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This article waslast modified on 4 February 2019.
Lymphatics and Lymph Node Structure

The lymph system consists of a series of vessels, similar to blood vessels, and nodules called lymph nodes. The lymphatic vessels are spread throughout the body and carry lymph, a milky fluid filled with lymphocytes, the cells that control the immune system. The lymphatics pass through lymph nodes as they circulate through the lymphatic system. The lymphocytes can also leave the lymphatics to enter the blood stream and tissues and return to the lymphatics at any time.

Lymph nodes can be found throughout the body, including in the neck, armpits, middle of the chest, and back of the abdomen. Additional lymphoid tissue can be found in the tonsils, adenoids, thymus, bone marrow, spleen, lung, and areas in the gastrointestinal tract.

What is lymphoma?
Lymphoma is a tumour of lymphocytes. There are several different types of lymphocytes, the major types being the B-lymphocyte and the T-lymphocyte.

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’s 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 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 usually begins with the production of one or more abnormal cells in one or more of the lymph nodes, areas where lymphocytes congregate. 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.


Accordion Title
About Lymphoma
  • Signs and Symptoms

    Patients who have lymphoma may experience painless swelling of the lymph nodes in the armpits, neck, and/or groin. They may experience fatigue, fever, unexplained drenching night sweats, unintended weight loss, a loss of appetite, or itchiness. If the lymph node is in the chest, it may affect the person’s breathing; if it is in their abdomen, it can cause abdominal discomfort. Lymphoma can sometimes be difficult to diagnose because the signs and symptoms are often mild or non-specific. Some patients 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 patient or physician.


  • Types

    There are two primary types of lymphoma: Hodgkin lymphoma (HL, also called Hodgkin’s disease), which is characterized by the presence of large distinctive cells called Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL), a large group of about 30 other lymphomas.

    Hodgkin Lymphoma
    Hodgkin lymphoma is most prevalent in two age groups: in those between about 25 and 35 years of age and in those over 55.

    Historically, Hodgkin lymphoma was divided into several subtypes (nodular lymphocyte-predominant, nodular sclerosing, mixed cellularity and lymphocyte-depleted). Nowadays the important distinction is between classical HL (cHL), which has some distinctive features, and nodular lymphocyte-predominant HL (nodular LPHD). LPHD behaves quite differently from cHL, and could be thought of as a low-grade non-Hodgkin lymphoma.

    Non-Hodgkin Lymphoma
    Non-Hodgkin lymphoma is the sixth most common cancer in the UK. The incidence of NHL increases with age and is higher in patients with HIV/AIDS and in patients whose immune systems are suppressed. According to Cancer Research UK, in the UK, about 10,000 people are diagnosed with non-Hodgkin lymphoma in one year.

    There are about 30 different types of non-Hodgkin lymphoma. Over the years, different classification systems have been used to describe the different types of non-Hodgkin lymphoma as knowledge about the condition has grown. New methods of evaluating the cells involved in non-Hodgkin lymphoma have led to changes in classification systems.

    The Revised European American Lymphoma (REAL) looks at the function that the cell should be providing. Some lymphocytes (B-lymphocytes) are responsible for producing antibodies while others (T-lymphocytes) are responsible for cell-to-cell interactions. The newest method, the World Health Organization or WHO Classification, tries to combine all of these characteristics with genetic studies of the cells. Click here to view a table of classifications.

    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. B-cell non-Hodgkin lymphomas are much more common than T-cell. 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 33% of all non-Hodgkin lymphomas. It is a fast growing lymphoma and can affect anyone of any age but occurs mostly in people over 60.
    • Follicular lymphomas: these make up about 16% of non-Hodgkin’s lymphoma in the UK. This may be a very slow growing lymphoma.
    • B cell chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL): these are identical diseases because they affect the same cell. CLL is found mainly in the bone marrow and the circulating 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 (leukaemia): a disease that can be considered either a lymphoma or leukaemia depending on whether affected cells are found in the blood or whether a certain percentage of bone marrow cells are abnormal. 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.
    • Mycosis fungoides (Sézary syndrome), are types of cutaneous T-cell lymphoma: These are less common forms of lymphoma, unusual because, while most lymphomas begin in lymphoid tissue or internal organs, they start in the skin.


  • Staging

    Because more than one lymph node or other area can be involved, it is important to find out how extensive a lymphoma is. This process is called staging. The following table contains an example of the “Ann Arbor” staging classification system that describes how widespread the disease is. Ann Arbor staging is more useful in Hodgkin than in non-Hodgkin lymphoma.

    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.
    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). An example of this would be the tonsils and one underarm lymph node.
    III Stage III occurs when there is involvement on both sides of the diaphragm, such as a node in the neck and another in the abdomen.
    IV Stage IV has involvement throughout the body and, in particular, in major sites such as the bone marrow.

    A more useful staging system for prognosis is the “International Prognostic Index” of IPI. This scores one point each for

    • Age over 60
    • Ann Arbor stage 3 or 4 disease
    • More than one non-nodal site involved (for example, bone marrow, liver or lung)
    • High serum LDH
    • an ECOG score greater than 1 (feeling unwell enough to spend a proportion of the day in bed resting).

    Staging allows the physician to determine what choices of therapy are available. For example, localised disease may be cured by surgery or radiotherapy, with or without chemotherapy. More advanced disease may require chemotherapy. In some circumstances, chemotherapy may also have to be given into the fluid around the spinal cord (intrathecal chemotherapy, by lumbar puncture) to reduce the risk of spread of lymphoma to the brain.

    The most commonly used staging tests performed in the clinical laboratory are the FBC, liver and kidney function studies, and bone marrow biopsy. Non-laboratory tests may include ultrasound, CT, MRI and PET scans.


  • Testing

    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.

    The gold standard diagnostic test for both HL and NHL is the examination of lymph tissue by a pathologist (specialist). The sample is usually collected from an affected lymph node using a biopsy or fine needle aspiration procedure and is examined under the microscope. Other laboratory tests that may be useful include:

    Laboratory Tests

    • Full blood count (FBC) - may be requested to rule out non-lymphoma conditions (such as leukaemia) and/or to see if anaemia or low platelet and/or white blood cells counts are present, which may indicate that lymphoma is present in the bone marrow. 
    • Bone marrow biopsy and examination – to evaluate the cells present in the bone marrow.
    • Blood film to evaluate the quality of red and white blood cells and platelets
    • Immunophenotyping (or “cell markers” can identify the cells involved by testing for the presence or absence of surface markers on the membrane of the cells. These markers are called clusters of differentiation (CD) and are listed numerically. By evaluating the patterns of 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.
    • Cytogenetics – an evaluation of the chromosomes in the nucleus of cancer cells to determine if pieces of the chromosomes have moved (translocation) or are otherwise abnormal.
    • Molecular genetic analysis – evaluating the cancer cell’s DNA for genetic changes.

    Non-Laboratory Tests
    Primarily used to help stage and monitor lymphoma. They include:

    • Physical examination
    • Ultrasound scan
    • Computed tomography (CT) scan
    • Positron emission tomography (PET) scan
    • Chest X-ray
    • Exploratory surgery (occasionally necessary)
    • Magnetic Resonance Imaging (MRI)


  • Treatment

    Each lymphoma is unique; some are more aggressive than others. The best treatment of lymphoma depends on its type, stage and other factors and needs to be tailored for for individual patients.

    Slow growing (low grade) lymphomas may require either no treatment or surgery, radiotherapy or gentle chemotherapy (often in tablet form). Some stomach lymphomas can be cured with simple antibiotics. Faster growing (intermediate or high grade) lymphomas usually require injected chemotherapy with or without radiotherapy.
    Hodgkin’s lymphoma usually requires injected chemotherapy and/or radiotherapy.

    In some cases, high dose chemotherapy followed by stem cell transplantation may be used. Prognosis depends on the stage and grade of the disease and the general health of the patient. All patients, even those whose lymphoma has been “cured” or put into remission, must be monitored for a period of time, often 5 years, and sometimes the rest of their lives. Many never experience lymphoma again but in others, it may recur years after the first incidence.


  • Comparison Table

    The following table illustrates the two most commonly used classifications plus an older classification. Because of differences in how the lymphomas are described, there is not a one-to-one comparison between the systems, and a single disease could be known by multiple names.

    Comparison of Some Non-Hodgkin Lymphoma Classifications
    Note: These classifications cannot always be compared

    Comparison of Some Non-Hodgkin Lymphoma Classifications

    Note: These classifications cannot always be compared.
    NCI* (Working   Formulation) (Older Classification) REAL** WHO*** Classification
      B cell lineage/NHL Mature B cell lymphoma
    Low grade lymphoma
    Small lymphocytic lymphoma (plasmacytoid)
    Follicular lymphoma (small cleaved cell, large cell, mixed cell)        

    High Grade lymphoma
    Diffuse lymphoma (small  cleaved, large, mixed cell)
    Diffuse immunoloblastic lymphoma 
    Burkitt Lymphoma
    Burkitt-like Lymphoma Lymphoblastic lymphoma
    B-cell chronic lymphocytic leukaemia      
    Lymphoplasmacytic lymphoma            
    Nodal and extranodal marginal B-cell lymphoma               

    Follicular Center, grades I, II, and III lymphoma 

    Mantle Cell lymphoma
    B cell CLL / SLL 
    Splenic marginal zone B-cell lymphoma
    Extranodal marginal B cell lymphoma  

    Follicular lymphoma                       

    Mantle cell lymphoma 
    Diffuse large B-cell lymphoma        
    Burkitt’s lymphoma
    T and NK Cell Neoplasms   T and NK Cell Neoplasms
        Mature T cell lymphoma
    Small lymphocyte lymphoma

    Mycosis Fungoides

    Diffuse lymphoma (small cleaved, large, mixed cell) 

    Large cell immunoblastic lymphoma
      Adult T cell lymphoma    

    Mycosis fungoides

    Anaplastic large cell  lymphoma not otherwise characterised

    Immunoblastic T cell lymphoma
        Langerhans cell histiocytosis

    Langerhans cell sarcoma

    Interdigitating dendritic cell sarcoma/tumour

    Follicular dendritic cell sarcoma/tumour

    Dendritic cell sarcoma, not otherwise specified
    * NCI = National Cancer Institute
    ** REAL = Revised European American Lymphoma
    *** WHO = World Health Organisation