Liver & intrahepatic bile ducts

Benign / nonneoplastic

Intraductal papillary neoplasm of the bile ducts


Editorial Board Member: Monika Vyas, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Kimberley J. Evason, M.D., Ph.D.

Last author update: 1 May 2023
Last staff update: 1 May 2023

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PubMed Search: Intraductal papillary neoplasm of the bile duct

Kimberley J. Evason, M.D., Ph.D.
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Cite this page: Evason KJ. Intraductal papillary neoplasm of the bile ducts. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorintraductalpap.html. Accessed March 19th, 2024.
Definition / general
  • Papillary neoplasm consisting of fibrovascular stalks within cystically dilated intrahepatic bile ducts
Essential features
  • Papillary neoplasm within dilated intrahepatic bile duct(s)
  • Lacks ovarian stroma
  • High rate of associated invasive carcinoma (up to 74%) (Hepatology 2012;56:1352)
  • WHO classification
    • Premalignant: intraductal papillary neoplasm with low grade, intermediate grade or high grade intraepithelial neoplasia
    • Malignant: intraductal papillary neoplasm with associated invasive carcinoma
Terminology
  • Biliary papillomatosis
  • Biliary papilloma
ICD coding
  • ICD-O:
    • 8503/0 - intraductal papillary neoplasm with low grade intraepithelial neoplasia
    • 8503/2 - intraductal papillary neoplasm with high grade intraepithelial neoplasia
    • 8503/3 - intraductal papillary neoplasm with associated invasive carcinoma
  • ICD-11: 2E92.7 - benign neoplasm of liver or intrahepatic bile ducts
Epidemiology
Sites
  • Intrahepatic bile ducts
  • Similar lesions can involve extrahepatic bile ducts, pancreas or gallbladder
  • Often multifocal
Pathophysiology
  • Stepwise progression from low grade dysplasia to high grade dysplasia to invasive carcinoma involving inactivation of TP53 and p16 (early), activating mutations in KRAS (early) and loss of SMAD4 / DPC4 (late) (Mod Pathol 2014;27:73)
Etiology
Clinical features
  • Symptoms resulting from biliary obstruction: jaundice, abdominal pain
Diagnosis
  • Imaging (CT, MRI, ultrasound)
  • Surgical resection: extensive histologic sampling required to exclude invasive component
Laboratory
  • May have elevated bilirubin and alkaline phosphatase due to biliary obstruction
Radiology description
Radiology images

Images hosted on other servers:
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Dilated duct

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Papillary projections

Prognostic factors
Case reports
Treatment
  • Surgical resection is first line treatment
  • Palliative approaches include chemotherapy and laser ablation
Gross description
  • Soft, friable, villiform mass(es)
  • May be pedunculated, sessile or polypoid
Gross images

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Friable, villiform projections

Microscopic (histologic) description
  • Papillary neoplasm with complex tubulovillous or micropapillary architecture
  • Grows within dilated bile ducts
  • Lacks ovarian stroma
  • May form large, multilocular cysts with thin fibrous septations
  • Epithelium may be pancreaticobiliary (most common in European and North American patients), intestinal (more common in Asian patients), gastric (more common in Asian patients) or oncocytic
  • Can be classified into type 1 (pancreatic type) and type 2 (nonpancreatic type) intraductal papillary neoplasms of the bile ducts (IPNBs) (Histol Histopathol 2017;32:1001, J Hepatobiliary Pancreat Sci 2018;25:181)
    • Type 1 is similar to intraductal papillary mucinous neoplasms (IPMNs) of the pancreas
    • Type 1 is more frequently intrahepatic or hilar, while type 2 is more frequently extrahepatic
    • Type 2 is more aggressive, with more frequent associated invasive carcinoma
  • Reference: Am J Gastroenterol 2012;107:118
Microscopic (histologic) images

Contributed by Zachary Dong, M.D.
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Friable papillary projections

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Papillary lesion

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Pancreaticobiliary
type epithelium

Cytology description
  • Hypercellular, with broad and double layered sheets of columnar epithelial cells, fine stroma and complex, 3 dimensional branching papillary configurations
Positive stains
Negative stains
  • ER / PR staining is negative in stroma cells (unlike mucinous cystic neoplasm)
  • SMAD4 / DPC4 staining may be lost in invasive component
Sample pathology report
  • Liver, left lobe, lobectomy:
    • Intraductal papillary neoplasm with low and high grade dysplasia, involving left hepatic duct
    • No invasive carcinoma
Differential diagnosis
Board review style question #1

A 72 year old man presented with jaundice. CT scan showed dilatation of the left bile duct, which contained a papillary lesion. An image from the resection specimen is shown. Which of the following is true about this entity?

  1. It is almost always unifocal
  2. It lacks ovarian type stroma
  3. The epithelium is most commonly oncocytic
  4. There is a strong male predominance
  5. There is a very low risk of associated invasive carcinoma
Board review style answer #1
B. It lacks type ovarian stroma. This is an intraductal papillary neoplasm, which has a relatively high risk of associated invasive carcinoma (up to 74%). Sex preponderance varies by geographic region but the lesion is more common in men than women in Western countries. The epithelium is most commonly pancreatobiliary in European and North American patients. Intestinal and gastric epithelium are common in Asian patients. Oncocytic epithelium is relatively uncommon. The differential diagnosis of cystic hepatic lesions includes mucinous cystic neoplasms, which do have ovarian type stroma.

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Reference: Intraductal papillary neoplasm of the bile ducts
Board review style question #2
Intraductal papillary neoplasms of the bile ducts in North American and European patients most often have which type of epithelium?

  1. Gastric
  2. Intestinal
  3. Oncocytic
  4. Ovarian
  5. Pancreaticobiliary
Board review style answer #2
E. Pancreaticobiliary. Intraductal papillary neoplasms of the bile ducts are most commonly lined by pancreatobiliary epithelium in North American and European patients. Intestinal and gastric epithelium are common in Asian patients. Oncocytic epithelium is relatively uncommon. Ovarian type stroma is associated with mucinous cystic neoplasms, a different type of cystic hepatic lesion.

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Reference: Intraductal papillary neoplasm of the bile ducts
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