Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: McHugh KE, Plesec TP. Chronic cholecystitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladderchroniccholecystitis.html. Accessed January 17th, 2021.
Definition / general
- Chronic inflammation of the gallbladder, typically secondary to gallstones
Essential features
- The most common disease of the gallbladder, typically secondary to cholelithiasis
- Variety of histologic findings, including variable amounts of mononuclear cell predominant inflammation, mucosal changes including metaplasia, muscular hypertrophy and transmural fibrosis
- Rokitansky-Aschoff sinuses and ducts of Luschka should not be mistaken for invasive adenocarcinoma
Epidemiology
- Female predominance (StatPearls: Chronic Cholecystitis [Accessed 19 February 2020])
- Associated with cholelithiasis in > 90% of cases
Pathophysiology
- Can be a sequela of recurrent acute cholecystitis
- Typically related to cholelithiasis, either through direct mucosal irritation or via intermittent mechanical obstruction with associated alteration of bile chemistry
- Altered mechanics of gallbladder emptying plays crucial role
- Up to 33% of patients have bile cultures positive for bacteria (e.g. Escherichia coli, enterococci, Helicobacter pylori, etc.), the significance of which is uncertain (Br J Surg 2010;97:532, Scand J Gastroenterol 2005;40:96, Helicobacter 2018;23:e12457)
Etiology
- Cholelithiasis, though severity of disease poorly correlates with stone burden (In Vivo 2008;22:269)
- Risk factors correspond to those that increase risk of cholelithiasis: female sex, obesity, rapid weight loss, pregnancy, advanced age (Gastroenterol Nurs 2016;39:297)
Clinical features
- Does not always cause clinical symptoms
- Can present with dull right upper quadrant pain that radiates to mid back or right scapula (StatPearls: Chronic Cholecystitis [Accessed 19 February 2020])
- Murphy sign: right upper abdominal pain with deep palpation
- Abdominal discomfort often related to fatty food ingestion
- Nausea, vomiting, bloating, flatulence
Diagnosis
- Abdominal ultrasound (StatPearls: Chronic Cholecystitis [Accessed 19 February 2020])
- Abdominal CT with contrast
- HIDA (hepatobiliary iminodiacetic acid) scan demonstrating a reduced ejection fraction (< 35%)
Radiology description
- Gallbladder wall thickening with associated cholelithiasis
- Gallbladder may appear contracted or distended (Medicine (Baltimore) 2018;97:e11851)
Radiology images
Prognostic factors
- Majority of uncomplicated cases have an excellent outcome (Am J Surg 2003;185:91)
- With elective cholecystectomy, bile duct injuries do occur with regular frequency (Endoscopy 2018;50:577)
- Biliary leakage reported in up to 3% of cases (Visc Med 2017;33:184)
- Generally, a very low risk (< 0.5%) of associated incidental carcinoma (Rev Col Bras Cir 2020;46:e20192279, Surgery 2001;129:699)
Case reports
- 44 year old man with gallstones and chronic cholecystitis revealing metachronous gallbladder metastasis from renal clear cell carcinoma (ANZ J Surg 2019 Jun 23 [Epub ahead of print])
- 45 year old woman with porcelain gallbladder secondary to chronic cholecystitis, without adenocarcinoma (Mymensingh Med J 2019;28:694)
- 53 year old man with history of colorectal adenocarcinoma with progressively elevating CEA secondary to chronic cholecystitis (J Surg Case Rep 2019;2019:rjz138)
- 70 year old man with chronic cholecystitis secondary to biliary taeniasis (Am J Trop Med Hyg 2019;100:135)
Treatment
- Elective cholecystectomy (Am J Surg 2003;185:91)
Gross description
- Nearly normal to thickened gallbladder wall (StatPearls: Chronic Cholecystitis [Accessed 19 February 2020])
- Gallbladder may appear shrunken due to marked fibrosis
- Severe cases show adhesions to adjacent organs
- Variable mucosal appearance: can be granular, ulcerated, polypoid
Gross images
Microscopic (histologic) description
- Variable amounts of predominantly mononuclear inflammatory infiltrate in lamina propria, which may extend into the muscularis and pericholecystic tissues
- Inflammatory infiltrate predominantly consists of T lymphocytes, with some plasma cells, histiocytes and occasional eosinophils (Ann Diagn Pathol 2003;7:147)
- Inflammation typically rather minimal; occasional lymphoid follicles may be seen in lamina propria
- Hypertrophy of muscularis and variable degrees of mural fibrosis, elastosis, neural hyperplasia
- Accentuation of Rokitansky-Aschoff sinuses (pseudodiverticula)
- Adenomyomatous hyperplasia may occur
- Variable mucosal changes: normal, atrophic, ulcerated, hyperplastic
- Metaplastic changes common: foveolar metaplasia, pyloric gland metaplasia, intestinal metaplasia
- Hyalinizing variant: dense paucicellular hyalinizing fibrosis effacing ≥ 80% of normal histologic structures, resulting in a thinned gallbladder wall with (porcelain gallbladder) or without dystrophic calcification
- Increased frequency of associated carcinoma (Sultan Qaboos Univ Med J 2016;16:e416, Am J Surg Pathol 2011;35:1104)
- IgG4 associated variant: increased frequency of transmural lymphoplasmacytic inflammatory infiltrates, extramural inflammatory nodules, increased eosinophils, phlebitis and increased IgG4 plasma cells by immunostain
- Associated with autoimmune pancreatitis (Dig Dis Sci 2011;56:1290)
- 2 patterns of inflammation associated with idiopathic inflammatory bowel disease: marked chronic cholecystitis (ulcerative colitis or Crohn's disease) and nodular lymphoid aggregates (Crohn's disease > ulcerative colitis) (J Crohns Colitis 2012;6:895)
- Beware of invasive adenocarcinoma mimics: adenomyoma, Luschka ducts
- In rare instances, reactive / hyperplastic ducts of Luschka can be seen isolated to the gallbladder adventitia (Am J Surg Pathol 2011;35:883)
Microscopic (histologic) images
Virtual slides
Sample pathology report
- Gallbladder, cholecystectomy:
- Chronic cholecystitis and cholelithiasis
Differential diagnosis
- Normal gallbladder:
- Lacks significant expansion of the lamina propria by an inflammatory infiltrate, thickened muscularis or mural fibrosis
- Lymphoma:
- Lymphoma of the gallbladder is exceedingly rare (0.1 - 0.2% of cholecystectomies) and is generally identified as part of a systemic disease
- The most common primary lymphoma of the gallbladder is MALT lymphoma (BMJ Case Rep 2017;2017:bcr2017220161)
- Primary MALT lymphoma of gallbladder is typically identified on presurgical imaging as gallbladder wall thickening or a polypoid lesion
- Lymphoplasmacytic cholecystitis:
- Plasma cell rich inflammatory infiltrate that diffusely involves the mucosa and is primarily confined to the lamina propria (Am J Surg Pathol 2003;27:1313)
- Typically but not always associated with autoimmune disorders (e.g. ulcerative colitis, primary sclerosing cholangitis, autoimmune pancreatitis) (Am J Clin Pathol 2014;142:209)
- Also termed sclerosing cholangitis, as it is believed to fall within the spectrum of IgG4 related autoimmune disorders
- AIDS related cholecystitis:
- Typically presents as acalculous cholecystitis; > 50% of cases are idiopathic (Clin Infect Dis 1995;21:852)
- Can be related to infectious agents, particularly cytomegalovirus and cryptosporidia
- In cryptosporidia related cases, associated inflammation may be minimal
- Follicular cholecystitis:
- Numerous prominent lymphoid follicles in lamina propria throughout gallbladder
- Rare and accounts for < 0.1% of cholecystectomies (Hum Pathol 2019;88:1)
- Up to 5% of otherwise ordinary chronic cholecystitis may show scattered, occasional follicle formation
- Eosinophilic cholecystitis:
- Massive infiltration of the gallbladder by sheets of eosinophils with few, if any, other intervening inflammatory cells (Am J Surg Pathol 1994;18:215)
- Common to see eosinophils as part of the mixed inflammatory milieu of chronic (and acute) cholecystitis
- Xanthogranulomatous cholecystitis:
- Prominent proliferation of foamy macrophages, in addition to admixed lymphocytes, plasma cells and foreign body type giant cells
- Thought to be secondary to mucosal ulceration or rupture of Rokitansky-Aschoff sinuses with bile extravasation
- Grossly, may display diffuse plaque-like thickening of gallbladder wall or a discrete mass lesion (pseudotumor)
Additional references
Board review style question #1
A 40 year old woman with a BMI of 36 undergoes cholecystectomy for intermittent, dull right upper quadrant abdominal pain, reproducible on physical examination with deep palpation. Sections of gallbladder wall show the following:
What is the best interpretation of these findings?

What is the best interpretation of these findings?
- Chronic cholecystitis
- Cystadenocarcinoma
- Dilated ducts of Luschka
- Intracholecystic papillary tubular neoplasm (ICPN)
- Invasive adenocarcinoma
Board review style answer #1
Board review style question #2
What is the most common cause of elective cholecystectomy in the United States?
- Acute cholecystitis
- Chronic cholecystitis
- Eosinophilic cholecystitis
- Follicular cholecystitis
- Xanthogranulomatous cholecystitis
Board review style answer #2
Board review style question #3
Which of the following variants of chronic cholecystitis has an established increased risk of associated adenocarcinoma?
- Adenomyomatous chronic cholecystitis
- Diffuse lymphoplasmacytic cholecystitis
- Follicular cholecystitis
- Hyalinizing cholecystitis
- IgG4 associated cholecystitis
Board review style answer #3