Non Hodgkin's Lymphoma

Also called: Lymph Node Cancer, Lymphatic System Cancer

Reviewed By:
Mark Oren, M.D., FACP


Lymphoma is cancer of the lymphoid tissue, which is part of the lymphatic system. A major component of the immune system, the lymphatic system consists of organs, lymph nodes and lymphatic vessels. This system manufactures lymphocytes and transports lymph (fluid made of plasma and white blood cells) from tissues to the bloodstream. Although other forms of cancer may spread to parts of the lymphatic system, lymphoma is the only form that originates in the system.

Lymphoid tissue is formed by various types of immune cells that work together to resist some types of infection and other threats, such as cancer. Lymphocytes are the main type of cell found in the lymphoid tissue. In lymphoma, abnormal lymphocytes continually grow for no reason. This results in abnormal enlargement of the lymph nodes and other body organs containing lymphocytes, causing lumps to develop in the body.

Lymphomas can be categorized into two main groups. One group, characterized by the presence of specific cells (called Reed-Sternberg cells), is known as Hodgkin’s lymphoma or Hodgkin’s disease. All other forms of lymphomas are known as non-Hodgkin’s lymphoma. Cases of non-Hodgkin’s lymphoma are far more common.

Most lymphomas develop as a result of noninherited mutations in the genes of growing lymphocytes. According to the National Cancer Institute (NCI), lymphomas account for about 5 percent of all cases of cancer in the United States. They can occur in both children and adults.

About lymphoma

Lymphoma is cancer of the lymphoid tissue. Lymphoid tissue comprises the lymphatic system, which is a critically important component of the immune defense system. Although other forms of cancer may spread to parts of the lymphatic system, lymphoma is the only cancer that originates in the system.

The lymphatic system consists of organs, such as the spleen, lymph nodes and lymphatic vessels that manufacture leukocytes. It is also responsible for moving lymph fluid to the bloodstream. This fluid is made of plasma and various types of white blood cells, which fight some types of infection and other threats, such as cancer. 

Lymphoid tissue is formed by various types of immune cells that work together to resist infection and other threats, such as cancer.  Lymphocytes are the main type of cell found in the lymphoid tissue. In patients with lymphoma, the lymphocytes become abnormal and grow in an uncontrolled fashion. As the cells continue to grow and divide, the lymph glands or other organs in which the lymphocytes grow begin to enlarge. The cells form tumors that begin to develop in the body. Organ function may become affected as the lymphocyte masses grow larger, making it more difficult for normal cells to function.

The two main types of lymphocytes are:

  • B lymphocytes (B-cells). B-cells defend the body from bacteria and other invading threats by changing into plasma cells, which make antibodies. These antibodies then mark antigens or other invaders for destruction.
  • T lymphocytes (T-cells). T-cells destroy germs, cancer cells and infected cells directly.

Both forms can develop into lymphoma (either the Hodgkin’s or non-Hodgkin’s type). However, B-cell lymphomas are more common.  

In this condition, tumors generally develop in the lymph nodes, or in some situations, in patches of lymphatic tissue in organs, such as the stomach or intestines. Lymph nodes are small, bean-shaped organs located in groups in various areas of the body, including the neck, armpit, chest and groin. Their functions include producing immune cells (e.g., lymphocytes and plasma cells), and filtering bacteria, cancer cells and other foreign material from lymph. These materials have surface proteins called antigens. When the lymph nodes recognize antigens and other foreign material in the lymph fluid, the nodes respond by enlarging and producing additional white blood cells to help combat these threats.

Because lymphoid tissue is present in many parts of the body, lymphomas can develop almost anywhere. In addition, lymphomas are capable of spreading to other areas of the body including the liver, bone marrow and spleen.

Most lymphomas develop as a result of noninherited mutations in the genes of growing leukocytes. Some forms of cancer are caused by DNA mutations that “turn on” oncogenes (genes that speed cell division) or “turn off” tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). In most people with lymphoma, these mutations are acquired after birth. The mutations may occur from exposure to radiation or cancer-causing chemicals, but many times the mutations occur for no apparent reason. Researchers have noted that they appear to happen more often as people age, making age the greatest risk factor for some forms of lymphoma.

Another defect that can cause lymphoma is a translocation. A translocation is the transfer of DNA from one chromosome to another. This abnormality can “turn on” oncogenes or “turn off” tumor suppressor genes.

According to the National Cancer Institute (NCI), lymphomas account for about 5 percent of all cases of cancer in the United States. They can occur in children and adults.

Although there is no single cause of lymphoma, researchers have identified some risk factors that can increase the chances of developing lymphoma. Regardless of type, lymphoma tends to occur more often in:

  • White men
  • People with certain immune deficiencies, such as infection with human immunodeficiency virus (HIV)
  • Individuals who have been treated with immunosuppressive drugs, as after a kidney or other organ transplant.

Certain medical conditions have also been linked to lymphoma. The Epstein Barr virus (which causes infectious mononucleosis) has been identified as a risk factor for Hodgkin’s lymphoma. In addition, researchers have noted high rates of hepatitis C among lymphoma patients. It is believed that infection with hepatitis C virus affects the immune system, resulting in lymphoma. A bacterium known as Helicobacter pylori also has been associated with the development of lymphoma in the stomach wall.

In general, people who have received either radiation treatments or chemotherapy for other types of cancer as a child, appear to have a higher risk of developing lymphoma later in life. There is also an apparent increase in incidences of the condition in areas where farming is prevalent. Researchers believe certain herbicide ingredients may be responsible for increasing lymphoma in this population.

Scientists also have discovered an association between some genes and the development of lymphoma. In research studies, HMG-1, an oncogene (cancer-causing gene), was linked to aggressive lymphoma and leukemia in children and adults.

Further studies have identified a gene associated with the human herpes virus 8 (HHV8) that may cause lymphoma by activating a pathway involved in the production of lymphocytes. These abnormal lymphocytes are cells that repeatedly divide and eventually develop into lymphoma. More research is necessary to determine the exact relationship between genes and the development of lymphoma

The annual rate of occurrence of lymphoma has nearly doubled over the last 35 years. The increase may be partly due to AIDS-related non-Hodgkin’s lymphoma, because the incidence of Hodgkin’s lymphoma has stabilized.  In 2007, the American Cancer Society (ACS) predicts nearly 72,000 new cases of lymphoma and nearly 20,000 deaths from the disease. These statistics include both Hodgkin’s and non–Hodgkin’s lymphoma.

Types and differences of lymphomas

There are more than 25 different types of tumors that are considered lymphomas. These tumors can be classified into two categories – Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). Hodgkin’s lymphoma category, also known as Hodgkin’s disease, is named after the physician who identified it in 1832. All other types of lymphomas are considered non-Hodgkin’s lymphoma.

Cases of non-Hodgkin’s lymphoma are far more common. In 2003, an estimated 7,600 new cases of Hodgkin’s lymphoma were diagnosed in the United States, compared with 53,400 new cases of non-Hodgkin’s lymphoma.

Hodgkin’s lymphoma can usually be distinguished from NHL when tissue is examined under a microscope. The cells found in Hodgkin’s lymphoma, known as Reed-Sternberg cells, are named after the physicians who first described them in detail. Many researchers believe that Reed-Sternberg cells are a form of malignant B-cells.

Many classification systems have been developed for lymphomas, and experts disagree on exactly how they should be organized. The most recent classification system was an update of the Revised European American Lymphoma (REAL) Classification by the World Health Organization (WHO). While previous classification mainly relied on the appearance of the lymphoma cells, the updated WHO/REAL classification system relies on the genetic and chemical characteristics of the cells as well.

Hodgkin’s lymphoma is classified as:

  • Nodular lymphocyte-predominant Hodgkin’s lymphoma

  • Classical Hodgkin’s lymphoma:

    • Nodular sclerosis Hodgkin’s lymphoma
    • Mixed-cellularity Hodgkin’s lymphoma
    • Lymphocyte-depleted Hodgkin’s lymphoma
    • Lymphocyte-rich Hodgkin’s lymphoma

Types of non-Hodgkin’s lymphoma are first divided by cell type into B-cell or T-cell groups. They are then further classified by whether the tumors were derived from precursor (immature) or peripheral (mature) cells.

Non-Hodgkin’s lymphoma classification is lengthy and complicated. The most common forms of non-Hodgkin’s lymphomas include:

  • B-cell chronic lymphocytic leukemia (CLL)/small cell lymphocytic lymphoma (SCLL)

  • Follicular lymphoma

  • Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type

  • Hairy cell leukemia

  • Diffuse large cell B–cell lymphoma (DLBCL)

  • Burkitt’s lymphoma

  • Precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma

Occasionally, lymphoma can develop from bone marrow lymphocytes. Lymphocytic leukemia is another form of cancer that develops from bone marrow lymphocytes. As a result, cases of leukemia and lymphoma can be very similar. For example in some forms of lymphoma, the malignant (cancerous) cells may be the same and the only difference is where the cancer occurs. B-cell chronic lymphocytic leukemia (CLL)/small cell lymphocytic lymphoma (SCLL) is one such disease. When the cancer is mostly in the blood, the disease is considered CLL. It is considered SCLL when the cancer is mainly in the lymph nodes. In addition, CLL can transform into a high-grade or aggressive non-Hodgkin’s lymphoma (Richter syndrome).

Precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma is another example. The disease can be classified as lymphoma or leukemia, depending on the amount of bone marrow cells which are lymphoma cells. When more than 25 percent of the bone marrow is involved, the disease is classified and treated as leukemia, whereas lymphoma involves less bone marrow. There is also another group of leukemias unrelated to lymphomas called myeloid and monocytic leukemias.

Ongoing research about lymphomas

There is a considerable amount of research being conducted on lymphoma by various groups, including the Lymphoma Research Foundation. Clinical trials are underway to further understand causes, treatment and prevention of the disease. Some of the most promising areas in lymphoma research include:

  • Better classification of the diseases
  • Role of genetics in lymphoma
  • Improvement of monoclonal antibody therapy
  • Use of other advanced biological therapies
  • New chemotherapy drugs and drug combinations
  • Improved treatments with fewer side effects
  • Development of tumor-specific vaccines
  • Use of immune-cell therapy
  • Advancing stem cell transplantation

Questions for your doctor about lymphomas

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their condition. Patients may wish to ask their doctor the following questions about lymphomas:

  1. What are the different types of lymphoma?

  2. What is the difference between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma?

  3. Do I have any conditions that place me at greater risk for lymphoma?

  4. What tests will be used to diagnose my condition?

  5. What type of lymphoma do I have?

  6. Where did my lymphoma start?

  7. Can you determine if the lymphoma has spread elsewhere in my body?

  8. What are my treatment options for this type of lymphoma?

  9. What are the risks with these treatments?

  10. What type of specialists will I need to see?

  11. What is the prognosis for my form of lymphoma?

  12. Does my lymphoma place me at higher risk for other cancers?

  13. After my lymphoma is treated, what are the chances it will return?

  14. How will my lymphoma be monitored?

  15. Are my children at greater risk for lymphoma if I have it?
  16. Can you recommend a support group?
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