Gallbladder

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

Normal histology

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

Image:

Note:

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

Overview

Most common:

  • Cholelithiasis with cholecystitis.

Common:

  • Antral-type metaplasia.

Uncommon:

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

Common

Chronic cholecystitis

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).
      • Normal gallbladder mucosa = smooth.
  • +/-Congestion/erythema.
  • +/-Wall thickening.

Microscopic

Features:

  • Rokitansky-Aschoff sinuses.[1]
    • Entrapped epithelial crypts -- pockets of epithelium in the wall of the gallbladder.
  • +/-Foamy macrophages in the lamina propria (cholesterolosis of the gallbladder).
  • Chronic inflammatory cells (lymphocytes - most common).
  • Fibrotic thickening of the gallbladder wall.

DDx:

Acute cholecystitis

General

  • Less common than chronic cholecystitis.
  • Usually due to gallstones.[2]
  • Classically older individuals (50s and 60s) with a slight female predominance.[2]

Gross

Features:[2]

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

Microscopic

Features:[2]

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

Special types

Gangrenous cholecystitis

General:[4]

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

Microscopic:

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 (not the colour).

Microscopic

Features:

  • Foamy macrophages in the lamina propria.

Image:

Cholelithiasis

  • AKA gallstones.

General

  • Often accompanies cholecystitis/contributes and/or causes cholecystitis.

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:[6]

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

Additional:

  • Family history.

Cholesterol stones

  • More common than pigment stone.

Appearance:

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

Image:

Pigment stones

Appearance:

  • Black - key feature.
  • Dull.

Less common pathologic diagnoses

Adenomyoma of the gallbladder

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

General

  • Glands in muscle.
  • Analogous to what happens in the uterus.
  • Significance - may mimic malignant tumours of the gallbladder.[8][9]
  • Uncommon.

Gross

  • Cystic spaces (Rokitansky-Aschoff sinuses) - may be seen on imaging.[10][11]
  • Gallbladder wall thickening.

Microscopic

Features:

  • Glands in muscularis propria of the gallbladder wall.
  • 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:[12]

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

Premalignant lesions

General

  • Metaplasia associated with carcinoma.[13]

Hypothesis:[14]

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

Intestinal metaplasia of the gallbladder

Main article: Intestinal metaplasia

General

Significance:

  • Increased risk of carcinoma.[13]

Microscopic

Features:[15]

Note:

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

DDx:

Image:

Antral type metaplasia

General

  • AKA pyloric metaplasia, pseudopyloric metaplasia, mucous gland metaplasia.[16]

Microscopic

Features:[16]

  • 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[16] and common bile duct.[17]
    • 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 dysplasia

General

  • Premalignant lesion.

Microscopic

Features:

  • Nuclear crowding.
  • Nuclear hyperchromasia.

Notes:

  • Like in the colon.

DDx:

Gallbladder carcinoma

General

Epidemiology

Notes:

  • Diffuse calcification of gallbladder wall, AKA "porcelain gallbladder" is not associated with carcinoma - based on a series of 10,741 cholecystectomies.[18]
    • Focal mucosal calcification is associated with malignancy.[19]
  • Cholangiocarcinoma is dealt with in the liver neoplasms article.

Gross

  • Classically mass projects into the lumen.

Image:

Microscopic

Features:

Notes:

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

DDx:

See also

References

  1. ↑ URL: http://www.whonamedit.com/synd.cfm/983.html. Accessed on: 29 October 2011.
  2. ↑ 2.0 2.1 2.2 2.3 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
  3. ↑ 3.0 3.1 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 174. ISBN 978-0470519035.
  4. ↑ 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.
  5. ↑ STC. 25 February 2009.
  6. ↑ Szwed, Z.; Zyciński, P. (2007). "[4F's--still up to date risk factors of cholelithiasis].". Wiad Lek 60 (11-12): 570-3. PMID 18540184.
  7. ↑ 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.
  8. ↑ Saul, WM.; Herrmann, PK. (1988). "[Adenomyoma of the gallbladder].". Dtsch Z Verdau Stoffwechselkr 48 (2): 112-6. PMID 3168899.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 11.0 11.1 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.
  12. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 172. ISBN 978-0470519035.
  13. ↑ 13.0 13.1 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.
  14. ↑ 14.0 14.1 14.2 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.
  15. ↑ 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.
  16. ↑ 16.0 16.1 16.2 16.3 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.
  17. ↑ Cutz, E. 3 March 2011.
  18. ↑ 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.
  19. ↑ 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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