Difference between revisions of "Granuloma"

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#redirect [[Basics#Granulomas]]
[[Image: Crohn's disease - colon - very high mag.jpg | thumb | right| [[Micrograph]] showing a granuloma (bottom of image) in [[Crohn's disease]]. [[H&E stain]].]]
[[Image:Seminoma with granulomas - alt --- high mag.jpg|thumb| right| [[Micrograph]] showing a granuloma (bottom of image) in [[seminoma]]. [[H&E stain]].]]
A '''granuloma''', also '''granulomatous inflammation''', is a distinctive histomorphologic finding.
 
Granulomas can be elusive to the novice.
 
The plural of ''granuloma'' was ''granulomata''; ''granulomas'' (an anglicized version) is, however, now generally accepted.
 
There is a specific disease called ''chronic granulomatous disease''; it is dealt with in the ''[[chronic granulomatous disease]]'' article.
 
==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.<ref name=Ref_PBoD82>{{Ref PBoD|82}}</ref>
**"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.<ref name=pmid937513>{{cite journal |author=Adams DO |title=The granulomatous inflammatory response. A review.  |journal=American Journal of Pathology |volume=84 |issue=1 |pages=164&ndash;191 |year=1976 |pmid=937513 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032357/?tool=pubmed}}</ref>
**The macrophages must form a small ball/cluster of cells, i.e. touch one another.
 
Other pathologic definitions include the presence of:<ref name=pmid937513/>
*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===
#Infectious, e.g. [[tuberculosis]], [[MAC]], [[leprosy]], [[syphilis]], [[cat-scratch disease]], schistosomiasis,<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref> fungal infection.
#Neoplastic, e.g. [[seminoma]], Lennert lymphoma,<ref name=pmid19775391>{{Cite journal  | last1 = Summers | first1 = TA. | last2 = Rush | first2 = W. | last3 = Aguilera | first3 = N. | last4 = Lupton | first4 = G. | title = Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature. | journal = J Cutan Pathol | volume = 36 Suppl 1 | issue =  | pages = 25-30 | month = Oct | year = 2009 | doi = 10.1111/j.1600-0560.2008.01203.x | PMID = 19775391 }}</ref> ruptured ovarian teratoma,<ref name=pmid15526210>{{Cite journal  | last1 = Phupong | first1 = V. | last2 = Sueblinvong | first2 = T. | last3 = Triratanachat | first3 = S. | title = Ovarian teratoma with diffused peritoneal reactions mimicking advanced ovarian malignancy. | journal = Arch Gynecol Obstet | volume = 270 | issue = 3 | pages = 189-91 | month = Nov | year = 2004 | doi = 10.1007/s00404-003-0479-8 | PMID = 15526210 }}</ref> [[Hodgkin lymphoma]].<ref name=pmid17143374>{{Cite journal  | last1 = Al-Maghrabi | first1 = JA. | last2 = Sawan | first2 = AS. | last3 = Kanaan | first3 = HD. | title = Hodgkin's lymphoma with exuberant granulomatous reaction. | journal = Saudi Med J | volume = 27 | issue = 12 | pages = 1905-7 | month = Dec | year = 2006 | doi =  | PMID = 17143374 }}</ref>
#Autoimmune/inflammatory, e.g. [[Granulomatosis with polyangiitis]] (Wegener's granulomatosis), [[Eosinophilic granulomatosis with polyangiitis]] (Churg-Strauss syndrome).
#Allergic, e.g. [[hypersensitivity pneumonitis]].
#Foreign body, e.g. [[pulmonary talcosis]], silicosis, berylliosis,<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref> [[suture material]].
#Drug reaction.
#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''.<ref name=pmid10908370>{{Cite journal  | last1 = James | first1 = DG. | title = A clinicopathological classification of granulomatous disorders. | journal = Postgrad Med J | volume = 76 | issue = 898 | pages = 457-65 | month = Aug | year = 2000 | doi =  | PMID = 10908370 }}</ref>
 
==Microscopic==
===Features that assist one in finding granulomas===
#Collection of cells that have abundant bubbly cytoplasm - '''most useful feature'''.
#'''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.
#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''.
 
====As a list====
Features:<ref>Santos, G. 26 January 2010.</ref>
#Foamy/bubbly cytoplasm, abundant - '''low power'''.
#Epithelioid morphology - cell borders ''near'' indistinct - '''key feature'''.
#"Footprint" pattern nuclei/bean-shaped nuclei - '''key feature'''.
#*Macrophages usu. have an ovoid nucleus.
#+/-Nucleoli, small.
#+/-Fibrosis.
#+/-Palisading at edge.
 
====DDx====
*Reactive germinal centre - especially if there are abundant surrounding lymphocytes.<ref name=Ref_GLP170>{{Ref GLP|170}}</ref>
 
====Images====
<gallery>
Image:Granuloma mac.jpg | Granuloma due to [[MAC]]. (WC)
Image:Granuloma_20x.jpg |Granulomas showing abundant bubbly cytoplasm. (WC)
Image:Asteroid_body_intermed_mag.jpg |Granulomas with multinucleated giant cells in sarcoidosis. (WC)
Image: Asteroid_body_very_high_mag.jpg | Granuloma with [[asteroid bodies]]. (WC)
Image:Necrogran10x.jpg|Granuloma with necrosis. (WC)
<gallery>
Image: Seminoma with granulomas -- intermed mag.jpg | [[Seminoma]] with granulomas - intermed. mag. (WC)
Image: Seminoma with granulomas -- high mag.jpg | Seminoma with granulomas - high mag. (WC)
Image: Seminoma with granulomas -- very high mag.jpg | Seminoma with granulomas - very high mag. (WC)
</gallery>
 
=====Cytology=====
{{Main|Cytopathology#Granulomata}}
<gallery>
Image: Granulomatous inflammation -- intermed mag.jpg | GI - intermed. mag. (WC)
Image: Granulomatous inflammation -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation - alt -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation -- very high mag.jpg | GI - very high mag. (WC)
</gallery>
 
====Histologic classification of granulomas====
#Necrosing (also ''caseating'').
#*More likely to be infectious.
#*Examples: [[Tuberculosis]] (TB).
#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).<ref name=pmid17257125>{{Cite journal  | last1 = El-Zammar | first1 = OA. | last2 = Katzenstein | first2 = AL. | title = Pathological diagnosis of granulomatous lung disease: a review. | journal = Histopathology | volume = 50 | issue = 3 | pages = 289-310 | month = Feb | year = 2007 | doi = 10.1111/j.1365-2559.2006.02546.x | PMID = 17257125 }}</ref>
*Infectious non-necrosing infections: [[Mycobacterium avium complex]] (MAC), [[cryptococcus]], infections in immunosuppressed individuals.<ref name=pmid17257125/>
 
===Special granulomas===
====Fibrin ring granuloma====
*Classically associated with ''[[Q fever]]''.
**DDx:<ref name=pmid11881318>{{cite journal |author=Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W |title=Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature |journal=Acta Clin Belg |volume=56 |issue=6 |pages=341–8 |year=2001 |pmid=11881318 |doi= |url=}}</ref> infections (Coxiella burnetii (causes [[Q fever]]), [[CMV]], [[EBV]] + others), drug reaction, malignancy (e.g. Hodgkin lymphoma<ref name=pmid8514044>{{cite journal |author=de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B |title=Hepatic fibrin-ring granulomas in giant cell arteritis |journal=Gastroenterology |volume=105 |issue=1 |pages=272–3 |year=1993 |month=July |pmid=8514044 |doi= |url=}}</ref>).
*Appearance:
**Epithelioid macrophages (i.e. a granuloma) surrounding a fibrin ring with a clear (lipid-filled) vacuole at its center.
***Images:
****[http://en.gooword.com/picture/864449/ FRG (gooword.com)].
====Naked granuloma====
*Minimal (lymphoid) inflammation.
**Classically [[sarcoidosis]] <ref name=pmid18948765>{{Cite journal  | last1 = Brinster | first1 = NK. | title = Dermatopathology for the surgical pathologist: a pattern-based approach to the diagnosis of inflammatory skin disorders (part II). | journal = Adv Anat Pathol | volume = 15 | issue = 6 | pages = 350-69 | month = Nov | year = 2008 | doi = 10.1097/PAP.0b013e31818b1ac6 | PMID = 18948765 }}</ref><ref name=pmid24138972>{{Cite journal  | last1 = Noiles | first1 = K. | last2 = Beleznay | first2 = K. | last3 = Crawford | first3 = RI. | last4 = Au | first4 = S. | title = Sarcoidosis can present with necrotizing granulomas histologically: two cases of ulcerated sarcoidosis and review of the literature. | journal = J Cutan Med Surg | volume = 17 | issue = 6 | pages = 377-83 | month =  | year =  | doi =  | PMID = 24138972 }}</ref> - DDx large.
 
==Specific sites==
===Lung granulomas===
There are many causes.<ref name=pmid17257125/>
 
Infectious:
*Myocbacterial: [[Tuberculosis]], [[MAC]], other.
*Fungal: [[Histoplasmosis]], [[Cryptococcosis]], [[Blastomycosis]], [[Coccidioidomycosis]].
*[[Aspiration pneumonia]].
Non-infectious:
*Pneumoconioses/[[hypersensitivity pneumonitis]]: Talcosis, Berylliosis.
Idiopathic/autoimmune:
*[[Sarcoidosis]].
*[[Granulomatosis with polyangiitis]] (Wegener's granulomatosis).
*[[Eosinophilic granulomatosis with polyangiitis]] (Churg-Strauss disease).
*[[Rheumatoid nodules]].
 
===Prostate granulomas===
{{Main|Granulomatous prostatitis}}
 
===Stomach granulomas===
{{Main|Granulomatous gastritis}}
 
===Lymph node granulomas===
{{Main|Lymph node pathology}}
Includes:
*[[Tuberculosis]].
*[[Fungi|Fungal infection]].
*[[Cat-scratch disease]].
*[[Xanthogranulomatous lymphadenitis]].
*Others.
 
===Skin granulomas===
{{Main|Inflammatory_skin_disorders#Granulomatous}}
 
==See also==
*[[Basics]].
*[[Giant cells]].
*[[Schaumann bodies]].
*[[Asteroid bodies]].
*[[Chronic granulomatous disease]].
 
==References==
{{Reflist|2}}
 
==External links==
*[http://granuloma.homestead.com/ Altas of Granulomatous Diseases by Yale Rosen (granuloma.homestead.com)].
 
[[Category:Basics]]

Latest revision as of 14:46, 29 September 2017

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

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

Granulomas can be elusive to the novice.

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

There is a specific disease called chronic granulomatous disease; it is dealt with in the chronic granulomatous disease article.

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] Hodgkin lymphoma.[6]
  3. Autoimmune/inflammatory, e.g. Granulomatosis with polyangiitis (Wegener's granulomatosis), Eosinophilic granulomatosis with polyangiitis (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.[7]

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.

As a list

Features:[8]

  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.[9]

Images

  • Granuloma due to MAC. (WC)

  • Granulomas showing abundant bubbly cytoplasm. (WC)

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

  • Granuloma with asteroid bodies. (WC)

  • Granuloma with necrosis. (WC)

  • Seminoma with granulomas - intermed. mag. (WC)

  • Seminoma with granulomas - high mag. (WC)

  • Seminoma with granulomas - very high mag. (WC)

Cytology
Main article: Cytopathology#Granulomata

  • GI - intermed. mag. (WC)

  • GI - high mag. (WC)

  • GI - high mag. (WC)

  • GI - very high mag. (WC)

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).[10]
  • Infectious non-necrosing infections: Mycobacterium avium complex (MAC), cryptococcus, infections in immunosuppressed individuals.[10]

Special granulomas

Fibrin ring granuloma

  • Classically associated with Q fever.
    • DDx:[11] infections (Coxiella burnetii (causes Q fever), CMV, EBV + others), drug reaction, malignancy (e.g. Hodgkin lymphoma[12]).
  • 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.[10]

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. ↑ Al-Maghrabi, JA.; Sawan, AS.; Kanaan, HD. (Dec 2006). "Hodgkin's lymphoma with exuberant granulomatous reaction.". Saudi Med J 27 (12): 1905-7. PMID 17143374.
  7. ↑ James, DG. (Aug 2000). "A clinicopathological classification of granulomatous disorders.". Postgrad Med J 76 (898): 457-65. PMID 10908370.
  8. ↑ Santos, G. 26 January 2010.
  9. ↑ 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.
  10. ↑ 10.0 10.1 10.2 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.

External links

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