A 73-year-old male presented with general weakness and dyspnea for 1 month, and 3 kg of weight loss over 5 months. He had a past history of occupational exposure to carbon disulfide for 20 years and a history of right hemicolectomy due to colon cancer 25 years ago. He was an ex-smoker who quit smoking 30 years ago and had a 22 pack-year smoking history. No significant findings were demonstrated upon physical examination. Initial laboratory tests showed an elevated C-reactive protein (6.55 mg/L) and erythrocyte sedimentation rate levels (21 mm/h); the total white blood cell count (WBC) was in a normal range (8.0 × 10⁹/L), but the ratio of neutrophil was mildly increased (76.4%). Tumor markers, including alpha-fetoprotein, carcinoembryonic antigen, cancer antigen 19–9, and squamous cell carcinoma antigen were all within a normal range. A chest radiograph showed a patchy increased opacity in the right upper lobe.

A chest CT was conducted for further evaluation, and it revealed two spiculated nodular consolidations with an air bronchogram in the right upper lobe (Fig. 1A). The lesions showed a slightly heterogeneous contrast enhancement (about 86 Hounsfield units) and the longest diameters of these two lesions were 21 and 22 mm, respectively. An approximately 4 mm sized satellite ground-glass nodule was shown adjacent to the larger one. Diffuse and nodular wall thickening of trachea and esophagus was also noted, but mediastinal lymph nodes were unremarkable. The first clinical impression was primary lung cancer, and a radiologic differential diagnosis included focal pneumonia such as fungal pneumonia and granulomatous inflammation. The pathologic specimen obtained by a percutaneous core needle biopsy (PCNB) revealed interstitial chronic inflammation with organizing fibrosis. There was neither granuloma nor fungal hyphae in the specimen, proven by Periodic acid-Schiff and Grocott's methenamine silver stains.

In the follow-up chest CT 3 months later, previous consolidative lesions were slightly decreased in size (21 mm → 16 mm, 22 mm → 16 mm). However, about 5 mm to 7 mm sized new noncalcified nodular lesions had developed in both upper lobes. Over this period, no specific medication for these lesions was taken except for antibiotics. Additional follow-up chest CT after 7 months showed a markedly increased size in the prior lesions of both upper lobes. The largest one was measured to be 32 mm in size. The next follow-up chest CT was also taken 7 months later with contrast enhancement. In this CT scan, a mass larger than 5 cm was shown in the right upper lobe (Fig. 1B). This mass was thought to be enlarged and coalesced previous nodular lesions in the right upper lobe. Significant enlargement of a spiculated nodule in the left upper lobe was also noted (14 mm → 22 mm). In addition, prominent interstitium and interstitial nodules were shown in both upper lobes, with progression of tracheal and esophageal wall thickening (Fig. 1C). Multiple mediastinal, right hilar and interlobar lymph nodes were also enlarged. For all these findings, primary lung cancer with multiple metastasis involving both lungs and mediastinum was considered to be a radiologic impression, and PCNB was repeated for pathologic confirmation. Fibrosclerotic lesion with lymphoplasmacytic infiltration was finally reported with 20 cells of IgG4-positive plasma cells per high-power field, and the ratio of IgG4-positive plasma cell to IgG-positive plasma cell was 0.34 (34%). There were neither granulomas nor malignant cells in the specimen. The level of serum IgG4 was slightly elevated (91.8 mg/dL). By the comprehensive diagnostic criteria for a IgG4-related disease, a diagnosis of IgG4-related lung disease was probable in this patient (1).

A 65-year-old male with a history of carcinoid tumor in the stomach was incidentally found to have abnormal findings in the basal lungs on a contrast-enhanced stomach CT scan. He was a non-smoker and had a past history of old pulmonary tuberculosis, which was cured 30 years ago. A physical examination was unremarkable and revealed no issues. Initial laboratory findings were compatible with systemic lupus erythematosus; decreased levels of serum C3 (16.2 mg/dL) and C4 (3.47 mg/dL), decreased total count of WBC (3.7 × 10⁹/L and 2.93 × 10⁹/L, measured consecutively), high titer of fluorescent antinuclear antibody (> 1:1280) with a homogeneous pattern, and a positive serum anti-dsDNA. A chest radiograph showed bronchiectasis in the left lower lung zone and an inactive pulmonary tuberculosis lesion in the right upper lobe.

In the chest CT scan after an endoscopic mucosal resection of carcinoid tumor, localized bronchiectasis and multiple nonspecific small nodules were shown in the left lower lobe and lingular segment of the left upper lobe. Paraseptal emphysema was found in the left lower lobe and calcified nodules with fibrotic bands in the right upper lobe. Since he did not have any respiratory complaints, no further evaluation but observation was performed.

Three years later, he was hospitalized due to dyspnea developed one day before, along with coughing and sputum for fifteen days. Crackle was audible in the right lower lung field, and bilateral patchy increased opacity was noted on the chest radiograph. Despite the administration of antibiotics for three days under the impression of pneumonia, clinical symptoms and radiologic findings had not improved. In a high-resolution CT scan for further evaluation, multifocal diffuse and patchy groundglass opacity (GGO) with interlobular septal thickening in both lungs were characteristic findings (Fig. 2A). Additionally, focal nodular consolidations in the area of subpleural GGO were demonstrated in the right upper and lower lobes. With slightly increased extent of emphysematous change in the left lower lobe, bronchiectasis in both lungs was also observed. For these bilateral diffuse and subpleural GGO with focal nodular consolidations, atypical pneumonia such as Pneumocystis jirovecii pneumonia was suggested as a possible differential diagnosis. However, bronchoalveolar lavage did not reveal any pathogens, so a video-assisted thoracoscopic surgery biopsy targeted for consolidative lesions in the right lung was performed. Biopsies from the right upper and lower lobes showed diffuse alveolar damage in interstitial lung disease of an undetermined type associated with IgG4-related lung disease. Diffuse lymphoplasmacytic infiltration and increased IgG4-positive plasma cells (IgG4-positive plasma cell to IgG-positive plasma cell ratio: about 0.28) were shown in fibrotic stroma. Initial serum IgG4 concentration of the patient was significantly elevated (275.98 mg/dL). By the comprehensive diagnostic criteria for IgG4-related disease, a diagnosis of IgG4-related lung disease was definite in this patient (1). The patient had started glucocorticoid therapy.

One month later, a follow-up chest CT was done and it revealed a newly developed extensive consolidation with air bronchogram, predominant in the right lung (Fig. 2B). Instead, prior GGO lesions showed a slight decrease. Next, a follow-up CT taken 8 months later demonstrated peripherally located reticular densities, replacing the previous consolidation and GGO areas. Honeycombing cysts in both basal lungs were the key image finding in this CT scan. Progression of traction bronchiectasis in both lungs was also noted. Steroid administration was completely tapered off at this time. Aggravation of these honeycombing cysts and fibrosis was shown in the last follow-up CT four years later, combined with a new nodular lesion in the right upper lobe and multiple enlarged mediastinal lymph nodes (Fig. 2C).