Hepatoid adenocarcinoma is a rare form of cancer. Its defining characteristic is the microscopic resemblance of its cells to primary liver cells, known as hepatocytes. Despite this resemblance, these tumors originate in organs other than the liver, a condition referred to as extrahepatic. The rarity of this cancer is notable, with an estimated annual incidence of just 0.58 to 0.83 cases per million people. This low frequency can contribute to challenges in its recognition and management.
Primary Sites and Clinical Presentation
Hepatoid adenocarcinoma (HAC) most commonly develops in the stomach, which accounts for the majority of cases. However, these tumors can also arise in other organs, including the ovaries, lungs, pancreas, colon, and uterus.
The symptoms associated with HAC are often non-specific and largely depend on the tumor’s location. For instance, a tumor in the stomach may cause epigastric pain, abdominal distention, or weight loss. If the cancer originates in the lungs, a patient might experience shortness of breath. Other general symptoms can include fatigue and anemia. This lack of distinct early warning signs makes early detection difficult.
The Diagnostic Process
Diagnosing hepatoid adenocarcinoma often begins with imaging technologies. Computed tomography (CT) scans are used to visualize the tumor and can reveal characteristics like eccentric wall thickening in the affected organ. These imaging studies help locate the primary tumor and identify if the cancer has spread to other parts of the body, such as the lymph nodes or liver.
Blood tests for specific tumor markers are another component of the diagnostic workup. A primary marker for HAC is Alpha-fetoprotein (AFP). While produced by the tumor, the serum levels of AFP can vary dramatically among patients, ranging from normal levels to extremely high concentrations. An elevated AFP level, particularly in the absence of primary liver disease, can lead physicians to suspect HAC, though it is not definitive on its own. The diagnosis can be complicated or delayed if elevated AFP is the only sign, sometimes leading to a misdiagnosis of primary liver cancer.
The definitive diagnosis of HAC is achieved through a biopsy of the tumor tissue. A pathologist examines the tissue sample under a microscope to identify its unique features. The primary finding is the presence of cells that look like liver cells, which is known as hepatoid differentiation. This morphological similarity to hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a defining characteristic.
To confirm the diagnosis, a technique called immunohistochemistry (IHC) is used. This laboratory method uses specific antibodies to detect proteins on the surface of the cancer cells. Pathologists look for markers like SALL4 and Glypican-3 to confirm the hepatoid nature of the adenocarcinoma.
Treatment Approaches
The primary treatment for localized hepatoid adenocarcinoma is surgical resection. For localized disease, the goal of surgery is the complete removal of the tumor. This approach is considered a potentially curative intervention. The decision to proceed with surgery is based on the tumor’s size, location, and whether it can be safely and completely excised.
For more advanced or metastatic disease, systemic treatments like chemotherapy are utilized. Due to its rarity, there is no single standardized chemotherapy regimen for HAC. Treatment plans are often adapted from protocols used for either primary liver cancer or adenocarcinomas of the originating organ. Commonly used chemotherapy agents include platinum-based drugs like cisplatin and oxaliplatin, as well as 5-fluorouracil.
Researchers are exploring other treatment avenues, including targeted therapy and immunotherapy. For tumors that test positive for specific genetic markers, such as HER2 amplification, targeted drugs may be an option. The use of immunotherapy, which helps the body’s own immune system fight cancer, is also under investigation. The effectiveness of these newer therapies for HAC is still being established.
Prognosis and Disease Characteristics
Hepatoid adenocarcinoma is an aggressive cancer that tends to spread early. The most common sites for metastasis are the lymph nodes and the liver, followed by the lungs and peritoneum. The disease is often diagnosed in advanced stages, with over 60% of patients presenting with stage III or IV cancer.
A patient’s outlook is influenced by several factors. The stage at diagnosis and whether the tumor can be completely removed by surgery are primary determinants of long-term outcomes. Very high preoperative serum AFP levels have also been associated with poorer overall survival, and the 5-year survival rate has been reported to be as low as 9%.
The overall prognosis is often poor compared to more common adenocarcinomas in the same organ, but outcomes vary. Early detection followed by complete surgical removal can be curative for some patients. Combining treatments like surgery and chemotherapy can also lead to longer survival times.