17例误诊为IgG4相关疾病患者的临床特点及误诊原因分析

doi:10.19723/j.issn.1671-167X.2019.06.008

摘要/Abstract

摘要：

目的总结误诊为IgG4相关疾病患者的临床特征,寻找误诊原因,提高对该病的认识。方法回顾性分析北京大学人民医院收治的17例在院外误诊为IgG4相关疾病患者的一般资料、临床表现、实验室检查结果和病理特征。结果 17例患者中男性9例,女性8例,中位年龄45岁,自发病到确诊的中位时间为12个月,大多数患者的首诊科室不是风湿免疫科。6例最终诊断为淋巴增殖性疾病,4例为自身免疫性疾病,2例为感染性疾病,Rosai Doffman病、硬纤维瘤病、口底高分化黏液表皮样癌、嗜酸粒细胞增多综合征、过敏性鼻炎合并哮喘各1例。有14例患者出现IgG4相关疾病的典型部位受累,主要包括6例腮腺、2例颌下腺、3例胰腺、2例腹膜后病变。10例患者血清IgG4升高,7例血清IgG4/IgG的值大于10%,7例IgE升高,4例补体降低,3例嗜酸性粒细胞比例升高。在15例患者的病理检查结果中,10例患者可见淋巴浆细胞浸润,5例存在IgG4 ⁺浆细胞,4例IgG4 ⁺浆细胞与IgG ⁺浆细胞的比值小于40%,1例大于40%,但均未见到典型的席纹状纤维化和闭塞性静脉炎。结论多种疾病均可出现类似IgG4相关疾病的典型部位受累、血清IgG4升高,甚至组织病理也可表现为IgG4 ⁺浆细胞浸润,临床医生要注意鉴别,综合评估患者的临床表现、实验室检查结果,及时进行组织病理检查,甚至重复多次病理检查以明确诊断。

关键词: IgG4相关疾病, 淋巴组织增殖性疾病, 误诊

Abstract:

Objective: To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease.Methods: The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed.Results: Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients’ initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4 ⁺ plasma cells were present in 5 patients, the ratio of IgG4 ⁺ plasma cells to IgG ⁺ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis.Conclusion: A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be cha-racterized by pathological IgG4 ⁺ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient’s clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

Key words: IgG4-related disease, Lymphoproliferative disease, Diagnostic errors

中图分类号:

R593.2

王子乔,刘燕鹰,张霞,刘田,任立敏,沈丹华,王屹,栗占国. 17例误诊为IgG4相关疾病患者的临床特点及误诊原因分析[J]. 北京大学学报（医学版）, 2019, 51(6): 1025-1031.

Zi-qiao WANG,Yan-ying LIU,Xia ZHANG,Tian LIU,Li-min REN,Dan-hua SHEN,Yi WANG,Zhan-guo LI. Analysis of the clinical features and misdiagnosis reasons of 17 patients misdiagnosed with IgG4-related disease[J]. Journal of Peking University(Health Sciences), 2019, 51(6): 1025-1031.

图/表 4

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表3

误诊为IgG4-RD患者的病理特征"

Case	Biopsy site	N/S	SF	OP	IgG4⁺plasma cells/HP	IgG4⁺/IgG⁺ plasma cell	Pathological features	Pathological diagnosis
1	Retroperitoneum	S	-	-	30	50%	Large allotypic lymphocytes infiltrate diffusely, CD19(+), CD20(+), CD79a(+)	Non-Hodgkin’s lymphoma, B-cell derived (diffuse large B-cell lymphoma)
2	Lymph node	S	-	-	-	-	Follicular growth of central cells and centroblasts, CD19(+), CD20(+), CD10(+), Bcl-2(+), Bcl-6(+)	Non-Hodgkin’s lymphoma, B-cell derived lymphoma (follicular lymphoma)
3	Submandibular gland	S	-	-	-	-	The central cell-like cells invade the glandular epithelium, CD20(+), CD79a(+), CD5(-), CD10(-), CD23(-), cyclinD1(-)	Non-Hodgkin’s lymphoma, B-cell derived lymphoma (mucosa-asso-ciated lymphoid tissue lymphoma)
4	Parotid gland	N	-	-	-	-	Allotypic lymphocytes infiltrate the marginal area around the lymphoid follicle, CD20(+), CD79a(+), CD10(-), CD23(-)	Non-Hodgkin’s lymphoma, B-cell derived (peripheral B-cell lymphoma)
5	Parotid gland	N	-	-	-	-	The central cell-like cells invade the glandular epithelium, CD20(+), CD79a(+), CD5(-), CD10(-), CD23(-), cyclinD1(-)	Non-Hodgkin’s lymphoma, B-cell derived lymphoma (mucosa-asso-ciated lymphoid tissue lymphoma)
6	Retroperitoneal lymph node	N	-	-	100	<40%	Lymphoid hyperplasia with numerous plasma cell lamellar infiltration, CD20(+), CD79a(+), CD3(+), CD38(+), CD138(+)	Castleman disease
7	ND	ND	ND	ND	ND	ND	ND	ND
8	Parotid gland	S	-	-	-	-	Lymphocyte infiltration	Chronic mumps
9	Lacrimal gland	S	-	-	>50	>30%	Glands atrophy, fibrous hyperplasia, lymphocyte plasma cell infiltration and lymphoid follicular formation	Lymphoepithelial lacrimal adenitis
10	Pancreas	S	-	-	-	-	Lymphocyte plasma cell infiltration	Pancreatitis
11	Bile duct	S	-	-	-	-	Multiple granulomatous lesions	Parasidiosporidium biliary tract infection
12	Lung	S	-	-	30	<40%	Dilated bronchial tube cavity, damaged tube wall, fibrinous necrosis and fibrous hyperplasia accompanied by patchy lymphocyte plasma cells and neutrophils infiltration, and abscess formation	Bronchiectasis with infection
13	Parotid gland	S	-	-	>50	<40%	Macrophage penetration	Rosai Doffman disease
14	Neck	N	-	-	-	-	Proliferate fibroblasts	Desmofibromatosis
15	Sublingual gland	N	-	-	-	-	Numerous clusters of typical mucinous cells and some epidermoid cells	Highly differentiated mucoepidermoid carcinoma
16	Myocardium	N	-	-	-	-	Infiltration of eosinophilic cells in car-diac tissue	Hypereosinophilic syndrome
17	ND	ND	ND	ND	ND	ND	ND	ND

表3

图1

参考文献 13

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Case no.	Gender	Age/ years	Time from onset to diagnosis/ month	Initial admission department	Mainly affected organs	Final diagnosis
1	Male	66	10	Urology	Retroperitoneal	Non-Hodgkin’s lymphoma
2	Male	64	4	Gastroenterology	Pancrea, lymph node	Non-Hodgkin’s lymphoma
3	Male	59	96	Rheumatology & Immunology	Submandibular gland, parotid gland	Non-Hodgkin’s lymphoma
4	Male	75	48	Rheumatology & Immunology	Parotid gland, submandibular gland, periorbital	Non-Hodgkin’s lymphoma
5	Female	61	72	Stomatology	Parotid gland	Non-Hodgkin’s lymphoma
6	Male	16	29	Hematology	Retroperitoneal	Castleman disease
7	Female	31	6	Rheumatology & Immunology	Parotid gland	Sj?gren’s syndrome
8	Female	45	60	Stomatology	Parotid gland	Sj?gren’s syndrome
9	Male	10	5	Ophthalmology	Lacrimal gland, extraocular muscle, auricle	ANCA associated vasculitis
10	Female	37	15	General surgery	Pancreas, gastrointestinal tract	Type 2 autoimmune pancreatitis
11	Male	31	9	Gastroenterology	Pancreas, bile duct	Biliary tract fungal infection
12	Male	44	1	Thoracic surgery	Lung	Bronchiectasis with infection
13	Male	28	48	Head and neck surgery	Parotid gland, chest wall	Rosai Doffman disease
14	Female	56	24	Head and neck surgery	Neck	Desmofibromatosis
15	Female	66	3	Stomatology	Sublingual gland	Highly differentiated mucoepidermoid carcinoma of the bottom of the mouth
16	Female	27	7	Gastroenterology	Myocardium, gastrointestinal tract	Hypereosinophilic syndrome
17	Female	45	12	Pneumology	Trachea, nasal	Asthma and allergic rhinitis

Case	EO%↑	IgG4/ (g/L)	IgG/ (g/L)	IgG4/ IgG	IgE/ (IU/mL)	C3↓	C4↓	Kappa light chain↑	Lambda light chain↑	Autoantibodies
1	No	1.053	11.7	9.0%	109.2	No	No	No	No	-
2	No	3.070	10.2	30.1%	251.7	Yes	No	No	No	-
3	No	0.006	9.2	0.1%	16.0	Yes	Yes	No	No	-
4	No	0.213	101.0	0.2%	25.4	Yes	Yes	Yes	No	-
5	No	0.545	12.6	4.3%	3.4	No	Yes	No	No	ANA(+)
6	No	4.540	34.2	13.3%	129.5	No	No	Yes	Yes	ANA(+), RF(+)
7	No	2.230	20.0	11.2%	ND	No	No	ND	ND	anti-SSA(+), anti-Ro-52(+), RF(+)
8	No	1.822	21.4	8.5%	ND	No	No	ND	ND	ANA(+), anti-SSA(+), anti-SSB(+), anti-Ro-52(+)
9	No	1.476	ND	ND	ND	No	No	ND	ND	MPO-ANCA(+)
10	No	0.058	14.6	0.3%	290.4	No	No	ND	ND	-
11	Yes	12.600	17.3	72.8%	2 153.0	No	No	ND	ND	-
12	No	0.501	12.5	4.0%	32.6	No	No	ND	ND	-
13	No	2.660	13.6	19.6%	22.5	No	No	ND	ND	-
14	No	2.360	18.8	12.6%	ND	No	No	ND	ND	ANA(+)
15	No	0.731	15.3	4.8%	54.5	No	No	ND	ND	ANA(+)
16	Yes	3.380	ND	ND	340.0	No	No	ND	ND	ANA(+)
17	Yes	3.520	15.1	23.3%	137.6	No	No	ND	ND	AECA(+)