Marginal Zone Lymphoma - Causes, Diagnosis, and Treatment

What Is Marginal Zone Lymphoma?

The marginal zone B-cell lymphomas (MZL) are a kind of non-Hodgkin's lymphoma that arises from the marginal zone of lymphoid tissue. The marginal zone of lymphoid tissue is a separate micro-anatomic compartment of the B-follicle that is strongly developed in lymphoid organs and known to have a high antigen inflow in the spleen, mesenteric lymph nodes, and mucosa-associated lymphoid tissue (MALT). Marginal zone lymphomas account for around 10 % of all non-Hodgkin's lymphomas, ranking third behind diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma.

What Is the Classification Of Marginal Zone Lymphoma?

The World Health Organization (WHO) divides them into three types:

1. Splenic marginal zone lymphomas.

2. Nodal marginal zone lymphomas.

3. MALT lymphoma (mucosa-associated lymphoid tissue) or extranodal marginal zone lymphoma.

Despite histologic and genetic similarities, clinical differences were the fundamental cause for these three marginal zone lymphoma subtypes being categorized as distinct clinicopathological entities.

What Is the Epidemiology Of Marginal Zone Lymphoma?

MALT lymphoma (mucosa-associated lymphoid tissue) or extranodal marginal zone lymphoma is rather frequent, accounting for around eight percent of all non-Hodgkin's lymphomas. Nodal and splenic marginal zone lymphomas are extremely rare, accounting for less than one percent of all non-lymphomas.

What Is the Etiology Of Marginal Zone Lymphoma?

Neoplastic cells (cells that cause abnormal growth in the tissue) in marginal zone lymphomas can penetrate and destroy the epithelium, resulting in lymphoepithelial lesions. The abnormal growth primarily consists of marginal zone B-cells (centrocyte-like cells), although the cell makeup is typically varied.

All marginal zone lymphomas, regardless of location, may contain a polymorphous combination of centrocyte-like cells, tiny lymphocytes, plasma cells, and dispersed giant blast cells.

Chronic infections such as Helicobacter pylori, hepatitis C virus, Campylobacter jejuni, Chlamydia psittaci, and Borrelia burgdorferi have been linked to the pathogenesis of these lymphomas.

A thick coating of viscous mucus and gastric acid prevents bacterial colonization of the stomach in healthy people. H. pylori, a gram-negative bacteria linked to peptic ulcers and gastric cancer, lives in acid by secreting a pH buffering urease and triggering lymphoid infiltration. This H. pylori infection thus causes stomach MALT lymphoma (mucosa-associated lymphoid tissue) or extranodal marginal zone lymphoma.

What Are the Clinical Features Of Marginal Zone Lymphoma?

• Marginal zone lymphomas are most commonly diagnosed as extranodal (outside a lymph node) diseases localized to the site of origin.

• The clinical presentation of nodal marginal zone lymphomas without extranodal involvement is peripheral and around the aorta of the heart (para-aortic) lymphadenopathy and late-stage illness.

• The symptom of this disease is comparable to other low-grade nodal non-lymphomas, such as follicular lymphoma and Hodgkin's lymphoma.

• The most usually afflicted locations are the salivary glands, stomach, conjunctiva, thyroid, lacrimal, gut, and skin.

• Splenic marginal zone lymphomas affect the elderly and are characterized by an enlarged spleen, peripheral blood, and bone marrow involvement.

How Is Marginal Zone Lymphoma Diagnosed?

Marginal zone lymphomas are diagnosed by:

1. Biopsy.

2. Clinical signs and symptoms.

3. Immunophenotyping.

4. Genetic testing.

Residual reactive germinal centers are a common observation in all marginal zone lymphomas, regardless of location. However, they might be challenging to detect in the case of abnormal growth (neoplasia) colonization of the germinal center. For example, the architecture of a lymph node affected by primary nodal marginal zone lymphoma is often intact, with the abnormal growth spreading into the interfollicular region and surrounding remaining reactive germinal centers as discrete rings.

However, the white pulp in splenic marginal zone lymphomas is hyperplastic, with large peripheral zones and variable invasion into the red pulp, culminating in significant splenic growth. Surface immunoglobulin (IgM > IgA, IgG), pan B-cell markers (CD20, CD19, CD79a), and complement receptors are all positive (CD21, CD35) in marginal zone lymphoma.

What Is the Treatment for Marginal Zone Lymphoma?

MALT Lymphoma (Mucosa-Associated Lymphoid Tissue) - Antibiotic eradication of H. pylori is the first line of treatment for MALT lymphoma (mucosa-associated lymphoid tissue). It might take anywhere from a few weeks to more than a year to achieve full remission.

Radiation Therapy - When antibiotic treatment fails or presents a localized H. pylori-negative stomach marginal zone lymphoma, low-dose involved-field radiation can be used successfully.

Immunotherapy - Immunotherapy with anti-CD20 monoclonal antibodies (Rituximab) with chemotherapy is frequently recommended for disseminated illness.

Surgery - Surgery is only used to treat stomachMALT lymphoma (mucosa-associated lymphoid tissue) if local problems such as perforation develop.

Splenectomy - Chemotherapy has poor success; thus, splenectomy was the treatment of choice for splenic marginal zone lymphoma patients. Approximately 90 % of people respond to splenectomy. Patients with splenic marginal zone lymphoma are frequently older and offer surgical risks. Treating such people with Rituximab alone or in combination with chemotherapy has yielded outstanding results, as Rituximab may enhance progression-free survival even more. Thus, splenectomy is not regarded as initial therapy for splenic marginal zone lymphoma but rather as palliative therapy for patients who have not responded to immunotherapy alone or in combination with chemotherapy.

What Is the Differential Diagnosis For Marginal Zone Lymphoma?

The absence of typical markers in marginal zone lymphoma is significant in differential diagnosis with other small B-cell lymphomas:

IgD expression: It is positive in marginal zone lymphoma.

CD5: It is positive in splenic marginal zone lymphoma, mantle cell lymphoma, and small lymphocytic lymphoma.

Cyclin D1: It is positive in splenic marginal zone lymphoma, mantle cell lymphoma, and small lymphocytic lymphoma.

Molecular methods such as polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) are developed as novel diagnostic tools in hematopathology to further support the diagnosis of a marginal zone lymphoma by recognizing B-cell clonality.

What Is the Prognosis Of Marginal Zone Lymphoma?

Marginal-zone lymphomas are often slow-growing cancers with a restricted stage of illness. Localized illness may be managed with local treatments. Unlike other low-grade lymphomas, it has a reasonable cure rate. The prognosis for gastrointestinal and non-gastrointestinal types appears to be comparable, with five-year overall survival of more than 90 % and ten-year survival of 75 to 80 %. Recurrences can occur years after therapy, with a median of five years, and include the same organ (60 % of cases) or different extranodal locations. Dissemination (spread) occurs in 30 % of extranodal forms, typically to additional extranodal sites, with a long disease-free period. When these lymphomas expand, they preferentially spread to different mucosal sites, with little involvement of the peripheral blood or bone marrow.

Conclusion

To summarise, marginal zone lymphoma comprises three distinct entities that must be diagnosed by combining clinical and pathologic criteria. Treatment is selected and begun based on the appearance, symptoms, and underlying subtype. Additional gains are predicted as new drugs are examined. However, further research is required to properly inform treatment selection and sequencing of therapy.