Diffuse pulmonary infiltrates: unfolding a diagnostic challenge

SESSION TITLE: Not all Lung Problems Start Within the Lungs SESSION TYPE: Case Reports PRESENTED ON: 10/10/2023 08:30 am - 09:30 am INTRODUCTION: Multiple myeloma (MM) accounts for 17% of hematologic malignancies and typically presents in the sixth to seventh decade of life.1 Thoracic and pulmonary manifestations are variable and include extramedullary plasmacytoma, thoracic skeletal lesions, and focal and diffuse pulmonary infiltrates which are often infectious in etiology.2 CASE PRESENTATION: A 69-year-old male former smoker with IgG lambda MM presented for evaluation of dyspnea and dry cough of one year duration, requiring supplemental oxygen use for three months. He had numerous emergency department evaluations for respiratory-related symptoms, which responded transiently to steroid and/or antibiotic treatment. MM was diagnosed in 2017 with 80% bone marrow cellularity. Nephrotic-range proteinuria was demonstrated although indices of renal function were normal. Rheumatologic evaluation was negative. Pulmonary function tests revealed a borderline restrictive defect with severe reduction in diffusing capacity. Transthoracic echocardiography demonstrated a LVEF 64% with mildly increased LV thickness, and RVSP 49 mmHg. Pulmonary examination was normal. Exercise oximetry showed desaturation to a nadir of 74% on 2 LPM supplemental oxygen. Computed tomography imaging (Figure 1) demonstrated diffuse ground glass opacities throughout both lungs. Right heart catheterization demonstrated pre-capillary pulmonary hypertension with a mean pulmonary artery pressure of 32 mmHg and pulmonary capillary wedge pressure of 8 mmHg. Bronchoalveolar lavage yielded 87% monocytes with negative infectious studies. Transbronchial biopsy (Figure 2) demonstrated extensive alveolar-septal amyloidosis, prompting a new diagnosis of AL amyloidosis. Bortezomib-based chemotherapy was initiated without a change in his radiologic abnormalities or symptoms. DISCUSSION: AL amyloidosis is a common manifestation of MM,3 with overt amyloidosis in 10-15% of patients; occult AL amyloid deposits are found with higher prevalence, particularly in autopsy studies. Effective treatment of hematologic disease suppresses production of amyloidogenic monoclonal light chains, improving end organ function over time. Pulmonary manifestations of AL amyloid include tracheobronchial disease, alveolar-septal infiltration, nodular disease, pleural and/or diaphragmatic deposition, and adenopathy.4,5 Found in roughly 25% of AL amyloid patients, pulmonary disease is highly correlated with degree of cardiac amyloid deposition,6 in the absence of which it is rarely found. Diffuse alveolar-septal amyloidosis such as that found in our patient is the least common subtype of pulmonary amyloidosis—reported in only 3% of patients—and is rarely diagnosed ante-mortem. Prognosis in this subset of patients is poor with a median survival of less than two years.8 Pulmonary vascular amyloid infiltration has also been reported.9 Treatment with bortezomib-based chemotherapy has been described with hematologic response rate of 81%,10 although limited data exists on pulmonary improvement. CONCLUSIONS: We report a case of MM complicated by AL amyloidosis resulting in diffuse alveolar-septal pulmonary disease, which is particularly rare in the apparent absence of cardiac involvement. Pre-capillary pulmonary hypertension was also observed, raising concern for amyloid deposition in the pulmonary vasculature, although surgical lung biopsy would be required to make this diagnosis and was not pursued. Treatment with bortezomib-based chemotherapy failed to yield a clinical response. A high index of suspicion for pulmonary amyloidosis is required when evaluating a patient with MM and diffuse or nodular pulmonary disease. REFERENCE #1: Kintzer JS, Rosenow EC, Kyle RA. Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases. Arch Intern Med. 1978;138(5):727-730. REFERENCE #2: Berk JL, O'Regan A, Skinner M. Pulmonary and tracheobronchial amyloidosis. Semin Respir Crit Care Med. 2002;23(2):155-165. doi:10.1055/s-2002-25304 REFERENCE #3: Road JD, Jacques J, Sparling JR. Diffuse alveolar septal amyloidosis presenting with recurrent hemoptysis and medial dissection of pulmonary arteries. Am Rev Respir Dis. 1985;132(6):1368-1370. Doi:10.1164/arrd.1985.132.6.1368 DISCLOSURES: No relevant relationships by Jane Dematte D Amico No relevant relationships by Anthony Esposito No relevant relationships by Timothy Rowe No relevant relationships by Anjana Yeldandi