Diagnostic Considerations

The patient's age at the manifestation of signs/symptoms of pulmonary alveolar proteinosis is crucial in the establishing differential diagnosis and determining the correct diagnosis.^[2]Essential to the diagnostic approach is identifying potential genetic or autoimmune etiologies, exposure to environmental agents, and associations to other diseases.^[2]

Thus, the differential diagnosis includes other diseases associated with intra-alveolar exdudates, such as pulmonary edema, pneumocystis pneumonia, and alveolar mucinosis. Pulmonary edema has a homogenous appearance and lacks the granularity typical of PAP (see the images below). The exudate of pneumocystis pneumonia has a frothy or foamy appearance due to the negative image of the cyst form of Pneumocystis jiroveci (formerly known as carinii).

Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (A) (hematoxylin and eosin, x400) and broncheoalveolar lavage (BAL).

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Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (B) (Papanicolaou, x600). Note the negative images of the cysts impart the foamy characteristic of the exudate.

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Differential Diagnoses

Workup

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Media Gallery

Pulmonary alveolar proteinosis. A periodic acid-Schiff histochemical stain of transbronchial biopsy: Alveolar spaces contain considerable amounts of granular material.
Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (A) (hematoxylin and eosin, x400) and broncheoalveolar lavage (BAL).
Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (B) (Papanicolaou, x600). Note the negative images of the cysts impart the foamy characteristic of the exudate.
Pulmonary alveolar proteinosis. Intra-alveolar material is strongly periodic acid-Schiff (PAS) positive (diastase-PAS, x200).
Pulmonary alveolar proteinosis. Cytologic appearance of intra-alveolar granular material from a bronchoalveolar lavage sample (diastase-periodic acid-Shiff [DPAS], x400).
Pulmonary alveolar proteinosis. Bronchoalveolar lavage sample depicting dense globules with sharp borders seen in patients with pulmonary alveolar proteinosis (PAP) (Papanicolaou, x400).
Pulmonary alveolar proteinosis. Alveoli are filled with an eosinophilic granular material. Note the preservation of the normal lung architecture (hematoxylin and eosin, x200).
Pulmonary alveolar proteinosis. High magnification illustrating the granular material and alveolar macrophages surrounded by intact alveolar septal tissue with minimal reaction (hematoxylin and eosin, x400).

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Author

Roger B Olade, MD, MPH Medical Director, Genesis Health Group

Roger B Olade, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine, American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Oluwatoyin E Ijitola, MD, PhD Dean and Professor, International University for Graduate Studies (IUGS)

Oluwatoyin E Ijitola, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Tropical Medicine and Hygiene, International AIDS Society, American College of Healthcare Executives, HIV Medicine Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Philip T Cagle, MD Professor, Department of Pathology, Weill Medical College of Cornell University; Director, Pulmonary Pathology, The Methodist Hospital; Senior Member, The Methodist Hospital Research Institute

Philip T Cagle, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Chest Physicians, American Medical Association, American Society for Investigative Pathology, American Thoracic Society, College of American Pathologists, European Society of Pathology, Federation of American Societies for Experimental Biology, Harris County Medical Society, Texas Medical Association, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Rodolfo Laucirica, MD Professor, Department of Pathology and Immunology, Baylor College of Medicine; Medical Director of Cytopathology, Ben Taub General Hospital

Rodolfo Laucirica, MD is a member of the following medical societies: American Society for Investigative Pathology, American Society of Cytopathology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Acknowledgements

Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Ali Hmidi, MD Staff Physician, Department of Internal Medicine, Brooklyn Hospital Center, Cornell University

Disclosure: Nothing to disclose.