A40-04 Isolated Primary Pulmonary Al Amyloidosis With Mixed Tracheobronchial and Cavitary Nodular Involvement: A Rare and Progressive Presentation

Abstract Amyloidosis encompasses disorders caused by extracellular deposition of misfolded proteins, most commonly of the amyloid light-chain (AL) subtype. Pulmonary involvement occurs in approximately half of systemic cases; however, isolated pulmonary amyloidosis is exceedingly rare. Its variable imaging features often mimic malignancy, infection, or vasculitis, making diagnosis challenging. Pulmonary amyloidosis manifests in three morphologic patterns—tracheobronchial, nodular parenchymal, and diffuse alveolar-septal. We describe a rare case of isolated pulmonary AL amyloidosis with overlapping tracheobronchial and cavitary nodular involvement, highlighting the diagnostic ambiguity and therapeutic limitations of this uncommon entity. A 71-year-old man with 50 pack-year smoking history presented with cough and dyspnea, initially treated as pneumonia. Computed tomography (CT) imaging revealed multiple pleural-based nodules and cavitary lesions, the largest 3.6 × 7.4 cm in the left lower lobe, along with right upper-lobe endobronchial opacities. Positron emission tomography (PET)-CT demonstrated mild-to-moderate fluorodeoxyglucose (FDG) uptake, raising concern for malignancy. After a two-year lapse in follow-up, he returned with progressive dyspnea and enlargement of bilateral nodules. CT-guided biopsy showed a paucicellular eosinophilic matrix with Congo red positivity and apple-green birefringence under polarized light. Mass spectrometry confirmed AL-type amyloid. Bone marrow biopsy revealed no plasma cell dyscrasia, and serum studies showed a small monoclonal lambda spike (0.5 g/dL), consistent with isolated pulmonary AL amyloidosis. He received bortezomib, cyclophosphamide, and dexamethasone (CyBorD) with a partial hematologic response. Due to radiologic progression, daratumumab was added but discontinued for intolerance. Over time, he developed chronic hypoxemic respiratory failure requiring 2-3 L/min oxygen. Repeat imaging showed progressive nodules and pleural thickening. He transitioned to palliative care and died under hospice management. Discussion This case illustrates an exceedingly uncommon presentation of isolated pulmonary AL amyloidosis with combined tracheobronchial and cavitary nodular AL deposition without systemic disease. Such overlap forms are rarely reported and frequently mimic metastatic malignancy radiographically making diagnosis challenging. The disease course is unpredictable; while many localized cases remain indolent, others like this progress relentlessly despite plasma cell-directed therapy. Systemic regimens such as CyBorD and daratumumab may stabilize hematologic parameters yet fail to halt local amyloid deposition, suggesting distinct pathogenic mechanisms within pulmonary tissue. Early recognition through tissue diagnosis and multidisciplinary management remains critical. This case underscores the importance of considering amyloidosis in atypical or FDG-avid pulmonary lesions, recognizing that radiologic progression may occur despite hematologic control. A high index of suspicion and individualized care plans are essential, as current therapies offer limited benefit once advanced pulmonary involvement develops. This abstract is funded by: none