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==Granulomas==
==Granulomas==
*Granulomas can be elusive to the novice.
{{Main|Granuloma}}
*Plural of ''granuloma'' was ''granulomata''; ''granulomas'' (an anglicized version) is, however, now generally accepted.
 
===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.
 
===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''.
 
Images:
<gallery>
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:Necrogran10x.jpg|Granuloma with necrosis. (WC)
</gallery>
====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>
 
===Classification of granuloma===
====Histologic classification====
#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/>
 
====Etiologic classification====
#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>
#Autoimmune/inflammatory, e.g. [[Wegener's granulomatosis]], [[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>
 
===Lung granulomata===
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]].
*[[Wegener's granulomatosis]].
*[[Churg-Strauss disease]].
*[[Rheumatoid nodules]].
 
===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.


==Common morphologic problems==
==Common morphologic problems==
Michael
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