clinicopathology

中图分类号:

曾东, 宋曙, 杨月香, 许晶晶, 郭文娟, 郑叶, 石雨涵, 冯艳玲. AIDS合并CMV感染的临床病理特征及其鉴别诊断[J]. 诊断学理论与实践, 2025, 24(03): 320-327.

ZENG Dong, SONG Shu, YANG Yuexiang, XU Jingjing, GUO Wenjuan, ZHENG Ye, SHI Yuhan, FENG Yanling. Clinicopathological features and differential diagnosis of AIDS with CMV infection[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(03): 320-327.

图/表6

表1

HIV合并CMV感染患者的临床资料

CMV infection case	Number	Age range	Sex	Clinical manifestation and gastrointestinal endoscopy	CD4⁺T cell（number/μL）	Effect & prognosis
Stomach	10	27-65	Male 9，Female 1	nausea, poor appetite, stomach pain and discomfort mainly, hemateesis in 1 case, fever in 4 cases, gastroscopic congestion and erosion mainly, ulcer in 3 cases, bleeding in 1 case	9-80	5 cases improved, 3 cases showed no obvious therap-eutic effect, 2 cases were lost to follow-up.
Esophagus	5	31-55	Male 4, Female 1	dysphagia with pain in 3 cases, fever in 3 cases, poor appetite with vomiting in 1 case. gastroscopic congestion and edema with erosion, ulcer in 1 case.	5-34	1 cases improved, 3 cases showed no obvious therap-eutic effect, 1 case with death
Intestine	7	17-63	Male 6, female 1	abdominal pain and diarrhea mainly, hematochezia 1 case, fever 4 cases, nausea and vomiting 2 cases. enteroscopic ulcer 1 case, bleeding 1 case, the rest congested and erosion	47-362	2 cases improved,4 cases showed no obvious therap-eutic effect,1 cases were lost to follow-up
More than two parts of the digestive tract	10	24-57	Male 10	nausea and vomiting, loss of appetite, stomach pain, abdominal pain and diarrhea and other combined symptoms predominate, hematochezia 1 case, fever 6 cases. gastroenteroscopic erosion and congestion, ulcer 3 cases, bleeding 1 case	12-130	2 cases improved, 2 cases showed no obvious therap-eutic effect, 2 case with death,4 cases were lost to follow-up
Lung	1	29	Male	cough, hemoptysis, fever	6	death
Skin	1	52	Male	abscess, localized pain	188	improved
Perianal	1	35	Male	purulent secretion, skin lesions	44	improved
Lymph node	2	18-33	Male 2	enlarged lymph nodes	79-125	2 cases improved
Submandibular gland	1	30	Male	localized swelling and pain	14	improved

表1

图1

图2

图3

图4

图5

参考文献12

[1]	ZHAO M, ZHUO C, LI Q, et al. Cytomegalovirus (CMV) infection in HIV/AIDS patients and diagnostic values of CMV-DNA detection across different sample types[J].Ann Palliat Med,2020,9(5):2710-2715.
[2]	中华医学会感染病学分会艾滋病丙型肝炎学组, 中国疾病预防控制中心. 中国艾滋病诊疗指南(2021年版)[J].中国艾滋病性病,2021,27(11):1182-1201.
	Acquired Immunodeficiency Syndrome and Hepatitis C Professional Group, Society of Infectious Diseases, Chinese Medical Association, Chinese Center for Disease Control and Prevention. Chinese guidelines for diagnosis and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome (2021 edition)[J].Chin J AIDS STD,2021,27(11):1182-1201.
[3]	张莉. 艾滋病合并巨细胞病毒感染特点及危险因素的研究[J].国际检验医学杂志,2018,39(3):293-295,299.
	ZHANG L. Characteristics of AIDS complicating cytomegalovirus infection and the risk factors[J].Int J Lab Med,2018,39(3):293-295,299.
[4]	SPIES R, JOUBERT P, CHETTY D, et al. Multisystem cytomegalovirus end-organ disease in a patient with advanced HIV[J].S Afr J Infect Dis,2022,37(1):468. doi:10.4102/sajid.v37i1.468pmid:36483572
[5]	SUN L, CHEN J M, YANG K, et al. Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS[J].Diagn Pathol,2022,17(1):9. doi:10.1186/s13000-022-01193-9pmid:35027044
[6]	FANG M, LIN X, WANG C, et al. High cytomegalovirus viral load is associated with 182-day all-cause mortality in hospitalized people with human immunodeficiency virus[J].Clin Infect Dis,2023,76(7):1266-1275.
[7]	李明远, 徐志凯.医学微生物学[M]. 第3版. 北京: 人民卫生出版社, 2016:383-397.
	LI M Y, XU Z K.Medical microbiology[M]. 3rd ed. Beijing: People's Medical Publishing House,2016:383-397.
[8]	姜支农, 石雪迎, 周炜洵, 等. 活检标本炎症性肠病规范化病理诊断建议[J].中华病理学杂志,2019,48(2):81-86.
	JIANG Z N, SHI X Y, ZHOU W X, et al. Proposal of standardized pathological diagnosis for inflammatory bowel disease through biopsies[J].Chin J Pathol,2019,48(2):81-86.
[9]	GRABAR S, LE MOING V, GOUJARD C, et al. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy[J].Ann Intern Med,2000,133(6):401-410. doi:10.7326/0003-4819-133-6-200009190-00007pmid:10975957
[10]	AFFANDI J S, MONTGOMERY J, BRUNT S J, et al. The immunological footprint of CMV in HIV-1 patients stable on long-term ART[J].Immun Ageing,2015,12:14.
[11]	韦林华, 张彤, 吴锋耀, 等. HAART时代HIV/AIDS住院病人机会性感染疾病谱分析[J].中国艾滋病性病,2018,24(5):454-457.
	WEI L H, ZHANG T, WU F Y, et al. Analysis of the opportunistic infections′spectrum in hospitalized patients with HIV/AIDS in the era of HAART[J].Chin J AIDS STD,2018,24(5):454-457.
[12]	陈永宏. HAART治疗对AIDS机会性感染的影响研究[J].河北医药,2016,38(2):218-220.
	CHEN Y H. Effect of HAART treatment on AIDS opportunistic infection[J].Hebei Med J,2016,38(2):218-220.

[1]	周晓蝶, 戚荣鑫, 王璇, 余波, 王建军, 石群立, 饶秋, 鲍炜.尿路上皮癌PD-L1、AR及P53表达及其与临床预后相关性[J]. 诊断学理论与实践, 2025, 24(03): 286-292.
[2]	魏静静, 银浩强, 王延文, 张晓云.以微囊状形态为主的乳腺分泌性癌2例报告及文献复习[J]. 诊断学理论与实践, 2025, 24(03): 349-354.
[3]	龚静青, 曹端荣, 庄义欣, 邱立, 李晓鸣.双表型鼻腔鼻窦肉瘤1例临床病理分析[J]. 诊断学理论与实践, 2025, 24(01): 100-105.
[4]	阮淼, 笪倩, 许海敏, 董磊, 费晓春.HER2低表达乳腺癌临床病理学特征及预后研究[J]. 诊断学理论与实践, 2024, 23(05): 500-508.
[5]	王玉蓉, 汪元元, 翁海燕.胃肠道平滑肌肉瘤临床病理分析3例报告[J]. 诊断学理论与实践, 2024, 23(05): 537-541.
[6]	倪亚平, 陈一峰, 杨晓群, 陈晓炎.原发性肺腺癌伴肠母细胞分化2例临床病理及预后分析[J]. 诊断学理论与实践, 2024, 23(03): 324-329.
[7]	金哲, 唐峰, 杜尊国.成人结肠重复畸形伴上皮低级别异型增生1例报道[J]. 诊断学理论与实践, 2023, 22(04): 385-388.
[8]	周晓蝶, 陈巍魏, 余波, 王璇, 王建军, 石群立, 饶秋, 鲍炜.尿路上皮癌的临床病理学特征[J]. 诊断学理论与实践, 2023, 22(03): 292-299.
[9]	许建昆, 周露婷, 张文净, 许海敏, 王朝夫.CA9在透明细胞肾细胞癌预后评估中的价值[J]. 诊断学理论与实践, 2023, 22(01): 37-43.
[10]	谢吻, 梁怀予, 董磊, 袁菲, 王朝夫, 郭滟.胰腺导管腺癌重要驱动基因突变与临床病理特征、预后间相关性的分析[J]. 诊断学理论与实践, 2022, 21(05): 581-587.
[11]	陈志敏, 何浩岚.艾滋病合并马尔尼菲篮状菌病的诊治现状[J]. 诊断学理论与实践, 2022, 21(04): 425-430.
[12]	沈银忠.《人类免疫缺陷病毒感染/艾滋病合并结核分枝杆菌感染诊治专家共识》解读[J]. 诊断学理论与实践, 2022, 21(04): 431-436.
[13]	陈志敏, 刘波, 何浩岚, 何耀祖, 冯理智, 刘新华, 张坚生, 蔡卫平, 李凌华.133例艾滋病合并马尔尼菲篮状菌病死亡病例分析[J]. 诊断学理论与实践, 2022, 21(04): 444-449.
[14]	陈宏, 沈银忠.人类免疫缺陷病毒感染/艾滋病合并结核病的诊治进展[J]. 诊断学理论与实践, 2022, 21(04): 530-534.
[15]	顾怡瑾, 李安琪, 董磊, 许海敏, 申霞, 谢嘉玲, 袁菲, 王朝夫.原发、复发及转移胃肠道间质瘤KIT及PDGFRA突变与临床病理特征间的关系[J]. 诊断学理论与实践, 2021, 20(03): 257-264.