Clinicopathological characteristics of IgG4-related lung disease

Abstract

Background Immunoglobulin G4-related lung disease (IgG4-RLD) is a rare entity. We retrospectively analyzed the clinical and histopathological characteristics of patients with pathologically confirmed IgG4-RLD to improve the diagnosis rate and reduce the risk of misdiagnosis. Methods We screened the pathological reports of 4838 patients with pulmonary surgery and/or biopsy specimens from April 2017 to April 2021 at Sun Yat-Sen Memorial Hospital affiliated with Sun Yat-Sen University, and specimens from 65 patients with suspected IgG4-RLD were subjected to immunohistochemical staining for IgG4 and IgG. Finally, 10 patients with definite IgG4-RLD that was pathologically confirmed were enrolled and analyzed. Results The incidence of pathologically confirmed IgG4-RLD was 0.2% (10/4838). The ten patients had an average age of 59.7 years at diagnosis, and the male-to-female ratio was 9:1. The initial clinical manifestations were nonspecific, and cough was the most common symptom (4/10). More than one organ was involved in most patients (8/10), and mediastinal/hilar lymph node involvement was often observed (7/10). Serum IgG4 was analyzed in 6 patients and found to be elevated. Serum tumor marker levels were within the normal range or were slightly elevated. Computed tomography (CT) of the chest and/or 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging revealed that 5 patients had a mixed type, 3 patients had the solid nodular type, and 2 patients had the bronchovascular type. All pulmonary masses and large nodules with solid patterns had spiculated margins and inhomogeneous enhancement with or without pleural indentation and a lobulated appearance. Abundant lymphoplasmacytic cell infiltration and fibrosis were observed in all patients. The expression of IgG4 and IgG was upregulated in the pulmonary sections. Seven patients were treated with glucocorticoids with or without additional immunosuppressants and responded well. Conclusions The results of our study suggest that multiple imaging findings, an elevated serum IgG4 concentration, and no significant increase in serum tumor biomarkers could provide diagnostic support for IgG4-RLD, especially for isolated IgG4-RLD or IgG4-RLD that includes other organ involvement that does not aid in establishing the diagnosis.

Chest CT Findings for IgG4-related Disease

“…The clinical and imaging manifestations of IgG4-RLD were nonspeci c, and the symptoms depended on the lesion site, including cough, chest pain, dyspnea and hemoptysis. In addition, there may be low fever and weight loss, and about half of the patients had no respiratory symptoms (13)(14)(15)(16)(17). In this study, 9 (13.43%) patients were admitted due to lung symptoms, and the main symptoms were cough, expectoration, chest pain, asthma and dyspnea; 58 (86.57%) patients were diagnosed with other organs as the rst involved organ, and all patients had two or more organs involved at the time of diagnosis.…”

IgG4-related disease - a clinical case

“…The possible involvement of multiple organs and systems is the reason for the multidisciplinary approach in this disease. Among the most frequent pathological findings are deviations in the function of the lacrimal and salivary glands, kidneys, lungs, aorta, pancreas, hepatobiliary duct, lymph nodes, as well as retroperitoneal fibrosis [1,2,4,5,6,7,11,12].…”

“…Initially, clinical manifestations of pulmonary involvement are nonspecific and most commonly include cough, shortness of breath, chest or back pain, hemoptysis, low-grade fever, weight loss [2,3,8,12,13,14]. Patients may be asymptomatic, and lung changes (nodules, lymphadenopathy, septal thickening and fibrosis) can be detected on imaging of the chest as an incidental finding [2,3,12,14].…”

“…Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease presenting with tumor-like changes in one or more organs, caused by tissue infiltration of IgG4 plasma cells, serum IgG4 level above 1.35 g/l and subsequent fibrosis [1,2,3,4,5,6,7].…”

Thoracic manifestations of IgG4‐related disease

“…Regarding the lungs, histopathology of lesions shows diffuse lymphoplasmacytic infiltration, obliterative vascular changes and fibrosis with occasional eosinophilic infiltration. 71 The most frequent histopathological pattern is a lymphangitic distribution of inflammatory infiltrates rich in plasma cells. Several specificities should be noted.…”