Gallbladder

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

Normal

Anatomy

  • Body.
  • Fundus.
  • Neck.

Variations:

  • Hartmann's pouch - invagination of the gallbladder wall at the origin of the cystic duct.

Image:

Histology

  • No muscularis mucosae.
  • Small amount of lymphocytes in the lamina propria.

Note:

  • As there is no muscularis mucosae, the cancer staging is different; pT1a is lamina propria invasion. pT1b is muscle layer invasion.

Image

  • Normal gallbladder - intermed. mag. (WC/Nephron)

Overview

Most common:

  • Cholelithiasis with cholecystitis.

Common:

  • Antral-type metaplasia.

Uncommon:

  • Intestinal metaplasia.
  • Gallbladder dysplasia.
  • Gallbladder carcinoma.

Common

Chronic cholecystitis

  • Abbreviated CC.

General

Epidemiology

  • Female, fat, fertile, family history, forty (though now getting younger... as people get fatter).

Etiology

  • Cholelithiasis.
  • Thick bile (acalculous cholecystitis).

Clinical (classic)

  • Constant right upper quadrant pain after a fatty meal.
  • Positive Murphy's sign (physical exam, with ultrasound).

Gross

  • +/-Cholelithiasis - strongly associated pathology.
  • +/-Strawberry-like appearance - common (due to gallbladder cholesterolosis).
    • Small ridges (microvillus architecture) + yellow.
      • Normal gallbladder mucosa = smooth, green.
  • +/-Congestion/erythema.
  • +/-Wall thickening - typically ~ 6-7 mm.[2]

Note:

  • Wall thickening (due to congestion/edema) is the important gross finding in acute cholecystitis.
  • Wall thickenss greater than 10 mm should raise the suspicion of malignancy.[2]

Microscopic

Features:[3]

  • Thickening of the gallbladder wall - due to fibrosis/muscular hypertrophy - key feature.
  • Chronic inflammatory cells - usu. "minimal".
    • Lymphocytes - most common.
  • Rokitansky-Aschoff sinuses - common.[4]
    • Entrapped epithelial crypts -- pockets of epithelium in the wall of the gallbladder.
  • +/-Foamy macrophages in the lamina propria (cholesterolosis of the gallbladder).

DDx:

Sign out

GALLBLADDER, CHOLECYSTECTOMY: 
- CHRONIC CHOLECYSTITIS. 
- CHOLELITHIASIS.

Liver present

GALLBLADDER, CHOLECYSTECTOMY: 
- CHRONIC CHOLECYSTITIS. 
- CHOLELITHIASIS.
- SMALL AMOUNT OF LIVER WITHOUT APPARENT PATHOLOGY.

Micro

The sections shows gallbladder wall with Rokitansky-Aschoff sinuses and a moderate mixed inflammatory infiltrate predominantly consisting of lymphocytes. No nuclear atypia is seen.

Acute cholecystitis

General

  • Less common than chronic cholecystitis.
  • Usually due to gallstones.[5]
  • Classically older individuals (50s and 60s) with a slight female predominance.[5]

Notes:

  • Pathologic diagnosis very often discordant with clinical impression.[6]

Gross

Features:[5]

  • Wall thickening - due to edema and hemorrhage.†
  • Gallstone(s) - classically obstructing the gallbladder neck.

Note:

  • † The sonographic criterium for "thick" is greater than 3 mm.[7][2]

Microscopic

Features:[5]

  • Edema.
  • Hemorrhage.
  • +/-Fibrin thrombi in small veins.
  • +/-Mucosal erosions.
  • +/-Neutrophils - useful
    • Not essential for the Dx of acute cholecystitis.
    • Neutrophils usually secondary to necrosis/ulceration or infection.[8]
  • +/-Reactive epithelial changes.[3]

Notes:

  • May see activated fibroblasts.

DDx:

Special types

Gangrenous cholecystitis

General:[9]

  • Older.
  • Clinically "sicker".
  • Worse outcome than (acute) non-gangrenous cholecystitis.

Microscopic:

Sign out

GALLBLADDER, CHOLECYSTECTOMY: 
- ACUTE CHOLECYSTITIS.
- CHOLELITHIASIS.

GALLBLADDER, CHOLECYSTECTOMY:
- ACUTE AND CHRONIC CHOLECYSTITIS WITH MULTIPLE MUCOSAL EROSIONS AND FOCAL NECROSIS OF THE GALLBLADDER WALL.

GALLBLADDER, CHOLECYSTECTOMY:
- GANGRENOUS CHOLECYSTITIS.
- CHOLELITHIASIS.

Micro

The sections show gallbladder wall with hemorrhage, and activated fibroblasts. The superficial mucosa has clusters of neutrophils.

Gallbladder cholesterolosis

  • AKA cholesterolosis.
  • Informally known as strawberry gallbladder.

General

  • Common in cholecystitis.
  • Associated with yellow gallstones (cholesterol type gallstones).

Gross

Features:

  • Mucosa has strawberry-like appearance.
    • The similarity is in the surface texture.
    • The colour (yellow) is not strawberry-like.

Image

  • Gallbladder cholesterolosis. (WC/euthman)

Microscopic

Features:

  • Numerous foamy macrophages in the lamina propria.

Image

  • Cholesterolosis - intermed. mag. (WC)

  • Cholesterolosis. (WC)

Sign out

GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH CHOLESTEROLOSIS.
- CHOLELITHIASIS.

GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH FOCAL FOAMY MACROPHAGES IN LAMINA PROPRIA.
- CHOLELITHIASIS.

Cholelithiasis

  • AKA gallstones.

General

  • Often accompanies cholecystitis/contributes and/or causes cholecystitis.
  • Gallbladder removed following biliary pancreatitis (gallstone pancreatitis) to reduce recurrence risk.[11][12]

The two types of gallstones:

  • Cholesterol stones.
  • Pigment stones.

Note:

  • Most stones technically speaking are a mix, i.e. cholesterol and pigment. Many call yellow stones that are a mix "cholesterol stones".

Epidemiology

Classic risk factors for gallstones - 4 Fs:[13]

  • Female.
  • Fat.
  • Forty.
  • Fertile.

Additional:

  • Family history.

Cholesterol stones

  • More common than pigment stone.

Appearance:

  • Clear or yellow.
  • Opaque or translucent.
  • Sometimes shinny.
Image

  • Yellow gallstones. (WC)

Pigment stones

Appearance:

  • Black - key feature.
  • Dull.

Sign out

GALLBLADDER CHOLECYSTECTOMY:
- CHOLELITHIASIS.
- MILD CHRONIC CHOLECYSTITIS.

Less common pathologic diagnoses

Adenomyoma of the gallbladder

  • AKA gallbladder adenomyosis.
  • AKA adenomyomatosis of the gallbladder.
  • AKA gallbladder adenomyoma.

General

  • Glands in muscle.
  • Analogous to what happens in the uterus.
  • Significance - may mimic malignant tumours of the gallbladder.[15][16]
  • Uncommon.

Gross

  • Cystic spaces (Rokitansky-Aschoff sinuses) - may be seen on imaging.[17][18]
  • Gallbladder wall thickening.

Microscopic

Features:[3]

  • Glands in muscularis propria of the gallbladder wall - key feature.
  • Significant muscular hypertrophy - key feature.
  • No nuclear atypia.

DDx:

Image:

Gallbladder polyps

General

  • Polyps are significant as they may be adenomatous, i.e. pre-cancerous.
  • These are similar to polyps found elsewhere GI tract.

Microscopic

See intestinal polyps.

Flat dysplasia:[19]

  • Nuclear changes.
    • Increased NC ratio.
    • Hyperchromasia (essential).
    • +/-Intestinal metaplasia --> goblet cells.

Gallbladder diverticulosis

General

  • Uncommon.
  • Thought to arise in the context of an outflow obstruction.[20]

Microscopic

Features:

  • Mucosal pouch penetrating the muscularis propria of the gallbladder wall - key feature.

DDx:

Sign out

GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH DIVERTICULOSIS.
- CHOLELITHIASIS.

Premalignant lesions

General

  • Metaplasia associated with carcinoma.[21]

Hypothesis:[22]

  • Antral type metaplasia --> intestinal metaplasia --> dysplasia --> carcinoma.

Intestinal metaplasia of the gallbladder

General

Significance:

  • Increased risk of carcinoma.[21]

Microscopic

Features:[23]

Note:

  • Often accompanied by antral type metplasia.
    • Gastric antral-type epithelium - may form glands.

DDx:

Image:

Sign out

GALLBLADDER, CHOLECYSTECTOMY: 
- INTESTINAL METAPLASIA OF THE GALLBLADDER, FOCAL. 
- CHRONIC CHOLECYSTITIS. 
- CHOLELITHIASIS.
- NEGATIVE FOR DYSPLASIA.

Antral type metaplasia

General

  • AKA pyloric metaplasia, pseudopyloric metaplasia, mucous gland metaplasia.[24]

Microscopic

Features:[24]

  • Columnar cells with:
    • Abundant, pale, apical mucin.
    • Small basal nucleus.
  • Cells often in nests -- below luminal surface.
  • Cells vaguely resemble foveollar epithelium of the stomach.

Notes:

  • May look similar to cells of the gallbladder neck[24] and common bile duct.[25]
    • 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:

Gallbladder adenoma

Gallbladder dysplasia redirects here.

General

Microscopic

Features:

  • Gallbladder epithelium with:
    • Nuclear atypia - key feature.
      • Nuclear hyperchromasia.
      • Nuclear crowding (pseudostratification) or round enlarged nuclei.
    • +/-Goblet cells.

Architectural subclassification:[27]

  • Papillary ~ 45%.
  • Tubulopapillary ~ 30%.
  • Tubular ~ 25%.

Notes:

  • All of the gallbladder should be submitted prior to sign out to exclude non-sampled adenocarcinoma.

DDx:

Image:

Sign out

GALLBLADDER, CHOLECYSTECTOMY:
- BILIARY TYPE TUBULAR ADENOMA WITH HIGH GRADE DYSPLASIA.
- MARGINS CLEAR OF ADENOMA (NEAREST MARGIN 1.0 CM).

Malignant

Gallbladder carcinoma

  • AKA gallbladder adenocarcinoma.

General

  • Uncommon.

Treatment:

  • Cholecystectomy +/- lymph nodes +/- partial hepatectomy.[28]

Epidemiology

Notes:

  • Diffuse calcification of gallbladder wall, AKA "porcelain gallbladder" is not associated with carcinoma - based on a series of 10,741 cholecystectomies.[29]
    • Focal mucosal calcification is associated with malignancy.[30]
  • Cholangiocarcinoma is dealt with in the liver neoplasms article.

Gross

  • Classic: mass projecting into the lumen.
  • Marked gallbladder wall thickening.
    • >10 mm should be considered with suspicion.[2]

Image:

Microscopic

Features:

Notes:

  • May be very subtle, i.e. difficult to differentiate from normal glands.

DDx:

See also

References

  1. ↑ URL: 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.
  2. ↑ 2.0 2.1 2.2 2.3 Kim, HJ.; Park, JH.; Park, DI.; Cho, YK.; Sohn, CI.; Jeon, WK.; Kim, BI.; Choi, SH. (Feb 2012). "Clinical usefulness of endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening.". Dig Dis Sci 57 (2): 508-15. doi:10.1007/s10620-011-1870-0. PMID 21879282.
  3. ↑ 3.0 3.1 3.2 3.3 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. 439. ISBN 978-0443066573.
  4. ↑ URL: http://www.whonamedit.com/synd.cfm/983.html. Accessed on: 29 October 2011.
  5. ↑ 5.0 5.1 5.2 5.3 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 1606. ISBN 978-0781779425. Cite error: Invalid <ref> tag; name "Ref_Sternberg5_1606" defined multiple times with different content Cite error: Invalid <ref> tag; name "Ref_Sternberg5_1606" defined multiple times with different content Cite error: Invalid <ref> tag; name "Ref_Sternberg5_1606" defined multiple times with different content
  6. ↑ Fitzgibbons, RJ.; Tseng, A.; Wang, H.; Ryberg, A.; Nguyen, N.; Sims, KL. (Dec 1996). "Acute cholecystitis. Does the clinical diagnosis correlate with the pathological diagnosis?". Surg Endosc 10 (12): 1180-4. PMID 8939838.
  7. ↑ Tsung, JW.; Raio, CC.; Ramirez-Schrempp, D.; Blaivas, M. (Mar 2010). "Point-of-care ultrasound diagnosis of pediatric cholecystitis in the ED.". Am J Emerg Med 28 (3): 338-42. doi:10.1016/j.ajem.2008.12.003. PMID 20223393.
  8. ↑ 8.0 8.1 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 174. ISBN 978-0470519035.
  9. ↑ Nikfarjam, M.; Niumsawatt, V.; Sethu, A.; Fink, MA.; Muralidharan, V.; Starkey, G.; Jones, RM.; Christophi, C. (Aug 2011). "Outcomes of contemporary management of gangrenous and non-gangrenous acute cholecystitis.". HPB (Oxford) 13 (8): 551-8. doi:10.1111/j.1477-2574.2011.00327.x. PMID 21762298.
  10. ↑ STC. 25 February 2009.
  11. ↑ Bouwense, SA.; Besselink, MG.; van Brunschot, S.; Bakker, OJ.; van Santvoort, HC.; Schepers, NJ.; Boermeester, MA.; Bollen, TL. et al. (2012). "Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial.". Trials 13: 225. doi:10.1186/1745-6215-13-225. PMID 23181667.
  12. ↑ van Baal, MC.; Besselink, MG.; Bakker, OJ.; van Santvoort, HC.; Schaapherder, AF.; Nieuwenhuijs, VB.; Gooszen, HG.; van Ramshorst, B. et al. (May 2012). "Timing of cholecystectomy after mild biliary pancreatitis: a systematic review.". Ann Surg 255 (5): 860-6. doi:10.1097/SLA.0b013e3182507646. PMID 22470079.
  13. ↑ Szwed, Z.; Zyciński, P. (2007). "[4F's--still up to date risk factors of cholelithiasis].". Wiad Lek 60 (11-12): 570-3. PMID 18540184.
  14. ↑ URL: http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20%28General%20Monographs-%20U%29/URSOFALK.html. Accessed on: 29 October 2011.
  15. ↑ Saul, WM.; Herrmann, PK. (1988). "[Adenomyoma of the gallbladder].". Dtsch Z Verdau Stoffwechselkr 48 (2): 112-6. PMID 3168899.
  16. ↑ Sasatomi, E.; Miyazaki, K.; Mori, M.; Satoh, T.; Nakano, S.; Tokunaga, O. (Oct 1997). "Polypoid adenomyoma of the gallbladder.". J Gastroenterol 32 (5): 704-7. PMID 9350002.
  17. ↑ Ching, BH.; Yeh, BM.; Westphalen, AC.; Joe, BN.; Qayyum, A.; Coakley, FV. (Jul 2007). "CT differentiation of adenomyomatosis and gallbladder cancer.". AJR Am J Roentgenol 189 (1): 62-6. doi:10.2214/AJR.06.0866. PMID 17579153.
  18. ↑ 18.0 18.1 Boscak, AR.; Al-Hawary, M.; Ramsburgh, SR.. "Best cases from the AFIP: Adenomyomatosis of the gallbladder.". Radiographics 26 (3): 941-6. doi:10.1148/rg.263055180. PMID 16702464.
  19. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 172. ISBN 978-0470519035.
  20. ↑ Beilby, JO. (Aug 1967). "Diverticulosis of the gall bladder. The fundal adenoma.". Br J Exp Pathol 48 (4): 455-61. PMC 2093791. PMID 4963758. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2093791/.
  21. ↑ 21.0 21.1 Duarte I, Llanos O, Domke H, Harz C, Valdivieso V (September 1993). "Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples". Cancer 72 (6): 1878–84. PMID 8364865.
  22. ↑ 22.0 22.1 22.2 Mukhopadhyay S, Landas SK (March 2005). "Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens". Arch. Pathol. Lab. Med. 129 (3): 386–90. PMID 15737036. http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2.
  23. ↑ Albores-Saavedra, J.; Nadji, M.; Henson, DE.; Ziegels-Weissman, J.; Mones, JM. (Jun 1986). "Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study.". Hum Pathol 17 (6): 614-20. PMID 2872152.
  24. ↑ 24.0 24.1 24.2 24.3 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 1789. ISBN 978-0781740517.
  25. ↑ Cutz, E. 3 March 2011.
  26. ↑ 26.0 26.1 Levy, AD.; Murakata, LA.; Abbott, RM.; Rohrmann, CA.. "From the archives of the AFIP. Benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts: radiologic-pathologic correlation. Armed Forces Institute of Pathology.". Radiographics 22 (2): 387-413. PMID 11896229. http://radiographics.rsna.org/content/22/2/387.full.
  27. ↑ Adsay, V.; Jang, KT.; Roa, JC.; Dursun, N.; Ohike, N.; Bagci, P.; Basturk, O.; Bandyopadhyay, S. et al. (Sep 2012). "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.". Am J Surg Pathol 36 (9): 1279-301. doi:10.1097/PAS.0b013e318262787c. PMID 22895264.
  28. ↑ Biswas, PK. (Jul 2010). "Carcinoma gallbladder.". Mymensingh Med J 19 (3): 477-81. PMID 20639849.
  29. ↑ Towfigh S, McFadden DW, Cortina GR, et al (January 2001). "Porcelain gallbladder is not associated with gallbladder carcinoma". Am Surg 67 (1): 7?0. PMID 11206901.
  30. ↑ Stephen, AE.; Berger, DL. (Jun 2001). "Carcinoma in the porcelain gallbladder: a relationship revisited.". Surgery 129 (6): 699-703. doi:10.1067/msy.2001.113888. PMID 11391368.
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