Lymphoma



Last Review Date: August 28, 2020


What is it?

Lymphomas are cancers of the lymphoid cells, a particular type of white blood cell which fight infection and monitor the immune system. Lymphomas form solid tumours found in lymph nodes and all other parts of the body. Lymph nodes are commonly involved because this is the part of the body where lymphocytes carry out their main functions. Lymphoma is distinguished from leukaemia by the lymphoid cells of leukaemia which are easily found in the peripheral blood whereas this occurs rarely and usually only in very advanced stages of lymphoma.

Lymphoma is not a single disease but rather a number of diseases grouped together because of the abnormality in the lymphoid cell and how patients present when they have these diseases.  Over the centuries, these diseases have been described and re-described, grouped in one way and then another, leading to confusion and contradictory naming conventions. 

The current convention is to categorise each lymphoma by its lymphoid cell type through a series of diagnostic tests. These are grouped under the main umbrella lymphoid neoplasms. Lymphoid neoplasms are then divided into three major categories, Mature B-cell neoplasms, Mature NK-cell/T-cell neoplasms and Hodgkin lymphoma. Figure 1 below shows the current classification. Although the category non Hodgkin lymphoma is not part of the current classification system, the term still remains in frequent use and has been included in the diagram for clarity.

 

Figure 1: Classification of lymphomas


Lymphatics and Lymph Node Structure

The lymph system consists of a series of vessels, similar to blood vessels, and larger areas called nodes or nodules. These lymphatic vessels are spread throughout the body and carry 'lymph', an off-white fluid that is filled with lymphocytes, the cells that control the immune system and fight infections. The lymphatics enter nodes of varying size and importance and then leave to complete the circuit. The lymphocytes can leave the lymphatics to enter the blood stream and return to the lymphatics at any time.

Lymph nodes can be found throughout the body, including in the neck, armpits, abdomen, pelvis, and all the way down to the feet. In addition, there are other lymph tissue that plays a role in the immune system and this includes the tonsils and adenoids, thymus, bone marrow, spleen, and areas in the gastrointestinal tract.

There are several different types of cells present in any node and any one of these cells or a combination of them can be involved in lymphoma. Within a normal lymph node, one might find mature (functional) lymphocytes, immature lymphocytes, macrophages (cells that can ingest bacteria, viruses and damaged cells), and dendritic cells (specialised cells that help lymphocytes to function). Knowing which particular cells are involved is relevant to diagnosis.

Two of the most common cells within lymph nodes are called T and B cells. 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 neutralise several different types of foreign attackers. B lymphocytes make antibodies. It is these cells that you are training to respond to an attack when you get immunised against diseases, such as measles, mumps or hepatitis. T cells can attack on their own while B cells need T cells to help them.


Recognising Lymphoma

 


People with lymphoma may experience 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 appetitte
  • Itchiness
  • Neck or flank pain
 

However, lymphoma is difficult to diagnose because these signs and symptoms are usually mild. 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 because they may be confined to areas inside the chest or abdomen.

Tiredness, loss of appetite and a general sense of not feeling well are very common complaints but are not specific and cannot be used as a sole basis of diagnosis. Therefore, the usual method of diagnosis is to take a biopsy of the node and have a pathologist examine it.


Hodgkin's lymphoma

In 1832, Thomas Hodgkin described a malignant disease of the lymph nodes. In 1898 a characteristic abnormal cell - the Reed-Sternberg cell - was identified. Hodgkin's lymphoma (HL) is seen most often in two age groups: those between 20-40 years of age and in those over 55 years of age. It is slightly more common in males than in females.

HL can be subdivided based on the structure of the abnormal lymph node and the types of cells that are present. As shown in figure 1 there are two main categories of Hodgkin lymphoma, nodular lymphocyte-predominant HL and Classical HL (CHL). CHL is further divided into 4 subgroups, nodular sclerosis CHL; mixed cellularity CHL, lymphocyte rich CHL and lymphocyte depleted CHL.

The diagnosis is made by examination of an involved lymph node. This requires careful examination under a microscope of both the structure of the lymph node and the cells it contains. The individual cells are then stained to see if they have particular antigens on their cell surface or sometimes inside the cells. The presence or absence of these antigens can distinguish between T cells, B cells and various cancer cells. 

Once a diagnosis of lymphoma has been confirmed the stage of the disease must be made using either computed tomography (CT) or Positron emission tomography (PET) scans. Patients are scanned from the neck to the pelvis to show all the places in the body that the lymphoma has spread to. A bone marrow biopsy is also done to check if the lymphoma has spread to the bone marrow, although this is very uncommon. Patients are given one of the following stages I, II, III, III1, III2, or IV according to the sites of the lymphoma. The type of HL, the stage, results of other blood tests and how the lymphoma looks on the scan as well as some patient factors such as age provide information to help with treatment and prognosis.

Treatment is with chemotherapy and usually radiotherapy. Some early stage lymphomas can be treated with radiotherapy alone.


Non-Hodgkin’s lymphoma (NHL): Mature B-cell neoplasms and Mature NK-cell/T-cell neoplasms

As shown in figure 1 the current classification for NHL is into either Mature B-cell neoplasms or Mature NK-cell/T-cell neoplasms. The term Non-Hodgkin’s lymphoma (NHL) is no longer part of the classification system, however it is still used commonly to identify lymphomas that are not HL. In this group it is possible to have lymphoma with changes in the mature lymphocytes, in the immature lymphocytes, in the macrophages, in the dendritic cells, or in a combination of these cells.

Mature B-cell neoplasms

Some neoplasms in this group are categorised as chronic leukaemias such as chronic lymphocytic leukaemia; B-cell prolymphocytic leukaemia; hairy cell leukaemia and are discussed briefly in the leukaemia section. The difference is that the abnormal cells are present mainly in the peripheral blood and bone marrow in leukaemia rather than mostly in the lymph nodes as in lymphoma.

There are over 20 additional types of Mature-B cell neoplasms. The diagnosis of each is made through a study of the type of abnormal cell by identifying surface antigens and their location throughout the body or how the abnormal cells distribute within a lymph node. Some neoplasms have specific genetic abnormalities which can be detected by chromosomal or other genetic studies.

Once a diagnosis of lymphoma has been confirmed the stage of the disease must be made using either computed tomography (CT) or Positron emission tomography (PET) scans. A bone marrow biopsy is also done to check if the lymphoma has spread to the bone marrow.  This is more common in some of the mature B-cell neoplasms then in others.

There are a range of treatments available for the mature B-cell neoplasms and the treatments are targeted to specific diagnoses.  Ensuring the correct diagnosis is made can sometimes be difficult but is very important for selecting treatment options. 

Mature T-cell and NK-cell neoplasms

Some neoplasms in this group are categorised as chronic leukaemias such as T-cell prolymphocytic leukaemia and are discussed briefly in the leukaemia section.  Their distinction is that the abnormal cells are present predominantly in the blood and bone marrow rather than mostly in the lymph nodes, although both occur.

There are over 20 additional types of Mature-T cell and NK-cell and diagnosis is made in the same way as the mature B-cell neoplasms.  

Once a diagnosis of lymphoma has been confirmed the stage of the disease must be made using either computed tomography (CT) or Positron emission tomography (PET) scans. Patients are scanned from the neck to the pelvis to show all the places in the body that the lymphoma has spread to. A bone marrow biopsy is also done to check if the lymphoma has spread to the bone marrow. 

There are a range of treatments available for the mature T-cell and NK-cell neoplasms and these are targeted to specific diagnoses. Ensuring the correct diagnosis is made can sometimes be difficult but is very important for selecting treatment options just as it is with other types of leukaemia.


Laboratory tests

In the clinical laboratory, there are few tests that clearly indicate the presence of lymphoma. The full blood count (FBC) may be used to exclude diseases other than lymphoma (such as leukaemia) or to see if anaemia or low platelet and/or white blood cell counts are present, which may indicate that lymphoma is present in the bone marrow. There is only one true diagnostic test for lymphoid neoplasms and that is for a pathologist to examine lymph tissue (usually from a lymph node) obtained by biopsy or fine needle aspiration.

Additional lymphoid tissue can be examined by further techniques.

Flow cytometry is another technique that can categorise cells by testing for the presence or absence of cell markers. These markers are called clusters of differentiation (CD) and each antigen is allocated a number, for example CD20, CD10 etc. The pattern of CDs present on the cells helps to classify the lymphoma. 

Immunohistochemistry is the technique of demonstrating antigens on cells in histological tissue sections.

Chromosome studies may show abnormalities specific for a type of lymphoma, for example, follicular lymphoma shows a translocation between two different chromosomes, 14 and 18, denoted t(14;18). Studies using a technique called Fluorescent In-Situ Hybridisation (FISH) uses chromosome 'paints' to mark when specific genes are missing, have extra copies or are joined together in the wrong way.

Other genetic studies using the Polymerase Chain Reaction (PCR) which replicates strands of DNA, bring greater sensitivity and can look for specific genes joined together in the wrong way, or for those with subtle defects in their DNA. For example see: B-cell Immunoglobulin Gene Rearrangement and T-cell Receptor Gene Rearrangement.

Once a diagnosis of a lymphoid neoplasm is made, the stage of the disease is determined with the use of either computed tomography (CT) or Positron emission tomography (PET) scans. A bone marrow biopsy is also done to check if the lymphoma has spread to the bone marrow.


The best treatment of lymphoma depends on its type, stage and other factors and needs to be tailored for individual patients.

Slow growing (low grade) lymphomas may require either, no treatment or surgery, radiotherapy or gentle chemotherapy (often in tablet form). Faster growing (intermediate or high grade) lymphomas usually require injected chemotherapy with or without radiotherapy.

Hodgkin’s disease usually requires injected chemotherapy and/or radiotherapy.


On this site
Tests: FBCplatelet countWBCbone marrow biopsyblood film

Elsewhere on the web
Leukaemia Foundation
Lymphoma Australia
Cancer Council Victoria

 
REFERENCES
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition
WHO Classification of Tumours, Volume 2
IARC WHO Classification of Tumours, No 2