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Original Research: Diffuse Lung Disease |

Pulmonary Necrotizing Granulomas of Unknown CauseNecrotizing Granulomas of Unknown Cause: Clinical and Pathologic Analysis of 131 Patients With Completely Resected Nodules

Sanjay Mukhopadhyay, MD; Bradley E. Wilcox, DO; Jeffrey L. Myers, MD, FCCP; Sandra C. Bryant, MS; Seanne P. Buckwalter, MS; Nancy L. Wengenack, PhD; Eunhee S. Yi, MD; Gregory L. Aughenbaugh, MD; Ulrich Specks, MD; Marie-Christine Aubry, MD, FCCP
Author and Funding Information

From the Department of Laboratory Medicine and Pathology (Drs Mukhopadhyay, Myers, Wengenack, Yi, and Aubry and Ms Buckwalter), the Department of Pulmonary and Critical Care Medicine (Drs Wilcox and Specks), the Division of Biomedical Statistics and Informatics (Ms Bryant), and the Department of Radiology, Section of Thoracic Radiology (Dr Aughenbaugh), Mayo Clinic, Rochester, MN.

Correspondence to: Sanjay Mukhopadhyay, MD, Department of Anatomic Pathology, Cleveland Clinic, Robert J. Tomsich Pathology and Laboratory Medicine Institute, 9500 Euclid Ave/L25, Cleveland, OH 44195; e-mail: mukhops@ccf.org


Dr Mukhopadhyay is currently at the Department of Anatomic Pathology, Cleveland Clinic (Cleveland, OH).

Dr Myers is currently at the Department of Pathology, University of Michigan (Ann Arbor, MI).

Dr Wilcox is currently at Chest, Infectious Disease and Critical Care Associates (Clive, IA).

Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(3):813-824. doi:10.1378/chest.12-2113
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Background:  The cause of pulmonary necrotizing granulomas is often unclear, even after histologic examination. Our aim was to determine the clinical significance of histologically unexplained necrotizing granulomas.

Methods:  Pulmonary necrotizing granulomas surgically resected at the Mayo Clinic (1994-2004) were retrieved and reviewed retrospectively. Cases in which a cause was evident at the time of initial histologic examination were excluded. The analysis cohort comprised 131 completely resected histologically unexplained pulmonary necrotizing granulomas. Clinical and laboratory information was abstracted from medical records, chest CT scans were reviewed, histologic slides were reexamined, and additional ancillary studies were performed in selected cases.

Results:  A cause was determined on review in more than one-half of the histologically unexplained necrotizing granulomas (79 of 131, 60%) by reexamining histologic slides (47), incorporating the results of cultures (26), fungal serologies (14), and other laboratory studies (eight), and correlating histologic findings with clinical and radiologic information (13). Infections accounted for the majority (64 of 79), the most common being histoplasmosis (37) and nontuberculous mycobacterial infections (18). Noninfectious diagnoses (15 of 79) were rheumatoid nodule (five), granulomatosis with polyangiitis (Wegener) (five), sarcoidosis (four), and chronic granulomatous disease (one). Many cases remained unexplained even after extensive review (52 of 131, 40%). Most of these patients received no medical therapy and did not progress clinically or develop new nodules (median follow-up, 84 months).

Conclusions:  A cause, the most common being infection, can be established in many surgically resected pulmonary necrotizing granulomas that appear unexplained at the time of initial histologic diagnosis. Patients whose granulomas remain unexplained after a rigorous review have a favorable outcome. Most do not develop new nodules or progress clinically, even without medical therapy.

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