Lymphoma is a group of cancers that develop in white blood cells called lymphocytes. The two main categories of lymphoma are Hodgkin’s and non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma is more common and can be broken into more than 90 subtypes.

In most cases, non-Hodgkin’s lymphoma develops in lymph nodes. About 20 to 30 percent of cases are extranodal, meaning they develop outside of these nodes. The most common place extranodal lymphoma develops is in the gastrointestinal tract.

In this article, we take a deeper look at extranodal non-Hodgkin’s lymphoma, including where it develops, how it’s diagnosed, and how it’s treated.

Extranodal non-Hodgkin’s lymphoma is when non-Hodgkin’s lymphoma develops outside of your lymph nodes. It can be further categorized as:

  • Primary extranodal non-Hodgkin’s lymphoma: originates outside of your lymph nodes
  • Secondary extranodal non-Hodgkin’s lymphoma: spreads from your lymph nodes

Extranodal non-Hodgkin’s lymphoma can originate in almost any organ. It’s possible to have non-Hodgkin’s lymphoma in both nodal and extranodal sites.

The most common place for extranodal non-Hodgkin’s lymphoma to develop is inside your gastrointestinal tract, which makes up about 30 to 40 percent of cases of extranodal lymphoma.

Gastrointestinal symptoms

Symptoms vary widely depending on where the cancer develops. In the gastrointestinal tract, it can cause many vague and nonspecific symptoms like:

Head and neck symptoms

The next most common place for extranodal non-Hodgkin’s lymphoma to develop is in your head or neck. When it develops in the head or neck, it most often develops in Waldeyer’s ring, a ring of lymph tissue in your throat that includes your tonsils and adenoids.

About 0.1 to 5 percent of cases of non-Hodgkin’s lymphoma develop in your mouth.

Other places in your head and neck lymphoma can develop include:

  • eye sockets
  • thyroid
  • sinuses or nasal cavity
  • brain

Potential symptoms of head and neck non-Hodgkin’s lymphoma are broad and nonspecific. Some but not all the potential symptoms include:

The development of extranodal lymphoma seems to be multifactorial and the precise cause of most lymphomas remains unknown.

Non-Hodgkin’s lymphoma develops when changes in the DNA of white blood cells called lymphocytes cause them to replicate uncontrollably. It’s not clear why this happens, but some risk factors have been identified.

General risk factors for non-Hodgkin’s lymphoma include:

  • being over the age of 60
  • male sex, but women are at a higher risk of some specific types of non-Hodgkin’s lymphoma
  • being white
  • family history
  • exposure to some chemicals like benzene or some herbicides
  • exposure to drugs like some chemotherapy drugs
  • radiation exposure
  • weakened immune system, like in people with untreated HIV
  • having some autoimmune conditions like rheumatoid arthritis
  • some types of viruses like human herpes virus 8 and Epstein-Barr virus
  • some other infections like long-term hepatitis C or Helicobacter pylori (H. pylori)
  • possibly being overweight or obese

Non-Hodgkin’s lymphoma is the second most common cancer in people with HIV. Research suggests people with HIV have a 60 times greater chance of developing non-Hodgkin’s lymphoma than the general population.

Immunodeficiency is the only known risk factor for lymphomas originating in your central nervous system. Prior to the invention of modern HIV drugs, people with HIV had a 3,600 times higher risk of developing these lymphomas.

People who have had non-Hodgkin’s lymphoma are at an increased risk of developing a second cancer.

Many different tests are used to diagnose lymphoma. Your doctor will likely start by examining your medical history, performing a physical exam, and considering your symptoms.

A biopsy of cancer cells is usually needed to confirm a lymphoma diagnosis. Many other tests can provide supportive evidence. They include:

Depending on where the cancer is suspected, your doctor may order other specific tests. For example, a procedure called a gastrointestinal endoscopy may be used to help the doctor view abnormal tissue and take a biopsy of your gastrointestinal tract.

Treatment for non-Hodgkin’s lymphoma depends on factors like where it develops, your overall health, and how advanced the cancer is.

Chemotherapy and radiation therapy are used to treat many types of extranodal non-Hodgkin’s lymphoma, like those that develop in your:

  • gastrointestinal tract
  • head or neck
  • bones
  • breast

Surgery or immunotherapy may also be considered depending on where cancer develops.

Non-Hodgkin’s lymphoma is the most common testicular cancer in adults and is usually treated with the removal of the affected testicle.

About two-thirds of cases of a type of non-Hodgkin’s lymphoma called mucosa-associated lymphoid tissue (MALT) are associated with H. pylori infection. Treatment with antibiotics is usually recommended as the first-line therapy.

In a 2021 study, researchers calculated the 3-year overall survival rate based on 220 people with primary extranodal lymphoma. The most common sites of lymphoma in the study were in the digestive system, head and neck, and central nervous system.

The researchers divided people into the study into four risk groups and calculated the 3-year overall survival for each. The researchers used the International Prognostic Index (IPI) to calculate their risk group.

Risk group3-year overall survivalIPI score

Each of the following criteria is one point on the IPI:

  • being older than 60
  • lymphoma in stage III or IV
  • elevated lactate dehydrogenase levels
  • poor general health
  • more than one extranodal site

Most cases of non-Hodgkin’s lymphoma develop inside your lymph nodes. It’s known as extranodal lymphoma when it develops outside of these nodes.

The most common place for extranodal lymphoma to develop is in your digestive system. It’s not clear why it develops, but researchers have identified many risk factors.

Symptoms of extranodal lymphoma are often vague and have many potential causes. It’s important to see your doctor as soon as possible if you notice any new symptoms that could indicate non-Hodgkin’s lymphoma.