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Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries
  1. Sanjay Mukhopadhyay1,
  2. Carol F Farver2,
  3. Laszlo T Vaszar3,
  4. Owen J Dempsey4,
  5. Helmut H Popper5,
  6. Haresh Mani6,
  7. Vera L Capelozzi7,
  8. Junya Fukuoka8,
  9. Keith M Kerr9,
  10. E Handan Zeren10,11,
  11. Venkateswaran K Iyer12,
  12. Tomonori Tanaka8,
  13. Ivy Narde7,
  14. Angheliki Nomikos9,
  15. Derya Gumurdulu10,
  16. Sudheer Arava12,
  17. Dani S Zander6,
  18. Henry D Tazelaar13
  1. 1Department of Pathology, State University of New York Upstate Medical University, Syracuse, New York, USA
  2. 2Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Department of Pulmonary Medicine, Mayo Clinic, Scottsdale, Arizona, USA
  4. 4Department of Respiratory Medicine, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, UK
  5. 5Department of Pathology, Medical University of Graz, Graz, Austria
  6. 6Department of Pathology, Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania, USA
  7. 7Department of Pathology, University of São Paulo, São Paulo, Brazil
  8. 8Laboratory of Pathology, Toyama University Hospital, Toyama, Japan
  9. 9Department of Pathology, Aberdeen Royal Infirmary and Aberdeen University Medical School, Foresterhill, Aberdeen, Scotland, UK
  10. 10Department of Pathology, Çukurova University, Adana, Turkey
  11. 11Acibadem Health Group, Istanbul, Turkey
  12. 12Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
  13. 13Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona, USA
  1. Correspondence to Dr Sanjay Mukhopadhyay, Department of Pathology, State University of New York Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, USA; mukhopas{at}upstate.edu

Abstract

Background The frequencies of various causes of pulmonary granulomas in pathological material are unknown, as is the influence of geographical location on aetiology. The aim of this study was to identify the causes of pulmonary granulomas in pathological specimens, to define their frequencies, and to determine whether these causes vary by geographical location.

Methods 500 lung biopsies and resections containing granulomas were reviewed retrospectively by expert pulmonary pathologists from 10 institutions in seven countries. Fifty consecutive cases from each location were assigned a diagnosis based on histological features and available clinical/microbiological data.

Results A specific cause was identified in 58% of cases (290/500), most commonly sarcoidosis (136, 27%) and mycobacterial or fungal infections (125, 25%). Mycobacteria were identified in 19% of cases outside the USA versus 8% within the USA. In contrast, fungi accounted for 19% cases in the USA versus 4% in other locations. Fungi were mostly detected by histology, whereas most mycobacteria were identified in cultures. In 42% of cases (210/500) an aetiology could not be determined.

Conclusions Across several geographical settings, sarcoidosis and infections are the most common causes of pulmonary granulomas diagnosed in pathological specimens. Fungi are more commonly identified than mycobacteria in the USA, whereas the reverse is true in other countries. A definite aetiology cannot be demonstrated in more than a third of all cases of pulmonary granulomas, even after histological examination. These findings highlight the need to submit material for histology as well as cultures in all cases in which granulomatous disease enters the differential diagnosis.

  • Fungal
  • granulomatous
  • immunohistochemistry
  • infection
  • lung cancer
  • mycobacterial
  • pulmonary pathology
  • sarcoidosis
  • Wegener granulomatosis

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Footnotes

  • This work was performed at multiple institutions: Department of Pathology, State University of New York Upstate Medical University, Syracuse, New York, USA; Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Pulmonary Medicine, Mayo Clinic, Scottsdale, Arizona, USA; Department of Respiratory Medicine, Aberdeen Royal Infirmary and Aberdeen University Medical School, Foresterhill, Aberdeen, Scotland, UK; Department of Pathology, Medical University of Graz, Graz, Austria; Department of Pathology, Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania, USA; Department of Pathology, University of São Paulo, São Paulo, Brazil; Laboratory of Pathology, Toyama University Hospital, Toyama, Japan; Department of Pathology, Aberdeen Royal Infirmary and Aberdeen University, Medical School, Foresterhill, Aberdeen, Scotland, UK; Department of Pathology, Çukurova University, Adana, Turkey; Department of Pathology, All India Institute of Medical Sciences, New Delhi, India; Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona, USA.

  • Competing interests None.

  • Ethics approval Institutional review boards (IRB) or equivalent bodies from all contributing institutions approved the study or exempted it from review (corresponding author IRB: SUNY Upstate Medical University IRB for the Protection of Human Subjects; exempt number: 40-09).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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