Also Known As
Hodgkin Lymphoma
HL
Hodgkin Disease
Non-Hodgkin lymphoma
NHL
This article was last reviewed on
This article waslast modified on June 12, 2018.
What is lymphoma?

Lymphoma is a cancer of certain types of white blood cells (WBCs) called lymphocytes that localize in one or more lymph nodes. Lymphocytes circulate throughout the body in both the blood and the lymphatic system. The lymphatic system consists of a network of lymph nodes and vessels (lymphatics) that drain fluids from the tissues and carry them as "lymph" through the body and back to the bloodstream. Lymph nodes are found singly and in chains along the lymphatic vessels, in areas that include the neck, armpits, chest, abdomen, and groin. The nodes are small lymphoid tissue organs that filter lymph fluid as it passes through them and destroy microorganisms and abnormal cells. They contain macrophages and collections of lymphocytes, including B-lymphocytes, T-lymphocytes, and natural killer cells. Photo: Lymphatic system, Source: National Cancer Institute

T-lymphocytes can be thought of as the controllers of the immune system. They initiate the immune response, control how big or small it should be, and shut it down when it is not needed. In addition, they can neutralize several different types of foreign attackers. B-lymphocytes make antibodies. It is these cells that are activated when a person is vaccinated against diseases such as measles, mumps, or hepatitis. Natural killer (NK) cells are also a type of lymphocyte and make up about 10-15% of total lymphocytes in the blood. NK cells attack and "kill" abnormal cells such as cancer cells or those infected with viruses.

Any one of these cells or a combination of them can be involved in lymphoma. Lymphoma begins with the emergence of abnormal cells in one or more of the lymph nodes or lymphoid tissues. These cells reproduce uncontrollably, begin to outnumber normal cells in the node, lead to the enlargement of the lymph node, and eventually travel to one or more other lymph nodes. They may also spread to and from other lymph-system-related organs including the spleen, bone marrow, tonsils, adenoids, and thymus.

B-cell lymphomas are more common than T-cell lymphomas. For more about specific lymphomas, read the sections below.

Accordion Title
About Lymphoma
  • Signs and Symptoms

    People who have lymphoma may experience painless swelling of the lymph nodes in the armpits, neck, or groin and/or enlargement of the spleen. They may also be found to have an increase in abnormal lymphocytes in the blood. Those with lymphoma may experience other signs and symptoms such as:

    • Fatigue
    • Fever and chills
    • Night sweats
    • Unexplained weight loss (as much as 10% of body weight or more)
    • Loss of appetite
    • Itchiness
    • Neck or flank pain

    If the affected lymph node is in the chest, it may affect the person's breathing; if it is in the abdomen, it can cause abdominal discomfort. Lymphoma can sometimes be difficult to diagnose because these signs and symptoms are often mild. Some people may have no noticeable signs while others might have a low-grade fever. Usually there are swollen lymph nodes, but the node may not be visible or felt by the person or a healthcare provider.

  • Hodgkin Lymphoma

    Hodgkin lymphoma (HL, also called Hodgkin's disease), which is characterized by the presence of large distinctive cells called Reed-Sternberg cells. 

    Hodgkin lymphoma is most prevalent in two age groups: in those between about 20 and 40 years of age and in those over 55. According to the American Cancer Society (ACS), about 9,000 people in the United States are diagnosed with Hodgkin lymphoma each year and about 1,300 people die of it.

    There are many different theories concerning the cause of HL. Some think that a type of infectious agent, such as a virus, might be involved. Others think that a mutation in a cell is the cause. While this is an area of active research, specific causes have not yet been identified. Likewise, there is no clear understanding of why males seem to be slightly more susceptible to the disease.

    HL can be subdivided based on the structure of the abnormal lymph node and the types of cells that are present. Lymph nodes may have a predominance of small lymphocytes, the presence of bands of scarring (fibrosis), a mixture of different cell types, or lymphocyte depletion. In HL, tumor cells (so-called Reed-Sternberg cells) are the minority, while the majority is a benign, often mixed, reactive cell population.

  • Non-Hodgkin Lymphoma

    Non-Hodgkin lymphoma represents just over 4% of all new cancer cases in the United States. It is slightly more common in men than women and more common in Caucasians. The incidence of NHL increases with age and is higher in those with HIV/AIDS and in people whose immune system is suppressed.

    According to the ACS, non-Hodgkin lymphoma accounts for about 4% of all cancers. About 72,000 people are diagnosed with non-Hodgkin lymphoma per year and about 20,000 people die from it. Incidence rates of NHL have almost doubled since the 1970s. The reasons for this are not yet known, but the greatest increase has been in women. However, death rates from non-Hodgkin lymphoma have been decreasing since the late 1990s.

    There are many types of non-Hodgkin lymphoma and as knowledge about them grows, the systems used to classify them has evolved. New methods of evaluating the cells involved in non-Hodgkin lymphoma have led to changes in classification systems.

    In the 1990s, the Revised European American Lymphoma (REAL) classification was proposed by the International Lymphoma Study Group and adopted by many physicians. It looked at the function that the cell should be providing. B-lymphocytes are responsible for producing antibodies, for instance, while T-lymphocytes are responsible for cell-to-cell interactions. The newest method, the World Health Organization or WHO Classification, combines these characteristics with phenotypic and genetic studies of the cells. The WHO classification expanded on REAL and has been accepted by many as the current standard.

    Some Types of Non-Hodgkin Lymphomas
    Classification of non-Hodgkin lymphomas can be confusing because there are so many different types and because of the various classification systems that have been developed and amended over the years. In the United States, B-cell non-Hodgkin lymphomas are much more common than T-cell and NK-cell lymphomas. About 85% of non-Hodgkin lymphomas involve mature B-lymphocytes with about 15% affecting T-lymphocytes.

    Some of the more common forms of B-cell lymphomas include:

    • Diffuse large B-cell lymphoma (DLBCL): this form constitutes about one in three cases of all non-Hodgkin lymphomas in the United States. It is a fast-growing lymphoma and can affect anyone of any age but occurs mostly in older people.
    • Follicular lymphomas: these make up about one in five of all lymphomas in the U.S. This is generally a very slow-growing lymphoma, but over time about one in three turns into a fast-growing DLBCL.
    • B cell chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL): this is a slow-progressing disease in which the lymphoma cells are predominantly small in size. CLL / SLL is the same disease; however, CLL mainly involves the bone marrow and the blood while SLL is found mainly in the lymph nodes. These two together make up approximately 24% of all lymphomas.
       

    Some of the more common forms of T-cell lymphomas include:

    • Precursor T-lymphoblastic lymphoma (leukemia): a disease that can be considered either a lymphoma or leukemia depending on whether affected cells are found in the blood and/or in the bone marrow. About 1% of all lymphomas are this type.
    • Mature or peripheral T-cell lymphomas: there are many different kinds of mature T-cell lymphomas that all together make up about 4% to 5% of all lymphomas.
    • Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome, and others): these are less common forms of lymphoma but are unusual because, while most lymphomas begin in lymphoid tissue or internal organs, these types start in the skin. This group of skin cancers makes up less than 1% of nonmelanoma skin cancers. Skin lymphomas make up 5% of all lymphomas.
  • Tests

    The goals with testing are to diagnose and stage lymphoma, to distinguish it from other conditions, and to identify and monitor any associated complications. There are few blood tests that clearly indicate lymphoma.

    Laboratory tests

    The gold standard diagnostic test for both Hodgkin lymphoma and non-Hodgkin lymphoma is the examination of involved lymph nodes or lymphoid tissue by a pathologist. The sample is usually collected from an affected lymph node or tissue using a biopsy or fine needle aspiration procedure and is examined under the microscope. (To learn more about biopsies, read the article on Anatomic Pathology.)

    Other laboratory tests that may be useful include:

    • Complete blood count (CBC) – may be ordered to rule out non-lymphoma conditions (such as leukemia) and/or to see if anemia is present. A CBC can determine if the platelet count and/or white blood cell count are low, which may indicate that lymphoma is present in the bone marrow and/or blood.
    • Bone marrow biopsy and examination – used to evaluate the cells present in the bone marrow. The presence of abnormal lymphoid cells and/or lymphoid aggregates may be seen with lymphoma.
    • Blood smear – used to evaluate the quality of red and white blood cells and platelets as well as abnormal cells (lymphoma cells, for example), if present.
    • Immunophenotyping can identify the cells involved by testing for the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. By developing a list of the CDs present on the cells, it is possible to classify the cells. This test can be done by several different methods, including flow cytometry and immunohistochemistry.
    • Chromosome analysis – an evaluation of the chromosomes in the nucleus of cancer cells to determine if pieces of the chromosomes have moved (translocation). This is rarely used for lymphomas. 
    • Molecular genetic analysis – evaluating the cancer cell's DNA for genetic changes, particularly to determine whether all of the cells belong to a single clone. (See B-cell Immunoglobulin Gene Rearrangement and T-cell Receptor Gene Rearrangement.)
    • If it is thought that lymphoma has spread (metastasized) to other areas of the body, analysis of cerebrospinal fluid or other body fluids may be performed. 
    • Beta-2 microglobulin – this test may be used to help predict the prognosis.
    • Serum creatinine – levels may be elevated if a kidney disease called nephrotic syndrome is associated with Hodgkin lymphoma
    • Serum chemistry studies, including lactate dehydrogenase (LDH) – to help determine the prognosis
    • Hepatitis B – this testing is done for patients who will undergo rituximab therapy because there are negative side effects associated with that treatment and hepatitis B
    • Human immunodeficiency virus (HIV) testing – this is recommended because treating people with antiretroviral can improve their lymphoma outcome if they have HIV
       

    Non-laboratory tests
    Primarily used to help stage and monitor lymphoma, non-laboratory tests include:

    • Physical examination
    • Computed tomography (CT) scans
    • Positron emission tomography (PET) scan
    • Chest X-ray
    • Exploratory surgery (occasionally necessary)
    • Magnetic resonance imaging (MRI)

    For more on these imaging studies, visit RadiologyInfo.org.

  • Staging

    Because more than one lymph node can be involved, it is important to find out which ones are affected and where they are located in the body. This process is called staging. The following table contains an example of a classification system that describes how widespread the disease is. The Ann Arbor staging system is most commonly used for non-Hodgkin lymphoma in adults.

    Stages Found in Lymphomas

    Stage Description
    I Stage I occurs when there is a single lymphoid area (such as the spleen), a pair of areas (tonsils), or a group of related areas (the tonsils and adenoids) involved. It also occurs when cancer is found only in one area of a single organ outside of the lymph system.
    II Stage II occurs when there are two or more lymphoid areas involved, but they are on the same side of the diaphragm (the muscle under the rib cage that controls breathing and separates the chest and abdomen). An example of this would be the tonsils and one underarm lymph node. It also occurs when the lymphoma extends from a single lymph node group into a nearby organ, or when it affects groups of lymph nodes on the same side of the diaphragm.
    III Stage III occurs when there is involvement on both sides of the diaphragm (above and below), such as a node in the neck and another in the abdomen. It also occurs if the cancer has spread into an area or organ next to the lymph nodes, into the spleen, or both.
    IV Stage IV has involvement throughout the body and, in particular, in major sites such as the bone marrow.

    Staging allows the health practitioner to determine what choices of therapy are available. For example, if a person has Stage I with only one node involved, then surgically removing that node may result in a cure. On the other hand, if the person is at Stage IV, then surgical removal is not generally possible.

    The most commonly used staging tests performed in the clinical laboratory are the complete blood count (CBC), liver and kidney function studies, and bone marrow biopsy. Non-laboratory tests include CT scans, MRI evaluations, and X-ray procedures.

  • Treatment

    Each lymphoma is unique; some are more aggressive than others. The healthcare provider will "grade" the cancer based on its apparent aggressiveness. This information, along with the type and location(s) of the lymphoma, are used to guide treatment. The ultimate goal of treatment is to cure the affected person. When a cure is not possible, the goals are to put the lymphoma into remission for as long as possible, slow it down, relieve symptoms, and minimize and address complications. 

    Lymphoma treatment often uses combinations of cancer chemotherapy with or without radiation therapy. For some cases, high-dose chemotherapy followed by stem cell transplantation may be used. Prognosis depends on the type, stage and grade of the disease and the general health of the person. All people diagnosed with lymphoma, even those whose lymphoma has been "cured" or put into remission, must be monitored for the rest of their lives. Many never experience lymphoma again but in others, it may recur years after the first incidence.

  • World Health Organization classifications

    2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues

    Mature B-cell lymphoma
    Chronic lymphocytic leukemia/small lymphocytic lymphoma
    B-cell prolymphocytic leukemia
    Splenic marginal zone lymphoma
    Hairy cell leukemia
    Splenic lymphoma/leukemia, unclassifiable*
       Splenic diffuse red pulp small B-cell lymphoma*
       Hairy cell leukemia variant*
    Lymphoplasmacytic lymphoma
    Waldenström macroglobulinemia
    Heavy chain diseases
       Alpha Heavy chain disease
       Gamma Heavy chain disease
       Mu Heavy chain disease
    Plasma cell myeloma
    Solitary plasmacytoma of bone
    Extraosseous plasmacytoma
    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)
    Nodal marginal zone lymphoma
       Pediatric nodal marginal zone lymphoma*
    Follicular lymphoma
       Pediatric follicular lymphoma*
    Primary cutaneous follicle centre lymphoma
    Mantle cell lymphoma
    Diffuse large B-cell lymphoma (DLBCL), not otherwise specified
       T-cell/histiocyte rich large B-cell lymphoma
       Primary DLBCL of the CNS
       Primary cutaneous DLBCL, leg type
       EBV-positive DLBCL of the elderly*
    DLBCL associated with chronic inflammation
    Lymphomatoid granulomatosis
    Primary mediastinal (thymic) large B-cell lymphoma
    Intravascular large B-cell lymphoma
    ALK-positive large B-cell lymphoma
    Plasmablastic lymphoma
    Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease
    Primary effusion lymphoma
    Burkitt lymphoma
    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma
    Mature T-cell and NK-cell neoplasms
    T-cell prolymphocytic leukemia
    T-cell large granular lymphocytic leukemia
    Chronic lymphoproliferative disorder of NK cells*
    Aggressive NK-cell leukemia
    Systemic EBV-positive T-cell lymphoproliferative disease of childhood
    Hydroa vacciniforme-like lymphoma
    Adult T-cell leukemia/lymphoma
    Extranodal NK/T-cell lymphoma, nasal type
    Enteropathy-associated T-cell lymphoma
    Hepatosplenic T-cell lymphoma
    Subcutaneous panniculitis-like T-cell lymphoma
    Mycosis fungoides
    Sézary syndrome
    Primary cutaneous CD30+ T-cell lymphoproliferative disorders
       Lymphomatoid papulosis
       Primary cutaneous anaplastic large cell lymphoma
    Primary cutaneous γδ T-cell lymphoma
    Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma*
    Primary cutaneous CD4+ small/medium T-cell lymphoma*
    Peripheral T-cell lymphoma, not otherwise specified
    Angioimmunoblastic T-cell lymphoma
    Anaplastic large cell lymphoma, ALK-positive
    Anaplastic large cell lymphoma, ALK-negative*
    Hodgkin lymphoma
    Nodular lymphocyte predominant Hodgkin lymphoma
    Classical Hodgkin lymphoma
        Nodular sclerosis classical Hodgkin lymphoma
        Lymphocyte-rich classical Hodgkin lymphoma
        Mixed cellularity classical Hodgkin lymphoma
        Lymphocyte-depleted classical Hodgkin lymphoma
    Histiocytic and dendritic cell neoplasms
    Histiocytic sarcoma
    Langerhans cell histiocytosis
    Langerhans cell sarcoma
    Interdigitating dendritic cell sarcoma
    Follicular dendritic cell sarcoma
    Fibroblastic reticular cell tumor
    Intermediate dendritic cell tumor
    Disseminated juvenile xanthogranuloma
    Posttransplantation lymphoproliferative disorders (PTLDs)
    Early lesions
       Plasmacytic hyperplasia
       Infectious mononucleosis–like PTLD
    Polymorphic PTLD
    Monomorphic PTLD (B- and T/NK-cell types)†
    Classical Hodgkin lymphoma type PTLD†

    ALK, anaplastic lymphoma kinase; HHV8, human herpesvirus 8; and NK, natural killer.
    *These histologic types are provisional entities for which the WHO Working Group felt there was insufficient evidence to recognize as distinct diseases at this time.
    †These lesions are classified according to the leukemia or lymphoma to which they correspond.

    Source: Campo E, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011 May 12; 117(19): 5019–5032.

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