Pulmonary amyloidosis has three primary presentations consisting of tracheobronchial amyloidosis, nodular pulmonary amyloidosis, and diffuse alveolar-septal amyloidosis. While diffuse alveolar-septal amyloidosis is normally related to the systemic AL form, tracheobronchial and nodular pulmonary involvement are generally due to localized production of AL light chains. Diffuse-alveolar septal involvement results in deposition of amyloid in the distal airways, alveoli, septal walls, and blood vessels which may lead to restrictive lung function and pulmonary hemorrhage. Nodular pulmonary amyloidosis occurs in the setting of bilateral nodules or cystic masses consisting of immunoglobulin light chains produced by a localized process. These bilateral masses are often mistaken for a multifocal pneumonia or malignancy. Tracheobronchial amyloidosis similarly results from localized production of AL light chains that are deposited in the proximal airways. This form may manifest as dyspnea, cough, or hemoptysis related to airway damage or obstruction .
Few cases have been reported on pulmonary amyloidosis and its various manifestations. Invariably, these cases have led to massive pulmonary hemorrhage and death before the diagnosis was discovered. One of the earliest cases reported by Lee et. al. in 1983 described a patient with intermittent hemoptysis who later died of massive pulmonary hemorrhage . This patient was found to have amyloid extending into alveolar septa and blood vessel walls, similar to subsequent reported cases. Another case report by Sterlacci et. al. detailed a patient presenting with dyspnea, recurrent pleural effusions, and hemoptysis who was found to have systemic amyloidosis and diffuse alveolar septal amyloidosis. In a similar fashion, this patient succumbed to massive pulmonary hemorrhage before the diagnosis was confirmed. Notably, on bronchoscopy, no bleeding source was identified . In a rare case describing the successful treatment of pulmonary amyloidosis, Shenin et. al. reported a patient with small-volume intermittent hemoptysis and dyspnea who was treated with steroids for presumed vasculitis. Notably, this patient had positive antinuclear antibody titers and atypical antineutrophil cytoplasmic antibody (ANCA) along with negative myeloperoxidase and proteinase-3. Only after stabilization and wedge resection was the patient found to have severe diffuse alveolar hemorrhage from pulmonary amyloidosis . Another case report by Yong et. al. described a patient who presented with recurrent exudative pleural effusions. An incidental pulmonary infarct was discovered during their work-up which was attributed to a pulmonary embolism. After wedge biopsy, the diagnosis of pulmonary amyloidosis was confirmed, and the infarct was believed to be related to amyloid deposition . In two more recent cases, patients who died from massive pulmonary hemorrhage initially presented with small-volume hemoptysis and normal bronchoscopy. In both cases, patients were treated for pneumonia based on the discovery of bilateral consolidations later found to be pulmonary infarcts from vascular amyloidosis [7,8]
In this report, a notable similarity to previous cases include small volume hemoptysis with no clear bleeding source on bronchoscopy. These initial minor bleeding episodes are often the herald for massive pulmonary hemorrhage and death. Nearly half of the reports also describe pulmonary infarcts, which led to the large cavitary lesion in this case. Notably, the patient also had positive myeloperoxidase, proteinase-3, and ANA, not demonstrated in previous cases. Our patient was also found to have hypogammaglobulinemia on serum protein electrophoresis and elevated serum free light chains. In nearly all cases previously described, the diagnosis of amyloidosis was only made after death.
Given that the clinical signs of systemic amyloidosis are relatively nonspecific, there was no clear indication of the diagnosis, although every case was a result of AL light chain deposition. Although not confirmed on autopsy, the elevation in free light chains in this case points to systemic AL amyloidosis. This suggests that pulmonary amyloidosis may present in a more insidious manner given its predisposition for localized disease. These reports also raise the importance of recognizing patients at risk for pulmonary amyloidosis given the dismal outcomes.