Marginal zone lymphoma (MZL)

Marginal zone lymphoma is a cancer of B cells, the white blood cells that normally make antibodies to fight infection. It begins in B cells from a part of the lymph tissue called the marginal zone. It is usually indolent, which means it grows slowly.

There are three main types, named for where the lymphoma starts. Extranodal MZL, also called MALT lymphoma (short for mucosa-associated lymphoid tissue), starts outside the lymph nodes: most often in the stomach, but also around the eye, in the lung, the salivary glands, the thyroid, the skin and other places. Nodal MZL starts in lymph nodes. Splenic MZL starts in the spleen and may spread to the blood and bone marrow.

In the United States, MZL makes up about 7 in every 100 non-Hodgkin lymphomas; an estimated 7,460 people were diagnosed with it in 2016. It becomes more common with age.

MZL often grows out of long-lasting inflammation. When an infection or an autoimmune disease keeps the immune system switched on for years, B cells keep dividing. Over time one of them can pick up gene changes and start growing out of control.

Stomach MALT lymphoma is strongly linked to Helicobacter pylori (H. pylori), a common stomach bacterium that is involved in about two out of three cases. Other links include hepatitis C virus and autoimmune diseases such as Sjögren syndrome, lupus and Hashimoto thyroiditis. Having a close relative with non-Hodgkin lymphoma modestly raises the risk.

Most people with these infections or conditions never develop lymphoma. The lymphoma itself cannot be caught from another person, even when an infection helped set it off.

Symptoms depend on where the lymphoma grows, and some people have none at first. MALT lymphoma may cause problems in the organ involved, such as the stomach, the tissues around the eye or a salivary gland. Nodal MZL usually shows up as swollen lymph nodes, often in the head and neck. Lymphoma can also cause fever, drenching night sweats, weight loss and tiredness.

Splenic MZL often causes a large spleen, which can bring pain or fullness in the upper left belly, along with low blood counts and extra lymphocytes in the blood. Some people also have autoimmune problems, such as autoimmune hemolytic anemia, in which the immune system destroys red blood cells.

In a small share of people, MZL changes over time into a faster-growing lymphoma. This is called transformation. It needs a different treatment plan, so a new biopsy may be done if a lymph node grows quickly or new symptoms appear.

Because MZL usually grows slowly, many people live with it for years, moving between periods of watching and periods of treatment. Being watched without treatment can feel strange after a cancer diagnosis, but for many people it is a careful, standard choice, with regular checkups and tests.

Side effects depend on the treatment. Rituximab and chemotherapy can lower immune defenses, and BTK inhibitors are taken every day and need regular monitoring. CAR-T therapy has its own serious risks, including cytokine release syndrome, a strong immune reaction that can cause high fever, and effects on the nervous system, so people are watched closely afterward.

After antibiotics for stomach MALT lymphoma, people usually have a breath test to check that the infection is gone, then a repeat endoscopy (a camera look inside the stomach) a few months later to check the lymphoma. Anyone being watched can ask the care team which new symptoms, such as a fast-growing lump, should prompt an earlier visit.

Most people with MZL will never need a donor. Treatment is usually antibiotics, radiation or medicines. When a transplant is used, it is most often an autologous transplant, which gives back the person’s own stored stem cells. The approved CAR-T therapy also starts from the person’s own cells. Neither uses a registry donor.

A donor (allogeneic) transplant is uncommon in MZL and is usually considered only after other treatments, including an autologous transplant, have stopped working. When one is needed, the donor can be a matched brother or sister, another relative or an unrelated volunteer found through a registry.

So joining a registry is not the usual next step for someone with MZL. But registries serve patients with many blood cancers and blood disorders, and each volunteer adds to the chance that a patient without a matched relative can find a donor.