Introduction

Lymphoma is a type of blood cancer. It affects thousands of people worldwide each year. It constitutes approximately 5% of all cancer cases. The overall survival rate of this cancer is around 72%. This cancer affects the lymphocytes (a type of white blood cell). When they grow abnormally and uncontrollably, it leads to lymphoma.¹ This article provides an overview of lymphoma, including its aetiology, types, symptoms, diagnostic methods, and treatment options.

Aetiology

Various causes and risk factors include:^1,3

• Exposure to herbicides and pesticides
• Certain infections like H. pylori, Borrelia, Chlamydia psittaci, etc
• Viruses such as hepatitis C and human herpesvirus 8 are associated with certain types of lymphoma
• Chronic infections with Epstein-Barr virus and cytomegalovirus can lead to lymphoma
•  Immunodeficiency from HIV, transplants, or genetic disorders raises lymphoma susceptibility
• Tumour necrosis factor-alpha inhibitors and long-term immunosuppressive therapy increase lymphoma risk
•  Autoimmune diseases like Inflammatory bowel disease, rheumatoid arthritis, and Sjögren’s syndrome

Types of lymphoma

Lymphomas are divided into two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma, accounting for 10% and 90% of cases, respectively.¹

Hodgkin lymphoma

Hodgkin lymphoma is subdivided into classical and non-classical forms. Classical Hodgkin lymphoma is divided into four subtypes, i.e., nodular sclerosing, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. Non-classical Hodgkin lymphoma consists of a single subtype: nodular lymphocyte-predominant. Hodgkin lymphoma shows a bimodal age distribution, with peaks in the early 20s and mid-60s. Histologically, it is characterised by the presence of Hodgkin Reed-Sternberg cells. These cells originate from B cells. Hodgkin Reed-Sternberg cells are large, atypical, bilobed cells with two nuclei, found among non-cancerous inflammatory cells.¹

Non-hodgkin lymphoma

Non-Hodgkin Lymphoma has different subtypes. These include diffuse large B-cell lymphoma, follicular Lymphoma, lymphoma of Mucosa-Associated Lymphoid Tissue, Mantle Cell Lymphoma, Burkitt Lymphoma, and peripheral T-cell lymphomas, among many others. Some of these are discussed in further detail.¹

Diffuse large B-cell lymphoma

• It is the most common type. It represents 25–30% of cases
• It is an aggressive lymphoma that typically originates in lymph nodes but can arise in other parts of the body, with the gastrointestinal tract being the most frequent extra-nodal site
• It is termed primary extra-nodal diffuse large B-cell lymphoma when the disease is limited to extra-nodal sites with little or no lymph node involvement; if both nodal and extra-nodal areas are involved, it is classified as nodal lymphoma
• Histologically, it shows diffuse infiltration by large lymphoid cells

Follicular lymphoma

• Follicular lymphoma is a slow-growing, i.e., indolent lymphoma, and represents about 20% of all lymphoma cases, making it the second most common type
• It originates from follicular centre B cells within the germinal centre of lymph nodes
• Histologically, it shows prominent follicular proliferation in lymph nodes, primarily composed of BCL-2 positive B cells
• Follicular lymphoma follicles contain a mix of small cells (centrocytes) and large cells (centroblasts); the number of centroblasts per high-power field determines the grade of lymphoma(Grades I, II, III, IIIA, IIIB)

Burkitt lymphoma

• Burkitt lymphoma is a highly aggressive B-cell lymphoma first identified by Irish surgeon Denis Burkitt in 1958
• It has three subtypes, i.e., endemic, sporadic, and immunodeficiency-associated
• Endemic Burkitt lymphoma is common in African children, typically appears as a jaw (mandibular) mass, and is strongly linked to chronic Epstein-Barr virus infection
• Sporadic Burkitt lymphoma is the most frequent form in the U.S., often presenting with abdominal tumours or lymphadenopathy
• In individuals with HIV, Immunodeficiency-associated Burkitt lymphoma occurs
• It shows medium to large B-cells with an extremely high proliferation rate histologically. The tissue displays a classic "starry sky" pattern caused by scattered macrophages among the tumour cells

Symptoms

Common symptoms include:^1,3

• Lymphadenopathy (Swollen Lymph Nodes): It is the most common symptom, often appearing as painless lumps in the neck, armpit, etc
• Fever: Unexplained fever, especially if it's recurrent or prolonged
• Night sweats: Drenching night sweats that soak clothes and bedding, even in a cool room
• Unexplained weight loss
• Fatigue: Persistent and overwhelming tiredness that doesn't improve with rest
• Itching: Severe itching (pruritus)
• Alcohol-induced pain: Pain occurs immediately after the intake of alcohol. It is localised to regions of lymphadenopathy

Diagnosis

Diagnosis of lymphoma involves a multifaceted approach. Various diagnostic approaches include:^1,2

• The clinician checks for swollen lymph nodes, an enlarged spleen or liver, and other signs of disease
• Lymphoma is confirmed by tissue biopsy. A small tissue sample (from a swollen lymph node, bone marrow, or other affected area) is removed and examined under a microscope by a pathologist. A bone marrow biopsy is also commonly performed for diagnosis of this cancer
• After lymphoma is confirmed by tissue biopsy, the next step is identifying the site with the highest disease activity.
• Positron emission tomography/Computed tomography scans using radiolabelled fluorodeoxyglucose are done to assess lymphoma metabolic activity
• Staging is done before starting treatment and follows the Ann Arbor system for both Hodgkin lymphoma and non-Hodgkin lymphoma
• Blood tests, which are done, include Lactate dehydrogenase, Complete blood count with differential, comprehensive metabolic panel, and uric acid test

Staging

The Ann Arbor staging system is used for staging of lymphoma cancer:¹

• It is classified as Stage I if there is involvement of one lymph node region (e.g., spleen, thymus) or one extra-lymphatic site.
• It is classified as Stage II if the lymphoma is in two or more lymph node regions on the same side of the diaphragm, or one extranodal organ.
• It is classified as Stage III if the lymphoma is in lymph node regions on both sides of the diaphragm, or lymph nodes above the diaphragm.
• It is classified as Stage IV if lymphoma has spread widely to one or more extra-lymphatic organs (e.g., bone marrow, liver, lung) with or without lymph node involvement.

Treatment and management

Common treatment modalities include:^1,2

• Chemotherapy is the most commonly used treatment method for lymphoma. It involves the use of drugs to kill cancer cells or stop their growth. Different regimens are prescribed by clinicians that depend on the subtype
• Radiation therapy is used as an adjunct treatment. In this method, clinicians use radiation to destroy cancer cells in specific areas. It is often used for localised lymphoma
• Treatment intensity varies by disease type and grade: aggressive lymphomas require urgent, high-intensity regimens, while indolent lymphomas may be observed or treated less aggressively
• Stem cell transplantation (autologous or allogeneic) is used in relapsed or high-risk cases, particularly after chemotherapy.
• Maintenance therapy (e.g., rituximab) is used to prolong progression-free survival
• Supportive care (e.g., infection prophylaxis, monitoring for secondary malignancies, and cardiotoxicity) is done, especially in young survivors and those receiving anthracyclines

Summary

Lymphoma is a type of blood cancer that originates in lymphocytes, a type of white blood cells, and accounts for about 5% of all malignancies globally. The overall survival rate of this cancer is approximately 72%. Several risk factors contribute to the development of lymphoma, including exposure to herbicides and pesticides, infections such as Helicobacter pylori, and viruses like hepatitis C. It is mainly divided into two types, i.e., Hodgkin lymphoma and non-Hodgkin lymphoma, comprising about 10% and 90% of cases, respectively. Hodgkin lymphoma is characterised by the presence of Hodgkin Reed-Sternberg cells and has two forms: classical (with subtypes like nodular sclerosing, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted) and non-classical (nodular lymphocyte-predominant). Non-Hodgkin lymphoma includes many subtypes; the most common ones are diffuse large B-cell lymphoma, follicular lymphoma, and Burkitt lymphoma.

Typical symptoms of lymphoma include painless lymphadenopathy, unexplained fever, night sweats, weight loss, fatigue, pruritus, and alcohol-induced pain in affected nodes. Diagnosis of lymphoma involves physical examination, biopsy, PET/CT scan, blood tests, and bone marrow biopsy. The Ann Arbor staging system ranges from Stage I (localised disease) to Stage IV (widespread organ involvement). Treatment and management options depend on the type and grade of lymphoma. Chemotherapy is the most commonly used treatment method; it is often combined with radiation therapy for localised disease. Future approaches include targeted therapies, immunotherapy, and precision medicine using genomic profiling to tailor individualised treatment, aiming to improve outcomes and minimise toxicity.