Gallbladder carcinoma
Author: Ashwin S. Akki, M.D, Ph.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Topic Completed: 21 April 2020

Minor changes: 22 April 2020

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

Definition / general

Carcinoma arising from the gallbladder epithelium (WHO Classification of Tumours Editorial Board: Digestive System Tumours (Medicine), 5th Edition, 2019)

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

Commonly occurs in the sixth and seventh decades

F:M = 3:1

Highest incidence in women from Chile (27.3/100 000), India (21.5/100 000), Pakistan (13.8/100 000) and Ecuador (12.9/100 000) (Int J Cancer 2010;127:2446, Histopathology 2009;55:218)

Incidence 1.1 per 100,000 in the United States (Cancer Epidemiol Biomarkers Prev 2015;24:1319)

Overall 5 year survival rate of < 10%

Sites

Primarily affects the fundus (60%), body (30%) or neck (10%) of gallbladder

Advanced tumors involve the liver and extrahepatic biliary tree

Pathophysiology

Longstanding cholelithiasis and cholecystitis give rise to metaplastic changes (intestinal or pseudopyloric types) in the gallbladder mucosa (Cancer 1993;72:1878)

Metaplasia (especially intestinal type) gives rise to epithelial dysplasia and carcinoma in situ (J Hepatobiliary Pancreat Surg 2000;7:556)

Progression from dysplasia to advanced gallbladder carcinoma takes around 15 years (Gastroenterology 1996;111:232)

Etiology

Risk factors include:

Cholelithiasis (major risk factor)

Chronic cholecystitis, especially hyalinizing cholecystitis

Obesity

Infections (esp. Salmonella and Opisthorchis viverrini)

Porcelain gallbladder

Primary sclerosing cholangitis

Pancreaticobiliary maljunction (supra-Oddi union of common bile duct with the main pancreatic duct)

Occasionally occurs in patients with Lynch syndrome or familial adenomatous polyposis (FAP)

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

Elevated alkaline phosphatase in advanced cancers (HPB (Oxford) 2008;10:446)

CEA only has 50% sensitivity (Int J Cancer 1990;45:821)

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\

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

22 year old man with primary signet ring cell carcinoma of gallbladder in the absence of choleliths (Int J Surg Pathol 2010;18:358)

56 year old woman with clear cell carcinoma of the gallbladder (Int J Surg Case Rep 2017;32:36)

59 year old woman with hepatoid carcinoma of the gallbladder (World J Surg Oncol 2011;9:103)

62 year old man with carcinosarcoma of the gallbladder with chondroid differentiation (Int J Clin Exp Pathol 2015;8:7464)

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.