Lymphoma: Symptoms, Causes, Types, Diagnosis, Treatment & Prevention

Lymphoma definition

Lymphoma is a type of blood cancer that affects the immune system, specifically the white blood cells called lymphocytes. These lymphocytes are an important part of the immune system of the body. Lymphoma has primarily two main types: Hodgkin lymphoma and non-Hodgkin lymphoma. There is no exact known cause of lymphoma but there are a few factors such as age, sex, family history, and low immunity which can increase the risk of development of lymphoma. 

Swollen lymph nodes in the neck, armpits, or groin, fever, weakness and fatigue, weight loss, and sweating are some of the symptoms of lymphoma. Medical oncologists, radiation oncologists, hematologists, and hematopathologists can treat lymphoma.

Lymphoma meaning 

The term lymphoma comprises of two words: lymph and oma

The term lymph is derived from the French “lymphe,” from the Latin “lympha” which means water, clear water, a goddess of water. In physiology, lymph refers to a colorless fluid found in animal bodies. 

The term oma is derived from Greek -oma, especially taken in medical use to indicate morbid growth or a tumor.

Lymphoma statistics

Lymphoma statistics worldwide

According to the GLOBOCAN studies, the incidence and mortality of Hodgkin lymphoma were 0.98 and 0.26 per 100,000 in 2020. A high incidence was observed in high-income countries, while higher mortality was seen in low-income countries. 

Non-Hodgkin lymphoma ranks as the 5th to 9th most common cancer globally, with an estimated 544,000 new cancer cases and 260,000 cancer deaths in 2020. The highest age-standardized incidence rates for both males and females (per 100,000) were observed in Australia and New Zealand (12.5) and North America (12), while the lowest rates of incidence were in South-Central Asia (2.7).

Lymphoma statistics India

The number of newly diagnosed lymphomas in India in 2020, was 11,230 for Hodgkin lymphoma and 41,607 for non-Hodgkin lymphoma (NHL). The age-standardized incidence and mortality ratio in low or medium High Development Index (HDI) countries is 4.0/2.5 for men and 2.8/1.7 for women per 100,000 population.

Types of lymphoma

Lymphoma occurs when immature lymphocytes start multiplying rapidly because of a genetic mutation or other alteration. This leads to tumors in the lymph nodes or other organs. Lymphomas are of two main types: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). However, within these two broad categories, there are more than 90 different subtypes of lymphoma. The following are the types of lymphoma: 

• Non-Hodgkin lymphoma: It is the most common form of lymphoma and accounts for about 90 percent of diagnosed lymphomas. Non-Hodgkin lymphoma is more likely to occur in older individuals but can also occur at any time. These are divided further into two categories: B-cell lymphomas and T-cell lymphomas. B-cell lymphomas are far more common and occur in about 80 percent of patients with non-Hodgkin lymphoma. B-cell and T-cell lymphomas include different subtypes. Some of Non-Hodgkin lymphoma are aggressive, requiring immediate treatment but there are some slow-growing types of non-Hodgkin lymphoma which can be watched for years without any treatment.

       Examples of B-cell lymphomas:

• Diffuse large B-cell lymphoma: It is the most common type of non-Hodgkin lymphoma, and it is a type of cancer which affects B cells, which is a type of white blood cell. 
• Burkitt lymphoma: It is a fast growing and an aggressive form of non-Hodgkin lymphoma that affects B lymphocytes. 
• Primary mediastinal B cell lymphoma: It is a type of non-Hodgkin lymphoma which is sometimes called primary thymic mediastinal lymphoma and develops when B-cells become abnormal (cancerous).
• Mantle cell lymphoma: It is a rare type of B cell non-Hodgkin lymphoma, and it results from cancerous B-lymphocytes in the ‘mantle zone’ of lymph nodes, which is a ring of lymphocytes which surrounds the certain structures inside lymph nodes.
• Marginal lymphoma: It is a rare type of non-Hodgkin lymphoma which develops from chronic inflammation or because of a random error in DNA which can lead to the creation of abnormal cells.
• Post-transplant lymphoproliferative disorder: It is a rare, well-known complication of solid organ transplants and stem cell transplantation. And it is related to the Epstein-Barr virus and immunosuppression therapy. 

       Examples of T cell lymphoma

• Anaplastic large cell lymphoma: It is a rare form of non-Hodgkin lymphoma which is usually made up of either malignant T-cells (a type of cells in the immune system), or ‘null-lymphocytes’ (they lack both B and T-cell markers).
• Angioimmunoblastic lymphoma: This is an aggressive forms of peripheral T-cell lymphoma. It is one of the more common subtypes of T-cell lymphomas and elderly patients are more likely to be diagnosed with this type of lymphoma. 
• Extra nodal NK/T-cell lymphoma: This lymphoma is a rare subtype of non-Hodgkin lymphoma and commonly present with a nasal mass, nasal obstruction, or nasal bleeding.
• Peripheral T cell lymphoma not otherwise specified: It is a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer (NK) cells. 

• Hodgkin lymphoma: It is also known as Hodgkin’s lymphoma or Hodgkin disease which occurs in only 10 percent of the lymphoma patients. It is diagnosed when the patient has mutated cells called Reed-Sternberg cells and it occurs more commonly in young individuals. This lymphoma is a highly treatable form, and many patients can be cured. Chemotherapy is primarily used as an initial treatment. If Hodgkin's lymphoma recurs, stem cell transplants coupled with high-dose chemotherapy can be used and are effective at eliminating the disease. Hodgkin lymphoma is primarily of two main types:

• Classical lymphocyte predominant: It is characterized by the presence of both Hodgkin and Reed Stenberg cells. About 95 percent of patients with Hodgkin lymphoma have classical lymphocyte predominant type
• Nodular lymphocyte predominant: This type of lymphoma accounts for about 5 percent of Hodgkin lymphoma patients. It affects people aged between 30 to 50 years old.

Lymphoma symptoms

Symptoms of lymphoma can vary depending on the type of lymphoma. The symptoms are not the same in every individual and most patients will not have any symptoms while some may develop all the symptoms. 

Common lymphoma symptoms

The common symptoms of lymphoma are listed below:

• Swollen glands 
• Extreme tiredness
• Chest pain, cough or breathlessness 
• Feeling uncomfortably full or sick 
• Itching 
• Infections 
• Skin rashes or lumps
• Bone pain 
• Unusual bleeding or bruising

Other symptoms of lymphoma

Waldenstrom macroglobulinemia is a type of lymphoma which causes the following symptoms:

• Headaches and dizziness
• Confusion
• Blurred vision
• Kidney problems
• Nose bleeds
• Numbness in the legs and feet.
  

Lymphoma risk factors

Different environmental, infections, and genetic factors have been identified which can increase the risk of lymphoma. The following are some of the common risk factors of lymphoma: 

• Older age: With increasing age the risk of developing lymphoma also increases. Older individuals are more likely to develop lymphoma, particularly non-Hodgkins’s lymphoma. Due to a weak immune system and other co-morbidities, the prognosis of lymphoma is poor in older patients. 

• Occupational exposure: Exposure to chemicals such as herbicides and pesticides can significantly increase the risk of developing lymphoma. These chemicals contain carcinogenic agents which damage the immune system and cause mutations in lymphocytes. 

• Infectious organisms: Organisms such as Helicobacter pylori, Borrelia burgdorferi, Chlamydia psittaci, Campylobacter jejuni, human T-cell lymphotropic virus, hepatitis C & human herpesvirus 8 can increase the risk of developing lymphoma.

• Immunodeficiency: In individuals with HIV infection, transplant recipients, and those with genetic immunodeficiency disorders, the risk of developing lymphoma is high. 

• Drugs: Tumour necrosis factor-alpha inhibitors are linked with T-cell lymphoma. The risk of lymphoma increases in post-transplant patients (both in recipients of solid organ transplants and bone marrow transplant) with chronic immunosuppression. 

• Autoimmune disease: Inflammatory bowel disease (IBD), rheumatoid arthritis, and Sjögren’s syndrome are some of the autoimmune diseases that increase the risk of lymphoma development. 

• Geographic location: In Southern Asia and some parts of Latin America the incidence of Extra nodal Natural Killer /T-cell lymphoma is high.

Complications of lymphoma

Like all cancers, lymphoma can cause a wide range of side effects and complications. The following are the complications of lymphoma:

Complications of Hodgkin’s lymphoma

Hodgkin lymphoma occurs when the patient develops mutant cells called Reed-Sternberg cells. The following are the complications of Hodgkin lymphoma:

• Paraneoplastic syndromes: It occurs when the immune system, in addition to attacking cancer cells, starts attacking the normal healthy cells of the nervous system, including parts of the brain, spinal cord, peripheral nerves, or muscles. They include: 
• Limbic encephalitis: It is a rare autoimmune disease which causes inflammation of the brain. Few cases of limbic encephalitis are associated with Hodgkin lymphoma, and it causes symptoms such as memory loss, psychiatric symptoms, and confusion. 

• Primary CNS angiitis: It is a rare disease that causes inflammation of blood vessels in the brain and spinal cord. This condition is also known as primary central nervous system vasculitis. 

• Cerebellar degeneration: It is a process where neurons (nerve cells) in the cerebellum—the area of the brain that controls coordination and balance start to deteriorate and die. 

• POEMS Syndrome: It is a rare blood disorder which affects the nerves and other various parts of the body. It is characterized by the following: 

• Polyneuropathy: It is a diffuse peripheral nerve disorder which is not confined to the distribution of a single nerve or single limb and typically affects both sides symmetrically. 

• Organomegaly: It is defined as an abnormal enlargement of an organ, particularly organs of the abdominal cavity such as the liver (hepatomegaly), spleen (splenomegaly), and other organs. 

• Endocrinopathy: It is a central feature of POEMS syndrome and refers to diseases which affects the endocrine gland and its hormones. 

• Monoclonal plasma cell disorder: It is a group of diseases which occur when plasma cells multiply abnormally producing a monoclonal antibody called M protein. 

• Skin changes: In about 50 to 90 percent of POEMS syndrome patients’ hyperpigmentation occurs. Along with this, skin thickening and tightening are also reported.

Complications of non-Hodgkin’s lymphoma

This is the most common form of lymphoma and accounts for about 90 percent of the lymphomas diagnosed. Non-Hodgkin lymphoma and its treatments cause a wide range of complications. The following are some of the complications: 

• Weakened immune system: Treatment of non-Hodgkin lymphoma causes the immune system to weaken, and this weakening is called immunosuppression. It is important to be extra careful to avoid infections because infections can be serious in immunosuppressed patients. 

• Fertility problems: Some of the cancer treatments can affect fertility in patients and these effects can be temporary or permanent. 

• Secondary cancer: Patients with lymphoma have an increased risk of developing secondary cancers and this risk depends on the type of lymphoma. Radiotherapy during lymphoma treatment can also increase the risk of secondary cancers. 

• Organ damage: Both chemotherapy and radiotherapy can cause long-term damage to organs such as hearts and lungs. They can damage the nerves, causing symptoms such as tingling, numbness or pain.

Complications of chemotherapy for lymphoma

Complications associated with chemotherapy are as follows: 

• Pancytopenia: It is a condition in which the levels of all blood types such as red blood cells, white blood cells, and platelets drop. It occurs due to the suppression of blood cell production during chemotherapy. 

• Cardiomyopathy: In Hodgkin lymphoma patients there is always an increased risk for cardiovascular morbidity and mortality related to the long-term cardiotoxicity of treatment, particularly chemotherapy and radiotherapy.

• Pneumonitis: Pneumonitis affects 15 to 40 percent of patients who have undergone radiation therapy for lung cancer. It can also develop in patients who have undergone chest radiation for treating lymphoma. 

• Neuropathy: Both chemotherapy and radiation therapy-induced neuropathies are common in lymphoma patients. Long-term cancer survivors usually have an unavoidable tissue trace of their previous treatment, especially radiotherapy which is often clinically asymptomatic.

• Acute myeloblastic leukemia: With radiation therapy the risk of developing acute myeloblastic leukemia is high. Radiation directly damages DNA, causing mutations that either prevent a cell from maturing or cause the proliferation of cells beyond normal. 

Complications of radiotherapy for lymphoma

• Pericardial fibrosis: It is a condition where the pericardium which is the sac around the heart thickens or scars. Radiotherapy related to pericardial fibrosis is common and radiation causes fibrosis of all the heart components and increases the risk of various heart conditions. 

• Lung cancer: Radiation-induced lung cancer is the potential long-term complication of radiotherapy. Lung cancers are rare late complications of radiation therapy in both post-operative breast cancer and Hodgkin lymphoma patients. 

• Thyroid cancer: During radiotherapy, the thyroid gland absorbs too much radioactive iodine which may result in thyroid cancer. The radiation dose supplied to the thyroid gland and the age of exposure are the risk factors for thyroid cancer.

• Breast cancer: Lymphoma patients face a higher risk of breast cancer, and the risk increases over time in lymphoma patients. Many research studies have indicated that radiation therapy used in the treatment of lymphoma causes long-term damage to breast tissue, which leads to an increased chance of developing cancer. 

• Soft tissue sarcomas: Individuals who have undergone radiation therapy as a treatment for another cancer usually have a risk of developing soft tissue sarcoma. This risk is particularly high for Hodgkin lymphoma and non-Hodgkin lymphoma patients who received radiation therapy.
  

Lymphoma diagnosis

Diagnosis of lymphoma helps in understanding the type of lymphoma, how advanced it is, and helps in deciding which type of treatments will be most effective. The following are the steps involved in the diagnosis of lymphoma: 

Initial diagnosis 

• Medical history 
• Physical examination

Diagnostic tests 

• Blood tests 
• Complete blood count (CBC)
• Erythrocyte sedimentation rate (ESR)
• Lactate dehydrogenase (LDH)
• Blood smear
• Testing for certain viruses
• Other blood tests
• Biopsy techniques
• Bone marrow biopsy 
• Lymph node biopsy 
• Imaging studies
• X-ray
• Computed Tomography (CT) scan 
• Magnetic resonance imaging (MRI) scan 
• Ultrasound 
• Positron emission tomography (PET)
  

Lymphoma treatment

Treatment of lymphoma depends on factors such as age, general health of the patient, type of lymphoma, and whether the cancer has spread to other parts of the body. The following are the steps involved in treating lymphoma: 

• Bone marrow transplantation (BMT)
• Chemotherapy 
• CAR T-cell therapy 
• Immunotherapy 
• Radiation therapy
• Targeted therapy 
• Monoclonal antibody therapy
  

Lymphoma prevention

There is no proven way of preventing lymphoma but as lymphoma affects the immune system, there are steps that can be taken to prevent it, such as reducing the risk of contracting infections and making lifestyle changes which helps in maintaining a healthy immune system. The following are some of the measures to reduce the risk of lymphoma: 

• Physical activity: It is important for both the physical and mental health of the individual. It reduces fatigue and increases muscle strength and improves balance. 

• Diet: Including diets rich in fruits, vegetables, and whole grains reduces the risk of developing lymphoma. Avoiding foods such as processed meat and high energy foods can improve health. 

• Avoiding smoking: Smoking is one of the potential risk factors for developing lymphoma. Therefore, smoking cessation can reduce the risk of developing late effects after treatment. 

• Maintaining body weight: Maintaining a healthy weight is a part of leading a healthy lifestyle. To reach a healthy weight, people need to reduce food consumption and increase physical activity. Reducing daily calorie intake trying to decrease portion size at every meal and limiting the number of snacks throughout the day. 

• Avoiding contracting infections: Avoiding known risk factors for HIV, such as intravenous drug use or unprotected sex with multiple partners can reduce the risk of contracting infections.

Difference between Hodgkin’s lymphoma vs non-Hodgkin’s lymphoma

Hodgkin’s lymphoma vs non-Hodgkin’s lymphoma

Both Hodgkin and non-Hodgkin lymphoma are the two main types of lymphoma which affects the lymphatic system. Though they have many common characteristics, they differ in many aspects. The following are some of the parameters which differentiate Hodgkin and non – Hodgkin lymphoma:

Difference between Leukemia vs lymphoma

Leukemia vs lymphoma

Both leukemia and lymphoma are blood cancers which can originate in different parts of the body and can affect different types of white blood cells. The following are some of the key parameters which differentiate leukemia and lymphoma: