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The '''gallbladder''', in pathology (and '''general surgery'''), is a growth industry... due to the worsening obesity epidemic.
The '''gallbladder''', in pathology (and '''general surgery'''), is a growth industry... due to the worsening [[obesity]] epidemic.


==Normal==
=Normal=
===Histology===
==Anatomy==
*NO muscularis mucosae.
*Body.
*Fundus.
*Neck.
 
Variations:
*Hartmann's pouch - invagination of the gallbladder wall at the origin of the cystic duct.
 
Image:
*[http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder_fichiers/loadBinaryCAS7X571.jpg Hartmann's pouch (uni-plovdiv.bg)].<ref>URL: [http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder.htm http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder.htm]. Accessed on: 13 December 2012.</ref>
 
==Histology==
*'''No''' muscularis mucosae.
*Small amount of lymphocytes in the lamina propria.
*Small amount of lymphocytes in the lamina propria.


==Pathology==
Note:
*As there is no ''muscularis mucosae'', the [[cancer staging]] is different; pT1a is lamina propria invasion. pT1b is muscle layer invasion.
===Image===
<gallery>
Image:Gallbladder_-_intermed_mag.jpg | Normal gallbladder - intermed. mag. (WC/Nephron)
</gallery>
 
=Overview=
Most common:
Most common:
*Cholelithiasis with cholecystitis.
*Cholelithiasis with cholecystitis.


==Cholecystitis==
Common:
===Epidemiology===
*Antral-type metaplasia.
*Female, fat, fertile, family history, forty (though now getting younger... as people get fatter).


===Etiology===
Uncommon:
*Cholelithiasis.
*Intestinal metaplasia.
*Thick bile (acalculous cholecystitis).
*Gallbladder dysplasia.
*Gallbladder carcinoma.


===Clinical (classic)===
=Common=
*Constant right upper quadrant pain after a fatty meal.
==Chronic cholecystitis==
*Positive Murphy's sign (physical exam, with ultrasound).
{{Main|Chronic cholecystitis}}


===Gross===
==Acute cholecystitis==
*Strawberry-like appearance - common (due to cholesterolosis -- see below)
{{Main|Acute cholecystitis}}
**Small ridges (microvillus architecture).
 
***Normal gallbladder mucosa = smooth.
==Gallbladder cholesterolosis==
*Congestion/erythema.
{{Main|Gallbladder cholesterolosis}}
 
==Cholelithiasis==
*[[AKA]] ''gallstones''.
{{Main|Cholelithiasis}}


===Microscopic===
=Less common pathologic diagnoses=
*Rokitansky-Aschoff sinuses<ref>[http://www.whonamedit.com/synd.cfm/983.html http://www.whonamedit.com/synd.cfm/983.html]</ref>
==Adenomyoma of the gallbladder==
**Entrapped epithelial crypts -- pockets of epithelium in the wall of the gallbladder.
*[[AKA]] ''gallbladder adenomyosis''.
*+/-Foamy macrophages in the lamina propria.
*[[AKA]] ''adenomyomatosis of the gallbladder''.
*Inflammatory cells.
*[[AKA]] ''gallbladder adenomyoma''.
**[[Neutrophils]] are not essential for the Dx - usually secondary to necrosis/ulceration or infection.<ref>DCHHP P.174</ref>


==Cholesterolosis==
===General===
===General===
*Common in cholecystitis.
*Glands in muscle.
*Assoc. with yellow gallstones (cholesterol type gallstones).
*Analogous to what happens in the [[uterine adenomyosis|uterus]].
*Significance - may mimic malignant tumours of the gallbladder.<ref>{{Cite journal  | last1 = Saul | first1 = WM. | last2 = Herrmann | first2 = PK. | title = [Adenomyoma of the gallbladder]. | journal = Dtsch Z Verdau Stoffwechselkr | volume = 48 | issue = 2 | pages = 112-6 | month =  | year = 1988 | doi =  | PMID = 3168899 }}</ref><ref name=pmid9350002 >{{Cite journal  | last1 = Sasatomi | first1 = E. | last2 = Miyazaki | first2 = K. | last3 = Mori | first3 = M. | last4 = Satoh | first4 = T. | last5 = Nakano | first5 = S. | last6 = Tokunaga | first6 = O. | title = Polypoid adenomyoma of the gallbladder. | journal = J Gastroenterol | volume = 32 | issue = 5 | pages = 704-7 | month = Oct | year = 1997 | doi =  | PMID = 9350002 }}
</ref>
*Uncommon.


===Gross===
===Gross===
*Mucsoa has strawberry-like appearance.
*Cystic spaces (Rokitansky-Aschoff sinuses) - may be seen on imaging.<ref name=pmid17579153>{{Cite journal  | last1 = Ching | first1 = BH. | last2 = Yeh | first2 = BM. | last3 = Westphalen | first3 = AC. | last4 = Joe | first4 = BN. | last5 = Qayyum | first5 = A. | last6 = Coakley | first6 = FV. | title = CT differentiation of adenomyomatosis and gallbladder cancer. | journal = AJR Am J Roentgenol | volume = 189 | issue = 1 | pages = 62-6 | month = Jul | year = 2007 | doi = 10.2214/AJR.06.0866 | PMID = 17579153 }}</ref><ref name=pmid16702464>{{Cite journal  | last1 = Boscak | first1 = AR. | last2 = Al-Hawary | first2 = M. | last3 = Ramsburgh | first3 = SR. | title = Best cases from the AFIP: Adenomyomatosis of the gallbladder. | journal = Radiographics | volume = 26 | issue = 3 | pages = 941-6 | month =  | year =  | doi = 10.1148/rg.263055180 | PMID = 16702464 | URL = http://radiographics.rsna.org/content/26/3/941.long}}</ref>
*Gallbladder wall thickening.


===Microscopic===
===Microscopic===
*Foamy macrophages.
Features:<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Glands in muscularis propria of the gallbladder wall - '''key feature'''.
*Significant muscular hypertrophy - '''key feature'''.
*No nuclear atypia.


Image:
DDx:
*[http://commons.wikimedia.org/wiki/File:Gallbladder_cholesterolosis_micro.jpg Cholesterolosis (micrograph)] - wikipedia.org.
*[[Gallbladder carcinoma]].
*[[Chronic cholecystitis]] - has less muscular hypertrophy; overlaps with this diagnosis.<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Phrygian cap.<reF>URL: [http://radiopaedia.org/articles/phrygian_cap http://radiopaedia.org/articles/phrygian_cap]. Accessed on: 16 May 2014.</ref>


==Cholelithiasis==
====Image====
*Often accompanies cholecystitis/contributes and/or causes cholecystitis
*[http://pubs.rsna.org/na101/home/literatum/publisher/rsna/journals/content/radiographics/2006/radiographics.2006.26.issue-3/rg.263055180/production/images/medium/g06ma19c05x.jpeg Adenomyomatosis of the gallbladder (radiographics.rsna.org)].<ref name=pmid16702464/>


The two types of gallstones:
===Sign out===
*Cholesterol stones
<pre>
**More common than pigment stone.
GALLBLADDER, CHOLECYSTECTOMY:
**Appearance:
- CHRONIC CHOLECYSTITIS WITH MILD CHOLESTEROLOSIS AND ADENOMYOSIS (FUNDUS).
***Clear or yellow.
- CHOLELITHIASIS.
***Opaque or translucent.
</pre>
***Sometimes shinny.
*Pigment stones
**Due to high RBC turnover, e.g. sickle cell anemia, thalassemia.
**Appearance:
***Black - '''key feature'''.
***Dull.


Note: Most stones are a mix technically speaking, i.e. cholesterol and pigment. Many call yellow stones that are often a mix "cholesterol stones".
==Gallbladder polyps==
===General===
*Polyps are significant as they may be adenomatous, i.e. pre-cancerous.
*These are similar to [[intestinal polyps|polyps]] found elsewhere GI tract.
===Microscopic===
:See ''[[intestinal polyps]]''.


Crystalline gallstones -- UC association (?):<ref>http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1358536</ref>
Flat dysplasia:<ref name=Ref_DCHH172>{{Ref DCHH|172}}</ref>
*Nuclear changes.  
**Increased [[NC ratio]].
**Hyperchromasia (essential).
**+/-Intestinal metaplasia --> goblet cells.


==Less common pathologic diagnoses==
==Gallbladder diverticulosis==
==Adenomyosis==
===General===
===General===
*Glands in muscle.
*Uncommon.
*Analogous to what happens in the uterus.
*Thought to arise in the context of an outflow obstruction.<ref name=pmid4963758>{{Cite journal  | last1 = Beilby | first1 = JO. | title = Diverticulosis of the gall bladder. The fundal adenoma. | journal = Br J Exp Pathol | volume = 48 | issue = 4 | pages = 455-61 | month = Aug | year = 1967 | doi =  | PMID = 4963758 | PMC = 2093791 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2093791/}}</ref>
*Significance??? -- consequence of long standing cholecystitis/Rokitansky-Aschoff sinuses???
 
===Microscopic===
Features:
*Mucosal pouch penetrating the muscularis propria of the gallbladder wall - '''key feature'''.


===Histology===
DDx:
*Glands in muscularis propria of the gallbladder wall.
*[[Chronic cholecystitis]].
*[[Gallbladder adenomyosis]].


==Gangrenous gallbladder==
===Sign out===
*Necrosis of gallbladder wall (muscularis propria).<ref>STC 25 Feb 2009.</ref>
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH DIVERTICULOSIS.
- CHOLELITHIASIS.
</pre>


==Polyps==
==Xanthogranulomatous cholecystitis==
*Polyps - significant as they may be adenomatous, i.e. pre-cancerous.
*Abbreviated ''XGC''.
{{Main|Xanthogranulomatous cholecystitis}}


Flat dysplasia<ref>DCHHP P.172</ref>
==Pancreatic heterotopia==
*Nuclear changes
[[File:Gallbladder mass benign A sl 1.png|Pancreatic heterotopia in 35 year old women]]
**Incr. [[NC ratio]],
[[File:Gallbladder mass benign A sl 2.png|Pancreatic heterotopia in 35 year old women]]
**Hyperchromasia (essential),
[[File:Gallbladder mass benign A sl 3.png|Pancreatic heterotopia in 35 year old women]]
**+/-Intestinal metaplasia --> goblet cells.
[[File:Gallbladder mass benign A sl 4.png|Pancreatic heterotopia in 35 year old women]]<br>
Pancreatic heterotopia near cystic duct in 35 year old women. A. The cystic duct margin is at right; the heterotopia, at left. This cannot be a portion of the pancreas because the cystic duct margin lies proximal to the common bile duct. B. Pancreatic ducts with lobular proliferation, but without the inflammation that would usually be present were this obstruction by a gallstone. C. Nuclei of the duct and the proliferated bile ductules are bland. D. Acini are unremarkable; no pancreatic islets were seen in this case.


==Premalignant lesions - metaplasia/dysplasia==
=Premalignant lesions=
*Metaplasia assoc. with carcinoma.<ref name=pmid8364865>{{cite journal |author=Duarte I, Llanos O, Domke H, Harz C, Valdivieso V |title=Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples |journal=Cancer |volume=72 |issue=6 |pages=1878–84 |year=1993 |month=September |pmid=8364865 |doi= |url=}}</ref>
===General===
*Metaplasia associated with carcinoma.<ref name=pmid8364865>{{cite journal |author=Duarte I, Llanos O, Domke H, Harz C, Valdivieso V |title=Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples |journal=Cancer |volume=72 |issue=6 |pages=1878–84 |year=1993 |month=September |pmid=8364865 |doi= |url=}}</ref>


Hypothesis:<ref>{{cite journal |author=Mukhopadhyay S, Landas SK |title=Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens |journal=Arch. Pathol. Lab. Med. |volume=129 |issue=3 |pages=386–90 |year=2005 |month=March |pmid=15737036 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=129&page=386}}</ref>
Hypothesis:<ref name=pmid15737036>{{cite journal |author=Mukhopadhyay S, Landas SK |title=Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens |journal=Arch. Pathol. Lab. Med. |volume=129 |issue=3 |pages=386–90 |year=2005 |month=March |pmid=15737036 |doi= |url=http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 }}</ref>
*Antral type metaplasia --> intestinal metaplasia --> dysplasia --> carcinoma.
*Antral type metaplasia --> intestinal metaplasia --> dysplasia --> carcinoma.


==Intestinal metaplasia==
==Intestinal metaplasia of the gallbladder==
Definition:
*[[AKA]] ''gallbladder [[intestinal metaplasia]]''.
*Presence of [[goblet cell]]s -/+ paneth cells<ref>Sternberg DSP4 P.1789</ref>
{{Main|Intestinal metaplasia of the gallbladder}}
 
Significance:
*Increased risk of carcinoma.<ref name=pmid8364865/>


==Antral type metaplasia==
==Antral type metaplasia==
General
===General===
*[[aka]] ''pyloric metaplasia'', ''pseudopyloric metaplasia'', ''mucous gland metaplasia''.<ref>Sternberg DSP4 P.1789</ref>
*[[AKA]] ''pyloric metaplasia'', ''pseudopyloric metaplasia'', ''mucous gland metaplasia''.<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref>


Micro.
===Microscopic===
*Cells with...<ref>Sternberg DSP4 P.1789</ref>  
Features:<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref>  
*Columnar cells with:
**Abundant, pale, apical mucin.
**Abundant, pale, apical mucin.
**Small basal nucleus.
**Small basal nucleus.
Line 115: Line 155:
*Cells vaguely resemble foveollar epithelium of the stomach.
*Cells vaguely resemble foveollar epithelium of the stomach.


==Dysplasia==
Notes:
*Premalignant lesion.
*May look similar to cells of the gallbladder neck<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref> and common bile duct.<ref>Cutz, E. 3 March 2011.</ref>
**These glandular cells are not as columnar and have less well-defined cell borders.
***Cells with antral type metaplasia >2:1 (height:width), benign mucosal glands <2:1.
 
Images:
*[http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 Gallbladder metaplasias (archivesofpathology.org)].<ref name=pmid15737036>{{cite journal |author=Mukhopadhyay S, Landas SK |title=Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens |journal=Arch. Pathol. Lab. Med. |volume=129 |issue=3 |pages=386–90 |year=2005 |month=March |pmid=15737036 |doi= |url=http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 }}</ref>


===Microscopic===
===Sign out===
Features:
<pre>
*Nuclear crowding.
Gallbladder, Cholecystectomy:
*Nuclear hyperchromasia.
- Chronic cholecystitis with antral-type metaplasia, NEGATIVE for dysplasia.
- Cholelithiasis.
</pre>
 
==Gallbladder adenoma==
:''Gallbladder dysplasia'' is covered in ''[[gallbladder adenoma]]''.
{{Main|Gallbladder adenoma}}


Notes:
==Intracholecystic Papillary Neoplasm<ref>{{Cite journal  | last1 = Adsay | first1 = V. | last2 = Jang | first2 = KT. | last3 = Roa | first3 = JC. | last4 = Dursun | first4 = N. | last5 = Ohike | first5 = N. | last6 = Bagci | first6 = P. | last7 = Basturk | first7 = O. | last8 = Bandyopadhyay | first8 = S. | last9 = Cheng | first9 = JD. | title = Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. | journal = Am J Surg Pathol | volume = 36 | issue = 9 | pages = 1279-301 | month = Sep | year = 2012 | doi = 10.1097/PAS.0b013e318262787c | PMID = 22895264 }}
*Like in the colon.
</ref>==


==Carcinoma==
===General===
===Epidemiology===
*Probably some overlap with 'adenoma' above
*Associated with gallstones.
*Lesion defined as being >1cm.
*Sex: female > male.
*Low-grade lesions previously designated “papillary adenoma”
*Location: usually fundus, sometimes body.
*High-grade lesions previously designated “noninvasive papillary carcinoma.”
*Oten arise in a background of pyloric-gland metaplasia.  
*May be associated with invasive adenocarcinoma, which should be reported as intracystic papillary neoplasm with an associated invasive carcinoma and staged.


Notes:
*Population
*Calcification of gallbladder wall aka "Porcelain gallbladder" -- '''not''' associated with carcinoma.<ref>{{cite journal |author=Towfigh S, McFadden DW, Cortina GR, ''et al'' |title=Porcelain gallbladder is not associated with gallbladder carcinoma |journal=Am Surg |volume=67 |issue=1 |pages=7?0 |year=2001 |month=January |pmid=11206901 |doi= |url=}}</ref>
**Female (F/M=2:1)
*Cholangiocarcinoma is dealt with in the ''[[liver neoplasms]]'' article.
**Mean age 61
*Presentations
**Pain
**Incidental
*No particular association with gallstones.


===Microscopic===
===Microscopic===
*Usually adenocarcinoma.
*Cell types
**Mimics appearance of pancreatic ductal adenocarcinoma-- but less cellular mucin.<ref>DCHHP P.174</ref>
**Pancreatobiliary type
**Intestinal types with goblet, Paneth, and/or serotonin-containing cells.
*Architecture
**Papillary
**Tubulopapillary
**Tubular
*Dysplasia - high or low grade
 
<gallery>
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma LP CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - Low power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP3 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP2 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma MP CTR.jpg|Gall Bladder - - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - Malignant gland infiltrating stroma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP4 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma -  - Malignant gland infiltrating stroma - Very high power (SKB)
Image:Gallbladder IntracysticPapillaryNeoplasm HighGradeDysplasia LP PA.JPG|Gall Bladder - Intracholecystic Papillary Neoplasm with high grade dysplasia - Low power (SKB)
Image:Gallbladder IntracysticPapillaryNeoplasm HighGradeDysplasia MP PA.JPG|Gall Bladder - Intracholecystic Papillary Neoplasm with high grade dysplasia - Medium power (SKB)
</gallery>


Notes:
Notes:
*May be very subtle, i.e. difficult to differentiate from normal glands.
All of the gallbladder should be submitted prior to sign out to exclude invasive adenocarcinoma.
 
=Malignant=
==Gallbladder carcinoma==
{{Main|Gallbladder carcinoma}}


==See also==
=See also=
*[[Liver]].
*[[Liver]].
*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Gallbladder]]
[[Category:Gastrointestinal pathology]]
[[Category:Gastrointestinal pathology]]
Michael
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