Lymphoma
Comprehensive information on the causes, symptoms, diagnosis, and treatment of different types of cancer affecting the lymphatic system.
Symptoms and Causes
Lymphoma is a type of cancer that occurs in the lymphatic system, which is part of the immune system responsible for defending the body against diseases. It originates in white blood cells (lymphocytes). Lymphoid tissue is present in lymph nodes located in the neck, chest, armpits, abdomen, pelvis, and groin, as well as in the tonsils, adenoids, bone marrow, lungs, thymus, gastrointestinal tract, spleen, and liver, meaning lymphoma can develop in nearly any part of the body.
Depending on the lymphocytes affected, lymphoma is classified into two main groups:
- Hodgkin lymphoma (HL): characterized by Reed-Sternberg cells, which are large lymphocytes with abnormal features, sometimes with more than one nucleus.
- Classical Hodgkin lymphoma (CHL): the most common form. Based on the characteristics of the tumor cells, it can be:
- Nodular sclerosis Hodgkin lymphoma (NSHL): shows nodules of scar tissue surrounding the cancer cells. It is common in adolescents and young adults.
- Mixed cellularity Hodgkin lymphoma (MCHL): contains inflammatory cells (lymphocytes, histiocytes, and eosinophils). It is more frequent in older adults and patients with HIV.
- Lymphocyte-rich Hodgkin lymphoma (LRHL): uncommon. Tumors contain a high number of lymphocytes and occur more often in older adults.
- Lymphocyte-depleted Hodgkin lymphoma (LDHL): the rarest form, with the worst prognosis due to delayed diagnosis. It features Reed-Sternberg cells with minimal lymphocyte presence and is often observed in HIV-positive individuals.
- Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): accounts for approximately 5% of all classical Hodgkin lymphomas. Tumors consist of large "popcorn"-shaped cancer cells and generally have a good prognosis as they are usually localized.
- Non-Hodgkin lymphoma (NHL): the most frequent type, lacking Reed-Sternberg cells.
- B-cell lymphomas: affect lymphocytes responsible for producing antibodies against bacteria and viruses.
- Diffuse large B-cell lymphoma (DLBCL): one of the most common types, fast-growing and aggressive.
- Follicular lymphoma: also called indolent B-cell lymphoma due to its slow growth. Originates in lymph node follicles, which are clusters of white blood cells developed to fight infections.
- Mantle cell lymphoma (MCL): very rare. Tumors grow rapidly and are usually resistant to chemotherapy.
- Burkitt lymphoma: highly aggressive, often detected after spinal involvement.
- T-cell lymphomas: affect T lymphocytes, which originate in the bone marrow and mature in the thymus to fight infections and cancer.
- Chronic lymphocytic leukemia (CLL): results in increased B lymphocytes. It is a slowly progressing form of lymphoma.
The prognosis of lymphoma varies according to type, stage at diagnosis, and aggressiveness. Based on this, lymphoma is further classified as:
- Aggressive lymphomas: tumors grow rapidly, making the disease more severe, but they generally respond well to intensive chemotherapy.
- Indolent lymphomas: slower-growing and less malignant but harder to treat.
Generally, the five-year survival rate for Hodgkin lymphoma is approximately 80%, and for non-Hodgkin lymphoma, around 74%.
Symptoms
The most characteristic symptoms of lymphoma include:
- Enlarged lymph nodes, which may be easily palpable in the neck, armpits, or groin.
- Persistent high fever without apparent cause.
- Night sweats.
- Unintentional weight loss.
- Extreme fatigue unrelieved by rest.
- Pruritus (itchy skin).
Causes
The exact causes of lymphoma are currently unknown. However, it is known that cancerous tumors arise due to DNA alterations in cells, causing them to proliferate faster than normal and survive longer than expected. This accumulation of cells leads to tumor formation.
Risk Factors
Factors associated with an increased risk of lymphoma include:
- Age:
- Hodgkin lymphoma: more common between 15–35 and 50–70 years.
- Non-Hodgkin lymphoma: usually occurs after age 65.
- HIV infection.
- Infection with Epstein-Barr virus or Helicobacter pylori.
- Family history of lymphoma.
Complications
Common complications of untreated or therapy-resistant lymphoma include:
- Recurrent infections.
- Anemia.
- Thrombocytopenia: decreased platelet count.
- Metastasis: lymphoma can spread to other lymphatic organs and, in advanced stages, reach the liver, lungs, small intestine, stomach, or brain.
- Relapse: the cancer reappears despite successful treatment.
- Death.
Prevention
There is currently no way to prevent any type of lymphoma.
Which Specialist Treats Lymphoma?
Diagnosis and treatment of lymphoma involve medical oncology, radiation oncology, and hematology and hemotherapy specialists.
Diagnosis
Lymphoma diagnosis involves various tests, including:
- Medical history: information is collected on the patient’s personal and family medical background, lifestyle, and reported symptoms.
- Physical examination: lymph nodes are palpated to detect swelling or tenderness.
- Blood tests: a complete blood count provides information on overall health. Abnormal blood cell counts, tumor markers, liver or kidney dysfunction, or elevated erythrocyte sedimentation rate may indicate disease.
- Biopsy: a sample of the suspected lymph node is obtained for laboratory analysis. Techniques include incisional biopsy (partial node) or excisional biopsy (whole node). For nodes in the abdomen or chest, general anesthesia may be required.
- Hodgkin lymphoma diagnosis is confirmed by identifying Reed-Sternberg cells (large, binucleated with ample cytoplasm).
- Non-Hodgkin lymphoma is confirmed by finding cancerous cells that proliferate excessively, evade normal cell death, and can form new blood vessels.
- Flow cytometry: analyzes biopsy samples to determine the specific lymphoma type.
- Chromosomal tests: some lymphomas present chromosomal abnormalities (excess, deficiency, or anomalies).
- Karyotype: examines cell morphology for alterations.
- Fluorescent in situ hybridization (FISH): detects minimal genetic changes using fluorescent dyes.
- Polymerase chain reaction (PCR): identifies even very small chromosomal changes or when cell samples are limited.
- Bone marrow biopsy: fine-needle aspiration is performed if marrow involvement is suspected or other tests are inconclusive.
- Computed tomography (CT): X-rays from multiple angles create cross-sectional body images to detect enlarged lymph nodes in the head, neck, chest, abdomen, or pelvis.
- Magnetic resonance imaging (MRI): provides detailed three-dimensional images using radio waves and a high-strength magnetic field. Typically used when spinal cord or brain involvement is suspected.
- Positron emission tomography (PET): imaging detects areas of radioactivity after injection of a radioactive tracer that binds to tumor cells. Performed after lymphoma confirmation to identify regions not clearly visualized with other imaging or to monitor treatment response.
These tests also determine lymphoma staging:
- Stage I: involvement of a single lymph node group or lymphatic organ.
- Stage II: two or more lymph node groups on the same side of the diaphragm, or one non-lymphatic organ plus adjacent lymph nodes.
- Stage III: cancer cells in lymph nodes on both sides of the diaphragm.
- Stage IV: cancer spreads from the lymphatic system to other organs.
Treatment
Lymphoma treatment requires thorough evaluation of cancer type, stage, and patient characteristics to develop a personalized therapy plan. Often, a combination of approaches is used to achieve optimal results. Common treatment strategies include:
- Chemotherapy: systemic drugs inhibit or slow cancer cell growth. Administered via the bloodstream, chemotherapy predominantly affects rapidly dividing tumor cells.
- Radiotherapy: usually complementary to chemotherapy, high doses of ionizing radiation target cancer cells. Modern techniques, such as Involved-Site Radiation Therapy (ISRT), focus radiation specifically on affected nodes to minimize damage to healthy tissue.
- Immunotherapy: aims to strengthen the patient’s immune system to fight cancer:
- Monoclonal antibody therapy: a targeted treatment using an antibody-drug conjugate (ADC) that binds specifically to tumor cell surface molecules, destroying them more selectively than conventional chemotherapy.
- Stem cell or hematopoietic progenitor transplantation: can be autologous or from a compatible donor. Cells are harvested from blood or bone marrow, then reinfused to replace damaged marrow.
- CAR-T therapy: patient’s own T cells are genetically modified with a chimeric antigen receptor (CAR) to recognize and destroy cancer cells more effectively.
- Bispecific antibody therapy: antibodies designed to bind both the cancer cell antigen and T cells, enhancing immune-mediated destruction.
