Bone marrow nonneoplastic

Infectious / inflammatory

Granulomatous inflammation

Topic Completed: 1 May 2014

Minor changes: 29 January 2021

Copyright: 2002-2019,, Inc.

PubMed Search: Bone marrow granulomatous inflammation

Dragos C. Luca, M.D.
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Cite this page: Luca DC. Granulomatous inflammation. website. Accessed December 3rd, 2021.
Definition / general
Clinical presentation and diagnosis
  • Associated with fever and anemia
  • Disorders with epithelioid granulomas:
    • Tuberculosis: generally large with central caseation and frequent giant cells; organisms rarely identified
    • Histoplasmosis: variably sized, caseation or giant cells in ~50% of cases; organisms rare to moderately abundant
    • Mycobacterium avium complex: variably sized, generally noncaseating; organisms usually abundant
    • Viral: small, ill defined, with no caseation or giant cells; rarely ring shaped; predominantly lymphocytes, plasma cells, immunoblasts
    • Lymphoma and other neoplasms: usually small epithelioid granulomas
    • Sarcoidosis: diagnosis of exclusion (perform GMS and acid fast stains to rule out fungi and mycobacteria) (eMedicine: Pediatric Sarcoidosis)
    • Other conditions: posttherapy, immune disorders, bone marrow transplantation, BCG
Case reports
Microscopic (histologic) description
  • Variably sized but usually small, focal and nonnecrotic
  • Composed of cohesive clusters of histiocytes, usually with admixed lymphocytes, eosinophils, neutrophils
  • Granulomas often paratrabecular
  • Ring or "doughnut" granulomas: fibrin and inflammatory cells arranged around a central clear space; associated with Q fever (but not specific)
  • Lipid granulomas: frequent; up to 1μ; associated with sinusoids or lymphoid aggregates; macrophages with fat vacuoles of varying size; also lymphocytes, plasma cells, eosinophils; giant cells in 5%; lipogranulomas generally considered insignificant
  • Small and rare epithelioid granulomas may also be clinically insignificant
  • Larger epithelioid granulomas, especially if containing a central area of necrosis (caseation) are significant and usually indicate infection (Brucella, Rickettsia, fungi)
  • Ring granulomas are also significant and also likely infectious (Q fever, Brucella, typhoid, rare viral infections)
  • Granulomas with distinctive finely vacuolated cells (Virchow cells) in leprosy
  • Rarely, foreign body granulomas can occur
  • Mycobacteria: clusters of histiocytes with needle-like inclusions resembling Gaucher cells (J Clin Pathol 2005;58:1113); rarely hemophagocytosis in dialysis patients with TB
  • Sarcoidosis: multiple noncaseating granulomas in 10% (Haematologia (Budap) 2002;32:419); occasional fibrinoid necrosis in active cases
Microscopic (histologic) images

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Peritrabecular sarcoid-like lesion

Bone marrow ring granulomas

Infiltrating lobular carcinoma of breast: H&E and keratin


CML treated with interferon

Noncaseating BM granuloma

Multinucleated giant cell

Granuloma in BM aspirate smear

CD68 immunostain

Histoplasmosis - BM granuloma

Histoplasmosis - organisms visible on H&E

Histoplasmosis - GMS stain

Caseating tuberculous granulomas


Histiocytes with needle-like inclusions

MAC infection within clusters of histiocytes

Acid fast stain

Necrotic lymph node

Bone marrow granuloma

Acid fast stain of lymph node

Acid fast stain of bone marrow


Small focus of necrosis

Larger focus of necrosis

Lymph node with extensive necrosis

Lymph node with large foci of confluent necrosis

Granuloma exhibiting suppurative necrosis

Apoptotic bodies

Apoptotic bodies with small focus of necrosis

Fragmentation of apoptotic bodies

Apoptotic bodies with small foci of necrosis

Apoptotic bodies without necrosis

Cytoplasmic eosinophiiia is evident

  • CD68 highlights the clustering of histiocytes
  • Mycobacteria: acid fast
Differential diagnosis
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