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Sanjay Mukhopadhyay, MD; Jeffrey L. Myers, MD, FCCP; Marie-Christine Aubry, MD, FCCP
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From the Department of Anatomic Pathology (Dr Mukhopadhyay), Cleveland Clinic; Department of Pathology (Dr Myers), University of Michigan; and Department of Laboratory of Medicine and Pathology (Dr Aubry), Mayo Clinic College of Medicine.

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


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2014;145(2):434. doi:10.1378/chest.13-2763
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To the Editor:

We thank Dr Rossi and colleagues for their interest in our study.1 As they correctly point out, an etiology could not be determined in 40% of resected pulmonary necrotizing granulomas in our study (the denominator being cases in which organisms were not found at the time of initial pathologic examination), even after an exhaustive reexamination of all available clinical, radiologic, microbiologic, and histologic data.1 We believe that such lesions are “burnt out” infectious granulomas, mainly fungal or mycobacterial, in which the organisms have been destroyed or removed by the granulomatous inflammatory response to such an extent that they are undetectable by currently available methods, including microbiologic cultures and polymerase chain reaction for mycobacteria.

This interpretation is supported by our analysis of the histologic features of these granulomas in that they were indistinguishable in every respect from those granulomas in which specific pathogens were identified.1 Additional evidence comes from routine diagnostic practice in which it is common for organisms to be irregularly distributed in samples of infectious granulomatous disease.

Mycobacteria or fungi are etiologic in the majority of necrotizing granulomas in the lung.2 In this context, the contention of Rossi et al3 that chickenpox may be a cause of necrotizing granulomas in the lung is intriguing. Because there is no precedent for a viral etiology for pulmonary necrotizing granulomas, we did not specifically look for a history of chickenpox in the patients. An interesting avenue for further investigation would be to examine whether the virus can be demonstrated within the granulomas themselves rather than in the surrounding lung tissue alone. Showing that the viral particles are located within the granulomas rather than in the surrounding lung would strengthen the argument that the virus is an etiologic agent.

References

Mukhopadhyay S, Wilcox BE, Myers JL, et al. Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic analysis of 131 patients with completely resected nodules. Chest. 2013;144(3):813-824. [CrossRef] [PubMed]
 
Mukhopadhyay S, Farver CF, Vaszar LT, et al. Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries. J Clin Pathol. 2012;65(1):51-57. [CrossRef] [PubMed]
 
Rossi G, Cavazza A, Gennari W, et al. Chickenpox-related pulmonary granulomas in immunocompetent adults: clinicopathologic and molecular features of an underrated occurrence. Am J Surg Pathol. 2012;36(10):1497-1502. [CrossRef] [PubMed]
 

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References

Mukhopadhyay S, Wilcox BE, Myers JL, et al. Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic analysis of 131 patients with completely resected nodules. Chest. 2013;144(3):813-824. [CrossRef] [PubMed]
 
Mukhopadhyay S, Farver CF, Vaszar LT, et al. Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries. J Clin Pathol. 2012;65(1):51-57. [CrossRef] [PubMed]
 
Rossi G, Cavazza A, Gennari W, et al. Chickenpox-related pulmonary granulomas in immunocompetent adults: clinicopathologic and molecular features of an underrated occurrence. Am J Surg Pathol. 2012;36(10):1497-1502. [CrossRef] [PubMed]
 
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