Non Hodgkin's Lymphoma: Symptoms, Causes, Treatment

Non-Hodgkin’s lymphoma (NHL) is a cancer affecting the lymphatic system, a crucial part of the immune system. It occurs when the body’s lymphocytes, a type of white blood cell, start to grow abnormally and uncontrollably. Lymphocytes may develop in just one place or many sites in the body. Non-Hodgkin’s lymphoma is different from Hodgkin’s lymphoma. 

The incidence rates for non-Hodgkin’s lymphoma for men and women in India are 4.0/100,000 and 2.8/100,000,2 respectively. Non-Hodgkin's lymphoma is more common than the other type of lymphoma, Hodgkin’s lymphoma. The primary differentiating characteristic of Hodgkin’s lymphoma vs non-Hodgkin’s lymphoma is the presence of Reed-Sternberg cells in Hodgkin’s lymphoma.

Types of Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma comprises a diverse group of lymphoid cancers, each with its own unique characteristics. There are over 60 subtypes of non-Hodgkin lymphomas. They can either be indolent (slow-growing) or aggressive (fast-growing). The most common non-Hodgkin’s lymphoma types include:

Aggressive B-cell Non-Hodgkin’s Lymphomas

1. Diffuse Large B-cell Lymphoma (DLBCL): This is the most common type of NHL, accounting for 25%-30% of all cases. It is characterised by fast-growing, large B-cells. It can occur in lymph nodes or outside of the lymphatic system.

2. Mantle Cell Lymphoma: This type of NHL is characterised by the involvement of small B-cells in the lymph nodes’ mantle zone (outer ring of the small lymphocytes). Mantle cell lymphoma accounts for about 5% of all NHL cases. It tends to be aggressive and commonly affects older adults.

3. Burkitt Lymphoma: It is one of the fastest-growing forms of NHL, often occurring in children and young adults. However, it also has high rates of remission and cure. This type of cancer comprises approximately 1% to 5% of all NHL cases. 

Aggressive T-cell Non-Hodgkin’s Lymphomas

1. Peripheral T-Cell Lymphoma: It is characterised by the development of a group of T-cells and natural killer lymphomas in lymphoid tissues. This form of cancer accounts for about 6% of all non-Hodgkin lymphomas.

2. Anaplastic Large Cell Lymphoma: It is a rare type of lymphoma that typically affects lymph nodes and organs. This cancer has two subtypes: one affecting children and young adults and the other affecting older adults. 

Indolent B-cell Lymphomas

1. Follicular Lymphoma: This is the second most common type of NHL that accounts for about 30% of all cases. Follicular lymphoma is a slow-growing cancer in the lymph nodes, bone marrow and other organs. 

2. Marginal Zone Lymphoma: It arises in the marginal zone, an area between the lymphoid follicles and the surrounding tissue. There are three primary types of marginal zone lymphoma (nodal marginal zone lymphoma, splenic marginal zone lymphoma, and extranodal marginal zone lymphoma). It comprises 7% of all NHL cases. 

Indolent T-cell Lymphomas

1. Cutaneous T-Cell Lymphoma: It primarily affects the skin. This type of lymphoma involves abnormal T-cells accumulating in the skin, leading to skin lesions, itching, and rash. Common subtypes of cutaneous T-cell lymphoma include Mycosis fungoides and Sezary syndrome. 

Stages of Non-Hodgkin’s Lymphoma 4

Source: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/diagnosis/nhl-staging

The staging of non-Hodgkin’s lymphoma is typically done using the Ann Arbor staging system, which helps determine the spread of the disease. The stages are described by Roman numerals I-IV. Additionally, an “E” designation may be added to indicate the involvement of extranodal sites. Non-Hodgkin’s lymphoma stages are as follows:

Stage I: The disease in this stage can include either of the following:

1. The cancer is confined to a single lymph node or organ, like tonsils (I).

2. Lymphoma is found in a single group of lymph nodes outside the lymph system (IE).

Stage II: This stage can be categorised by either of the following:

1. Individuals have cancer in two or more lymph node groups on the same side of the diaphragm (either above or below) (II).

2. The cancerous cells are present in a group of lymph nodes or a single area of the nearby organ (IIE). 

Stage III: Either of the following describes this stage:

1. The presence of cancer in lymph node groups above and below the diaphragm. 

2. Lymphoma is found in lymph nodes above the diaphragm and the spleen. 

Stage IV: There is an extensive spread of cancer. It involves one or more organs outside the lymphatic system, like the bone marrow, liver, or lungs.

Symptoms of Non-Hodgkin’s Lymphoma 

Source: https://filinf.it/en/about-limphomas/non-hodgkin-lymphomas-nhl/

Non-Hodgkin lymphoma can present with various symptoms, although some individuals may experience no symptoms at all. However, one must remember that having these symptoms does not necessarily mean they have NHL. These symptoms are common to several conditions. Common non-Hodgkin’s lymphoma symptoms may include:

1. Swollen Lymph Nodes: Painless swelling of the lymph nodes, typically in the neck, armpits, or groyne, is a common symptom of NHL.

2. Abdominal Pain or Swelling: NHL can affect organs in the abdominal area, leading to discomfort, pain, or swelling. However, abdominal pain is not always a sign of serious illness. 

3. Chest Pain, Coughing, or Difficulty Breathing: NHL involvement in the lung tissues or lymph nodes inside the chest can cause chest pain, coughing, or trouble breathing. 

4. Fatigue: Persistent and unexplained fatigue or weakness that does not improve with rest can be a symptom of NHL.

5. Skin Rash or Itching: Some subtypes of NHL, such as cutaneous T-cell lymphoma, may cause skin-related symptoms, including rashes, itching, and skin lesions.

6. A Feeling of Fullness: Individuals may experience a feeling of bloating or fullness after eating just a little. This may happen due to an enlarged spleen.  

B Symptoms

Non-Hodgkin’s lymphoma may also cause certain B symptoms. These symptoms help with the prognosis and staging of the disease. B symptoms include:

1. Unexplained Fever: A body temperature above 103℉ that lasts two or more hours after home treatment or longer than two days may indicate a serious problem. 

2. Drenching Night Sweats: It is characterised by profuse sweating that drenches the sheets during the night.

3. Weight Loss: This includes losing 10% or more of body weight over six months without an apparent cause.

The exact non-Hodgkin’s lymphoma causes are not known. It develops when the body produces too many lymphocytes. Lymphocytes normally follow a predictable life cycle. The old lymphocytes die to make space for the new ones. However, in Non-Hodgkin’s lymphoma, lymphocytes do not die, and the body keeps producing new ones. This accumulation of lymphocytes in the lymph nodes causes them to swell. 

Non-Hodgkin’s lymphoma often begins in one of the following lymphocytes:

1. B cells (fights infection)

2. T cells (kills foreign invaders)

3. Natural killer cells (kills infected or cancerous cells)

NHL may develop due to chromosomal translocation or mutation/deletion.

Several risk factors can cause an increased chance of developing non-Hodgkin’s lymphoma. However, most cases of non-Hodgkin’s lymphoma occur in individuals with no identifiable risk factors. These factors include:

1. Age: NHL can occur at any age. However, it is more common in older adults, with the risk increasing in people aged 60 or above. This is possibly due to accumulated genetic mutations and age-related changes in the immune system. 

2. Gender: Generally, the risk of NHL is higher in men than women. However, some types of non-Hodgkin’s lymphoma are more common in women. The reason for the same is unknown. 

3. Family History: Having a parent or sibling with NHL can increase individuals’ risk of developing this disease. Some people may inherit DNA mutations from a parent, increasing their risk of NHL.  

4. Weakened Immune System: Individuals who have had an organ transplant and take drugs to control their immune system may have a higher risk of NHL. A weakened immune system can fail to control and eliminate abnormal lymphocytes properly. This contributes to the development of the NHL.

5. Viral and Bacterial Infections: Various infectious agents have been linked to different types of NHL. Some viruses may directly affect the DNA of lymphocytes, transforming them into cancer cells. Others may trigger chronic immune responses and genetic changes in lymphocytes, increasing the risk of NHL. These infections include:

1. Epstein-Barr Virus (EBV): It is one of the most common infections that spreads through bodily fluids. It increases the risk of certain types of NHL, such as Burkitt lymphoma. 

2. Human T-Cell Leukaemia Virus Type 1 (HTLV-1): It is an infection that affects the T-cells and causes adult T-cell lymphoma. 

3. Human Herpes Virus 8 (HHV-8): The infection is associated with primary effusion lymphoma (a rare type of lymphoma) and Kaposi sarcoma (cancer that develops in the lining of lymph and blood vessels). 

4. Hepatitis C Virus (HCV): A bloodborne infection that may increase the risk of splenic marginal zone lymphoma and diffuse large B-cell lymphoma.

5. Helicobacter Pylori: This infection is linked to an increased risk of mucosa-associated lymphoid tissue (MALT). 

6. Chemical Exposure: Prolonged exposure to certain chemicals, such as pesticides, herbicides, solvents, and wood preservatives, may increase the risk of NHL.   

7. Radiation Exposure: Exposure to radiation has been associated with an increased risk of NHL. This may result from atomic bombs, nuclear reactor accidents, and radiation therapy for other cancers.

8. Autoimmune Diseases: Some diseases can cause immune system dysfunction, leading to genetic mutations and an increased risk of NHL. These diseases include rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, celiac disease, etc.

While there is no guaranteed way to prevent non-Hodgkin’s lymphoma, some strategies may help reduce the risk. These strategies include:

1. Preventing Infections: Minimising exposure to certain viral and bacterial infections, like HIV, EBV, and HCV, can help reduce the risk of NHL. One should avoid known risk factors for these infections, like unprotected sex and intravenous drug use. 

2. Maintaining a Healthy Weight: Being overweight or obese can trigger hormonal changes, promoting abnormal cell growth. Therefore, individuals must maintain a healthy weight. 

3. Adopting a Healthy Lifestyle: People must follow a healthy lifestyle to reduce the risk of NHL. It includes regular physical activity, a balanced diet, and avoiding tobacco and excessive alcohol consumption. These lifestyle changes can support immune function and reduce chronic inflammation. This reduces the risk of NHL. 

4. Ensuring Occupational Safety: Chemical exposure can increase the risk of NHL. Therefore, employees who work around hazardous chemicals should ensure proper safety measures and protective equipment to reduce exposure.

5. Getting Regular Health Checkups: Regular medical checkups can help detect early signs of NHL or other health issues. This may help ensure timely intervention if needed.

Source: https://www.tallahasseecancer.com/services/bone-marrow-aspiration-and-biopsy

Non-Hodgkin’s lymphoma diagnosis typically involves a series of steps to confirm the presence of the disease and determine its type and stage. The diagnostic process begins with a medical history and physical examination of swollen lymph nodes and other abnormalities. Diagnostic tests for NHL may include:

1. Blood Tests: These tests may be done to assess blood cell counts, liver and kidney function. It also helps detect certain markers that may indicate NHL. 

1. Complete Blood Count (CBC): Measures and counts the blood cells, such as red blood cells, white blood cells, and platelets

2. Blood Chemistry Study: Measures the substances that the organs and tissues release in the bloodstream

3. Lactate Dehydrogenase (LDH) Levels: The test measures LDH levels (an enzyme found in almost all body tissues). High levels may indicate lymphoma. 

2. Imaging Tests: These are used to visualise lymph nodes and other organs to identify any abnormalities. Imaging tests for NHL include:

1. Computed Tomography (CT) Scan: It uses X-rays to create detailed cross-sectional body images.

2. Positron Emission Tomography (PET) Scan: This test uses a radioactive tracer to visualise areas with active cancer cells. 

3. Magnetic Resonance Imaging (MRI): During this test, radio waves and a powerful magnet is used to produce detailed pictures of organs and tissues.

4. Ultrasound: The test uses sound waves to create images of internal organs and tissues. 

3. Biopsy: A tissue biopsy is essential for a definitive NHL diagnosis. A biopsy may include:

1. Lymph Node Biopsy: The provider removes all or part of the lymph nodes to examine the sample under a microscope for Reed-Sternberg cells.

2. Bone Marrow Aspiration and Biopsy: If NHL is suspected, a bone marrow biopsy or aspiration may be performed to determine if the lymphoma has spread to the bone marrow. It involves removing a sample of bone marrow from the hipbone. This location provides easy access to bone marrow cells and minimises discomfort for the patient during the procedure.

4. Hepatitis B and Hepatitis C Test: The test involves checking a blood sample to measure the amounts of hepatitis B and hepatitis C-virus-specific markers. Markers are antigens or antibodies that show if an individual has been exposed to these viruses. 

5. HIV Test: The doctor may test a blood sample to measure HIV levels and help plan treatment. 

6. Immunophenotyping: It is a diagnostic test used to analyse the specific proteins or markers expressed on the surface of cells in non-Hodgkin’s lymphoma. This helps identify the type of lymphoma and guide treatment decisions.

How to Prepare for Doctor’s Consultation?

Preparing for a doctor’s consultation for non-Hodgkin’s lymphoma can help patients make the most of their appointment and ensure that all their concerns are addressed. Here are some tips to help them prepare:

1. Know Pre-Appointment Restrictions: Individuals must make a prior appointment with their provider. They should ask if anything needs to be done in advance, such as diet restriction. 

2. Note the Symptoms: It is best to list the symptoms experienced, even if they seem unrelated to NHL. 

3. Gather Key Personal Information: This includes major stresses and recent life changes. 

4. Enlist Medications: Individuals must list all their current medications, including vitamins, supplements, and herbs. They should also mention the dosages and frequency. This helps the doctor understand possible drug interactions. 

5. Write Down Questions: List questions and concerns to be discussed with the doctor.  

6. Bring a Trusted Companion: Having a family member or friend at the appointment can help provide emotional support and remember important details discussed during the consultation.

What to Expect from the Doctor?

During the non-Hodgkin’s lymphoma appointment, the doctor may ask several questions to better understand the patient’s medical history and current health status. Some common questions to expect include:

1. When did you first experience symptoms?

2. How severe are your symptoms?

3. Are the symptoms continuous or occasional?

4. Does anything improve or worsen these symptoms?

5. Have you had any previous health issues, medical conditions, or infections?

6. Do you have a family history of cancer?

7. Do you smoke or consume alcohol?

8. Have you been exposed to toxins?

9. Have you undergone treatments for previous cancers?

Questions to Ask the Doctor

Asking relevant questions during the NHL appointment can help individuals better understand their diagnosis, treatment options, and what to expect. The following are some questions patients may want to ask:

1. Is non-Hodgkin’s lymphoma causing my symptoms?

2. What type of NHL do I have?

3. What stage is my cancer?

4. Is my NHL aggressive or slow-growing?

5. Is non-Hodgkin’s lymphoma curable?

6. What are my treatment options? Which one do you recommend?

7. What are the side effects of these treatments?

8. What is the duration of the treatment?

9. Will the treatment affect my daily life?

10. What is the expected outcome or prognosis?

11. Are there any clinical trials available?

12. What lifestyle changes or supportive care do you recommend?

13. Should I seek a second opinion? How much will it cost?

Non-Hodgkin’s lymphoma treatment depends on several factors, including the type and stage of the disease, the location of the affected lymph nodes or organs, and the individual’s overall health. The main treatment options for NHL include:

1. Watchful Waiting: If an individual has a slow-growing non-Hodgkin’s lymphoma with no symptoms, treatment may not be needed right away. The doctor may recommend watchful waiting and regular monitoring every few months. This helps them understand if the patient’s cancer is progressing and needs treatment. 

2. Chemotherapy: This involves powerful drugs to kill or slow the growth of cancer cells. Chemotherapy is often used as the primary treatment for NHL and may be given alone or in combination with other therapies. It may also be a treatment option if lymphoma returns after initial treatment. 

3. Radiation Therapy: The treatment uses high-energy beams to target and destroy cancer cells. Radiation therapy may be the only required treatment for certain types of slow-growing NHL or those located in just one or two spots. Radiation is usually used after chemotherapy to kill any remaining lymphoma cells. 

4. Targeted Therapy: It focuses on specific molecules or pathways involved in cancer cell growth. By blocking these pathways, targeted drugs cause cancer cells to die. They are often combined with chemotherapy as an initial treatment or when cancer returns. 

5. Immunotherapy: This is one of the most promising cancer treatments. Immunotherapy helps the body’s immune system identify and attack cancer cells more effectively. Monoclonal antibodies may be used in NHL treatment.

6. CAR T-Cell Therapy: This innovative immunotherapy involves modifying a patient’s own T-cells to target and attack cancer cells more effectively. It might be used for some types of B-cell non-Hodgkin’s lymphoma that do not respond to other treatments. 

7. Bone Marrow Transplant: The doctor may consider a bone marrow transplant to replace damaged bone marrow with healthy stem cells if other treatments haven’t helped. The procedure may be performed after high doses of chemotherapy or radiation to suppress the bone marrow and immune system. 

Please Note: The selection of the treatment approach is based on the patient’s condition and the treating doctor’s opinion.

Non-Hodgkin’s lymphoma and its treatment can lead to various complications. Complications may arise depending on several factors. These may include the type and stage of the disease, treatment methods used, and overall health. Complications of the disease are as follows:

1. Weakened Immune System: The growth of lymphocytes in NHL can take up the space of healthy white blood cells that fight infection. The low level of these cells weakens the immune system. This makes individuals more susceptible to serious infections. 

2. Febrile Neutropenia: NHL can lead to low levels of neutrophils (white blood cells responsible for fighting infection), increasing the risk of infection. Febrile neutropenia is when a patient develops a fever during significant neutropenia. 

3. Hyperuricemia and Tumour Lysis Syndrome: Rapid tumour cell breakdown during treatment can lead to tumour lysis syndrome (TLS). This causes the release of uric acid into the bloodstream, leading to hyperuricemia and potential kidney damage. Symptoms of these conditions may include:

1. Fatigue

2. Nausea and vomiting

3. Numbness

4. Tingling in legs

5. Joint pain

6. Decreased urination

4. Spinal Cord and Brain Compression: The cancerous lymph nodes can grow and spread to surrounding tissues, including the spinal cord and brain. The growth of the lymph nodes near the spinal cord or brain may lead to compression of these organs. 

5. Hyperleukocytosis: The condition is characterised by a high white blood cell count. It occurs when cancerous lymphocytes multiply rapidly and accumulate in the bloodstream. 

6. Hypercalcemia: It is a condition in which the calcium level in the blood is above normal. It usually occurs due to adult T-cell lymphoma. This form of cancer releases substances that stimulate bone breakdown, leading to excess calcium in the bloodstream. 

7. Pericardial Tamponade: Cancerous cells can infiltrate the pericardium (the membrane surrounding the heart), leading to fluid accumulation. Fluid in the pericardial space compresses the heart and impairs its ability to pump effectively. 

8. Anaemia and Thrombocytopenia: NHL treatment, especially chemotherapy, affects the bone marrow. This may reduce the production of red blood cells and platelets, causing symptoms like:

1. Fatigue

2. Weakness

3. Bleeding

4. Bruising

9. Infertility: Chemotherapy and radiation therapy for NHL can affect the patient’s fertility.

10. Second Cancers: Treatment for NHL can increase the risk of second cancers in future. It happens because these treatments damage some healthy cells along with cancer cells. 

When to See a Doctor?

If an individual experiences any persistent or concerning non-Hodgkin’s lymphoma symptoms, they should visit their doctor. While these symptoms may not always indicate NHL, it is best to get them checked. Symptoms to look out for include:

1. Swollen glands for more than six weeks

2. Unexplained fever

3. Drenching night sweats

4. Significant weight loss

5. Unexplained fatigue

Source: https://addon.life/2020/10/31/diet-non-hodgkin-lymphoma/

While a nutritious diet may not cure non-Hodgkin’s lymphoma, it can support overall health during and after treatment. The following are some dietary tips for individuals with NHL:

1. Fruits and Vegetables: Fruits and vegetables have fibre, vitamins, and minerals, which are essential for the body. 

1. Examples of fruits include apples, bananas, berries, etc. 

2. Some of the vegetables include broccoli, cauliflower, kale, etc. 

2. Carbohydrates: A diet rich in carbohydrates helps provide energy. Sources of carbohydrates include:

1. Whole grain bread

2. Oatmeal

3. Brown rice

3. Proteins: A protein-high diet can help the body grow and repair cells and tissues. Sources of proteins include:

1. Pulses

2. Eggs

3. Meat

4. Fish

4. Dairy or Dairy Alternatives: Dairy products can help provide calcium, zinc, and protein. Good sources of dairy include:

1. Milk

2. Yoghurt

3. Cheese

5. Hydration: Drink lots of water and other fluids to stay hydrated, especially if experiencing side effects from treatments.

Foods to Avoid:

People with low levels of white blood cells are more prone to bacterial infections. Therefore, they must avoid certain foods or drinks that contain live bacteria. Examples of these foods include:

1. Yoghurts, foods, or drinks with live microorganisms that are intended to keep one healthy

2. Unpasteurised foods and drinks

3. Raw honey

4. Certain types of cheese, like blue cheese

Myth: Non-Hodgkin’s lymphoma is contagious. 

Fact: NHL is not contagious. This type of cancer develops due to chromosomal translocations or genetic mutations in the lymphocytes. It cannot be transmitted from one person to another. However, some viruses and infections can increase the risk. 

Myth: Everyone with non-Hodgkin’s lymphoma has the same type of cancer. 

Fact: There are over 60 subtypes of non-Hodgkin’s lymphoma. These subtypes are classified by the type of cells they arise from (B-cells or T-cells), their appearance under the microscope, and the chromosomal features of the cells. Some subtypes are slow-growing (indolent), while others are more aggressive and rapidly progressing.

Myth: Non-Hodgkin’s lymphoma is always fatal. 

Fact: With advances in treatment and early detection, the prognosis for NHL has significantly improved. Most cases of non-Hodgkin’s lymphoma are curable. The disease can also sometimes be cured in its advanced stage. 

Myth: Non-Hodgkin’s lymphoma always needs to be treated immediately. 

Fact: Not true! The urgency of treating NHL varies based on disease characteristics, stage, and symptoms. Immediate treatment may be necessary for aggressive NHL cases. However, watchful waiting is sometimes appropriate for indolent NHL in certain situations.

According to the American Cancer Society, the overall non-Hodgkin’s lymphoma survival rate is 74% for five years. However, it is important to note that survival rates are statistical estimates and may not accurately predict the outcome for an individual patient. They are usually expressed as the percentage of people who survive a certain period (often five years) after the diagnosis. 

Survival Rate for NHL may vary depending on several factors, such as:

1. The type and stage of the disease

2. Patient's age

3. Overall health

The five-year non-Hodgkin’s lymphoma survival rate by age may include:

1. Between 15 to 39 years: 82.4%

2. Between 40 to 64 years: 78.5%

3. Between 65 to 74 years: 72.1%

4. Ages 75 and older: 55.2%

The five-year survival rate according to the stage of the disease includes:

1. For stage I, the survival rate of non-Hodgkin’s lymphoma is more than 86%. 

2. The survival rate for stage II is 78%. 

3. For stage III, the survival rate is above 72%. 

4. Stage IV non-Hodgkin’s lymphoma survival rate is almost 64%. 

Prognosis of Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma prognosis varies depending on several factors. These factors may include:

1. The type and stage of the disease

2. The age and overall health of the patient

3. The treatment response

Generally, the prognosis for NHL can vary due to the many different subtypes.

1. Some NHL subtypes are more aggressive and have a poorer prognosis, while others are slower-growing and may have a better outlook. 

2. Many people who get treatment for NHL go into remission, i.e., they do not show signs and symptoms of the condition. 

3. Some individuals are also considered cured after they have remained in remission for many years.

Non-Hodgkin’s lymphoma is a type of cancer that affects the lymphatic system. Early diagnosis and suitable treatment are critical in managing the disease and improving patient outcomes. With advancements in therapies, many individuals with NHL can achieve remission and enjoy an improved quality of life.

You can consult the experts at HexaHealth if you experience any symptoms of NHL. The HexaHealth team provides comprehensive support and personalised care for individuals diagnosed with NHL. Our team of healthcare professionals offers expert guidance, the latest treatment options, and emotional support throughout the patient’s journey. Get in touch with us TODAY! 

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