Secondary Pulmonary Alveolar Proteinosis Associated with Primary Myelofibrosis and Ruxolitinib Treatment: An Autopsy Case

Abstract

Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence.

Pulmonary alveolar proteinosis – current and future therapeutical strategies

“…Hereditary PAP is caused by mutations in the genes encoding the alpha or beta chain of the GM-CSF receptor (CSF2RA and CSF2RB, respectively) [6,[8][9][10][11]. On the other side, secondary PAP results from dysfunction or reduced numbers of alveolar macrophages due to inhalational exposure or various infectious or malignant disorders [2,[12][13][14][15][16][17][18]. Mutations in the genes encoding surfactant protein (SP)-B (SFTPB), SP-C (SFTPC), thyroid transcription factor 1 (NKX2.1) and ATP-binding cassette protein 3 (ABCA3) underlie congenital PAP forms [6,[19][20][21][22][23][24][25][26].…”

Pulmonary Alveolar Proteinosis After Allogeneic Hematopoietic Stem-Cell Transplantation in Adults

“…8 A systematic review of patient medications should be performed, and the temporal relationships between PAP onset and a specific medication should be investigated carefully. Numbers of drugs have been linked to the occurrence of PAP, 3,9,10 whether they directly disrupt intracellular signaling pathways or induce genetic alterations that contribute to alveolar macrophages dysfunction. PAP occurrence was suspected to be induced by rapamycin in patients 4 and 5 and by ruxolitinib in patients 2 and 3.…”