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Liver cancer can be a complicated diagnosis. The disease presents few symptoms early on, so it’s usually only detected in advanced stages or found incidentally, when the patient undergoes scans for other diseases.

A pathological study “makes a diagnosis and guides the treatment of the liver cancer patient,” says Yale Medicine pathologist Xuchen Zhang, MD. “If there is a mass in the liver and it has been found to be cancerous, we need to know if it originated in the liver or elsewhere."

The Yale Medicine Department of Pathology has specialized expertise in the area of liver cancer.

What is liver cancer?

“Primary liver cancer (also called hepatic cancer) generally falls into one of two categories,” Dr. Zhang says. The most common type is hepatocellular carcinoma (HCC).

In the United States, most HCC cases have tended to arise in patients who have chronic liver disease with or without cirrhosis caused by hepatitis B or C, but that’s changing, Dr. Zhang says. “The risk profile is shifting,” he says. “We now see more cases of HCC in people who are obese, diabetic or who drink too much alcohol.”

The other type of primary liver cancer, less common, is cholangiocarcinoma (also called bile duct cancer). Other types of liver cancers such as hepatoblastoma, angiosarcoma or leiomyosarcoma are very rare.

Many more have what’s called secondary (or metastatic) liver cancer, which means that it started elsewhere in the body and traveled to the liver. Though early stage disease causes no symptoms, it eventually leads to digestive problems, weight loss and/or yellowish skin.

About 42,000 U.S. adults are diagnosed with primary liver cancer each year.

How does a liver biopsy work?

Some liver tumors grow large enough to be seen or felt. Imaging studies (typically computerized tomography (CT) scan, and/or magnetic resonance imaging (MRI) will reveal whether or not a mass is present, and if so, the number, size or sizes and in what location or locations.

Then, if appropriate, a biopsy can confirm a diagnosis and offer tumor tissue for further gene profiling analysis.

The biopsy, typically done on an outpatient basis, involves a needle inserted between two ribs into the liver. A small liver tissue sample is taken. “The biopsy is sent to the pathology department to process, and we try to figure out if it is a tumor and where the tumor is from,” Dr. Zhang says.

The analysis sometimes uses immunohistochemical staining or molecular tests to determine whether the affected cells originated in the liver or another organ, such as the lung or colon.

How do pathology findings affect treatment of primary liver cancer?

Pathologists try to learn as much as they can about a patient’s disease, starting with identifying its exact parameters.

“Once we have determined the type of cancer, we focus on the degree of malignancy and other characteristics, such as the underlying liver disease,” Dr. Zhang says. “The doctor may already know the size, number and location, based on the radiology findings. Is it small? Is there more than one mass? What type of tumor is it?”

Pathologists’ answers to these questions guide treatment decisions. “If there are three small tumors, the patient may qualify for a liver transplant or tumor resection,” Dr. Zhang says. “If there is just a single one, it may just be removed.” Other treatments, including ablation, chemoembolization and radioembolization, may be appropriate, based on the diagnosis.

Pathologists can also evaluate the efficacy of treatment. “We can see how many tumor cells died after treatment and evaluate if the tumor was completely excised,” he says.

How do pathology findings affect treatment of secondary liver cancer?

For patients with secondary liver cancer, it’s important to pinpoint the origin of the cancer.

“Sometimes the secondary liver cancer is the first sign of the disease, without knowing where it’s from,” Dr. Zhang says. “We do a series of studies to make sure we know.”

Imaging studies, he says, and sometimes additional studies (molecular or tumor gene profiling) may provide further detail that will help doctors to choose the most effective treatment.

“For example, with colon cancer and lung cancer, tumor gene profiling analysis using molecular techniques can identify whether targeted/personalized precision therapies might be helpful,” he says.

What makes Yale Medicine’s approach to diagnosing liver cancer unique?

In the realm of pathological medicine, Yale Medicine stands apart from other institutions, says Dr. Zhang.

“All our gastrointestinal and liver pathologists are specialized in GI and liver pathology with extensive experience in the field,” he says. "Yale Medicine fosters a collaborative spirit within departments and with others. Our oncologists, radiologists, surgeons and pathologists all work together to make decisions for patient management."

Also of value, Dr. Zhang says, is that Yale Medicine offers access to advanced treatments and ongoing clinical trials. “It’s very good for patients,” he says, “because we’re more connected than many other places.”