Non-Hodgkin Lymphoma: Types, Symptoms, Causes & Treatment

Non-Hodgkin Lymphoma (NHL) is a very diverse group of cancers that originate from lymphocytes, a type of white blood cell, and their precursors. There are many subtypes of NHL, each with distinct characteristics and behaviour. Here are some of the most common types of Non-Hodgkin lymphoma:

Diffuse Large B-cell Lymphoma (DLBCL)

This is the most prevalent type of Non-Hodgkin lymphoma (NHL), accounting for approximately 30% to 40% of cases. It primarily affects B-cells, a specific type of white blood cell involved in antibody production. DLBCL is an aggressive form of lymphoma characterised by rapid growth. It manifests as enlarged lymph nodes in the neck, armpits, or groin area. Moreover, DLBCL can also involve extranodal sites, including the gastrointestinal tract, bones, central nervous system, or skin. 

Follicular Lymphoma

This is the second most common subtype of Non-Hodgkin disease, accounting for roughly 20% to 30% of cases. This type of Non-Hodgkin lymphoma primarily affects B-cells and is characterised by the formation of abnormal B-lymphocytes within the lymph nodes. Unlike DLBCL, follicular lymphoma typically progresses slowly and exhibits less aggression. It commonly manifests as painless swelling in the neck, armpits, or groyne due to enlarged lymph nodes.

Mantle Cell Lymphoma

Mantle Cell Lymphoma, a less common type of Non-Hodgkin lymphoma, accounts for approximately 6% to 10% of cases. It primarily affects older adults and originates from B-cells in the mantle zone of the lymph nodes. This aggressive form of lymphoma has a tendency to spread to various organs.

Burkitt Lymphoma

Burkitt Lymphoma, a highly aggressive type of Non-Hodgkin lymphoma, is relatively rare and accounts for approximately 1% to 2% of cases in adults and 30% to 50% of cases in children. This particular form of lymphoma is more prevalent in regions with a higher incidence of malaria and Epstein-Barr virus (EBV) infection. Burkitt lymphoma primarily affects abnormal B-cells and is characterised by rapid tumour growth. It typically manifests as quickly expanding masses in the abdomen, jaw, or other areas.

Marginal Zone Lymphoma

Marginal Zone Lymphoma happens in the marginal zone of the lymphoid tissues. These subtypes are categorised into three main groups: extranodal marginal zone lymphoma (also known as MALT lymphoma), nodal marginal zone lymphoma, and splenic marginal zone lymphoma. MALT lymphoma is commonly associated with chronic inflammation, such as gastric MALT lymphoma caused by Helicobacter pylori infection.

T-cell Lymphomas

T-cell Lymphomas are a subset of NHL types that originate from abnormal T-lymphocytes rather than B-cells. These particular subtypes account for approximately 10% to 15% of Non-Hodgkin disease cases. Examples of T-cell lymphomas include Peripheral T-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, and Anaplastic Large Cell Lymphoma. Compared to B-cell lymphomas, T-cell lymphomas are typically more aggressive and carry a less favourable Non-Hodgkin Lymphoma prognosis.

Cutaneous Lymphomas

Cutaneous Lymphomas represent a subset of NHL types primarily affecting the skin. The most prevalent form is Cutaneous T-cell Lymphoma (CTCL), originating from abnormal T-cells within the skin. CTCL commonly manifests with skin rash, itching, and the development of patches or plaques on the skin.

The symptoms of Non-Hodgkin lymphoma (NHL) can vary based on factors like the subtype, stage of the disease, and tumour location. While some individuals may experience mild or no symptoms at all, others may exhibit more noticeable and concerning signs. Common symptoms of NHL include:

1. Painless Swelling of Lymph Nodes: When it comes to NHL, one of the most common symptoms is the enlargement of lymph nodes, also known as lymphadenopathy. These enlarged lymph nodes are painless lumps underneath the skin in areas such as the neck, armpits, or groin.
2. Unexplained Weight Loss: Unexplained weight loss often accompanies a loss of appetite, leading to the unintentional reduction in body weight. When someone loses 10% or more of their body weight within six months or less, this is considered a significant amount of weight loss.
3. Fatigue and Weakness: NHL can lead to fatigue and weakness throughout the body. And this feeling may not go even after rest. This exhaustion can impact daily activities and worsens as the disease advances.
4. Fever and Chills: Fever is a common symptom of NHL, especially in aggressive subtypes. The fever may come and go and can be accompanied by chills.
5. Night Sweats: Excessive sweating at night, often soaking the bedclothes, is a characteristic symptom of NHL. Night sweats can be severe and may disrupt sleep.
6. Abdominal Pain and Swelling: NHL can affect lymph nodes and organs in the abdomen, leading to abdominal pain or discomfort. Enlarged lymph nodes in the abdomen can cause a feeling of fullness or swelling.
7. Skin Rash or Itching: In certain types of NHL, such as cutaneous lymphomas, individuals may develop skin rashes, patches, or plaques on the skin. Itching (pruritus) may also be present and can be severe.
8. Chest Pain, Cough, or Shortness of Breath: When NHL affects the mediastinum or the lungs themselves, it can lead to various symptoms. These may include chest pain, a persistent cough, or shortness of breath.
9. Neurological Symptoms: In certain instances, NHL can affect the central nervous system (CNS), resulting in various neurological symptoms. These may include headaches, changes in vision, seizures, or challenges related to coordination and balance.
10. Swelling in the Face or Neck: In cases of NHL that specifically affects the lymph nodes in the neck or other regions, individuals may experience swelling in their face or neck area.

The exact reason behind Non-Hodgkin lymphoma (NHL) is unclear, but it is believed to be influenced by a combination of genetic, environmental, and immunological factors. Several elements may contribute to the development of NHL:

1. Genetic Factors: Although NHL is not typically inherited, certain genetic factors can increase the risk of developing it. Researchers have identified a few gene mutations that are linked to a higher likelihood of NHL, especially in families with a history of the disease. However, it's important to note that most cases of NHL are not directly associated with a family history of the condition.
2. Immune System Dysfunction: The immune system is responsible for identifying and eliminating abnormal cells, including cancer cells. When the immune system is compromised due to conditions like HIV/AIDS, organ transplant, or use of immunosuppressive medications, the risk of developing NHL increases. Hence, this highlights the importance of a functioning immune system in preventing the uncontrolled growth of lymphocytes.
3. Infections: Infections can increase the risk of developing NHL. For instance, certain viruses like Epstein-Barr virus (EBV) and human T-lymphotropic virus (HTLV-1) are associated with specific subtypes of NHL. EBV is known to be linked with Burkitt lymphoma, some Hodgkin lymphoma cases, and certain types of T-cell lymphoma. Additionally, Helicobacter pylori infection, a bacterium causing stomach ulcers, has been connected to the development of gastric MALT lymphoma.
4. Age and Gender: NHL, or Non-Hodgkin lymphoma, is more commonly found in older adults. Additionally, the risk of developing NHL increases with age. It's worth mentioning that certain subtypes of NHL prefer specific age groups or genders. For example, follicular lymphoma is more frequently observed among older adults, while Burkitt lymphoma tends to be seen more often in children and young adults.
5. Chemical Exposure: According to studies, certain chemicals and pesticides have been linked to an increased risk of developing NHL. For instance, individuals who were exposed to herbicides like Agent Orange during the Vietnam War showed higher chances of developing NHL.
6. Autoimmune Diseases: Certain autoimmune disorders, like rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus have been linked to an increased risk of developing NHL. This association is believed to stem from chronic inflammation and abnormal immune responses observed in these conditions, which can potentially contribute to the development of lymphoma.
7. Previous Cancer Treatment: Certain cancer treatments, like radiation therapy and chemotherapy drugs, have been linked to an increased risk of developing NHL as a late complication.

Non-Hodgkin lymphoma (NHL) is a complex disease that can be influenced by various risk factors. However, even though having one or more risk factors might increase the chances of developing NHL, it does not guarantee the occurrence of the disease. Similarly, individuals with NHL may lack identifiable risk factors. Here are some risk factors associated with Non-Hodgkin lymphoma:

1. Age: NHL, or non-Hodgkin's lymphoma, is commonly diagnosed in older adults. Also, the risk of developing Non-Hodgkin disease increases with age. And although this disease can affect people of all age groups, most cases are found in individuals over 60 years old.
2. Weakened Immune System: Individuals with a weakened immune system face an increased risk of developing Non-Hodgkin disease. This applies to individuals with conditions like HIV/AIDS, organ transplant recipients on immunosuppressive medications, and those with congenital immunodeficiencies.
3. Infections: Certain infections are known to increase the risk of Non-Hodgkin disease. For example, the Epstein-Barr virus (EBV) has been linked to Burkitt lymphoma, Hodgkin lymphoma, and certain types of T-cell lymphoma. Additionally, adult T-cell lymphoma is linked to the Human T-lymphotropic virus type 1 (HTLV-1). Lastly, Helicobacter pylori infection has been found to be connected to gastric MALT lymphoma.
4. Family History: Although NHL is not typically inherited, a family history of NHL or certain other cancers may slightly elevate the risk of developing NHL. Nevertheless, most cases of NHL are not directly associated with a family history of the disease.
5. Gender: Some subtypes of NHL affect different genders differently. For instance, follicular lymphoma tends to be slightly more common among women, while mantle cell lymphoma is predominantly diagnosed in men.
6. Ethnicity: Various subtypes of NHL have shown higher incidences in certain ethnic groups. For instance, individuals with Japanese, Caribbean, and South American ancestry are at a greater risk for adult T-cell lymphoma.

Preventing Non-Hodgkin lymphoma (NHL) is not that simple. Nevertheless, adopting certain lifestyle choices and measures can potentially reduce the risk of developing NHL and other cancers:

1. Eat a Balanced Diet: Consuming a balanced diet is essential for maintaining good health. It is recommended to include a variety of fruits, vegetables, whole grains, and lean proteins in your daily meals. However, it is important to limit the intake of processed and red meats as well as sugary and high-fat foods.
2. Stay Hydrated: Make sure that you keep yourself hydrated throughout the day.
3. Avoid Excessive Alcohol and Tobacco: You must refrain from excessive alcohol and tobacco consumption to reduce the risk of NHL. That's because both alcohol and tobacco use have been associated with an increased likelihood of developing NHL. Hence, limiting alcohol intake and seeking assistance in quitting smoking can significantly contribute to a healthier lifestyle.
4. Practise Safe Sex: It is important to practise safe sex to reduce the risk of contracting sexually transmitted infections. Using a condom can help ensure safer sexual encounters.
5. Vaccinations: Vaccinations can provide protection against certain infections that are associated with an increased risk of NHL, such as hepatitis B and human papillomavirus (HPV). Getting vaccinated against these infections may help reduce the likelihood of developing NHL.
6. Minimise Pesticide Exposure: Individuals who work with or around pesticides should take the necessary precautions to minimise exposure. This includes using protective clothing and strictly adhering to safety guidelines provided.
7. Exercise caution with chemicals: Avoid unnecessary exposure to harmful substances and always adhere to safety guidelines when handling hazardous materials to minimise risks.
8. Regular Physical Activity: Strive for a minimum of 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous-intensity exercise.
9. Achieve and Maintain a Healthy Weight: It is important to ensure that your body weight remains within a healthy range suitable for your age and height to achieve optimal health.
10. Practise Good Hygiene: It is important to practise good hygiene to reduce the risk of infections. One effective measure is regularly washing your hands with soap and water.
11. Manage Chronic Conditions: Communicate with their healthcare provider to manage chronic conditions such as diabetes or autoimmune disorders.
12. Get Tested for Viral Infections: If you have concerns or are at risk for conditions such as HIV, HTLV-1, or H. pylori, consider getting tested for viral infections. It is advisable to consult with a healthcare professional regarding screening options and appropriate guidance on managing these infections.
13. Regular Check-ups: Regular health check-ups allow healthcare professionals to closely monitor your well-being and identify any potential concerns at an early stage.

A comprehensive evaluation involving medical history, physical examination, imaging studies, laboratory tests, and tissue biopsy is conducted to diagnose Non-Hodgkin lymphoma (NHL). This diagnostic process aims to determine the type, subtype, stage, and extent of the lymphoma to guide appropriate treatment decisions. Here are the key steps involved in diagnosing Non-Hodgkin lymphoma: 

1. Medical History and Physical Examination: The process typically starts with a comprehensive medical history. Here, the healthcare provider will inquire about symptoms, risk factors, family cancer history, and overall health status. Afterwards, a physical examination is conducted to assess for enlarged lymph nodes, organ enlargement, or any other irregularities.
2. Blood Tests: Blood tests are often conducted to assess the complete blood count (CBC). The CBC provides vital information about the number and types of blood cells in the body. In individuals with NHL, specific changes can occur in their blood cell counts. These changes may include a decrease in red blood cells resulting in anaemia, a decrease in platelets known as thrombocytopenia, or abnormal lymphocyte counts.
3. Imaging Studies: Various imaging tests help identify the location, size, and spread of lymphoma in the body. Common imaging studies include:
4. X-rays: These could be used to examine the chest or other areas to identify enlarged lymph nodes or tumours.
5. Computed Tomography (CT) Scan:  A Computed Tomography (CT) Scan provides detailed cross-sectional images of the body. It enables the assessment of lymph nodes, organs, and other tissues for any abnormalities.
6. Positron Emission Tomography (PET) Scan: A PET scan utilises a radioactive tracer to detect regions of heightened metabolic activity in the body. This serves the purpose of distinguishing between active lymphoma and scar tissue.
7. Magnetic Resonance Imaging (MRI): Magnetic Resonance Imaging (MRI) utilises magnetic fields and radio waves to produce detailed images of organs and tissues.
8. Biopsy: A biopsy is the definitive diagnostic test for NHL. During a biopsy, a small sample of the affected lymph node or tissue is removed for examination under a microscope. There are different methods for obtaining a tissue sample:
9. Excisional Biopsy: The entire lymph node is removed for examination.
10. Incisional Biopsy: A portion of the lymph node or tissue is removed for analysis.
11. Needle Biopsy: A thin needle is used to extract a small tissue sample from the lymph node or mass. 

The biopsy sample is sent to a pathologist, who examines the cells for specific markers and characteristics to determine the type and subtype of NHL. Immunohistochemistry and flow cytometry may be used to identify specific proteins or markers on the lymphoma cells, helping to classify the disease further.

1. Bone Marrow Biopsy and Aspiration: Medical professionals conduct a bone marrow biopsy and aspiration procedure to assess the disease's extent and its possible spread to the bone marrow. During this process, a small sample of bone marrow is extracted from either the hipbone or another suitable bone. Subsequently, this sample is examined under a microscope to detect any presence of lymphoma cells. 
2. Lumbar Puncture (Spinal Tap): If doctors suspect the involvement of NHL in the central nervous system (CNS), they may perform a lumbar puncture. This procedure involves extracting a small amount of cerebrospinal fluid from around the spinal cord and examining it for lymphoma cells.

NHL staging system serves as a valuable tool for oncologists in devising effective treatment strategies and predicting patient Non-Hodgkin Lymphoma prognosis. The commonly utilised Ann Arbor staging system categorises NHL into four primary stages (I to IV) and includes supplementary classifications for bone marrow involvement (B) and central nervous system participation (C). Here are the different stages:

1. Stage I: In stage I NHL, the disease is confined to either a single lymph node region or a solitary extra lymphatic organ/site. This means that the lymphoma is localised within a specific area or one particular organ of the body. For instance, it might affect only a distinct group of lymph nodes like those in the neck or armpit, or it may involve just one organ, such as the spleen or tonsils.
2. Stage II: In stage II NHL, the disease affects two or more lymph node regions on the same side of the diaphragm. This stage may also involve lymphoma affecting one lymph node region and an adjacent extra lymphatic organ or site on the same side of the diaphragm. Stage II NHL does not include any lymph nodes or organs on the opposite side of the diaphragm.
3. Stage III: In stage III NHL, the disease is present in lymph node regions on both sides of the diaphragm. It can also extend from one side of the diaphragm to a neighbouring organ or tissue.
4. Stage IV: Stage IV NHL means that the disease has spread extensively to multiple organs and tissues, including those not directly connected to the lymphatic system. This stage indicates the widespread involvement of lymph nodes and multiple extra lymphatic organs or tissues throughout the body.

The management and treatment of Non-Hodgkin lymphoma (NHL) depend on several factors, including the specific type and subtype of NHL, the disease stage, the patient's age, and overall health condition, as well as their treatment preferences. The primary objective of Non-Hodgkin Lymphoma Treatment is to eliminate or control the lymphoma, alleviate symptoms, enhance the quality of life, and strive for long-term remission whenever feasible. Below are the main modalities utilised in treating NHL:

1. Chemotherapy: Chemotherapy refers to the utilisation of powerful medications for eliminating or slowing down the growth of cancer cells. It is a commonly employed treatment for certain types of NHL and is frequently combined with other therapeutic approaches. Chemotherapy can be administered orally, intravenously, or directly into the cerebrospinal fluid (intrathecal) if there is involvement of the central nervous system.
2. Immunotherapy: Immunotherapy uses the body's immune system to detect and combat cancer cells. One commonly employed form of immunotherapy in the treatment of NHL is monoclonal antibodies, which are specifically designed to target proteins on the surface of cancer cells. Consequently, the immune system eliminates these cells. Rituximab is a well-known monoclonal antibody frequently used for treating B-cell lymphomas in NHL patients.
3. Targeted Therapy: Targeted therapies in cancer treatment are medications that focus on blocking certain molecules or pathways responsible for the growth and survival of cancer cells. These therapies are designed to be more selective, causing less harm to normal cells than traditional chemotherapy. Effective examples of targeted therapies used in NHL treatment include drugs like ibrutinib, idelalisib, and venetoclax.
4. Radiation Therapy: Radiation therapy employs high-energy beams to pinpoint and eradicate cancer cells in some regions of the body. This Non-Hodgkin Lymphoma Treatment can be utilised alone for localised NHL or alongside other therapies for more advanced cases. Radiation therapy demonstrates impressive efficacy in addressing certain early-stage NHL subtypes like localised follicular lymphoma.
5. Stem Cell Transplantation: Stem cell transplantation is performed in cases where NHL (non-Hodgkin lymphoma) is high-risk or has relapsed. It is also known as a bone marrow transplant or peripheral blood stem cell transplant. This procedure involves using intensive chemotherapy or radiation to eliminate cancer cells. Subsequently, healthy stem cells are infused to restore the bone marrow. These stem cells can be obtained either from the patient themselves (autologous transplant) or from a matched donor (allogeneic transplant). 
6. Watchful Waiting: In certain situations, particularly for some low-grade NHLs with slow growth rates, a "watchful waiting" approach may be used. This involves closely monitoring the disease without initiating immediate treatment. Treatment is initiated if there is evidence of disease progression or the development of symptoms.
7. Clinical Trials: Participation in clinical trials is an essential option for some NHL patients, especially for those with aggressive or refractory disease. Clinical trials investigate new treatments, combinations of therapies, or experimental approaches that may offer better outcomes than standard therapies.

The journey towards recovery from Non-Hodgkin lymphoma (NHL) Non-Hodgkin Lymphoma Treatment involves supporting patients during the transition from active treatment to survivorship and long-term management. To ensure successful recovery and aftercare for individuals who have undergone Non-Hodgkin Lymphoma Treatment, several aspects should be considered:

Follow-up Visits

Regular follow-up visits with the healthcare team are essential for effective recovery. These visits enable healthcare professionals to closely monitor progress, detect any signs of recurrence, manage treatment side effects, and address new concerns or symptoms that may arise. The frequency of these follow-up visits varies based on factors such as the type and stage of NHL and the patient's overall health.

Managing Treatment Side Effects

Non-Hodgkin Lymphoma Treatments like chemotherapy and radiation therapy may give rise to a range of side effects both during and after the treatment. These side effects can encompass fatigue, nausea, hair loss, changes in blood counts, as well as potential long-term repercussions on the heart, lungs, and other vital organs. The healthcare team will offer guidance on managing these side effects while diligently monitoring the patient's health to address any concerns that may show up.

Emotional Support

Coping with a cancer diagnosis and the challenges of Non-Hodgkin Lymphoma Treatment can feel very overwhelming. Patients could experience feelings of anxiety, depression, or fear about the possibility of the illness returning. Seeking support through counselling, participating in support groups, or undergoing individual therapy can be beneficial to navigate these emotional aspects of recovery.

Physical Rehabilitation and Exercise

After completing treatment, some patients may experience physical deconditioning. This can be attributed to inactivity during treatment or treatment-related side effects. To address this issue and promote better overall well-being, physical rehabilitation, and exercise are recommended. However, it is important to start gradually and consult with the healthcare team before starting any exercise program.

Nutrition and Healthy Lifestyle

Maintaining a well-balanced and nutritious diet is crucial for both recovery and overall health. Consuming fruits, vegetables, whole grains, and lean proteins can greatly facilitate the healing process and bolster the immune system. Moreover, incorporating healthy habits into one's lifestyle through regular exercise, stress management, and abstaining from tobacco and excessive alcohol intake can contribute significantly to achieving holistic well-being.

1. Can Non-Hodgkin lymphoma be prevented?
   While NHL cannot be fully prevented, a healthy lifestyle may reduce the risk.
2. Is NHL inherited from family members?
   NHL is not directly inherited, but genetics may play a role in certain cases.
3. Are there different NHL subtypes?
   Yes, NHL has various subtypes with distinct characteristics and Non-Hodgkin Lymphoma Treatment.
4. Is NHL more common in children or adults?
   NHL occurs in both children and adults, but the risk increases with age.
5. What are the early warning signs of NHL?
   Early signs may include painless swollen lymph nodes, weight loss, fatigue, and night sweats.
6. Can NHL spread to other organs?
   Yes, NHL can spread to organs like the bone marrow, liver, and central nervous system.
7. What are the treatment options for NHL?
   Non-Hodgkin Lymphoma Treatment options include chemotherapy, radiation, immunotherapy, targeted therapy, and stem cell transplantation.
8. Is NHL curable?
   Outcomes vary, but some types of NHL have a high cure rate with advances in treatments.
9. What's the difference between NHL and Hodgkin lymphoma?
   Hodgkin lymphoma has Reed-Sternberg cells, which NHL lacks.
10. Can NHL recur after successful treatment?
    Yes, NHL can recur, making regular follow-ups vital.