Granuloma

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A granuloma, also granulomatous inflammation, is a distinctive histomorphologic finding.

Micrograph showing a granuloma (bottom of image) in Crohn's disease. H&E stain.

Granulomas can be elusive to the novice.

The plural of granuloma was granulomata; granulomas (an anglicized version) is, however, now generally accepted.

General

Definition of granuloma

  • Many definitions exist.
  • The term is used rather loosely by clinicans.
    • Radiologists occasionally call small lung nodules "granulomas".

Strict pathologic definition

Robbins definition:

  • Chronic inflammatory reaction characterized by the focal accumulation of activated macrophages, often with an epithelioid appearance.[1]
    • "Epithelioid" cells = cells whose morphology resembles that of epithelial cells; the cells appear to adhere to one another.

Adams definition - it's short & sweet:

  • A compact collection of macrophages.[2]
    • The macrophages must form a small ball/cluster of cells, i.e. touch one another.

Other pathologic definitions include the presence of:[2]

  • Plasma cells.
  • Lymphocytes.
  • Epithelioid macrophages.

Notes:

  • The textbook answer for what is a granuloma is: "A collection of epithelioid macrophages."
    • Granulomas are often associated with lymphocytes.

Etiologic classification of granulomas

  1. Infectious, e.g. tuberculosis, MAC, leprosy, syphilis, cat-scratch disease, schistosomiasis,[3] fungal infection.
  2. Neoplastic, e.g. seminoma, Lennert lymphoma,[4] ruptured ovarian teratoma.[5]
  3. Autoimmune/inflammatory, e.g. Wegener's granulomatosis, Churg-Strauss syndrome.
  4. Allergic, e.g. hypersensitivity pneumonitis.
  5. Foreign body, e.g. pulmonary talcosis, silicosis, berylliosis,[3] suture material.
  6. Drug reaction.
  7. Idiopathic, e.g. sarcoidosis.

Notes:

  • Memory device: DNF AAII = drug reaction, neoplasm, foreign body, allergy, autoimmune, idiopathic, infection.
  • A long DDx for granulomas is complied by James.[6]

Microscopic

Features that assist one in finding granulomas

  1. Collection of cells that have abundant bubbly cytoplasm - most useful feature.
  2. Multinucleated giant cells - these are easy to identify if you've seen some before.
    • Individual/singular multinucleated giant cells are not diagnostic of a granuloma... but should raise one's suspicion of one being present.
  3. Necrosis - too much pink (on H&E stained sections).

Notes:

  • Small round collection of lymphocytes - without a capsule (as seen in lymph nodes).
    • If there are no macrophages... it's a lymphoid nodule.

Images

  • Granulomas showing abundant bubbly cytoplasm. (WC)

  • Granulomas with multinucleated giant cells in sarcoidosis. (WC)

  • Granuloma with asteroid bodies. (WC)

  • Granuloma with necrosis. (WC)

As a list

Features:[7]

  1. Foamy/bubbly cytoplasm, abundant - low power.
  2. Epithelioid morphology - cell borders near indistinct - key feature.
  3. "Footprint" pattern nuclei/bean-shaped nuclei - key feature.
    • Macrophages usu. have an ovoid nucleus.
  4. +/-Nucleoli, small.
  5. +/-Fibrosis.
  6. +/-Palisading at edge.

DDx

  • Reactive germinal centre - especially if there are abundant surrounding lymphocytes.[8]

Histologic classification of granulomas

  1. Necrosing (also caseating).
  2. Non-necrosing.
    • Less likely to be infectious.
    • Examples: Crohn's disease, sarcoidosis, drug reaction.

Whether necrosis is present in a granuloma is affected by the immune function, e.g. a HIV/AIDS patient may have non-necrosing granulomata due to TB.

Notes:

  • A few people differentiate between caseating (fragments of recognizable tissue) and necrosing (dead debris only).[9]
  • Infectious non-necrosing infections: Mycobacterium avium complex (MAC), cryptococcus, infections in immunosuppressed individuals.[9]

Special granulomas

Fibrin ring granuloma

  • Classically associated with Q fever.
    • DDx:[10] infections (Coxiella burnetii (causes Q fever), CMV, EBV + others), drug reaction, malignancy (e.g. Hodgkin lymphoma[11]).
  • Appearance:
    • Epithelioid macrophages (i.e. a granuloma) surrounding a fibrin ring with a clear (lipid-filled) vacuole at its center.

Naked granuloma

Specific sites

Lung granulomas

There are many causes.[9]

Infectious:

Non-infectious:

Idiopathic/autoimmune:

Prostate granulomas

Main article: Granulomatous prostatitis

Stomach granulomas

Main article: Granulomatous gastritis

Lymph node granulomas

Main article: Lymph node pathology

Includes:

Skin granulomas

Main article: Inflammatory_skin_disorders#Granulomatous

See also

References

  1. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 82. ISBN 0-7216-0187-1.
  2. ↑ 2.0 2.1 Adams DO (1976). "The granulomatous inflammatory response. A review.". American Journal of Pathology 84 (1): 164–191. PMID 937513. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032357/?tool=pubmed.
  3. ↑ 3.0 3.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 47. ISBN 978-1416054542.
  4. ↑ Summers, TA.; Rush, W.; Aguilera, N.; Lupton, G. (Oct 2009). "Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature.". J Cutan Pathol 36 Suppl 1: 25-30. doi:10.1111/j.1600-0560.2008.01203.x. PMID 19775391.
  5. ↑ Phupong, V.; Sueblinvong, T.; Triratanachat, S. (Nov 2004). "Ovarian teratoma with diffused peritoneal reactions mimicking advanced ovarian malignancy.". Arch Gynecol Obstet 270 (3): 189-91. doi:10.1007/s00404-003-0479-8. PMID 15526210.
  6. ↑ James, DG. (Aug 2000). "A clinicopathological classification of granulomatous disorders.". Postgrad Med J 76 (898): 457-65. PMID 10908370.
  7. ↑ Santos, G. 26 January 2010.
  8. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 170. ISBN 978-0443066573.
  9. ↑ 9.0 9.1 9.2 El-Zammar, OA.; Katzenstein, AL. (Feb 2007). "Pathological diagnosis of granulomatous lung disease: a review.". Histopathology 50 (3): 289-310. doi:10.1111/j.1365-2559.2006.02546.x. PMID 17257125.
  10. ↑ Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W (2001). "Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature". Acta Clin Belg 56 (6): 341–8. PMID 11881318.
  11. ↑ de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B (July 1993). "Hepatic fibrin-ring granulomas in giant cell arteritis". Gastroenterology 105 (1): 272–3. PMID 8514044.
  12. ↑ Brinster, NK. (Nov 2008). "Dermatopathology for the surgical pathologist: a pattern-based approach to the diagnosis of inflammatory skin disorders (part II).". Adv Anat Pathol 15 (6): 350-69. doi:10.1097/PAP.0b013e31818b1ac6. PMID 18948765.
  13. ↑ Noiles, K.; Beleznay, K.; Crawford, RI.; Au, S.. "Sarcoidosis can present with necrotizing granulomas histologically: two cases of ulcerated sarcoidosis and review of the literature.". J Cutan Med Surg 17 (6): 377-83. PMID 24138972.
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