What is marginal zone lymphoma?

Marginal Zone Lymphoma (MZL) is a slow growing form of non-Hodgkin's Lymphoma a place where cancerous cells form in the lymphatic system.

The lymphatic system is a series of vessels that carry colourless liquid around the body. This liquid contains lymphocytes (white blood cells), which are stored in the lymph nodes that contain lymphoid follicles, split into two zones: mantle and marginal zones, the lymphocytes in the marginal zone mutating and becoming malignant is the cause of Marginal Zone Lymphoma. These particular lymphocytes are known as B lymphocytes or B cells, these white blood cells grow out of control and are mutated, that characterises as a non-Hodgkin’s lymphoma.¹ 

Types of marginal cell lymphoma

There are three different types of marginal cell lymphoma, the difference mainly arises due to the area in which the lymphoid follicles are affected. The different types are:

Mucosa-associated lymphoid tissue (MALT) lymphoma- this is the most common variation of MZL,0 this can then be split into two separate variations; gastric MALT (affecting the stomach lining) or non-gastric MALT (lungs, skin, thyroid, near the eyes or salivary glands may be affected). This may also be referred to as extranodal marginal cell lymphoma.

• Nodal marginal zone lymphoma - This affects the lymph nodes but can also be present in the bone marrow
• Splenic marginal zone lymphoma - This is a rarer form of MZL, and can affect the spleen, blood, and bone marrow²

Symptoms of marginal zone lymphoma

Symptoms of MZL may not be obvious at first; due to the slow-progressing nature of the lymphoma, these symptoms are quite broad and may be caused by other conditions. These symptoms are:

• Fever
• Night Sweats
• Weight Loss is unexpected
• Swollen Lymph nodes
• Fatigue

All these symptoms can be a sign of any form of non-Hodgkin’s Lymphoma.²

Further symptoms can be dependent on the part of the body where the lymphoma begins and the type.

MALT lymphoma symptoms can vary whether it is gastric or non-gastric they are as follows:

Gastric MALT:

• Nausea and vomiting
• Stomach ache
• The feeling of fullness, despite not eating

Non-gastric MALT:

• Change in the eyes' surface
• Change in tear glands

Splenic MZL would have the other more standard symptoms as well as an enlarged spleen due to the presence of more mutated lymphocytes in this area.³ 

Causes of marginal zone lymphoma

Those who suffer from MALT tend to have had some history of autoimmune disorders such as Hashimoto’s disease or Sjogren's syndrome, which are particularly linked to this form of lymphoma.

Bacterial infection can also lead to MZL development, this is caused in particular by H. pylori bacterial infection.

Splenic and nodal MZL are thought to be linked to Hepatitis-C infection and potentially autoimmune disorders having a role. People with a family history of lymphoma are also at a greater risk.⁵ 

Diagnosis of marginal zone lymphoma

The main way that MZL is diagnosed is through identifying the presence of a large population of abnormal marginal zone B cells.⁴ 

Positron Emission Tomography (PET) and computed tomography (CT) scans are generally used to great effect to view and understand the progression and stages of MZL.

The main tests used that can confirm a marginal zone lymphoma diagnosis are focused on the state of the blood as a whole. These tests would be:

• Complete blood count - measures all that makes up the blood; red blood cells, white blood cells, and platelets, including the size and shapes of each type of cell
• LDH (lactate dehydrogenase) test - higher levels may suggest damaged tissues
• Beta-2-microglobulin test - this is a marker for blood cancers

Bone marrow biopsies can also be done to see whether potential MZL has affected the marrow, and which form the lymphoma is.⁶

Treating marginal zone lymphoma

Treatment of MZL can be difficult to recommend specific treatment in many cases being different in organs affected and the progression of the disease. As such there is no widely accepted treatment for MZL.

For cases that have been caused by bacterial infection, the first call for treatment would be treating the bacterial infection with antibiotics, which can cause up to a 75% regression in MALT cases.⁸ 

For cases of splenic and nodal MZL that have been caused by hepatitis, antiviral medication can be useful and help in regression of MZL. Rituximab; a targeted cancer drug, and a splenectomy may be useful in those with splenic MZL. Nodal MZL can be treated with the use of radiotherapy.

For those without/very mild symptoms there may not be immediate treatment, with a ‘watchful waiting’ method being used. when action is needed there would be the use of radiotherapy or chemotherapy as needed, but this may differ due to different types of tissues that are affected.³ 

Marginal zone lymphoma is a lesser researched form of cancer comparatively, future research may be focused on the involvement of the immune system in the cause of MZL; this is due to the nature of it being caused by infection or autoimmune disorder and the lymphatic system.⁹ 

Summary

Marginal zone lymphoma (MZL) is a slow-progressing form of non-Hodgkin’s lymphoma, caused by the mutation and abnormal growth of B lymphocytes (white blood cells) in specific parts of the lymph nodes (marginal zone lymphatic follicles).

There are different types of MZl, which are categorised by the area in which the lymphoma is present, these are:

• Mucosa-associated lymphoid tissue (MALT) lymphoma; gastric (affects the stomach) or non-gastric (affects other tissues, lungs, skin, salivary glands, etc.)
• Nodal Marginal Zone Lymphoma
• Splenic Marginal Zone Lymphoma

These can be caused by bacterial infection, history of autoimmune disorders, hepatitis or can be more prevalent in those with a family history of lymphoma.

Symptoms are not specific but most commonly are fever, night sweats and unexplained weight loss, with some other symptoms based on the type of its origin.

• Splenic- enlarged spleen
• Nodal- swollen lymph nodes
• Gastric MALT- Stomach ache, nausea, and feeling of fullness despite not eating
• Non-gastric MALT- changes in the eyes' surface

Diagnosing MZL can be done with blood tests to assess the number of certain blood cells and their size and shape and imaging techniques such as PET/CT scans can be used to understand the effect that the cancer is having on the body as well as tracking its progression.

Treatment for marginal zone lymphoma has no main recommended course due to the different forms it can take. Initially, treatment may not be used, but rather a ‘waitful watching’ technique can be beneficial.

Initial treatment usually focuses on the treatment of the underlying cause; if it is treatable. This would be by treating the bacterial infection with antibiotics, or hepatitis-c vaccine that caused the development of marginal zone lymphoma, a splenectomy may be done in those with splenic MZL.

Depending on subtype different forms of radiotherapy or chemotherapy may be used as treatment.