Cholangiocarcinoma Histology: Key Features & Diagnosis

Cholangiocarcinoma is a cancer of the bile ducts, the tubes that carry bile from the liver to the small intestine. Its diagnosis depends on histology, the microscopic examination of tissue. Through this analysis, pathologists identify the cancer’s specific features, confirm the diagnosis, and gather information that guides medical decisions.

Understanding the Biliary System and Cholangiocarcinoma Origin

The biliary system is a network of organs and ducts that produce, store, and release bile to aid digestion. The liver produces bile, which travels through the bile ducts into the small intestine. Cholangiocarcinoma can arise in any part of this ductal system. Cancers that form in ducts within the liver are called intrahepatic, while those in ducts outside the liver are termed extrahepatic.

A tissue sample, or biopsy, is required for diagnosis. It can be obtained through procedures like endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which use instruments to reach the bile ducts and collect tissue.

A sufficient sample that preserves tissue structure is preferred for accurate analysis. Sometimes, combining a biopsy with brush cytology, which scrapes cells from the duct lining, can increase diagnostic accuracy.

Key Histological Features of Cholangiocarcinoma

Under the microscope, the most common form of cholangiocarcinoma is adenocarcinoma, a cancer originating in glandular tissue. This means the cancer cells attempt to form gland-like or duct-like structures. In healthy bile ducts, cells are neatly arranged in a single layer, forming uniform tubes. In adenocarcinoma, these structures are disorganized, irregularly shaped, and often invade surrounding tissue.

Individual cancer cells also display distinct features, known as cellular atypia. This includes pleomorphism, where cells and their nuclei vary in size and shape. The nuclei often appear hyperchromatic, staining darker than normal, and may have irregular contours and prominent nucleoli, which are small structures within the nucleus.

Cholangiocarcinoma can form distinct masses, grow in a tubular pattern, or have an infiltrative style where cells spread through tissue. A prominent feature is a desmoplastic reaction, the dense connective tissue the body produces in response to the tumor, making it feel firm.

Histological Variants and Grading

While most cholangiocarcinomas are adenocarcinomas, less common variants exist. Mucinous adenocarcinoma is characterized by excessive mucin production around the cancer cells. Signet ring cell carcinoma is a variant where mucin inside the cells pushes the nucleus aside. Adenosquamous carcinoma contains features of both adenocarcinoma and squamous cell carcinoma.

Pathologists also assign a grade to the tumor, which describes how much the cancer cells resemble normal cells, a concept known as differentiation. A tumor is graded as well-differentiated, moderately differentiated, or poorly differentiated.

Well-differentiated tumors have cells and structures similar to normal bile ducts, suggesting slower growth. Poorly differentiated tumors are composed of highly abnormal cells with little resemblance to normal tissue and are often associated with more aggressive behavior. Moderately differentiated tumors fall between these extremes.

The Role of Immunohistochemistry

Immunohistochemistry (IHC) is a laboratory technique that uses antibodies to detect specific proteins, or markers, in a tissue sample. Staining for these markers helps pathologists confirm the cancer’s origin and distinguish it from other cancers.

For cholangiocarcinoma, certain cytokeratins (CKs) are useful markers. Most cholangiocarcinomas test positive for Cytokeratin 7 (CK7) and Cytokeratin 19 (CK19), confirming the cancer originated from the bile duct epithelium. Other markers like CA19-9 and CEA may also be used.

This technique is helpful for differentiating cholangiocarcinoma from other cancers near the liver. For example, hepatocellular carcinoma, the most common primary liver cancer, stains negative for CK7 and CK19. If cancer has spread to the liver from another site, like the colon, an IHC panel can help identify the primary tumor’s origin.

Impact of Histological Findings

Histological findings offer prognostic information beyond the initial diagnosis. Pathologists look for lymphovascular invasion, the presence of cancer cells in blood vessels or lymphatic channels. This finding indicates the cancer may have begun to spread to other parts of the body.

The histological report, combined with molecular testing for genetic mutations, also influences treatment. The tumor’s specific characteristics help determine the most effective chemotherapy or if a patient is a candidate for targeted therapies, directly impacting clinical management.