Marginal Zone Lymphoma: Symptoms, Diagnosis & Treatment

Introduction

Marginal zone lymphoma (MZL) is a subtype of non-Hodgkin lymphoma (NHL) that originates in the marginal zone of lymphoid tissues, a vital part of the immune system. While MZL is considered an indolent, or slow-growing, lymphoma, it can have a significant impact on a patient’s health if not appropriately managed. First recognized as a distinct type of lymphoma in the 1990s, ongoing research has deepened our understanding of its causes, progression, and treatment options. This article offers a comprehensive overview of marginal zone lymphoma, including its risk factors, symptoms, diagnostic methods, treatment approaches, and strategies for managing symptoms at home. By understanding these aspects, patients can work closely with healthcare providers to create personalized treatment plans tailored to their needs.

What is Marginal Zone Lymphoma?

Marginal zone lymphoma is a type of non-Hodgkin lymphoma that affects the immune system. This article delves into its risk factors, symptoms, diagnostic techniques, treatment options, and practical strategies for managing symptoms at home.

Description of Marginal Zone Lymphoma

Marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma that develops from B-cells, a type of white blood cell essential for immune function. MZL typically arises in the marginal zone, which is the outer edge of lymphoid tissues such as the spleen, lymph nodes, or mucosa-associated lymphoid tissue (MALT). There are three main types of MZL: extranodal MZL (commonly referred to as MALT lymphoma), nodal MZL, and splenic marginal zone lymphoma (SMZL). While these types affect different parts of the body, they share many similar characteristics.

MZL generally progresses slowly, meaning symptoms may not appear for a long time. However, if left untreated, it can spread to other areas, including the bone marrow and bloodstream. The rate of progression varies widely; some individuals may live with minimal symptoms for years, while others may require more immediate treatment.

According to the American Cancer Society, MZL accounts for approximately 5-10% of all non-Hodgkin lymphomas. It is more commonly diagnosed in older adults, with the average age of diagnosis being around 60 years. Although MZL is rare, recognizing its symptoms and risk factors is essential for early detection and effective treatment.

Risk Factors for Developing Marginal Zone Lymphoma

Lifestyle Risk Factors

Although lifestyle factors are not the primary cause of marginal zone lymphoma, certain habits and environmental exposures may increase the risk. For example, smoking has been associated with a higher likelihood of developing MALT lymphoma, particularly in the stomach, as it can lead to chronic inflammation in mucosal tissues. Additionally, exposure to chemicals such as pesticides or industrial solvents may elevate the risk of MZL. Adopting a healthy lifestyle, including avoiding smoking and limiting exposure to harmful chemicals, can help reduce the risk of lymphoma and other health conditions.

Medical Risk Factors

Several medical conditions are linked to an increased risk of marginal zone lymphoma. Chronic infections, such as Helicobacter pylori (H. pylori) in the stomach, are strongly associated with MALT lymphoma. In some cases, treating these infections can lead to the regression of lymphoma. Other infections, such as hepatitis C virus (HCV), and autoimmune diseases like Sjögren’s syndrome or Hashimoto’s thyroiditis, are also connected to a higher risk of MZL. Individuals with these conditions should be closely monitored for any signs of lymphoma.

Genetic and Age-Related Risk Factors

Genetics and age play a significant role in the development of marginal zone lymphoma. MZL is more common in individuals over the age of 60, as the immune system naturally weakens with age, increasing vulnerability to lymphomas. While MZL is not typically hereditary, having a family history of lymphoma or other blood cancers may slightly elevate the risk. Additionally, genetic mutations in specific genes, such as BCL10 or MALT1, have been associated with MZL. These mutations are acquired during a person’s lifetime rather than inherited from family members.

Clinical Manifestations of Marginal Zone Lymphoma

Fatigue

Fatigue is one of the most common symptoms of marginal zone lymphoma, affecting 60-80% of patients. It may result from the body’s immune response to cancer, anemia, or the cancer itself interfering with normal bodily functions. Fatigue is often described as persistent exhaustion or a lack of energy that does not improve with rest. It may become more pronounced in advanced stages or during treatment. Managing fatigue typically involves addressing underlying causes, such as anemia, or making adjustments to medications.

Swollen Lymph Nodes

Swollen lymph nodes, also known as lymphadenopathy, are reported in 40-60% of MZL patients. Lymph nodes may enlarge when infiltrated by cancerous B-cells, a hallmark of MZL. These swollen nodes are usually painless and are often found in areas such as the neck, armpits, or groin. Swelling may be noticeable in the early stages but can persist or worsen as the disease progresses. Persistent lymph node swelling should prompt a consultation with a healthcare provider.

Fever

Fever occurs in 20-30% of MZL patients and is often caused by the immune system’s response to the lymphoma. Cancerous cells can release substances that trigger inflammation, leading to an increase in body temperature. Fever associated with MZL is typically low-grade and intermittent, but persistent or unexplained fevers should be evaluated by a healthcare provider. This symptom is more common in advanced stages or when the lymphoma has spread.

Night Sweats

Night sweats affect 30-40% of MZL patients. These episodes of excessive sweating during sleep can be severe enough to require changing clothes or bedding. Night sweats are often linked to the body’s attempt to regulate temperature in response to lymphoma. Like fever, they are more common in advanced stages. Persistent night sweats should be discussed with a healthcare provider, as they may indicate disease progression.

Weight Loss

Unintentional weight loss affects 20-30% of MZL patients. This can occur as the body expends more energy fighting cancer or when the lymphoma impacts the digestive system, impairing nutrient absorption. Weight loss is often gradual but can become significant over time. Monitoring and reporting unexplained weight loss to a healthcare provider is essential, as it may signal disease progression or complications.

Abdominal Pain

Abdominal pain is reported in 15-25% of MZL patients, particularly when the lymphoma involves the spleen or gastrointestinal tract. Pain may result from spleen enlargement (splenomegaly) or lymphoma cells infiltrating the stomach or intestines. The intensity of pain varies and may be accompanied by bloating or changes in bowel habits. Persistent or worsening abdominal pain should be evaluated by a healthcare provider.

Itching

Itching, or pruritus, affects 10-20% of MZL patients. It is thought to result from the release of chemicals like cytokines by lymphoma cells. Itching may be localized or widespread and can worsen at night. Although less common than other symptoms, it can significantly affect quality of life. Persistent itching should be addressed with a healthcare provider, who may recommend treatments to alleviate discomfort.

Anemia

Anemia, characterized by a low red blood cell count, occurs in 30-40% of MZL patients. It can develop when lymphoma affects the bone marrow or as a side effect of treatment. Symptoms of anemia include fatigue, weakness, and shortness of breath. Blood tests can confirm anemia, and treatment may involve medications, blood transfusions, or addressing the underlying cause.

Recurrent Infections

Recurrent infections are reported in 20-30% of MZL patients due to the immune system’s reduced ability to fight infections. Patients may experience frequent colds, respiratory infections, or other illnesses. Recurrent infections can indicate disease progression or further weakening of the immune system. Discussing frequent infections with a healthcare provider is crucial for proper management.

Splenomegaly

Splenomegaly, or an enlarged spleen, affects 30-50% of MZL patients. The spleen, which filters blood and helps fight infections, can enlarge when infiltrated by lymphoma cells. Symptoms include abdominal pain, a feeling of fullness, or difficulty eating large meals. In severe cases, treatment such as surgery or radiation therapy may be necessary. Symptoms of splenomegaly should prompt medical evaluation.

Health Conditions with Similar Symptoms to Splenic Marginal Zone Lymphoma

Chronic Lymphocytic Leukemia (CLL)

Definition: Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, characterized by an overproduction of abnormal white blood cells known as lymphocytes. This condition progresses slowly and is most commonly diagnosed in older adults. Symptoms may include persistent fatigue, swollen lymph nodes, and frequent infections.

How to Differentiate CLL from Splenic Marginal Zone Lymphoma:

CLL and splenic marginal zone lymphoma (SMZL) share overlapping symptoms such as swollen lymph nodes, fatigue, and an increased susceptibility to infections. However, CLL is often associated with a significantly elevated white blood cell count. Blood tests in CLL typically reveal high levels of lymphocytes, whereas SMZL may not cause such a pronounced increase. Additionally, CLL can lead to anemia and low platelet counts, which may result in easy bruising or bleeding—symptoms that are less common in SMZL.

Flow cytometry, a specialized blood test, can help identify specific markers on lymphocytes. In CLL, lymphocytes frequently express CD5 and CD23, markers that are generally absent in SMZL. A bone marrow biopsy may also aid in distinguishing between the two conditions, as high levels of abnormal lymphocytes in the bone marrow strongly suggest CLL.

Follicular Lymphoma

Definition: Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma that originates in the lymph nodes. It is characterized by clusters of abnormal B-cells forming follicle-like patterns. Common symptoms include painless swollen lymph nodes, fatigue, and night sweats, with the condition primarily affecting older adults.

How to Differentiate Follicular Lymphoma from Splenic Marginal Zone Lymphoma:

Follicular lymphoma and SMZL share symptoms such as painless lymph node swelling, fatigue, and night sweats. However, follicular lymphoma often involves widespread lymph node enlargement, while SMZL tends to be more localized, frequently affecting the spleen or stomach.

A lymph node biopsy is essential for differentiation. Follicular lymphoma typically displays a distinct follicular pattern of B-cells, whereas SMZL exhibits a diffuse pattern. Genetic testing may also reveal the t(14;18) translocation, a hallmark of follicular lymphoma that is absent in SMZL.

Diffuse Large B-Cell Lymphoma (DLBCL)

Definition: Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma that affects B-cells. It progresses rapidly, causing symptoms such as rapidly enlarging lymph nodes, fever, night sweats, and unintentional weight loss. Prompt treatment is critical due to its fast progression.

How to Differentiate DLBCL from Splenic Marginal Zone Lymphoma:

DLBCL and SMZL share symptoms like swollen lymph nodes, fever, and night sweats. However, DLBCL progresses much more quickly, with symptoms worsening over weeks or months, whereas SMZL is slow-growing. DLBCL often causes systemic symptoms such as significant weight loss and severe fatigue, which are less common in SMZL.

A biopsy is crucial for diagnosis. DLBCL is characterized by large, rapidly dividing B-cells, while SMZL typically involves smaller, more mature B-cells. Imaging tests, such as PET scans, may reveal more aggressive and widespread disease in DLBCL. Elevated lactate dehydrogenase (LDH) levels, a marker of rapid cell turnover, are also more frequently observed in DLBCL than in SMZL.

Hodgkin Lymphoma

Definition: Hodgkin lymphoma is a cancer of the lymphatic system, distinguished by the presence of Reed-Sternberg cells. It commonly affects younger adults and presents with symptoms such as swollen lymph nodes, fever, night sweats, and unexplained weight loss.

How to Differentiate Hodgkin Lymphoma from Splenic Marginal Zone Lymphoma:

Hodgkin lymphoma and SMZL share symptoms like swollen lymph nodes, fever, and night sweats. However, Hodgkin lymphoma typically follows a predictable pattern of lymph node involvement, often starting in the neck or chest and spreading in an orderly fashion. In contrast, SMZL may involve lymph nodes in less typical locations, such as the spleen or stomach.

A biopsy is necessary to confirm the diagnosis. Hodgkin lymphoma is identified by the presence of Reed-Sternberg cells, which are absent in SMZL. Additional symptoms, such as itching (pruritus) and pain in lymph nodes triggered by alcohol consumption, are more commonly associated with Hodgkin lymphoma. Imaging tests, such as CT or PET scans, can further clarify the pattern of lymph node involvement.

Reactive Lymphadenopathy

Definition: Reactive lymphadenopathy refers to the enlargement of lymph nodes caused by infection, inflammation, or other non-cancerous conditions. It is a common immune response to triggers such as viral or bacterial infections and autoimmune diseases.

How to Differentiate Reactive Lymphadenopathy from Splenic Marginal Zone Lymphoma:

Both reactive lymphadenopathy and SMZL can cause swollen lymph nodes. However, reactive lymphadenopathy is usually associated with an underlying infection or inflammation, and the lymph nodes typically return to normal size once the condition resolves. In contrast, SMZL-related lymph node swelling persists and may gradually worsen over time.

A biopsy or fine needle aspiration can help distinguish between the two. Reactive lymphadenopathy shows signs of inflammation and immune activity without cancerous cells, while SMZL reveals abnormal B-cells. Blood tests may also provide clues, as reactive lymphadenopathy often shows elevated white blood cell counts or inflammatory markers, which are not typical in SMZL.

Autoimmune Lymphoproliferative Syndrome (ALPS)

Definition: Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder that affects the immune system. It leads to excessive lymphocyte production, resulting in enlarged lymph nodes, an enlarged spleen, and autoimmune symptoms where the immune system mistakenly attacks the body’s own tissues.

How to Differentiate ALPS from Splenic Marginal Zone Lymphoma:

ALPS and SMZL both cause swollen lymph nodes and an enlarged spleen. However, ALPS is typically diagnosed in childhood or early adulthood, whereas SMZL is more common in older adults. ALPS often presents with autoimmune symptoms such as anemia or thrombocytopenia, which are less frequently seen in SMZL.

Genetic testing can confirm ALPS by identifying mutations in genes that regulate lymphocyte survival. Blood tests may reveal elevated double-negative T-cells, a characteristic feature of ALPS that is absent in SMZL. A biopsy of the lymph nodes or spleen can further differentiate the two, as ALPS shows distinct immune cell activity patterns compared to the abnormal B-cells seen in SMZL.

Treatment Options for Splenic Marginal Zone Lymphoma

Medications

Several medications are available to treat splenic marginal zone lymphoma, depending on the stage and severity of the disease. Common options include:

1. Rituximab: A monoclonal antibody targeting CD20 on B-cells, often used as a first-line treatment.
2. Bendamustine: A chemotherapy drug frequently combined with Rituximab for advanced cases.
3. Chlorambucil: An oral chemotherapy option suitable for older patients or those unable to tolerate more aggressive treatments.
4. Obinutuzumab: A monoclonal antibody used for relapsed cases.
5. Ibrutinib: A targeted therapy for relapsed or refractory SMZL.
6. Acalabrutinib: Another BTK inhibitor for patients who cannot tolerate Ibrutinib.
7. Lenalidomide: An immunomodulatory drug often combined with Rituximab.
8. Dexamethasone: A corticosteroid used to reduce inflammation and alleviate symptoms.
9. Cyclophosphamide: A chemotherapy drug for advanced cases.
10. Prednisone: A corticosteroid commonly used alongside chemotherapy.

Procedures

In addition to medications, certain procedures may be considered for treating splenic marginal zone lymphoma. These include:

1. Radiation Therapy: Often used for localized disease or to manage specific symptoms.
2. Stem Cell Transplants: Typically reserved for advanced or refractory cases.

Improving Marginal Zone Lymphoma: Lifestyle Changes and When to Seek Medical Help

In addition to medical treatments, embracing healthy lifestyle changes can enhance your overall well-being while managing splenic marginal zone lymphoma or other forms of non-Hodgkin lymphoma. Here are some practical strategies to consider:

Healthy Diet: A well-balanced diet rich in fruits, vegetables, whole grains, and lean proteins can strengthen your immune system and support your overall health. Limit processed foods and focus on nutrient-dense meals to help your body during lymphoma treatment.

Regular Exercise: Incorporating light to moderate physical activities, such as walking, swimming, or yoga, can boost your energy, reduce fatigue, and improve your mood. Always consult your healthcare provider before beginning a new exercise routine, especially during splenic lymphoma treatment.

Stress Management: Managing stress is vital for both your mental and physical health. Techniques like meditation, deep breathing exercises, or mindfulness practices can help reduce anxiety and promote a sense of calm and well-being.

Adequate Sleep: Prioritize quality sleep to aid in healing and recovery. Aim for 7-9 hours of rest each night to support your immune system and maintain your energy levels throughout the day.

Hydration: Staying hydrated is essential, particularly during lymphoma treatment. Drinking plenty of water helps flush toxins from your body and keeps you feeling energized and refreshed.

It’s important to seek medical attention if you experience new or worsening lymphoma symptoms, such as unexplained weight loss, night sweats, persistent fatigue, or abdominal discomfort. Telemedicine can provide a convenient way to consult with your healthcare provider, ensuring timely adjustments to your treatment plan and ongoing monitoring of your condition.

Living with Marginal Zone Lymphoma: Tips for a Better Quality of Life

Living with marginal zone B-cell lymphoma, including splenic marginal zone lymphoma (SMZL), can be challenging. However, these strategies can help you manage your condition effectively and improve your quality of life:

Stay Informed: Educate yourself about the symptoms of splenic marginal zone lymphoma, available treatment options, and potential side effects. Being informed empowers you to make confident, well-informed decisions about your care.

Build a Support System: Surround yourself with a network of supportive family members, friends, or peers in a cancer support group. Sharing your experiences with others who understand can provide emotional comfort and practical advice.

Communicate with Your Healthcare Team: Open and honest communication with your doctors and nurses is key. Regularly discuss your symptoms, treatment progress, and any concerns to ensure your care plan is tailored to your needs.

Manage Side Effects: Work closely with your healthcare team to address side effects from lymphoma treatment, such as nausea, fatigue, or changes in appetite. Proactively managing these issues can significantly improve your comfort and overall well-being.

Focus on Mental Health: The emotional impact of living with non-Hodgkin lymphoma can be profound. Consider speaking with a counselor or therapist to address feelings of anxiety, depression, or uncertainty. Mental health care is an essential part of your overall treatment plan.

Conclusion

Splenic marginal zone lymphoma is a slow-growing type of non-Hodgkin lymphoma that can often be effectively managed through a combination of medical treatments and lifestyle adjustments. Early diagnosis and treatment are critical for improving outcomes and achieving remission. If you or a loved one has been diagnosed with splenic lymphoma, collaborating closely with your healthcare team to develop a personalized treatment plan is essential.

Our telemedicine practice offers a convenient way to access expert care from the comfort of your home. Whether you’re seeking guidance on treatment options for splenic marginal zone lymphoma or support in managing your condition, we’re here to help. Don’t hesitate to reach out—early intervention can make a meaningful difference in your treatment journey.

James Kingsley

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