Lymphoma: Symptoms, Causes, Diagnosis, Treatment


The body has its own mechanism to fight with foreign substances, and the immune system of our body does this. To combat pathogens and fight infections, the immune system uses a group of cells that are collectively known as the immune cells. This group comprises lymphocytes, neutrophils, and macrophages. An important type of immune cell is the lymphocyte, mainly divided into B cells and T cells. Lymphocytes are primarily developed in the bone marrow and thymus gland but can be found in the lymph nodes and spleen in addition to these areas. When these cells start multiplying abnormally, it is known as lymphoma. 


Lymph nodes are secondary lymphoid organs of the lymphatic system that contain lymphocytes and work as filters for foreign substances. Lymphoma usually occurs when abnormal lymphocytes develop in the lymph nodes or other organs of the lymphatic system. The two main types are Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma.


Non-Hodgkin’s lymphoma is more common than Hodgkin’s lymphoma worldwide. In India, the incidence of Non-Hodgkin’s lymphoma in men is 2.9 per 100,000, while that for women is 1.5 per 100,000. The female to male ratio of Hodgkin’s lymphoma in India is 5.5:1.


According to a 2012 Globocan report, the ratio of mortality to the incidence in India is 69.7 %.

Commonly observed symptoms of Lymphoma

  • Painless swelling of one or more lymph nodes especially in the neck, armpits, or groin
  • Persistent fatigue
  • Sweating (often at night)
  • Unexplained weight loss ( by at least 10 % of the person’s body weight in less than six months )
  •  Cough 
  • Difficulty while breathing
  • Weakness
  • Loss of appetite
  • Nausea 
  • Vomiting
  • Seizures
  • Shortness of breath

The above symptoms may also indicate other illnesses. The patient is advised to consult the doctor to ascertain if these signs are indicative of lymphoma or not.

Lymphoma Causes:

The exact cause of lymphoma is unknown. It is widely believed that the lymphocyte’s genetic mutations cause these white blood cells to start multiplying at an abnormal rate. As this further spreads to the entire immune system, the patient gets weaker and prone to infection.


It is classified into different stages based on the extent of spread of the tumor as follows :

  • Stage I – Cancer is found in the lymph node and has not spread outside.
  • Stage II – cancer is localized to 2 or more lymph nodes on the same side of the diaphragm.
  • Stage III – Cancer has spread to the lymph nodes on both sides of the diaphragm.
  • Stage IV – Cancer has spread throughout the body to the liver, bone marrow, or lungs beyond the lymph nodes. Both stages III and IV are considered a single category as they have the same prognosis and treatment.

Progressive / refractory lymphoma – In this type, cancer spreads to the other parts of the body while the patient is under treatment for the original lymphoma.

Recurrent / relapsed lymphoma – Recurrence either shortly after treatment or after years of treatment in the same or different region is known as recurrent lymphoma.  

Types of Lymphoma:

Lymphomas mainly arise from either the B-cell or the T-cells and are broadly classified into two groups :

  • Hodgkin’s lymphoma
  • Non-Hodgkin’s lymphoma
  • Non- Hodgkin’s is the most common type that tends to develop in older adults. It is further subdivided into three main types as follows :

1, B-cell lymphoma – This is the most prevalent type of Non- Hodgkin’s that arises from the B-cells and is further subdivided into many types. The most common subtypes are :

    • Diffuse large B-cell lymphoma (DLBCL) – It is an aggressive type of lymphoma that spreads outside the lymph nodes. The treatment usually involves rituximab (chemotherapy) and radiation therapy if the tumor is localized.
    • Follicular lymphoma – This cancer begins in the lymph nodes and grows slowly. It may spread to the bone marrow and spleen at the later stages. This type is treatable and can be cured if discovered in the initial stages. 
    • Mantle cell lymphoma – is more common in older men than in women. It occurs due to a genetic change in the lymphoma cells involving chromosomes 11 and 14. The organs most affected are the bone marrow, lymph nodes, spleen, and gastrointestinal system, including the esophagus, stomach, and intestines.
    • Primary mediastinal large B-cell lymphoma is an aggressive form of DLBCL and appears as a large mass in the chest area. It is more common in women between 30 to 40 years of age.
    • Lymphoplasmacytic lymphoma – It is a slow-growing and rare type, characterized by the presence of “M” proteins in the blood. Most patients have a mutation in the MYD88 gene and have thickened blood that causes headaches, blurry vision, and dizziness. 

2. T-cell lymphoma – arises from the T-cells and is more common in Asian countries.

3. NK- cell lymphoma –  arises from the Natural Killer cells (NK cells). It affects less than 1 % of the world’s population.

The most common subtypes of T-cell and NK-cell lymphoma are :

  1. Anaplastic large cell lymphoma (primary cutaneous type and systemic type) – The primary cutaneous type is localized on the skin only. In contrast, the systemic type is more aggressive and characterized by the presence of ALK-1 protein in the cancer cells. 
  2. A peripheral T-cell lymphoma is an aggressive form that is often diagnosed at the later stages. The cancer cells usually possess CD4 or CD8 proteins on their surface.
  3. Adult T-cell lymphoma/ leukemia is caused by a virus called human T-cell lymphotropic virus and is an aggressive disease of the bone and skin. Chemotherapy is often ineffective for this type.
  4. Hepatosplenic T-cell lymphoma – It is an aggressive form of T-cell lymphoma that involves the liver and spleen. It occurs mostly in young men.
  • Hodgkin’s lymphoma is an uncommon form that is usually diagnosed in adults between 20 to 34 years of age. There are two main types :
    • Classical Hodgkin’s lymphoma – This is characterized by large abnormal tumor cells called Hodgkin Reed-Sternberg cells in the lymph nodes. This lymphoma’s most common symptoms are enlargement of the spleen, liver, cyclical fever, and nephrotic syndrome.
    • Nodular lymphocyte-predominant Hodgkin lymphoma –  is more predominant in males and is characterized by popcorn cells in the lymph nodes consisting of B cells.

Lymphoma is usually categorized as either indolent or aggressive type depending on the extent to which cancer spreads. Indolent lymphoma grows more slowly, and treatment is started only when the symptoms manifest in this type. Aggressive lymphoma develops and spreads rapidly, and treatment is started within weeks of diagnosis.

Risk factors: Lymphoma 

  • Age – Non- Hodgkin’s becomes more common in people over 55 years of age. Teens and young adults between the age group of 15 to 39 years and older adults ( above 75 years of age ) are at higher risk of Hodgkin’s lymphoma. 
  • Gender: Male are at a higher risk of developing Hodgkin’s and Non- Hodgkin’s lymphoma compared to women. Certain type like Mediastinal B-cell lymphoma is, however, more common in women.
  • Immunocompromised individuals – HIV-infected patients, renal and heart transplant recipients, and patients with Kaposi’s sarcoma are immunocompromised due to the use of immunosuppressive treatment. These patients are at a higher risk than healthy individuals. Studies have shown that the risk of Non- Hodgkin’s lymphoma increases by 123 times in HIV- infected patients and 20 to 120 times in renal and heart transplant recipients, especially during the first year. Patients with autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, celiac disease, and Sjogren disease are at a higher risk as the overactive immune system might increase the growth and multiplication of lymphocytes.
  • Exposure to radiation – Patients who have been exposed to radiation for treating any primary solid malignancy are at a higher risk of developing Non- Hodgkin’s lymphoma. This risk increases in people belonging to the age group of 35 years and above.
  • Obesity – A patient with a high body mass index, i.e., an obese patient is more susceptible to developing Non- Hodgkin’s lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia. This is because obesity causes chronic inflammation and enhances B-cells’ growth and survival by the production of cytokines.
  • Physical activity – low physical activity is a risk factor for Non- Hodgkin’s lymphoma, follicular lymphoma, and diffuse large B- cell lymphoma.
  • Diet – Excess intake of dietary fat, red meat, and food rich in saturated fat, polyunsaturated oil, trans unsaturated fats is considered a risk factor.
  • Exposure to certain substances – Benzene, organochlorine pesticides, and herbicides are risk factors. Chemotherapy and drugs used to treat rheumatoid arthritis-like methotrexate and tumor necrosis factor inhibitors may increase the risk of lymphoma, but this lacks proof.
  • Genetics – The risk of developing lymphoma is increased if a first-degree relative of the individual is diagnosed with it. The risk increases if the individual has a twin with lymphoma. This is probably due to genetic mutations that are acquired during life and not inherited. Studies have shown that lymphoma is mostly not hereditary. The risk increases due to acquired genetic mutations as most of the patients don’t have a family history of lymphoma.
  • Viral infections – Infections with a human T-cell lymphotropic virus, Epstein- Barr virus (EBV), or Human Herpesvirus 8 (HHV-8) are known to increase the risk of developing lymphoma. Among these, EBV is the only virus often associated with, especially in HIV patients.
  • Geography – People living in developed countries like the United States, Europe, and Canada are at a higher risk than those living in Asia and Africa. 

Diagnosis: How Is Lymphoma Diagnosed? 

The doctor first analyzes the patient’s complete medical history, and antibiotics are prescribed for any swelling in the lymph nodes. In case of persistence of swelling in the lymph nodes, the doctor recommends the following diagnostic tests to confirm the presence of lymphoma :

  • Physical examination is done to discover any signs of infections and other symptoms manifested.
  • Biopsy – A small sample of the tissue is removed from the lymph nodes in the neck, under the arm, or in the groin, and this is sent to the pathologist for microscopic examination. Biopsy of the skin may also be done if considered the cause of the symptoms. Needle biopsy is not usually preferred as it doesn’t remove enough tissue samples. For this reason, a core biopsy or surgical biopsy is done in most cases.
  • Computed Tomography scan (CT scan) – It helps to provide detailed 3-dimensional images of the body’s insides. Sometimes, a contrast medium (dye) is given intravenously to find the extent to which cancer has spread. 
  • Magnetic resonance imaging (MRI) – Magnetic fields are used to provide detailed images of the body and measure tumor size. A contrast medium is often given intravenously to the patient to get a clearer image.
  • Positron emission tomography (PET) scan – A small amount of radioactive sugar is administered to the patient, which tends to accumulate in the cancer cells. The tumor cells are captured using a scanner, and if after seeing these images, the doctor believes the bone marrow to be affected, then he recommends a bone marrow biopsy.
  • Bone marrow biopsy and aspiration – In bone marrow aspiration, a sample of the fluid is collected. In contrast, in a bone marrow biopsy, a small sample of solid tissue is collected using a needle. The common site for performing this test is the pelvic bone, and the area is anesthetized before the procedure. It is done to diagnose the lymphoma and determine its stage.
  • Laboratory tests – Other laboratory tests that are done to identify specific genes, proteins, and other factors that are characteristic of lymphoma are :
    • Cytogenetics – To discover abnormal chromosomes from the healthy ones in the dividing lymphocytes.
    • Fluorescent in situ hybridization – Specific changes in the chromosomes is detected using fluorescent probes and a special microscope.
    • Flow cytometry – Helps to identify the proteins located on or inside the cancer cells.
    • Immunohistochemistry –  Same as flow cytometry but differs in that it uses a special dye to stain the proteins for identification
    • Polymerase chain reaction – Helps to detect specific DNA sequences that are characteristic for certain types of lymphoma.
    • Extended molecular profiling – Helps to evaluate changes in the tumor cells.

What are the Complications?

  • · Persistent weight loss
  • · Other immune disorders
  • · Advancing stage of the cancer
  • · Weakness
  • ·Infertility

Treatment: How Is Lymphoma Treated? 

  • ChemotherapyIt is the main treatment used for Non-Hodgkin’s lymphoma. Combining drugs that are often prescribed for treating aggressive Non-Hodgkin’s lymphoma is called CHOP and contains Cyclophosphamide, Doxorubicin, Prednisone, and Vincristine. Other commonly used combinations are BR ( bendamustine and rituximab) and R-CVP (cyclophosphamide, prednisone, rituximab, and vincristine). Fludarabine is also often prescribed in combination with other chemotherapeutic drugs to treat lymphoma.
  • Radiation Therapy – High energy x-rays, protons, or electrons are used to destroy the cancer cells. It is given either in addition to or after chemotherapy, depending on the subtype of lymphoma and the extent of cancer spread. People with advanced disease with localized symptoms are often recommended very low doses of radiation therapy for at least 2 treatments. 
  • Targeted therapy CD20 monoclonal antibodies, namely rituximab, obinutuzumab, ofatumumab, rituximab-abbs, and rituximab-pvvr, are often used for treating lymphomas. These act by targeting the CD20 protein located on the B-cell and subsequently destroys the lymphoma cells or makes them more susceptible to chemotherapy. Kinase inhibitors like duveslisib, copanlisib, and ibrutinib are often used to target the kinase pathways. They effectively treat lymphomas like mantle cell lymphoma, small lymphocytic lymphoma, and follicular lymphoma, among others. Immunomodulatory drugs like lenalidomide modulate the body’s immune system and are specifically used for treating follicular lymphoma that has not responded to other treatments.
  • Immunotherapy Chimeric antigen receptor (CAR) T-cell therapy comes under this category. In CAR T-cell therapy, the T-cells removed from the patient’s blood are modified in the laboratory by adding specific proteins called receptors that recognize and destroy the cancer cells when returned to the patient’s body. Axicabtagene ciloleucel, Tisagenlecleucel, and Brexucabtagene autoleucel are the CAR T-cell therapies approved for treating lymphoma. Other therapies include the use of checkpoint inhibitors like Pembrolizumab that act on the PD-1 pathway and are used for treating mediastinal large B-cell lymphoma. 
  • Surgery – It is used to remove the spleen, thyroid, or stomach in cases where cancer originates from these organs. Surgery is rarely used and is often not recommended. Radiation therapy is often preferred over surgery, especially if the tumor is localized. 
  • Bone marrow/stem cell transplantation – In this procedure, either the bone marrow or the hematopoietic stem cells (blood-forming cells) found in the bloodstream and bone marrow are used as part of the treatment. The bloodstream stem cells are used for transplantation, not the cells from the actual bone marrow tissue. Bone marrow transplantation can be allogeneic (ALLO) or autologous (AUTO). Allogenic transplantation uses stem cells donated by a sibling or matched unrelated donor, while autologous transplantation uses the individual’s own stem cells. Chemotherapy is first used to destroy the cancer cells in the body, and then stem cells work to produce healthy bone marrow. ALLO transplantation is riskier than AUTO transplantation as the chances of graft rejection are more in the former.

Prevention: Ways to prevent

  • Exercise regularly. 
  • Consult your doctor for the changes in your diet plan. 
  • Increase the intake of tomatoes, cruciferous vegetables, lettuce, fiber, carrots, and citrus fruits as these are believed to reduce the risk of developing Non-Hodgkin’s lymphoma. 
  • Consumption of vitamin D supplements might help reduce the risk of lymphoma, but this precaution is not scientifically sound. 
  • Do the necessary test as early as possible if any signs or symptoms manifest.
  • Avoid unnecessary radiation exposure.
  • Avoid behaviors that increase the risk of getting AIDS and hepatitis C.

FAQs: Lymphoma

  • Is it curable?

Early diagnosis increases the chances of complete recovery, but the chances of relapse are still present. Stage IV lymphoma can also be cured to some extent, but this depends on the individual’s risk factor and the subtype of lymphoma.

  • What are the survival chances?

The five-year survival rate for Non-Hodgkin’s lymphoma is 72.7 %, while that for Hodgkin’s lymphoma is 87.4 %. The average five-year survival rate for stage IV lymphoma is 65 %.

  • What is the cost of treatment?

The cost of treating Hodgkin’s lymphoma is estimated to be 13.5 lakhs while that for Non-Hodgkin’s lymphoma is around 16 lakhs. The average cost of chemotherapy per cycle ranges up to 1 lakh, while that for stem cell transplantation is roughly 13 lakhs.

  • Where can I get the treatment for lymphoma?

Check here: Cancer Hospitals from India

Check here: Best Oncologists/Oncosurgeons in India

  • Are lymph nodes painful?

The lymph nodes are enlarged and usually painless. They have a rubbery feel and are found as lumps under the skin, usually in the neck, under the armpits, or in the groin.

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