Secondary alveolar proteinosis in cancer patients

Abstract

Pulmonary alveolar proteinosis (AP) is a rare cause of progressive respiratory failure in the normal host. It was first described by Rosen and coworkers in 1958 on the morphological basis of the accumulation of a PAS-positive material in the alveolar space. A couple of years later, AP was found to be unexpectedly associated with malignant diseases, especially with acute or chronic myeloid leukemias. These forms were called secondary AP in opposition to the primary forms observed in normal hosts. Probably because of its morphological definition and late diagnosis by means of histology or autopsy material, secondary AP has been considered to be life-threatening for a long time. However, recent observations show that AP can be diagnosed early in the course of the disease, especially through bronchoalveolar lavage, as long as the pathologist is aware of this possibility. Another point is that secondary AP can be reversible, both clinically and morphologically. This article summarizes the clinical features, morphological findings, and the main malignant diseases associated with secondary AP. We also comment on the hypotheses proposed in the literature to explain the association of AP, malignant disease, and immunosuppression. Alveolar macrophage is likely a key factor in the occurrence of secondary AP.

Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis

“…In secondary PAP, such as haematopoietic malignancies numerical deficiency and/or functional impairment of alveolar macrophages may be causal [8]. Although the present retrospective study is small and there was no intention to thoroughly investigate disease mechanisms, in those patients tested, measurable antibody to GM-CSF was demonstrated.…”

“…Although PAP may develop in association with haematological malignancies, dust exposure (e.g. silica) or immunodeficiency disorders [2,7,8], .90% of all reported cases of PAP have previously been considered ''idiopathic PAP'' [2].…”

Pulmonary Alveolar Proteinosis in a 67-Year-Old Woman with Wegener’s Granulomatosis

“…Chronic myeloid leukemia is most commonly associated with PAP 8 . However, the role of malignancy is complicated by the fact that the treatment for malignancies often involves the use of immunosuppressive medications.…”

“…GM-CSF works by stimulating alveolar macrophages to clear the surfactant 3 . Treatment of secondary PAP consists of treating the underlying disease or withdrawing immunosuppresion if possible 8 . If unsuccessful, whole lung lavage should be performed.…”

Secondary pulmonary alveolar proteinosis in hematologic malignancies

“…The GM-CSF investigational modality may be considered in patients who cannot tolerate or do not respond to whole lung lavage. [21][22][23][24][25] Neither whole lung lavage nor GM-CSF administration has been uniformly effective in HPAP but the effective treatment of underlying malignancies either by chemotherapy or by hematopoietic stem cell transplantation may lead to resolution of PAP as in our case. 6,18,25,28 PAP has been described after autologous hematopoietic stem cell transplantation (autoSCT), 26 and following allo-SCT utilizing matched unrelated donor (MUD), 27 matched related donor (MRD), 28 and unrelated umbilical cord blood transplantation (UCBT).…”