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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (6): 1025-1031. doi: 10.19723/j.issn.1671-167X.2019.06.008

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Analysis of the clinical features and misdiagnosis reasons of 17 patients misdiagnosed with IgG4-related disease

Zi-qiao WANG1,Yan-ying LIU1,△(),Xia ZHANG1,Tian LIU1,Li-min REN1,Dan-hua SHEN2,Yi WANG3,Zhan-guo LI1   

  1. 1. Department of Rheumatology & Immunology, Beijing 100044, China
    2. Department of Pathology, Beijing 100044, China
    3. Department of Radiology, Peking University People’s Hospital, Beijing 100044, China
  • Received:2019-08-02 Online:2019-12-18 Published:2019-12-19
  • Contact: Yan-ying LIU E-mail:liuyanying20030801@msn.com
  • Supported by:
    Supported by the National Key R&D Program of China(2017YFA01058022);the Peking University People’s Hospital Research and Development Funds(RDH2017-02)

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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

CLC Number: 

  • R593.2

Table 1

General information and clinical characteristics of patients misdiagnosed as IgG4-RD"

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

Table 2

Laboratory characteristics of patients misdiagnosed as IgG4-RD"

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(+)

Table 3

Pathological features of patients misdiagnosed as IgG4-RD"

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

Figure 1

Histopathologic features of IgG4-RD (HE ×100) A, an irregularly whorled pattern of fibrosis (storiform fibrosis); B, the vein which is completely obliterated by aggregated inflammatory cell infiltration (obliterative phlebitis)."

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