Home > Liver & intrahepatic bile ducts > Bile duct adenoma

Liver & intrahepatic bile ducts

Benign / nonneoplastic

Bile duct adenoma

Authors: Komal Ijaz, M.D., Feng Yin, M.D., Ph.D.

Editorial Board Members: Claudio Luchini, M.D., Ph.D., Monika Vyas, M.D.

Last author update: 16 June 2023

Last staff update: 16 June 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Bile duct adenoma

Table of Contents

Cite this page: Ijaz K, Yin F. Bile duct adenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorbileductadenoma.html. Accessed December 21st, 2024.

Definition / general

Bile duct adenoma is a benign biliary neoplasm consisting of uniformly distributed small bile ducts in a background of fibrotic stroma

Essential features

Benign epithelial tumor
Most commonly a solitary subcapsular nodule (90%)
Frequently an incidental finding at surgery or autopsy
Frequently submitted for frozen section to rule out metastatic process
Can be difficult to distinguish from adenocarcinoma, especially on frozen section
Uniform distribution of small tubules with no cytological atypia or mitotic figures
Frequent BRAF V600E mutation supports a neoplastic process

Terminology

Also known as peribiliary gland hamartoma, cholangioma, cholangioadenoma

ICD coding

ICD-O: 8160/0 - bile duct adenoma
ICD-11: 2E92.7 & XH6KR6 - benign neoplasm of liver or intrahepatic bile ducts & bile duct adenoma

Epidemiology

Usually adults (age > 20), no gender predilection
Accounts for 1.3% of primary liver tumors and 2.4% in a total of 1,456 resection cases for primary liver tumors and explant for liver cirrhosis (Am J Surg Pathol 1988;12:708, Pathol Int 2014;64:551)

Sites

Liver, typically subcapsular location

Pathophysiology

Originally considered to be a reactive ductular proliferation in response to focal injury, a localized biliary healing response equivalent to the function of a peribiliary gland or pyloric gland metaplasia in the foregut or a hamartomatous process (Am J Surg Pathol 1988;12:708, Am J Surg Pathol 2010;34:1312, Am J Surg Pathol 1996;20:858)
Presence of frequent BRAF V600E mutation supports a neoplastic process (Hepatology 2015;61:403, Histopathology 2015;67:562, Histopathology 2017;70:485)

Etiology

Unknown; whether focal injury acts as trigger event remains controversial

Clinical features

Mostly an incidental finding during surgery or autopsy
Frequently submitted for frozen section to rule out metastatic process

Diagnosis

Clinical presentation and histopathologic findings

Radiology description

Hypointense on T1 weighted images, hyperintense on T2 weighted images
Characteristic arterial phase hyperenhancement that persists into the portal venous and delayed phases on CT and MRI (Diagn Interv Radiol 2018;24:249)

Prognostic factors

Potential and controversial precursor to intrahepatic cholangiocarcinoma (Histopathology 2021;78:310, Hepatology 2015;61:403, Histopathology 2015;67:562)

Case reports

18 month old boy with a large (10 cm) exophytic solid liver tumor (World J Gastrointest Surg 2019;11:414)
35 year old woman with resolution of bile duct adenomas after discontinuing oral contraceptive pills (Middle East J Dig Dis 2016;8:327)
62, 65 and 76 year old men were identified as having a bile duct adenoma (Endosc Int Open 2018;6:E1312)
70 year old man with an incidental finding of intrahepatic bile duct adenoma during laparoscopic distal gastrectomy for gastric cancer (Int Cancer Conf J 2018;8:7)

Gross description

Usually subcapsular, well circumscribed but nonencapsulated
Majority are solitary but can be multiple
Firm, gray-white
Size ranging from 1 to 20 mm (mean: 5.8 mm) (Am J Surg Pathol 1988;12:708)

Gross images

Images hosted on other servers:

Well circumscribed
nonencapsulated
subcapsular lesion

Frozen section description

Usually solitary subcapsular lesion, well circumscribed and nonencapsulated
Bland small tubular proliferation in a background of fibrotic stroma
Lack of marked nuclear atypia, mitotic figures, necrosis or intraluminal bile
Potential diagnostic pitfalls: cellular stroma, back to back compact architecture, mucin production, unusual variant (oncocytic, clear cell, etc.), cytologic atypia enhanced by frozen section artifact

Frozen section images

Contributed by Feng Yin, M.D., Ph.D.

Well circumscribed unencapsulated lesion

Lack of atypical features

Microscopic (histologic) description

Relatively uniform distribution of small tubules with little to no lumen
Lined by single layer of cuboidal cells with no cytological atypia or mitotic figures
Well circumscribed with fibrotic stroma
No intraluminal bile; the ducts do not communicate with the biliary tree
Rarely, variants with clear cell change, oncocytic features, mucin secreting and alpha-1 antitrypsin droplets (Am J Surg Pathol 2001;25:956, Case Rep Pathol 2014;2014:874826, Case Rep Pathol 2014;2014:282010, Dig Surg 2002;19:324, Int J Surg Pathol 2008;16:218)

Microscopic (histologic) images

Contributed by Komal Ijaz, M.D. and Feng Yin, M.D., Ph.D.

Well circumscribed unencapsulated lesion

Subcapsular well circumscribed lesion

Tubules with fibrous stroma

Tubules with focal crowding

Tubules with bland cytology

Tubules with cytoplastic mucin

Fine needle biopsy

Cytology description

Abundant normal appearing biliary epithelium
Often admixed with benign hepatocytes
Cell block may be useful
Reference: Sidawy: Fine Needle Aspiration Cytology, 1st Edition, 2007

Positive stains

Typical biliary immunoprofile (positive for CK7 and CK19)
Expression of foregut antigens (positive for MUC5AC and MUC6) (Am J Surg Pathol 2010;34:1312)
Ki67 proliferation rate is low (should not be more than 10%)
BRAF V600E immunoreactivity in 53% of cases (Histopathology 2015;67:562)
p16INK4a immunoreactivity in 81% of cases (Am J Surg Pathol 2014;38:364)

Negative stains

EZH2 (Am J Surg Pathol 2014;38:364)

Molecular / cytogenetics description

Majority of bile duct adenomas are positive for albumin in situ hybridization, a feature that distinguishes it from metastatic pancreatic adenocarcinoma (Histopathology 2016;69:423)

Sample pathology report

Liver, wedge biopsy:
- Intrahepatic bile duct adenoma (see comment)
- Comment: The biopsy demonstrates the proliferation of small tubules with no cytological atypia embedded in the fibrous stroma, consistent with bile duct adenoma.

Differential diagnosis

Cholangiocarcioma or metastatic adenocarcinoma:
- Cytological atypia, mitosis, size may be > 2 cm
- Infiltrative growth pattern
- Extensive expression of EZH2, no or low expression of p16INK4a (Am J Surg Pathol 2014;38:364)
- Ki67 > 10%
- Lymphovascular or perineural invasion
Von Meyenburg complex (biliary microhamartoma):
- Angulated, branching and irregularly dilated ducts
- Intraluminal bile plugs

Board review style question #1

A 55 year old man with pancreatic adenocarcinoma was admitted for Whipple procedure. A small liver nodule was noted during surgery and sent for intraoperative consultation. A representative photomicrograph of the frozen section is shown. Which of the following is the most likely diagnosis?

Bile duct adenoma
Metastatic pancreatic adenocarcinoma
Reactive ductular proliferation
Von Meyenburg complex

Board review style answer #1

A. Bile duct adenoma. The diagnosis of a bile duct adenoma is favored during intraoperative consultation, largely attributed to the presence of uniform distribution of small tubules in a background of fibrous stroma. There are no worrisome morphological features, such as infiltrative growth pattern, desmoplastic stromal reaction, marked cytological atypia, frequent mitosis and necrosis.

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Reference: Bile duct adenoma

Board review style question #2

Which gene is most frequently mutated in bile duct adenoma?

BRAF
KRAS
p53
SMAD4

Board review style answer #2

A. BRAF mutations are present in about 53% of bile duct adenomas.

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Reference: Bile duct adenoma

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