Skip to main content
Log in

Secondary alveolar proteinosis in cancer patients

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akino T, Ohno K (1981) Phospholipids of the lung in normal, toxic, and diseased states. CRC Crit Rev Toxicol 9:201–274

    Google Scholar 

  2. Aymard JP, Gyger M, Lavalle R, Legresley LP, Desy M (1984) A case of pulmonary alveolar proteinosis complicating chronic myelogenous leukemia. Cancer 53:954–956

    Google Scholar 

  3. Bedrossian CWM, Luna MA, Conklin RH, Miller WC (1980) Alveolar proteinosis as a consequence of immunosuppression. Hum Pathol 11 [Suppl]:527–535

    Google Scholar 

  4. Bell DY, Hook GE (1979) Pulmonary alveolar proteinosis: analysis of airways and alveolar proteins. Am Rev Respir Dis 119:979–990

    Google Scholar 

  5. Bousser J, Zittoun R, Siguier F, Godeau P, Bousser MG (1973) Leucémie myélomonocytaire et protéinose alveolaire pulmonaire. Sem Hop 49:507–511

    Google Scholar 

  6. Clague HW, Wallace AC, Morgan WK (1983) Pulmonary interstitial fibrosis associated with alveolar proteinosis. Thorax 38:865–866

    Google Scholar 

  7. Cordonnier C, Bernaudin JF, Fleury, M, Feuilhade M, Haioun C, Payen D, Huet Y, Atassi K, Vernant JP (1985) Diagnostic yield of bronchoalveolar lavage in pneumonitis occurring after allogeneic bone marrow transplantation. Am Rev Respir Dis 132:1118–1123

    Google Scholar 

  8. Cordonnier C, Fleury-Feith J, Escudier E, Atassi K, Bernaudin JF (1994) Secondary alveolar proteinosis is a reversible cause of respiratory failure in leukemic patients. Am J Respir Crit Care Med 149:788–794

    Google Scholar 

  9. Corrin B, King E (1970) Pathogenesis of experimenal pulmonary alveolar proteinosis. Thorax 133:488–505

    Google Scholar 

  10. Costello JF, Moriarty DC, Branthwaite MA, Turner-Warwick M, Corrin B (1975) Diagnosis and management of alveolar proteinosis: the role of electron microscopy. Thorax 30:121–132

    Google Scholar 

  11. Davidson JM, Macleod WM (1969) Pulmonary alveolar proteinosis. Br J Dis Chest 63:13–28

    Google Scholar 

  12. Dranoff G, Crawford AD, Sadelain M, Ream B, Rashid A, Bronson RT, Dickersin GR, Bachurski CJ, Mark EL, Whitsett JA, Mulligan (1994) Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 264:713–716

    Google Scholar 

  13. Edmonson WR, Gere JB (1960) Pulmonary alveolar proteinosis. Ann Intern Med 52:1310–1318

    Google Scholar 

  14. Fraser RG, Paré JAP (1988) Diagnosis of diseases of the chest, vol 3. Saunders, Philadelphia

    Google Scholar 

  15. Golde DW (1979) Alveolar proteinosis and the overfed macrophage. Chest 76:119–120

    Google Scholar 

  16. Golde DW, Territo M, Finley TN, Cline MJ (1976) Defective lung macrophages in pulmonary alveolar proteinosis. Ann Intern Med 85:304–309

    Google Scholar 

  17. Green D, Dighe P, Ali N, Katele G (1980) Pulmonary alveolar proteinosis complicating chronic myelogenous leukemia. Cancer 46:1763–1766

    Google Scholar 

  18. Harris JO (1979) Pulmonary alveolar proteinosis: abnormal in vitro function of alveolar macrophages. Chest 76:156–159

    Google Scholar 

  19. Heppleston AG, Mc Dermott M, Collins MM (1975) The surface properties of the lung in rats with alveolar lipoproteinosis. Br J Exp Pathol 56:444–453

    Google Scholar 

  20. Hoffman RM, Rogers RM (1991) Serum and lavage lactate deshydrogenase iso-enzymes in pulmonary alveolar proteinosis. Am Rev Respir Dis 143:42–46

    Google Scholar 

  21. Hook GE (1991) Alveolar proteinosis and phospholipidoses of the lungs. Toxicol Pathol 19:482–513

    Google Scholar 

  22. Hook GE, Bell DY, Gilmore LB, Nadeau D, Reasor MJ, Talley FA (1978) Composition of BAL effluents from patients with pulmonary alveolar proteinosis. Lab Invest 39:342–357

    Google Scholar 

  23. Jones CC (1960) Pulmonary alveolar proteinosis with unusual complicating infections. Am J Med 29:713–722

    Google Scholar 

  24. Kikkawa Y, Smith F (1983) Cellular and biochemical aspects of pulmonary surfactant in health and disease. Lab Invest 49:122–139

    Google Scholar 

  25. Larson RK, Goldiner R (1965) Pulmonary alveolar proteinosis: report of six cases, review of the literature, and formulation of a new theory. Ann Intern Med 62:292–312

    Google Scholar 

  26. Lehne G, Lote K (1990) Pulmonary toxicity of cytotoxic and immunosuppressive agents: a review. Acta Oncol 29:113–124

    Google Scholar 

  27. Martin RJ, Coalson JJ, Rogers RM, Horton FO, Manous LE (1980) Pulmonary alveolar proteinosis: the diagnosis by segmental lavage. Am Rev Respir Dis 121:819–825

    Google Scholar 

  28. Meijer WG, Van Marwijk Kooy M, Ladde BE (1994) A patient with multiple myeloma and respiratory insuffi ciency due to accumulation of paraprotein in the alveolar space. Br J Haematol 87:663–665

    Google Scholar 

  29. Nishinakamura R, Nakayama N, Hirabayashi Y, Inoue T, Aud D, McNeil T, Azuma S, Yoshida S, Toyoda Y, Arai K (1995) Mice deficient for the IL3/GM-CSF/IL5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal. Immunity 2:211–222

    Google Scholar 

  30. Nugent KM, Pesanti EL (1983) Macrophage function in pulmonary alveolar proteinosis. Am Rev Respir Dis 127:780–781

    Google Scholar 

  31. Pesanti EL, Shanley JD (1984) Murine cytomegalovirus induced macrophage dysfunction. J Leukoc Biol 8:879–882

    Google Scholar 

  32. Prakash UBS, Barham SS, Carpenter HA, Dines DE, Marsh HM (1987) Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 62:499–518

    Google Scholar 

  33. Ramirez RJ (1967) Pulmonary alveolar proteinosis: treatment by massive bronchopulmonary lavage. Arch Intern Med 119:147–156

    Google Scholar 

  34. Ramirez RJ, Harlan WR Jr (1968) Pulmonary alveolar proteinosis. Am J Med 45:502–512

    Google Scholar 

  35. Ranchod M, Bissel M (1979) Pulmonary alveolar proteinosis and cytomegalovirus infection. Arch Pathol Lab Med 103:139–142

    Google Scholar 

  36. Rinehart JJ, Sagone AL, Balcerzak P, Ackerman GA, Lobugho AF (1975) Effects of corticosteroid therapy on human monocyte function. N Engl J Med 292:236–241

    Google Scholar 

  37. Rosen SH, Castleman B, Liebow AA (1958) Pulmonary alveolar proteinosis. N Engl J Med 258:1123–1142

    Google Scholar 

  38. Shapiro DL, Finkelstein DL, Penney DP, Sieman DW, Rubin P (1982) Sequential effects of irradiation on the pulmonary surfactant system. Int Radiat Oncol Biol Phys 8:879–882

    Google Scholar 

  39. Singh G, Katyal SL, Bedrossian CWM, Rodgers RM (1983) Pulmonary alveolar proteinosis staining for surfactant apoprotein in alveolar proteinosis and in conditions simulating it. Chest 83:82–86

    Google Scholar 

  40. Steer A (1969) Focal pulmonary alveolar proteinosis in pulmonary tuberculosis. Arch Pathol 87:347–352

    Google Scholar 

  41. Stover DE, Zaman MB, Hadju I, Lange M, Golde J, Armstrong D (1984) Bronchoalvolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host. Ann Intern Med 101:1–7

    Google Scholar 

  42. Teja K, Cooper PH, Squires JE, Schnatterly PT (1981) Pulmonary alveolar proteinosis in four siblings. N Engl J Med 305:1390–1392

    Google Scholar 

  43. Tran Van Nhieu J, Vojtek AM, Bernaudin JF, Escudier E, Fleury-Feith J (1990) Pulmonary alveolar proteinosis associated withPneumocystis carinii. Chest 98:801–805

    Google Scholar 

  44. Warner T, Balish E (1995) Pulmonary alveolar proteinosis: a spontaneous and inducible disease in immunodeficient germ-free mice. Am J Pathol 146:1017–1024

    Google Scholar 

  45. Webster JR, Battifora H, Furey C, Harrison RA, Shapiro B (1980) Pulmonary alveolar proteinosis in two siblings with decreased immunoglobulin A. Am J Med 69:786–789

    Google Scholar 

  46. Wright J, Dobbs L (1991) Regulation of pulmonary surfactant and clearance. Annu Rev Physiol 53:395–414

    Google Scholar 

  47. Yamamoto M, Yamane T, Hara H, Taketomi Y, Kuramoto Y (1975) Pulmonary alveoalar proteinosis asso ciated with chronic granulocytic leukemia. Jpn J Clin Hematol 16:347–353

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ladeb, S., Fleury-Feith, J., Escudier, E. et al. Secondary alveolar proteinosis in cancer patients. Support Care Cancer 4, 420–426 (1996). https://doi.org/10.1007/BF01880639

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01880639

Key words

Navigation