Abstract Pulmonary amyloidosis encompasses a heterogeneous group of disorders characterized by the extracellular deposition of misfolded proteins into the lung parenchyma and airways. Systemic amyloidosis is exceedingly rare (incidence of less than 17 cases per million person-years) and often has pulmonary involvement. Nodular pulmonary amyloidosis (NPA) is a localized form, with most cases being asymptomatic. We present a case of a patient with systemic sclerosis who developed an enlarging lung nodule, ultimately diagnosed with NPA. A 41-year-old non-smoking woman was referred to pulmonary clinic for incidental findings of multiple pulmonary nodules on high-resolution CT chest (the largest measuring 1.1 cm in the right upper lobe). The patient was recently diagnosed with diffuse cutaneous systemic sclerosis (SSc) and was started on mycophenolate mofetil. PET scan showed no hypermetabolic evidence of aggressive malignancy or adenopathy, however the lung nodule had enlarged to 1.5 cm. The patient underwent navigational bronchoscopy due to concern for lung cancer. The biopsy revealed amyloid by Congo Red staining, without evidence of malignancy. Mass spectroscopy confirmed Lambda immunoglobin light chains. There was no evidence of smoldering multiple myeloma, monoclonal gammopathy, plasma cell dyscrasia, or systemic amyloidosis, favoring the diagnosis of localized NPA. The coexistence of amyloidosis and SSc is exceptionally rare, with only isolated cases described in the literature. SSc is a multisystem autoimmune disease characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. Amyloidosis, in contrast, is defined by the extracellular deposition of misfolded protein fibrils. Three principal forms are recognized: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis (NPA), and tracheobronchial amyloidosis. It is imperative to distinguish NPA (localized disease) from systemic amyloidosis (ex. AL or AA amyloid), because the latter would require chemotherapy. There is no clear correlation between amyloidosis and SSc. AA amyloidosis has been associated with chronic inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease. Chronic inflammation can increase concentrations of serum amyloid A, an acute-phase reactant and precursor to AA amyloid fibrils. Of note, Colangelo, et al. described a patient with both SSc and AL amyloidosis, who was treated with amyloid based chemotherapy and experienced improvement in their SSc symptoms. Further studies are needed to explore the complex relationship between these two rare diseases. This abstract is funded by: None
Almeda et al. (2026) studied this question.