Your pathology report for biliary intraepithelial neoplasia (BilIN)

By Jason Wasserman MD PhD FRCPC
October 2, 2025

Biliary intraepithelial neoplasia (BilIN) is a precancerous change in the thin layer of cells that line the gallbladder and bile ducts. The abnormal cells are confined to the inner surface and have not yet invaded deeper tissues. Because it is microscopic, BilIN cannot be seen with the naked eye and is usually only discovered when the gallbladder or bile ducts are removed for another reason, such as gallstones.

What are the symptoms of biliary intraepithelial neoplasia?

BilIN itself does not cause symptoms. It is almost always found by chance in tissue samples taken for other conditions. If symptoms are present, they are usually due to the underlying condition, such as gallstones or inflammation of the bile ducts.

What causes biliary intraepithelial neoplasia?

Doctors believe BilIN develops after long-term irritation or inflammation of the gallbladder or bile ducts. Known risk factors for BilIN include:

  • Gallstones – Long-standing gallstones cause chronic irritation.

  • Primary sclerosing cholangitis – A condition where the bile ducts become scarred and inflamed.

  • Choledochal cysts – Fluid-filled sacs in the bile ducts.

  • Anomalous union of the pancreatic and bile ducts – A structural abnormality where pancreatic fluid can flow into the bile ducts.

  • Familial adenomatous polyposis – A rare inherited syndrome that increases the risk of growths in the digestive tract.

At the genetic level, mutations in the KRAS gene are often seen early, while mutations in TP53 tend to occur later as the lesion progresses. These changes alter how cells grow and divide.

How is the diagnosis made?

The diagnosis of BilIN can only be made by a pathologist examining tissue under the microscope. The abnormal cells form a flat or papillary (finger-like) growth along the inner lining of the gallbladder or bile ducts.

Because BilIN is microscopic, it is not visible on imaging scans and is usually found in tissue removed for another reason, such as gallstones or suspected cancer.

Microscopic features

Under the microscope, BilIN is made of abnormal epithelial cells (cells that form the inner lining of the gallbladder or bile ducts). These cells may look crowded, enlarged, or darker than normal, and they may form flat layers or papillary (finger-like) projections.

How do pathologists grade biliary intraepithelial neoplasia?

Pathologists separate BilIN into low grade and high grade based on how abnormal the cells appear under the microscope.

Low grade BilIN

In low grade BilIN, the cells show only mild abnormalities. The nuclei (the control centers of the cells) may look darker or slightly irregular, but the overall structure of the lining is still preserved. This type of BilIN is considered to have little to no immediate risk of turning into cancer, and on its own, it usually has no clinical significance.

High grade BilIN

In high grade BilIN, the cells are much more abnormal. They often lose their normal organization (loss of polarity), the nuclei become very irregular and dark, and more mitotic figures (dividing cells) are seen. High grade BilIN is also called carcinoma in situ, which means the cells are cancer-like but still confined to the inner lining. High grade BilIN has a significant risk of progressing to invasive adenocarcinoma if left untreated.

What stage is biliary intraepithelial neoplasia?

By definition, BilIN has not invaded deeper tissues, so it is staged differently from invasive cancer.

  • Low grade BilIN is not assigned a cancer stage because it is considered precancerous.

  • High grade BilIN is classified as Tis (carcinoma in situ), which means the abnormal cells are confined to the inner lining and have not spread further.

Prognosis

The outlook depends on whether the BilIN is low grade or high grade.

  • Low grade BilIN is usually of no clinical consequence and does not affect long-term health.

  • High grade BilIN is more serious. Most cases are cured if the gallbladder or affected bile duct is removed. However, a small number of patients may later develop new cancers in other parts of the biliary tract. This may be due to a field effect, meaning the entire biliary system has an increased risk of developing cancer.

Other features that may increase the risk of recurrence include:

  • Extensive high grade BilIN

  • Involvement of Rokitansky–Aschoff sinuses (small pockets that extend into the gallbladder wall)

  • Positive surgical margins (abnormal cells present at the cut edge of the removed tissue)

For these reasons, patients with high grade BilIN are often followed closely even after surgery.

Questions to ask your doctor

  • Was the BilIN in my sample low grade or high grade?

  • If high grade, was it completely removed?

  • Did the report mention margins, and were they clear of abnormal cells?

  • Do I need follow-up care or monitoring for future risk of cancer?

  • How does BilIN affect my overall prognosis?

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