Gallbladder & extrahepatic bile ducts
Gallbladder malignant
Gallbladder carcinoma

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Ashwin S. Akki, M.D, Ph.D.

Topic Completed: 21 April 2020

Minor changes: 22 April 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Gallbladder carcinoma[TI] bile ducts

Ashwin S. Akki, M.D, Ph.D.
Page views in 2019: 15,529
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Cite this page: Akki A. Gallbladder carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladdercarcinoma.html. Accessed August 8th, 2020.
Definition / general
Essential features
  • Aggressive cancer, with an overall 5 year survival rate of < 10%
  • Cholelithiasis is a major risk factor
  • Up to 50% are detected incidentally in routine cholecystectomy specimens due to absence of gross abnormalities; systematic sampling of these specimens is therefore crucial to detect incidental gallbladder adenocarcinomas (Am J Surg Pathol 2019;43:1668)
Terminology
  • Carcinoma of gallbladder; adenocarcinoma of gallbladder; malignant epithelial neoplasm of gallbladder
ICD coding
    ICD 10:
  • C23 - malignant neoplasm of gallbladder

    ICD-0:
  • 8140/3 - adenocarcinoma NOS
  • 8070/3 - squamous cell carcinoma NOS
  • 8020/3 - carcinoma, undifferentiated, NOS

    ICD 11:
  • 2C13.z - malignant neoplasms of gallbladder, unspecified
Epidemiology
Sites
  • Primarily affects the fundus (60%), body (30%) or neck (10%) of gallbladder
  • Advanced tumors involve the liver and extrahepatic biliary tree
Pathophysiology
Etiology
Clinical features
  • Asymptomatic in a large majority of patients
  • Symptoms when present are vague
    • Right upper quadrant pain (most common)
    • Weight loss
    • Fever
  • Disease is usually advanced by the time patient develops symptoms
Diagnosis
  • 50% are diagnosed incidentally on routine cholecystectomy specimens
  • Finding a thickened gallbladder wall or polypoid lesions in the gallbladder on imaging done for other reasons should prompt surgical resection
Laboratory
Radiology description
  • Imaging findings are variable from subtle (in early disease) to obvious (in late disease)
    • Thickening of the gallbladder wall
    • Raised / polypoid lesion in the gallbladder wall / lumen
    • Mass occupying or replacing the gallbladder lumen
    • Gallbladder mass invading the liver (in advanced disease)
  • Ultrasound is the primary imaging modality for screening purposes in suspected cases
  • Abnormal findings on ultrasound are further investigated by CT and MRI that provide detailed information, including staging parameters
Radiology images

Images hosted on other servers:
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Heterogeneous mass

Prognostic factors
  • Noninvasive papillary carcinomas, regardless of size and differentiation, do not metastasize
  • Invasive papillary carcinomas have the most favorable prognosis (Arch Pathol Lab Med 2005;129:905)
  • Prognosis of adenocarcinoma, NOS depends on tumor stage:
    • Superficially invasive cancers limited to the lamina propria (pT1a) have excellent prognosis as they are completely cured by cholecystectomy (Ann Surg 2017;266:625)
    • Advanced cancers (i.e. muscle invasive and beyond; pT1b - pT4) have a higher chance of recurrence and have poorer outcomes (J Gastrointest Surg 2007;11:631, Ann Surg 2011;254:320)
    • High histologic grade (poor differentiation) and vascular invasion have adverse outcomes (Cancer 1992;70:1493)
    • Rokitansky-Aschoff sinus involvement by carcinoma and cystic duct margin status are suspected predictors of progression (Am J Clin Pathol 2014;141:675)
Case reports
Treatment
  • Cholecystectomy with a negative cystic duct margin is curative in pT1a tumors (Ann Surg 2017;266:625)
  • Hilar / portal lymphadenectomy, plus resection of hepatic bed and the common bile duct to achieve negative margins, is necessary for tumors that extend into a muscle or beyond (pT1b - pT3) (HPB (Oxford) 2015;17:681)
  • Chemotherapy or radiation for metastatic tumors
Gross description
  • Incidental gallbladder cancer in routine cholecystectomy specimens can be grossly subtle, with areas of mucosal granularity / irregularity, minimally raised / polypoid mucosal lesions or focally thickened fundus / body (Am J Surg Pathol 2019;43:1668)
  • Frank tumors may have one or more of the following features:
    • Thickened and indurated gallbladder wall
    • Exophytic or polypoid friable mucosal lesions (especially those arising from intracholecystic papillary neoplasm)
    • Firm, gritty, tan-white to yellow-gray cut surface
Gross images

Contributed by Ashwin S. Akki, M.D., Ph.D.
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Papillary proliferation

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Carcinoma in a polyp

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Gallbladder cancer invading liver

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Diffusely thickened gallbladder wall

Microscopic (histologic) description
  • Histologic variants recognized by WHO include:
    • Biliary type adenocarcinoma (~75%):
      • Similar to pancreatic ductal adenocarcinoma
      • Includes adenocarcinoma, NOS (most common), papillary, micropapillary
      • Composed of tubules (lined by cuboidal to columnar cells) embedded in a desmoplastic stroma
      • Moderately differentiated is more common but has a wide histologic spectrum, from deceptively bland to poorly differentiated
    • Intestinal type adenocarcinoma:
      • Tubules lined by columnar cells with elongated hyperchromatic nuclei, very similar to colonic adenocarcinomas
    • Mucinous carcinoma:
      • Comprised of > 50% extracellular mucin
    • Clear cell carcinoma:
      • Sheets of clear cells in an alveolar arrangement separated by blood vessels, similar in appearance to metastatic clear cell renal carcinoma
    • Signet ring cell carcinoma:
      • Signet ring cells are the predominant or exclusive component
    • Hepatoid carcinoma:
      • > 50% with abundant eosinophilic cytoplasm, enlarged nuclei and prominent nucleoli arranged in a trabecular pattern
    • Sarcomatoid carcinoma (carcinosarcoma):
      • Predominant spindle cell morphology with or without heterologous differentiation (e.g. skeletal muscle, bone and cartilage)
  • Differentiation
    • Well differentiated:
      • Well formed glands lined by columnar cells with minimal cytologic abnormality
      • Glands in perimuscular connective tissue, nuclear irregularities and mitoses may be the only clues
      • Desmoplasia may be subtle
    • Moderately differentiated:
      • Irregular / angulated glands lined by polygonal tumor cells with enlarged nuclei showing vesicular chromatin, prominent nucleoli and increased mitoses
      • Desmoplasia is usually prominent
    • Poorly differentiated:
      • Incomplete or poorly formed tubules / glands, single cells or sheets of pleomorphic tumor cells with bizarre nuclei
Microscopic (histologic) images

Contributed by Ashwin S. Akki, M.D., Ph.D.
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Desmoplasia

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Well formed glands

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Intermediate gland formation

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Poor gland formation

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Sarcomatoid differentiation


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Papillary proliferation with invasion

Virtual slides

Images hosted on other servers:
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Invasive adenocarcinoma

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Carcinoma in situ arising in an ICPN

Positive stains
Negative stains
Molecular / cytogenetics description
Videos

Gross gallbladder

Extended cholecystectomy

Sample pathology report
  • Gallbladder; cholecystectomy:
    • Invasive adenocarcinoma, moderately differentiated, biliary type (2.7 cm in largest dimension), arising in a background of extensive high grade biliary intraepithelial neoplasia (BilIN).
    • Adenocarcinoma invades perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum).
    • Cystic duct margin is free from biliary intraepithelial neoplasia (BilIN) or carcinoma.
    • One lymph node, negative for carcinoma (0/1).
    • Lymphovascular invasion is not identified.
    • pT2a, N0, M-not applicable (AJCC 8th edition). Please see synoptic report
    • Background gallbladder with chronic cholecystitis.
    • Cholelithiasis.
Differential diagnosis
Board review style question #1

    A 58 year old woman presents with right upper quadrant pain. Imaging reveals a polypoid lesion in the gallbladder. Patient undergoes cholecystectomy. Pathology shows the finding seen in the image above. Which of the following is true about this entity?

  1. Has aggressive dissemination potential
  2. Has a more favorable prognosis than conventional nonpapillary gallbladder adenocarcinomas
  3. Immunoreactive to hepatocellular markers
  4. Is not detected early on imaging
Board review answer #1
B. Invasive papillary carcinomas have the most favorable prognosis than conventional nonpapillary gallbladder adenocarcinomas because they have an exophytic growth pattern, exhibit delayed invasion into the gallbladder wall, and are detected early due to obstructive symptoms (Arch Pathol Lab Med 2005;129:905).

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Reference: Gallbladder carcinoma
Board review style question #2
    What is the amount of extracellular mucin needed to diagnose a mucinous adenocarcinoma of the gallbladder?

  1. > 25%
  2. > 30%
  3. > 50%
  4. > 90%
Board review answer #2
C. > 50% extracellular mucin

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Reference: Gallbladder carcinoma
Board review style question #3
    What are actionable molecular targets in the treatment of advanced GBCs?

  1. HER2 and MSI
  2. KRAS and ARID1A
  3. TP53 and CDKN2A
  4. PIK3CA and CTNNB1 (beta-catenin)
  5. p16
Board review answer #3
A. HER2 and MSI

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Reference: Gallbladder carcinoma
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