Primary Sjögren’s syndrome is characterized by dry eyes, dry mouth, and lymphocytic infiltration of exocrine glands. Pulmonary amyloidosis in primary Sjögren’s syndrome is rare. It is often misdiagnosed or diagnosed delayed, as it is difficult to distinguish from infections and lymphoproliferative disorders. This study describes and analyzes the overall characteristics of patients with nodular pulmonary amyloidosis in primary Sjögren’s syndrome, highlighting radiological features that support early and accurate differentiation.

We retrospectively identified 8 patients at the Second Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou. All were diagnosed with primary Sjögren’s syndrome and had classic radiological or pathological findings of pulmonary amyloidosis. Additionally, we selected 8 patients diagnosed with primary Sjögren’s syndrome who had merely lymphoid interstitial disease as controls, matched primarily by age and disease course. Clinical, radiological, and histopathological data were analyzed.

Pulmonary amyloidosis predominantly affected women (7/8, 87.5%). Clinically, half of the patients presented with cough, chest tightness, and fatigue, while the other half remained asymptomatic regarding respiratory symptoms. Pulmonary amyloidosis was diagnosed subsequent to primary Sjögren’s syndrome, with a median delay of 7 years. On High-Resolution Computed Tomography (HRCT), all eight patients exhibited multiple nodules with calcification and scattered thin-walled cysts, which were predominantly peripheral or subpleural distributed. All 165 nodular lesions demonstrated intermediate CT values and were randomly distributed across different lung segments, with the highest concentrations in the right lower (33.94%), right upper (21.21%), and left upper (21.21%) lobes. Quantitative analysis of the five biopsied nodules showed a median CT value of 37.60 HU (range: -34.30 to 59.70). PET-CT showed slightly elevated 18F-FDG uptake (SUVmax = 8.51), which was higher than generally reported for pulmonary amyloidosis and approached the typical range of MALT lymphoma (SUVmax range: 3.3 to 7.5), making non-invasive differentiation challenging. Pertinent laboratory findings included positive anti-SSA/Ro-52 (100%) and anti-SSB (50%) antibodies, as well as elevated Immunoglobulin G and rheumatoid factor. Histopathological confirmation was essential for definitive diagnosis, necessitating surgical excision in two patients (25.0%) or CT-guided needle lung biopsy in three others (37.5%). Patients received appropriate drug treatments (Hydroxychloroquine, prednisolone, Mycophenolate Mofetil, and Iguratimod) during follow-up. Most (75.0%) achieved disease stability, although two cases showed persistent symptoms and progressive radiological worsening. 

Nodular pulmonary amyloidosis can occur in patients with primary Sjögren’s syndrome, typically manifesting as partially calcified nodules and often co-existing with lymphoid interstitial pneumonia. Radiologic evaluations, particularly chest HRCT and PET-CT, play a crucial role in differentiating amyloidosis from lymphoma and other carcinomas. Biopsy remains the gold standard for the diagnosis of amyloidosis. Surgical excision followed by a course of medication appears to yield moderate therapeutic outcomes. Long-term monitoring and timely medical intervention are warranted given the risk of progression.