What is Hepatic Lymphoma?
Primary hepatic lymphoma (PHL) is an uncommon type of non-Hodgkin lymphoma (NHL), which is a group of blood cancers. Unlike other types of NHL, which mainly affect the lymph nodes or spleen, PHL specifically involves the liver. The liver, being a key organ in our immune system, is often affected in patients with NHL, with about 40% of them experiencing liver involvement. Most people with PHL experience vague symptoms like nausea, vomiting, upper abdominal pain, or discomfort. About one in three also report general symptoms like fever, muscle pain, and weight loss. However, because these symptoms are nonspecific and the condition is rare, patients often go through numerous tests before doctors can make a definitive diagnosis. To confirm PHL, doctors need to do a liver biopsy, which is a procedure to remove a small piece of liver tissue that will be checked for lymphoma and ensure that there isn’t any other related disease outside the liver.
Additionally, PHL can sometimes be confused with other conditions that cause similar changes in the liver, such as hepatocellular carcinoma (liver cancer), hepatic adenoma (a benign liver tumor), focal hyperplasia of the liver (a benign condition where liver cells multiply and form a mass), and hepatic hemangioma (a noncancerous mass in the liver). When a doctor is dealing with such liver conditions, they need to consider PHL as a potential diagnosis, even if it is not common. Most notably, they should consider it as a possibility in the backdrop of more common conditions like hepatocellular carcinoma.
What Causes Hepatic Lymphoma?
Certain types of viruses, specifically those that tend to target the liver (known as hepatotropic) and those that don’t (non-hepatotropic), have been linked to primary hepatic lymphoma (PHL), a rare type of liver cancer. These hepatotropic viruses include hepatitis C virus (HCV) and hepatitis B virus (HBV). Some less common non-hepatotropic viruses, like HIV, hepatitis E virus (HEV), and Cytomegalovirus (CMV), have also been associated with PHL. Additionally, some autoimmune diseases, like systemic lupus erythematosus (SLE), can be linked to PHL.
In a large study of 69 patients with PHL, 20% were found to have HBV infections. However, it’s important to note that most of these patients were from the Western world. In contrast, a different study reported only 4% of PHL cases in 90 individuals were linked to HBV infection. These patients were largely of Asian origin, where HBV infection is endemic, meaning it’s commonly found in that area. Yet, another study from China found that 60% of Chinese patients with PHL tested positive for an antigen associated with HBV. Still, given that around 10% of the Chinese population tests positive for this antigen, it’s also possible that this connection could be a coincidence and not directly causing PHL.
Also, hepatitis C virus (HCV) was found in 21% of PHL patients who had a strong immune system. Most of these HCV-infected patients have also had a high-grade B-cell lymphoma, a type of blood cancer that impacts white blood cells.
Risk Factors and Frequency for Hepatic Lymphoma
Primary hepatic lymphoma is quite rare and its exact occurrence rate is not well-established. However, it’s reported that it makes up 0.4% of all extranodal non-Hodgkin lymphoma cases and 0.016% of all non-Hodgkin lymphoma cases. The average age of people who develop primary hepatic lymphoma is 50 years, and it is more commonly seen in males compared to females, with a ratio of 1.7 to 1.
Signs and Symptoms of Hepatic Lymphoma
Primary hepatic lymphoma is a condition that affects the liver and often produces vague symptoms that might include feeling sick, throwing up, discomfort in the upper part of the stomach, and turning yellow–a condition known as jaundice. Sometimes, the liver might also swell up–a condition called hepatomegaly–which can cause discomfort in the stomach. Just like non-Hodgkin lymphoma, with very few exceptions such as Burkitt lymphoma, primary hepatic lymphoma often develops slowly in most patients, and it might take some time before they notice any significant symptoms, such as a subtle pain or lump on the right side, until the tumor grows large enough to affect the liver.
- Nausea
- Vomiting
- Upper abdominal discomfort
- Jaundice
- Hepatomegaly (liver enlargement)
- Slow development of disease
- Subtle right-side pain or lump
In rare instances, this disease might lead to severe liver failure or chronic hepatitis. Additionally, it can also lead to an enlarged spleen (congestive splenomegaly) due to liver malfunction and increased blood pressure in the liver’s blood vessels (portal hypertension).
Testing for Hepatic Lymphoma
If you are experiencing symptoms linked to systemic lymphoma, like generalized swelling of the lymph nodes, your doctor will carry out a thorough check-up to rule out this and other similar conditions. This includes excluding common causes of liver abnormalities, such as liver cancer, metastatic liver disease (cancer that has spread to the liver from other parts of the body), liver adenomas (benign liver tumors), hemangiomas (a collection of small blood vessels that form a lump), and hydatid cysts (parasitic cysts usually caused by tapeworm infections).
To do this, your doctor might perform several tests. They could test for infections like hepatitis B, hepatitis C, Epstein-Barr virus (which causes glandular fever), and HIV. They might also measure different markers in your blood that might suggest the presence of a tumor. These markers include enzymes like lactate dehydrogenase, substances like alpha-fetoprotein which can be a sign of liver cancer, and other markers like B-2 microglobulin (which can show up in certain lymphomas), carcinoembryonic antigen (CEA, a protein involved in cell adhesion), CA 19-9 and CA-125. These tests are used to provide insight about the tumor and help distinguish whether the disease is originating from the liver itself or spreading from another part of the body.
In addition to these tests, your doctor might use imaging techniques, like a triphasic CT scan of the liver, to get a better look at any abnormalities in your liver. This can help spot things like liver cirrhosis (scarring of the liver due to long-term damage) and involvement of other organs. Unlike liver cancer, which shows varying phases of enhancement on the scan, lymphoma lesions may show enhancement only in the arterial phase. The lesions usually appear as regions of low density with mixed patterns, which might suggest the tumor has experienced areas of cell death or tissue breakdown.
From a radiographic perspective, primary hepatic lymphoma (a rare type of liver cancer) can appear in three ways: it could be a solitary lesion, it might appear as multiple lesions within the liver, or it could cause widespread abnormality throughout the liver.
Treatment Options for Hepatic Lymphoma
Primary hepatic lymphoma, or lymphoma that starts in the liver, is quite rare. That makes it difficult to establish treatment guidelines since most information about how patients respond to treatments is from individual case studies, rather than large-scale clinical trials.
For instance, a case series looked at the outcomes of eight patients who had surgery to remove their tumors. One patient unfortunately lost their life due to post-surgery complications. Out of the remaining seven, about 78% lived for at least six months after the surgery, 67% survived one year and about 56% lived for at least two years. The median survival time was about 23 months. Interestingly, whether or not a patient had chemotherapy after surgery was a significant factor in survival rates.
However, another study showed that combining several chemotherapy drugs helped the majority (83.3%) of patients eliminate their tumors completely. The percentage of patients who lived for at least five years without their disease progressing was approximately 70.1%, while around 87.1% of patients survived at least five years in general. Similarly, another study found that 70% of their patients responded to combination chemotherapy treatment.
Factors such as the size of the tumor, levels of certain substances in the blood (like lactate dehydrogenase and beta-2 microglobulin), and experiencing symptoms that affect the entire body can influence how well a patient responds to treatment and their chances of survival.
For patients who don’t have any high risk factors, a combination of chemotherapy drugs including cyclophosphamide, doxorubicin, vincristine, and prednisone is usually effective in achieving remission, or the disappearance of signs and symptoms of cancer. If a patient has one or more risk factors before treatment starts, doctors may consider using an alternating triple combination, which involves alternating between two different combinations of chemotherapy drugs.
What else can Hepatic Lymphoma be?
Primary hepatic lymphoma, a type of liver cancer, can be mistaken for other conditions that also show up as masses in the liver. These include:
- Hepatocellular carcinoma (another form of liver cancer)
- Metastatic liver disease (cancer that has spread to the liver from other parts of the body)
- Hepatic adenoma (a rare, benign liver tumor)
- Hemangioma (a non-cancerous growth made up of blood vessels)
- Liver abscess (a pocket of pus in the liver)
- Hydatic cyst (a fluid-filled sac caused by a parasitic infection)
In most cases, doctors can confirm the diagnosis of primary hepatic lymphoma by using imaging tests and then getting a sample of the mass with a targeted biopsy.
What to expect with Hepatic Lymphoma
Primary hepatic lymphoma, a type of liver cancer, is typically responsive to combination chemotherapy. In fact, over 80% of patients can achieve complete remission, or absence of signs of the disease, with this treatment. The survival rate specific to the disease after five years is approximately 87.1%.
The outlook after surgical removal of the cancer varies greatly among patients. Further, due to the tumor’s blood-rich nature, there’s a significant risk of severe bleeding after surgery. This risk can contribute to complications and can potentially increase the chances of illness or death following the surgical procedure.
Possible Complications When Diagnosed with Hepatic Lymphoma
Primary liver lymphoma patients may sometimes experience acute liver failure, a severe and potentially life-threatening condition. There are also instances of tumor-related bleeding and the spread of the disease to other nearby lymph nodes.
Issues May Develop:
- Acute liver failure
- Tumor-caused bleeding
- Disease spread to other close lymph nodes
Preventing Hepatic Lymphoma
People who have chronic viral hepatitis, problems with their liver function tests, persistent upper abdomen discomfort, or unusual growths in their liver should definitely take advice from a liver specialist, also known as a hepatologist. Generally, a CT scan (a type of X-ray that creates detailed pictures of the inside of your body) can help identify what’s wrong, but sometimes a biopsy (a procedure that extracts a small sample of tissue for examination in a lab) is necessary to confirm the diagnosis, particularly in cases that are unclear.
A hematologist, a doctor who specializes in blood diseases, is always needed to guide the next steps in treatment. This often includes chemotherapy, which uses drugs to stop the growth of cancer cells. Most people with primary liver lymphoma, a rare type of liver cancer, respond well to chemotherapy. In fact, more than 80% of treated individuals are able to live beyond five years following their diagnosis and treatment.
