title: Secondary pulmonary alveolar proteinosis in hematologic malignancies.
abstract: Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as "intra-alveolar coagulum". This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte-macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab.
authors.affiliation: Taussig Cancer Institute of Cleveland Clinic, Department of Hematology/Oncology, Cleveland Clinic in Weston, FL, USA. Electronic address: chaulac@ccf.org.
authors.forename: Chakra P
authors.initials: CP
authors.lastname: Chaulagain
authors.affiliation: Department of Pathology, Tufts Medical Center Cancer Center & Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Pilichowska
authors.affiliation: Department of Surgery, Tufts Medical Center Cancer Center & Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Brinckerhoff
authors.affiliation: Division of Critical Care, Pulmonary and Sleep Medicine, Tufts Medical Center Cancer Center & Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Maher
authors.initials: M
authors.lastname: Tabba
authors.affiliation: Division of Hematology/Oncology, Tufts Medical Center Cancer Center & Tufts University School of Medicine, Boston, MA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Erban
mesh_terms: D000328:Adult; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D011649:Pulmonary Alveolar Proteinosis / Q000209:etiology*; D055815:Young Adult
keywords: Bronchoalveolar lavage; Hematologic malignancy; Hematopoietic stem cell transplantation; Opportunistic infections; Secondary pulmonary alveolar proteinosis