IgG4-related pulmonary pseudotumor and pleuritis mimicking lung cancer and asbestos plaque: A case report

Abstract

We report the case of a 70-year-old man who presented with a two-month history of cough. He had a history of asbestos exposure. Chest imaging revealed a mass on the right upper lobe, bilateral hilar and mediastinal lymphadenopathies, bilateral pleural thickening, and partial calcification of the right pleura. Lung cancer and asbestos-related pleural disease were suspected initially. However, neither transbronchial lung biopsy nor computed tomography-guided percutaneous needle lung biopsy demonstrated evidence of malignancy. Subsequent video-assisted thoracoscopic surgery revealed storiform fibrosis, dense lymphoplasmacytic infiltration, and numerous IgG4-positive plasma cells in the lung mass along with asbestos bodies. The pleura exhibited similar histopathological features. The patient's elevated serum IgG4 levels, in combination with these histological features, fulfilled both the 2019 ACR/EULAR classification criteria and the Japanese comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD). The patient was treated with oral prednisolone, resulting in resolution of the lung mass, symptom improvement, and a decline in serum IgG4 levels. IgG4-RD is an immune-mediated condition characterised by T helper type 2 cell activation, elevated serum IgE levels, and regulatory T cell (Treg) dysfunction. The development of Treg dysfunction after asbestos exposure suggests a potential mechanistic link between asbestos and the pathogenesis of IgG4-RD. This case highlights the diagnostic challenges posed by IgG4-related lung disease, which can mimic malignancy and asbestos-related pathology, underscoring the importance of biopsy for accurate diagnosis. It also suggests a possible association between asbestos exposure and IgG4-RD development.

Highlights

• •An asbestos-exposed patient had a lung mass, lymphadenopathy, and pleural lesions.
• •Lung cancer and asbestos-related pleural disease were initially suspected.
• •Transbronchial and computed tomography-guided lung biopsies were inconclusive.
• •Thoracoscopic lung biopsy revealed IgG4-related inflammatory pseudotumour.
• •This case suggests an association between asbestos exposure and IgG4-RD development.

1. Introduction

Pulmonary tumours are common in clinical practice. Given the prevalence and clinical impact of lung cancer, excluding malignancy is essential when a pulmonary mass lesion is detected. Among the various differential diagnoses is inflammatory pseudotumour caused by IgG4-related disease (IgG4-RD), a chronic systemic fibro-inflammatory disorder characterised by infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated serum IgG4 levels [1,2]. Thoracic involvement is reported in approximately 50 % of cases, presenting as mediastinal lymphadenopathy, pulmonary consolidation, pericarditis, or pleural disease [3,4]. Although generally recognised as systemic disorders, isolated thoracic cases have been reported, and their diverse intrathoracic manifestations can mimic those of malignant diseases, particularly lung cancer [5,6]. Establishing a histopathological diagnosis can be challenging, with approximately 80 % of cases requiring video-assisted thoracoscopic surgery (VATS) biopsy [7], underscoring the importance of collaboration between thoracic surgeons and pathologists.

We report a rare case of IgG4-related pulmonary inflammatory pseudotumour and pleuritis in a patient with a history of asbestos exposure, initially suspected to be malignant based on imaging findings and definitively diagnosed by surgical biopsy performed for differential diagnosis.

2. Case presentation

A 70-year-old man visited a local clinic with a two-month history of cough. Chest computed tomography (CT) revealed a mass in the right upper lobe, raising the suspicion of primary lung cancer. He was referred to our hospital for further evaluation.

His medical history included atrial fibrillation and hypertension, and he was taking warfarin, amlodipine, valsartan, and hydrochlorothiazide. He had a history of smoking 20 cigarettes per day for 30 years. The patient had worked at a construction site with documented asbestos exposure for 30 years until approximately 10 years ago.

At the initial visit to our hospital, the patient's vital signs were as follows: body temperature, 36.4 °C; blood pressure, 149/89 mmHg; heart rate, 102 beats per min; respiratory rate, 12 breaths per min; and oxygen saturation, 97 % on room air. Physical examination revealed no conjunctival pallor, icterus of the bulbar conjunctiva, lymphadenopathy, or swelling of the salivary glands. Cardiac auscultation revealed an irregular rhythm without murmurs. Lung auscultation was clear bilaterally. The abdomen was soft and nontender. No skin lesions, digital clubbing, peripheral oedema, joint swelling, or muscle weakness were observed.

Laboratory tests revealed the following: white blood cell count, 6700/μL; eosinophil, 120/μL; haemoglobin, 17.1 g/dL; platelet count, 280,000/μL; C-reactive protein, 0.44 mg/dL; total protein, 8.2 g/dL; albumin, 4.3 g/dL, and Krebs von den Lungen-6, 236 U/mL. Serum electrolytes, amylase, renal function, and liver function biomarker levels were all within normal limits, with no evidence of proteinuria or haematuria. Tumour markers, including interleukin-2 receptor, carcinoembryonic antigen, carbohydrate antigen 19-9, squamous cell carcinoma antigen, cytokeratin 19 fragment, neuron-specific enolase, progastrin-releasing peptide, and soluble mesothelin-related peptide, were within the reference ranges. Tests for autoantibodies, including myeloperoxidase-antineutrophil cytoplasmic antibody, proteinase 3-antineutrophil cytoplasmic antibody, antinuclear antibody, and anti-SS-A antibody, were all negative. The levels of complement components, C3 and C4, were within normal limits. Tests for infections, including T-SPOT, β-D-glucan, and Aspergillus antigen, were negative.

Chest radiography revealed a mass-like lesion in the middle lung field (Fig. 1). CT revealed a spiculated 4 × 4 cm mass-like lesion in the right upper lobe extending beyond the interlobar pleura into the middle and lower lobes (Fig. 2A). Bilateral hilar lymphadenopathy, bilateral pleural thickening, and partial calcification of the right pleura were observed (Fig. 2B and C). Mediastinal lymph node enlargement was present but is not clearly demonstrated in the representative images shown. No lesions were observed in the lacrimal glands, salivary glands, bile ducts, pancreas, kidneys, or the retroperitoneum. Positron emission tomography-CT (PET-CT) revealed a right upper lobe mass-like lesion with increased fluorodeoxyglucose (FDG) uptake and a maximum standardised uptake value (SUVmax) of 6.0. Increased FDG uptake was also observed in the bilateral hilar and mediastinal lymph nodes and pleura (Fig. 3). No increase in FDG uptake was observed in organs outside the thoracic region.

Fig. 1.

Chest radiograph showing a mass-like lesion in the right middle lung field.

Fig. 2.

Contrast-enhanced chest computed tomography (CT). Lung window image (A) shows a spiculated mass-like lesion measuring approximately 4 cm in the right upper lobe, extending into the middle and lower lobes. Mediastinal window images (B, C) show a mass-like lesion in the right lung, bilateral pleural thickening, partial calcification of the right pleura, and bilateral hilar lymphadenopathy.

Fig. 3.

Positron emission tomography–computed tomography (PET-CT) showing increased fluorodeoxyglucose (FDG) uptake in the mass-like lesion in the right upper lobe, bilateral hilar and mediastinal lymph nodes, and the right pleura. Increased FDG uptake was also observed in the left pleura (not shown).

Given the clinical suspicion of primary lung cancer, both transbronchial lung biopsy and CT-guided percutaneous needle biopsy were performed; neither procedure yielded malignant findings. Considering the findings from a subsequent PET-CT scan, the possibility of primary lung cancer with regional lymph node metastases remained, and pleural lesions suggestive of pleural plaques raised additional concerns regarding carcinomatous pleuritis or malignant pleural mesothelioma. Accordingly, VATS was performed for diagnostic purposes, and biopsies of the right pulmonary mass-like lesion and pleura were obtained.

Histopathological examination of the pulmonary mass-like lesion with hematoxylin and eosin staining revealed storiform fibrosis and lymphoplasmacytic infiltration (Fig. 4A), along with scattered asbestos bodies (Fig. 4B). No malignant findings were identified. Immunohistochemical staining showed that IgG4-positive plasma cells accounted for more than 40 % of the total IgG-positive plasma cells, with more than 10 IgG4-positive plasma cells observed per high-power field (HPF) (Fig. 4C and D). Fig. 4C shows IgG immunostaining, while Fig. 4D shows IgG4 immunostaining. Examination of the pleura demonstrated typical plaques as well as histological features resembling those of the pulmonary tumor, consistent with IgG4-related pleuritis.

Fig. 4.

Histological findings of lung tissue obtained via video-assisted thoracoscopic surgery. Hematoxylin and eosin (H&E) staining at ×50 shows storiform fibrosis with lymphoplasmacytic infiltration (A). H&E staining at ×400 highlights an asbestos body (B). IgG immunostaining at ×100 (C). IgG4 immunostaining at ×100 demonstrates >40% IgG4+/IgG+ plasma cells (>10 per high-power field) (D).

Additional serological testing revealed elevated immunoglobulin G and IgG4 levels (2154 mg/dL and 501 mg/dL, respectively). The patient fulfilled the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD [8], with a total score of 33 points (histopathological findings, 13 points; immunohistochemical staining, 14 points; elevated serum IgG4 levels, 6 points). Furthermore, all three components of the comprehensive diagnostic criteria for IgG4-RD established in Japan [9] were met: pulmonary pseudotumour and pleuritis, serum IgG4 levels of 501 mg/dL, and lymphoplasmacytic infiltration with fibrosis. IgG4-positive plasma cells accounted for more than 40 % of the total IgG-positive plasma cells, with more than 10 IgG4-positive plasma cells observed per HPF. Based on these findings, the patient was diagnosed with IgG4-related inflammatory pulmonary pseudotumour and pleuritis.

Treatment was initiated with oral prednisolone at a dose of 30 mg/day (0.5 mg/kg). Four months after the start of treatment, the patient's cough improved, and the prednisolone dose was successfully tapered to 12.5 mg/day. At this time, the residual pulmonary mass had completely resolved, the pleural lesions had thinned slightly, and the hilar and mediastinal lymph nodes had mildly decreased in size. Serum IgG4 levels normalised to 113 mg/dL. Eighteen months after treatment initiation, the prednisolone dose was tapered to 7 mg/day, and the patient remained clinically stable. Along with further tapering of the corticosteroids, careful long-term outpatient follow-up is ongoing, considering the potential development of malignancy due to the patient's history of asbestos exposure.

3. Discussion

This case report describes a patient with a history of asbestos exposure who presented with a right lung mass-like lesion, bilateral hilar and mediastinal lymphadenopathy, and pleural lesions. Initial evaluations, including transbronchial and CT-guided lung biopsies, were inconclusive. A definitive diagnosis was made through thoracoscopic lung biopsy, revealing IgG4-related inflammatory pseudotumour and IgG4-related pleuritis. After glucocorticoid treatment, the pulmonary lesions resolved completely, and the pleural lesions improved.

IgG4-RD is a fibro-inflammatory condition characterised by IgG4-positive plasma cell infiltration and fibrosis in multiple organs. In the lungs, it can mimic malignancy, with localised pseudotumours resembling primary lung cancer on imaging and even demonstrating high uptake on PET-CT [10], making surgical biopsy often essential for accurate diagnosis. IgG4-related pleuritis may resemble pleural plaques or malignant pleural disease, complicating diagnosis in patients with asbestos exposure. Unlike benign calcified plaques, IgG4-related pleuritis shows active inflammation and fibrosis, requiring histopathological confirmation.

The pathogenesis of IgG4-RD remains unclear; however, both genetic predisposition and chronic environmental exposure may contribute to abnormal immune activation. Occupational exposure, particularly to mineral dust and asbestos, is strongly associated with this disease. Large case–control studies have identified asbestos as a risk factor for idiopathic retroperitoneal fibrosis, which has later been classified as IgG4-RD, with odds ratios ranging from 2.46 to 7.07 [11]. Mechanistically, a Th2-dominant immune response and regulatory T cell dysfunction appear central, and asbestos exposure promotes both processes, potentially triggering IgG4-RD [12].

In this case, the patient was treated with glucocorticoid monotherapy. However, regarding the treatment of IgG4-RD, Stone et al. reported that the anti-CD19 B cell-targeted therapy inebilizumab reduced the risk of relapse and increased the likelihood of achieving relapse-free complete remission at one year in the MITIGATE trial [13]. These findings suggest that CD19-targeted B cell–depleting therapies may be considered as potential treatment options for IgG4-RD.

This case supports a possible link between asbestos exposure and IgG4-related respiratory disease while underscoring the importance of histological diagnosis and multidisciplinary evaluation to distinguish it from malignancies with similar clinical and imaging presentations. Further studies should clarify the role of asbestos in the development of IgG4-RD.

CRediT authorship contribution statement

Riko Kamada: Conceptualization, Investigation, Writing – original draft, Data curation, Visualization. Makoto Hibino: Investigation, Supervision, Writing – review & editing, Conceptualization. Hikari Higa: Investigation, Writing – review & editing. Shigehiro Watanabe: Investigation, Writing – review & editing. Kazunari Maeda: Investigation, Writing – review & editing. Shigeto Horiuchi: Investigation, Writing – review & editing. Noriyoshi Ishikawa: Investigation, Writing – review & editing. Tetsuri Kondo: Conceptualization, Investigation, Writing – review & editing.

Patient consent

The patient presented in this report consented to the submission of the paper.

Patient's perspective

I have a history of smoking, and at first I was told that lung cancer was suspected, so the diagnosis of IgG4-related disease came as a surprise to me. It was challenging to undergo multiple procedures like the bronchoscopy and CT-guided biopsy without a diagnosis. I'm so glad the surgical biopsy finally provided a clear answer. This perspective was originally shared in Japanese during an outpatient visit and was translated into English by the authors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Glossary

IgG4-RD

IgG4-related disease

Treg

T cell

VATS

video-assisted thoracoscopic surgery

CT

chest computed tomography

PET

positron emission tomography

FDG

fluorodeoxyglucose

SUV

standardised uptake value

HPF

high-power field