Special SectionNonneoplastic Lung Disease

Nonneoplastic Lung DiseaseMore Than Just Usual Interstitial Pneumonia

Mary Beth Beasley, MD

onneoplastic lung disease frequently presents a diagnostic challenge to pathologists and clinicians alike. The idiopathic interstitial lung diseases, particularly usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), are a frequent topic of discussion in both publications and seminars; however, the spectrum of nonneoplastic lung disease as a whole is far more extensive than this group of entities. As such, the aim of this special section is to discuss entities that the practicing pathologist may encounter with some regularity outside of the realm of UIP and NSIP, yet that may be equally problematic. Granulomas are among the most frequent histologic abnormalities encountered in the lung. Infection, sarcoidosis, and hypersensitivity pneumonitis are usual considerations when a granuloma is encountered, but granulomas are not limited to these disorders. Hypersensitivity pneumonitis was the focus of a previous ARCHIVES special section.14 In the current issue, Drs Sanjay Mukhopadhyay and Tony Gal present a comprehensive review of pulmonary granulomatous disorders. Granulomas themselves have a surprising range of subtle morphologic differences and may be encountered in a wide range of clinical settings. In addition to detailed information on specific disorders, a practical approach is presented including clues that might point to a particular diagnosis or differential when a granuloma is encountered. Lymphoid infiltrates of the lung, particularly those that are extensive yet fall short of being a clear-cut lymphoma, can be particularly frustrating. Dr Donald Guinee reviews the more commonly encountered nonneoplastic lymphoid disorders, their differential diagnosis, and clinical significance. Also included in this article is a discussion of immunoglobulin (Ig) G4associated lung disease, which also has a prominent lymphoid component. IgG4 disease has been associated with pancreatitis and retroperitoneal fibrosis, but the full spectrum of organ involvement in this disorder is still being elucidated and pulmonary disease has only been more recently described.5,6 Small airway disorders have typically received less attention than the diffuse interstitial lung diseases but
Accepted for publication September 3, 2009. From the Department of Pathology, Mount Sinai Medical Center, New York, New York. The author has no relevant financial interest in the products or companies described in this article. Reprints: Mary Beth Beasley, MD, Department of Pathology, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029 (e-mail: mary.beasley@mountsinai.org). Arch Pathol Lab MedVol 134, May 2010

have experienced a recent resurgence of interest. In a normal state, the small airways contribute little to airway resistance but may have a disproportionate effect on lung function in a damaged state, so this renewed interest is well justified. The pathologic significance of small airway abnormalities is often difficult to determine when encountered in a specimen, given that the findings are often nonspecific and may be secondary to, or associated with, other changes in the lung. Like nonneoplastic lung disease as a whole, small airway disease must be evaluated in the entire clinical and radiographic context to determine if the changes are part of a primary or secondary process. Primary bronchiolitides are additionally challenging as the histologic findings are often extremely subtle, particularly those of constrictive bronchiolitis. Indeed, small airway disorders should be among the prime considerations in a superficially normal wedge biopsy from a patient with significant respiratory compromise clinically. In his review, Dr Tim Allen discusses the spectrum of small airway disorders and their potential etiologic significance, as well as several more recently described lung diseases that are centered on small airways. Finally, a biopsy specimen from an acutely ill patient presents a special set of challenges given the combination of clinical urgency and potentially challenging histologic findings. Acutely ill patients, particularly those requiring mechanical ventilation, most often will have diffuse alveolar damage (DAD) histologically.7 Most pathologists are well familiar with the histologic findings of DAD from the autopsy suite, especially the acute form with hyaline membranes, although the organizing phase may not be as readily recognized. In addition to DAD, there are several other entities that the pathologist should consider in the acutely ill patient, which are discussed herein, along with an approach to diagnosis and small biopsy specimens. It is my privilege to present this series of articles written by myself and my distinguished colleagues. It is our hope that this selection of topics will aid our fellow pathologists in evaluating some of the facets of nonneoplastic pulmonary disease outside of the realm of the idiopathic interstitial pneumonias. Finally, I wish to thank Dr Philip T. Cagle for his continued support and for providing the opportunity to compile this special section.
References
1. Barrios RJ. Hypersensitivity pneumonitis: histopathology. Arch Pathol Lab Med. 2008;132(2):199203. 2. Fraire AE. Hypersensitivity pneumonitis: a commentary. Arch Pathol Lab Med. 2008;132(2):192194.

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3. Madison JM. Hypersensitivity pneumonitis: clinical perspectives. Arch Pathol Lab Med. 2008;132(2):195198. 4. Woda BA. Hypersensitivity pneumonitis: an immunopathology review. Arch Pathol Lab Med. 2008;132(2):204205. 5. Inoue D, Zen Y, Abo H, et al. Immunoglobulin G4-related lung disease: CT findings with pathologic correlations. Radiology. 2009;251(1):260270.

6. Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T. Lung involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases and review of the literature. Am J Surg Pathol. 2008;32(11):16201626. 7. Patel SR, Karmpaliotis D, Ayas NT, et al. The role of open-lung biopsy in ARDS. Chest. 2004;125(1):197202.

Mary Beth Beasley, MD Mary Beth Beasley, MD, is currently associate professor of Pathology and Pulmonary Medicine at The Mount Sinai Medical Center, New York, New York. Dr Beasley received her medical degree from Tulane University School of Medicine in New Orleans, Louisiana, and completed her residency training at Duke University Medical Center in Durham, North Carolina, and at Tulane University. Following residency, Dr Beasley was a fellow and subsequently a staff pathologist in the Division of Pulmonary and Mediastinal Pathology at the Armed Forces Institute of Pathology (AFIP) in Washington, District of Columbia. After the AFIP, Dr Beasley was assistant professor of Pathology at Tulane University and at Providence Portland Medical Center in Portland, Oregon. Dr Beasley has been at Mount Sinai since 2007 where she is head of Pulmonary Pathology. Dr Beasley is the author of numerous articles and textbook chapters in various areas of pulmonary pathology and is a soughtafter speaker. She additionally serves on the editorial board of Archives of Pathology & Laboratory Medicine and is currently chair of the College of American Pathologists Surgical Pathology Committee.

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