Abstract Introduction Pulmonary alveolar proteinosis (PAP) is a rare lung disorder caused by the accumulation of surfactant within alveoli. While mechanisms behind this varies, it can result from a reduction in clearance secondary to reduced alveolar macrophages in the setting of hematological malignancy. This accumulation of intra-alveolar proteins impairs gas exchange, which can lead to worsening respiratory failure. Case 67-year-old female with a history of Multiple Myeloma (IgG with Kappa light chains), Hypertension, Heart Failure with Recovered Ejection Fraction, Diabetes Mellitus was transferred from outside hospital for higher level of care for persistent shortness of breath. Patient was diagnosed with Multiple Myeloma (MM) in 2018. She is status post autologous transplantation in 2019 with subsequent disease progression in 2020, now stable on Daratumumab-Pomalidomide-Dexamethasone. Chest x-ray on presentation showed diffuse bilateral pulmonary opacities. Computed Tomography (CT) Chest on day 1 showed diffuse ground glass opacities with interlobular septal thickening and confluent pulmonary consolidation within the bilateral lower lobes. Labs evidenced the following: Pro-BNP 143, D-Dimer 722, LDH 451, Procalcitonin 0.39, CMV 9065, and B-D-glucan positivity. Infectious Disease was consulted and recommended treatment with broad spectrum antimicrobials including prophylactic Bactrim and Valacyclovir. Repeat CT Chest on day 8 showed diffuse bilateral pulmonary consolidations, increased in density and extent. Pulmonology was consulted on day 9 recommending Video-Assisted Thoracoscopic Surgery (VATS). VATS was performed on day 12 on the right middle and lower lobe with pathology consistent with alveolar proteinosis, negative for GM-CSF. Patient subsequently underwent whole lung lavage (7 L Right, 8 L Left). Effluent was relatively clear compared to expected sediment. Patient extubated and gradually weaned to room air, doing well 6 months after discharge. Discussion Secondary PAP is a well-established complication of hematologic malignancies due to impaired alveolar macrophage function either from malignancy or its treatment. However, the relationship between PAP and MM is poorly described in the literature. In MM, an observed shift toward M2-polarized macrophages, which are anti-inflammatory and promote tissue repair, but may also contribute to tumor progression and fibrosis. Similarly, daratumumab activates macrophages and enhances phagocytosis, which theoretically should improve surfactant clearance. Pomalidomide enhances M1 macrophage phenotype and antitumor immunity, with case reports of alveolitis but never PAP. This case highlights a rare presentation of PAP in the setting of MM, without an evidence-based mechanistic explanation. This underscores the importance of considering PAP in the differential diagnosis of progressive respiratory failure in immunocompromised patients. This abstract is funded by: none
Guthrie et al. (Fri,) studied this question.