Definition of Lymphoma

Lymphoma is a type of blood cancer that begins in immune system cells called lymphocytes. Like other cancers, lymphoma occurs when lymphocytes are in a state of uncontrolled cell growth and multiplication. Lymphoma may develop in the lymph nodes, spleen, bone marrow, blood or other organs and eventually they form a tumor. 

Lymphocytes are white blood cells that move throughout the body in a fluid called lymph. They are carried by a network of vessels that make up the lymphatic system, part of the immune system. The lymphatic system – whose job it is to fight infections or anything else that threatens the body – is also comprised of lymph nodes that exist throughout the body to filter the lymph that flows through them. The lymph nodes swell and tenderize when a large number of microbial organisms collect inside of them, indicating local infection.

There are two primary types of lymphocytes: T cells (thymus cells) and B cells (bursa-derived cells) are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific “non-self” antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells.

Lymphoma occurs when lymphocyte B or T cells transform and begin growing and multiplying uncontrollably. Abnormal lymphocytes collect in one or more lymph nodes or in lymph tissues such as the spleen or tonsils, and eventually they form a mass of cells called a tumor. Tumors grow and invade the space of surrounding tissues and organs, depriving them of oxygen and nutrients.

If abnormal lymphocytes travel from one lymph node to the next or to other organs, the cancer can spread or metastasize. Lymphoma development outside of lymphatic tissue is called extranodal disease.

There are two types of lymphoma: Hodgkin lymphoma (HL, also called Hodgkin’s disease) and non-Hodgkin lymphoma (NHL). Both HL and NHL can occur in the same places and have similar symptoms. Their differences are visible at a microscopic level.

Hodgkin lymphoma develops from a specific abnormal lineage of B cells. There are five subtypes of HL. NHL may derive from either abnormal B or T cells, and its 30 subtypes are distinguished by unique genetic markers. The large number of lymphoma subtypes has led to a complicated classification scheme that involves microscopic appearance and well-defined genetic and molecular configurations.

Although several NHL subtypes look similar, they function differently and respond differently to therapies. HL subtypes are microscopically distinct, and classification is based upon the microscopic differences as well as the extent of disease.

Cause of Lymphoma

Normal cells in the body grow, divide, and die. Programmed cell death is called apoptosis, and when this process breaks down, cancer results. Scientists do not know exactly causes of lymphoma, but they have identified several potential risk factors.


Lymphoma can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life.


Carcinogens are a class of substances directly responsible for damaging DNA, promoting or aiding cancer. Lymphoma is associated with exposure to certain pesticides, herbicides, and solvents such as benzene. Similarly, black hair dye has been linked to higher rates of NHL. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. These free radicals damage cells, affecting their ability to function normally, and the result can be cancerous growths.

Other medical factors

With advancing age, there is an increase in the number of possible cancer-causing mutations in our DNA. The risk of NHL increases and HL is most common between ages 16-34 and 55 years and older. Additional medical conditions like infection with HIV, human T-lymphocytic virus type 1 (HTLV-1), Epstein-Barr virus, Helicobacter pylori, or hepatitis B or C; autoimmune disease (such as lupus); diseases that require therapies that suppress the immune system; and any other immunodeficiency diseases are associated with higher lymphoma rates.

Signs and Symptoms of Lymphoma

Often, the first sign of lymphoma is a painless swelling in the neck, under an arm, or in the groin.

  • Lymph nodes or tissues elsewhere in the body may also swell. The spleen, for example, often becomes enlarged in lymphoma.
  • The enlarged lymph node sometimes causes other symptoms by pressing against a vein or lymphatic vessel (swelling of an arm or leg), a nerve (pain, numbness, or tingling), or the stomach (early feeling of fullness).
  • Enlargement of the spleen may cause abdominal pain or discomfort.
  • Many people have no other symptoms.

Symptoms of lymphoma may include the following:

  • Fevers
  • Weight loss
  • Chills
  • Fatigue
  • Night sweats
  • Respiratory distress or dyspnoea
  • Itching (up to 25% of patients develop this itch, most commonly in the lower extremity but it can occur anywhere, be local, or spreading over the whole body)

These are nonspecific symptoms. That is they could be caused by any number of conditions unrelated to cancer. For instance, they could be signs of the flu or other viral infection, but in those cases, they would not last very long. In lymphoma, the symptoms persist over time and cannot be explained by an infection or another disease.

Risk Factors for Lymphoma


Generally, the risk of NHL increases as we age. HL in the elderly is associated with a poorer prognosis than that observed in younger patients.


  • HIV
  • Epstein-Barr virus (EBV), one of the etiologic factors in mononucleosis
  • Helicobacter pylori, a bacterium that lives in the digestive tract
  • Hepatitis B or hepatitis C virus

Medical conditions that compromise the immune system

  • HIV
  • Autoimmune disease
  • Use of immune suppressive therapy (often used following organ transplant)
  • Inherited immunodeficiency diseases (severe combined immunodeficiency, ataxia telangiectasia, among a host of others)

Exposure to toxic chemicals

  • Farm work or an occupation with exposure to certain toxic chemicals such as pesticides, herbicides, or benzene and/or other solvents
  • Hair dye use has been linked to higher rates of lymphoma especially in patients who started to use the dyes before 1980.


Family history of lymphoma

The presence of these risk factors does not mean a person will actually develop lymphoma. In fact, most people with one or several of these risk factors do not develop lymphoma.

Diagnosis of Lymphoma

If a person has swelling or any other symptoms of lymphoma, many questions about the symptoms (when they began, recent illnesses, past or current medical problems, any medications, workplace, health history, family history, and habits and lifestyle) asked. These questions are followed by a thorough examination.

If, after an initial interview and examination, the health-care provider suspects that a patient may have lymphoma, the patient will undergo a series of tests designed to provide further clarification. At some point in this workup, the patient will likely be referred to a specialist in blood diseases and cancer (hematologist/oncologist).

Blood tests

Blood is drawn for various tests.

  • These tests may be done to evaluate the function and performance of blood cells and important organs, such as the liver and kidneys.
  • Certain blood chemicals or enzymes (lactate dehydrogenase [LDH]) may be determined. High levels of LDH in cases in which NHL is suspected may indicate a more aggressive form of the disorder.
  • Other tests may be done to learn more about lymphoma subtypes.


If there is a swelling (also called lump or mass), a sample of tissue from the affected nodes or organs will be removed for examination by a pathologist. This is called a biopsy. Any of several methods can be used to obtain a biopsy of a mass.

  • Masses that can be seen and felt under the skin are relatively easy to biopsy. A hollow needle can be inserted into the mass and a small sample removed with the needle (called a core-needle biopsy). This is usually done in the health-care provider’s office with a local anesthetic.
  • Core-needle biopsy does not always obtain a good-quality sample. For that reason, many health-care providers prefer a surgical biopsy. This involves removal of the entire swollen lymph node through a small incision in the skin. This procedure often is done with a local anesthetic, but it sometimes requires a general anesthetic.
  • If the mass is not immediately under the skin but is instead deep inside the body, access is somewhat more complicated. The tissue sample is usually obtained via laparoscopy. This means making a tiny incision in the skin and inserting a thin tube with a light and a camera on the end (a laparoscope). The camera sends pictures of the inside of the body to a video monitor, and the surgeon can see the mass. A small cutting tool on the end of the laparoscope can remove all or part of the mass. This tissue is withdrawn from the body with the laparoscope.
  • A pathologist (a physician who specializes in diagnosing diseases by looking at cells and tissues) examines the tissue sample with a microscope. The pathologist’s report will specify whether the tissue is lymphoma and the type and subset of lymphoma.

Imaging studies

If there is no palpable mass in the presence of persistent symptoms, imaging studies will likely be carried out in order to determine whether a mass is present and, if so, how then to direct a biopsy.

  • X-rays: In certain parts of the body, such as the chest, a simple X-ray can sometimes detect lymphoma.
  • CT scan: This test provides a three-dimensional view and much greater detail and may detect enlarged lymph nodes and other masses anywhere in the body.
  • MRI scan: Similar to the CT scan, MRI gives three-dimensional images with excellent detail. MRI provides better definition than CT scan in certain parts of the body, especially the brain and the spinal cord.
  • Lymphangiogram: This approach, which provides an image of the lymphatic system by tracing a dye that moves though the system, has essentially been replaced by either CT scan, MRI, or PET.
  • Gallium scan: Lymphomas tend to collect a substance called gallium when injected into the body. For this test, a tiny amount of radioactive gallium is injected into the body. A scan is then done to find areas where the gallium has collected. Collections of gallium suggest a tumor.
  • Positron-emission tomographic (PET) scan: PET scan is a newer alternative to lymphangiogram and gallium scan for detecting areas in the body that are affected by lymphoma. A tiny amount of a radioactive substance is injected into the body and then traced on the PET scan. Sites of radioactivity on the scan indicate areas of increased metabolic activity, which implies the presence of a tumor.

Bone marrow examination

Most of the time, an examination of the bone marrow is necessary to see if the marrow is affected by the lymphoma. This is done by collecting a biopsy of the bone marrow.

  • Samples are taken, usually from a hip bone.
  • A pathologist examines the bone marrow under a microscope.
  • Bone marrow containing certain types of abnormal B or T lymphocytes confirms lymphoma.
  • Bone marrow biopsy can be an uncomfortable procedure, but it can usually be performed in a medical office. Most people receive pain medication prior to the procedure to make them more comfortable.

Other tests

  • Lumbar puncture: This test, sometimes called a spinal tap, is a method for collecting a sample of the fluid surrounding the brain and spinal cord. This fluid is called cerebrospinal fluid. If the lymphoma has affected the central nervous system, the cerebrospinal fluid will likely contain lymphoma cells.
  • Organ function tests: These tests are usually done before starting treatment to make sure that one’s organs are healthy enough to withstand the side effects of therapy. Examples include an echocardiogram or MUGA scan (a test that provides a movie-like image of the working heart) for the heart and pulmonary function tests for the lungs.


Staging is the classification of a cancer type by its size and whether and how much it has spread around the body. Determining a cancer’s stage is very important because it tells the oncologist which treatment is most likely to work and what are the chances of remission or a cure (prognosis).

Staging of lymphomas is based on the results of imaging studies and related tests that reveal the extent of the cancer involvement.

HL is often described as being “bulky” or “nonbulky.” Nonbulky means the tumor is small; bulky means the tumor is large. Nonbulky disease has a better prognosis than bulky disease.

NHL is a complicated set of diseases with a complex classification system. In fact, the classification system is continuously evolving as we learn more about these cancers. The newest classification system takes into account not only the microscopic appearance of the lymphoma but also its location in the body and genetic and molecular features.

Grade is also an important component of the NHL classification.

  • Low grade: These are often called “indolent” lymphomas because they grow slowly. Low-grade lymphomas are often widespread when discovered, but because they grow slowly, they usually do not require immediate treatment unless organ function is compromised. They are rarely cured and can transform over time to a combination of indolent and aggressive types.
  • Intermediate grade: These are rapidly growing (aggressive) lymphomas that usually require immediate treatment, but they are often curable.
  • High grade: These are very rapidly growing and aggressive lymphomas that require immediate, intensive treatment and are much less often curable.

The “staging,” or evaluation of extent of disease, for both HL and NHL, are similar.

  • Stage I (early disease): Lymphoma is located in a single lymph node region or in one area or organ outside the lymph node.
  • Stage II (locally advanced disease): Lymphoma is located in two or more lymph node regions all located on the same side of the diaphragm or in one lymph node region and a nearby tissue or organ. (The diaphragm is a flat muscle that separates the chest from the abdomen.)
  • Stage III (advanced disease): Lymphoma affects two or more lymph node regions, or one lymph node region and one organ, on opposite sides of the diaphragm.
  • Stage IV (widespread or disseminated disease): Lymphoma is outside the lymph nodes and spleen and has spread to another area or organ such as the bone marrow, bone, or central nervous system.

Both HL and NHL are further classified with letters.

  • An “A” or “B” designation indicates whether the person with lymphoma had symptoms such as fevers and/or weight loss at the time of diagnosis. “A” indicates no such symptoms, and “B” indicates symptoms.
  • An “E” designation indicates that the tumor spread directly from a lymph node into an organ or that a single organ outside the lymphatic system is affected with no apparent lymphatic involvement. If the spleen is involved an “S” designation is added.

Prognostic factors

Several risk factors have been extensively evaluated and shown to play a role in treatment outcome. For HL, the International Prognostic Index includes the following seven risk factors:

  • Male sex
  • Age 45 years or older
  • Stage IV disease
  • Albumin (blood test) less then 4.0 g/dL
  • Hemoglobin (red blood cell level) less than 10.5 g/dL
  • Elevated white blood cell (WBC) count of 15,000/mL
  • Low lymphocyte count less than 600/mL or less than 8% of total WBC

The absence of any of the above risk factors is associated with an 84% rate of control of Hodgkin’s disease, whereas the presence of a risk factor is associated with a 77% rate of disease control. The presence of five or more risk factors was associated with a disease control rate of only 42%.

The outcomes for these patients were also determined by the treatment they received, which occurred primarily in the 1980s. Newer treatments for Hodgkin’s lymphoma may improve these predicted outcomes. Furthermore, new treatments are being developed for patients with greater risk factors.

The International Prognostic Index for NHL includes five risk factors:

  1. Age older than 60 years
  2. Stage III or IV disease
  3. High LDH
  4. More than one extranodal site
  5. Poor performance status (as a measure of general health): From these factors, the following risk groups were identified:
  • Low risk: one risk factor, five-year lymphoma-free survival (LFS) of 70%
  • Intermediate risk: two to three risk factors, five-year LFS of 49%-50%
  • Poor risk: four to five risk factors, five-year LFS of 26%

The prognostic models were developed to evaluate groups of patients and are useful in developing therapeutic strategies. It is important to remember that any individual patient might have significantly different results than the above data, which represent statistical results for a patient group.

Prevention from Lymphoma

Lymphoma cannnot be prevented. To avoid the known risk factors for the disease is recommended. However, some risk factors for lymphoma are unknown, and therefore impossible to avoid. Infection with viruses such as HIV, EBV, and hepatitis are risk factors that can be avoided with frequent hand washing, practicing safe sex, and by not sharing needles, razors, toothbrushes, and similar personal items that might be contaminated with infected blood or secretions.

Many people live with lymphoma in remission for many years after treatment.

Treatment of Lyphoma

 For some forms of lymphoma, watchful waiting is often the initial course of action. If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice; although they do not cure the lymphoma, they can alleviate the symptoms, particularly painful lymphadenopathy. Patients with these types of lymphoma can live near-normal lifespans, but the disease is incurable. Treatment of some other, more aggressive, forms of lymphoma can result in a cure in the majority of cases, but the prognosis for patients with a poor response to therapy is worse. Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or RCHOP regimen. Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized. Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy.

The goal of medical therapy in lymphoma is complete remission. This means that all signs of the disease have disappeared after treatment. Remission is not the same as cure. In remission, one may still have lymphoma cells in the body, but they are undetectable and cause no symptoms.

  • When in remission, the lymphoma may come back. This is called recurrence.
  • The duration of remission depends on the type, stage, and grade of the lymphoma. A remission may last a few months, a few years, or may continue throughout one’s life.
  • Remission that lasts a long time is called durable remission, and this is the goal of therapy.
  • The duration of remission is a good indicator of the aggressiveness of the lymphoma and of the prognosis. A longer remission generally indicates a better prognosis.

Remission can also be partial. This means that the tumor shrinks after treatment to less than half its size before treatment.

The following terms are used to describe the lymphoma’s response to treatment:

  • Improvement: The lymphoma shrinks but is still greater than half its original size.
  • Stable disease: The lymphoma stays the same.
  • Progression: The lymphoma worsens during treatment.
  • Refractory disease: The lymphoma is resistant to treatment.