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Granulomas in bone marrow biopsies: clinicopathological significance and new perspectives
  1. Umberto Maccio1,
  2. Alessandra Gianolio2,
  3. Anton V Rets3,4
  1. 1Pathology and Molecular Pathology, University Hospital Zurich, Zürich, Switzerland
  2. 2Department of Medical Sciences, University of Turin, Torino, Piemonte, Italy
  3. 3Department of Hematopathology, ARUP Laboratories Inc, Salt Lake City, Utah, USA
  4. 4Pathology, The University of Utah School of Medicine, Salt Lake City, Utah, USA
  1. Correspondence to Dr Umberto Maccio, Pathology and Molecular Pathology, University Hospital Zurich, Zürich, Switzerland; umberto.maccio{at}


Bone marrow granulomas in trephine biopsies are a rare and usually incidental finding. Possible causes include infectious (especially tuberculous and rarer non-tuberculous mycobacteria, but also many other bacterial, viral, fungal and parasitic agents) and non-infectious causes (especially medications, autoimmune disease, sarcoidosis, haematological and non-haematological malignancy). Necrotising granulomas are generally suggestive of an infectious aetiology (tuberculosis being the most common), whereas fibrin ring granulomas are associated with Q-fever and Epstein Barr Virus, although exceptions are possible. Every case suspicious for infectious aetiology should undergo further analysis like special staining (Ziehl-Neelsen for acid-fast rods) or molecular studies. The histomorphology should always be clinically correlated. In cases in which no infectious cause can be identified, untargeted metagenomics may represent a valid diagnostic tool that may become standard in the near future for bone marrow diagnostics. In this review, we have analysed the published data from 1956 up to today, and we report aspects of epidemiology, aetiology, diagnostic algorithms, differential diagnosis and the role of metagenomics in bone marrow biopsies with granulomas.

  • bone marrow
  • PCR
  • granuloma

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  • Handling editor Runjan Chetty.

  • Contributors UM designed the review, researched and analysed the literature, performed statistical analysis, drafted the paper and tables, coordinated authors. AG researched and analysed the literature, drafted the paper and tables. AVR designed the review, searched and analysed the literature, drafted the paper, provided figures.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

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