These facts about lymphoma explain what type of blood cell cancer it is and include terminology that haematologists use when diagnosing lymphoma and discussing treatment options.
WHAT IS LYMPHOMA?
Lymphoma is a type of blood cancer that comes from the lymphoid tissue. The main cells of lymphoid tissue are lymphocytes. These are part of our immune system and play a very important role in protecting our body against infection and other diseases. Lymphocytes are present in blood and in lymphoid tissue throughout the human body. When lymphocyte development becomes abnormal, people may develop lymphoma. The main lymphoid tissue is present in lymph nodes (lymph glands), spleen, and bone marrow. Lymphoma usually develops in these sites, although it may affect any human organ.
There are many lymphocyte subtypes, with different functions and each one may give rise to a different type of lymphoma. The main subtypes of lymphocytes are B cells and T cells, both of which themselves have many subtypes. Most B cells are involved in production of antibodies, whilst T cells are involved both in direct destruction of infections and in the regulation of protection against infections. B cell lymphomas are more common (90%) than T cell lymphomas.
Each lymphoma subtype has its own natural course. Presenting symptoms, response to treatment and prognosis vary significantly among the different lymphoma subtypes.
WHAT CAUSES LYMPHOMA?
The exact cause of lymphoma is not known, but there are risk factors that may increase a person’s likelihood of developing lymphoma. Exposure to certain chemicals, including benzene, some pesticides, cigarettes and chemotherapy drugs used for cancer treatment increase the risk of developing lymphoma. Radiation including radiotherapy also increases the risk for lymphoma. Certain diseases of the immune system, including illnesses that impair the body’s ability to fight infection predispose to lymphoma. Also, certain infections may make people more susceptible. Viruses such as Epstein-Barr virus, HIV or Human T-lymphotropic virus (HTLV) increase the risk for lymphoma.
HOW DO I KNOW I HAVE LYMPHOMA?
Lymphoma often develops in lymph nodes: the lymph nodes swell and patients may notice lumps in the neck, underarms, groins or elsewhere. Sometimes patients develop fever, drenching night sweats and weight loss. There may also be loss of appetite and fatigue. All these together are called B symptoms. They are not specific for lymphoma. These symptoms may be seen in many other diseases, including infections and other cancers, so diagnosing lymphoma is not always straightforward. To reach a diagnosis, it is necessary to perform a biopsy of the affected lymph nodes or other affected lymphoid tissue. The biopsy result not only confirms the diagnosis, but also establishes the exact type of lymphoma. Sometimes, special genetic tests may also be required to reach an accurate diagnosis. This is very important, as lymphoma is not really a single type of cancer but rather a large group of distinct entities.
WHAT IS LYMPHOMA STAGING AND WHAT ARE THE MAIN TYPES OF LYMPHOMA?
The stage measures how widely has a lymphoma spread around the body. The Ann-Arbor staging system is the most commonly used and has four stages. Stages I and II are referred to as early stage and III and IV are considered advanced stages.
In addition to this the system uses the letter A for patients without significant night sweats, significant weight loss or lymphoma-associated fever, and the letter B for patient with these symptoms. The letter S is used for lymphoma that has spread to the spleen and the letter E if it has spread outside lymph nodes or spleen.
WHAT ARE THE MAIN TYPES OF LYMPHOMA?
There are two main types of lymphoma: Hodgkin lymphoma and Non-Hodgkin lymphoma. Each of these main types has many subtypes. All these can be distinguished by examining the biopsy sample.
Hodgkin lymphoma was named after Dr Thomas Hodgkin who described it in 1832. There are two major subtypes: Classical Hodgkin lymphoma, which is characterised by the presence of large cells called Hodgkin and Reed-Stenberg cells. These are abnormal cancer cells that are surrounded by inflammatory tissue. According to the appearance of this surrounding inflammatory tissue, different subtypes of classical Hodgkin lymphoma can be recognised. The rarer subtype of Hodgkin lymphoma is called nodular lymphocyte predominant Hodgkin lymphoma and this has slightly differently looking malignant cells called variant Reed-Stenberg cells or popcorn cells.
The treatment of Hodgkin lymphoma is very successful. Most patients, particularly those with early stage disease will be cured with chemotherapy alone or in combination with radiotherapy. A few patients may fail treatment or experience lymphoma relapses after the initial treatment. Many of these patients will be cured with further chemotherapy and a stem cell transplant.
The majority of patients with lymphoma are diagnosed with non-Hodgkin lymphoma. Like Hodgkin lymphoma this is not a single disease but a large group of very different cancers. Some of them are slow growing, indolent and may not even require any treatment. Other types can be very aggressive, fast growing and make patients unwell rapidly. Some types are well known to respond favourably to treatment and some are not. The subtypes are characterised by their appearance under the microscope, the pattern of proteins within the membranes of lymphoma cells and by changes in different genes. New types of rare lymphoma are still being described.
Most non-Hodgkin lymphomas are related to lymphocytes called B cells and are therefore called B cell lymphomas. Some lymphomas are related to T cells and rarely lymphomas can be related to other types of lymphocytes.
Common B cell lymphomas are:
- Diffuse large B cell lymphoma – this is the most common rapidly growing (aggressive) lymphoma. It can affect people of any age but is more common in older individuals. Treatment includes chemotherapy infused into the vein, often together with monoclonal antibodies (immunotherapy). Stem cell or bone marrow transplantation may sometimes be useful, particularly if the lymphoma relapses after initial treatment. Although aggressive lymphomas present with severe symptoms and complications, most patients will be cured with immunotherapy and chemotherapy.
- Marginal zone lymphoma – slow growing (indolent) lymphomas that affect older people. There are three subtypes of this lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma affects lymphoid tissue in stomach, bowels and endocrine glands. Sometimes a microorganism is responsible for causing MALT lymphoma. In these cases, treatment sometimes does not require chemotherapy but antibiotics may suffice. Nodal marginal zone lymphoma affects lymph nodes and splenic marginal zone lymphoma affects the spleen. Marginal zone lymphomas sometimes do not require therapy. If treatment is necessary it may be with localised radiotherapy or chemotherapy in combination with monoclonal antibodies.
- Follicular lymphoma – this is the most common type of slow growing (indolent) lymphoma. Follicle means a small sac, gland or an aggregate of cells and this type of lymphoma is called follicular because of the appearance of the affected lymph nodes under the microscope. Under magnification there are apparent aggregates or clumps of abnormal cells. (see figure below).
- Follicular lymphoma is more common in people aged over 50 years, but it can occur in people of any age. It usually grows slowly but occasionally it is known to change into fast growing diffuse large B cell lymphoma. This change is called transformation.
- Treatment of follicular lymphoma depends on its stage, the problems that it causes, but also on each individual patient’s fitness to cope with the side effects of chemotherapy and radiotherapy. Sometimes, if patients have no or only few medical complaints no treatment is needed. In stage I, radiotherapy to the affected lymph nodes offers a good treatment option with few side effects and can be suitable for frail patients. More advanced stages require chemotherapy given together with immunotherapy (monoclonal antibodies) to control the disease. Stem cell (bone marrow) transplantation is sometimes used. Chemotherapy can provide very good control of this lymphoma in most patients. However, the only treatment that can cure advanced follicular lymphoma is transplantation using stem cells from a different person (allogeneic transplantation). Because this treatment is complex and associated with many side effects, it is typically offered to fit patients who have relapsed several times.
- Mantle cell lymphoma – this type of lymphoma originates from the mantle zone of lymph nodes. Mantle cell lymphoma has the appearance of a slow growing lymphoma under the microscope, however it usually behaves as a relatively aggressive disease. It sometimes spreads to the bowel or bone marrow and is treated with chemotherapy given together with immunotherapy (monoclonal antibodies). Young and fit patients should also undergo Stem cell (bone marrow) transplantation to achieve a long-lasting remission.
- Burkitt lymphoma – this is a relatively rare type of lymphoma, which exists in many forms. It is very aggressive and grows very fast. Burkitt lymphoma tends to spread outside of lymph nodes. Sometimes Burkitt lymphoma presents as a medical emergency. Despite its aggressive presentation, Burkitt lymphoma can be cured in many patients with prompt treatment including inpatient, intensive chemotherapy and supportive care.
The most common T-cell lymphomas are:
- Peripheral T-cell lymphoma – this is not a single lymphoma but a group of many relatively rare T-cell lymphomas. The most common subtype in this group is peripheral lymphoma not otherwise specified (PTCL - NOS) and it is itself made of many different subtypes of peripheral T-cell lymphoma. These are more common in people over the age of 60 and they usually grow rapidly. Therapy is with chemotherapy given into the vein and Stem cell (bone marrow) transplantation is recommended in young and fit patients.
- Angioimmunoblastic lymphoma – this rare lymphoma is usually fast growing (aggressive) and it is more common in older individuals. Sometimes patients with this type of lymphoma develop itchy skin rashes or joint pains. It is also sometimes associated with other blood diseases in which the immune system attacks its own body such as autoimmune haemolytic anaemia. Treatment includes administration of corticosteroids and chemotherapy. Young and fit patients should be treated with Stem cell (bone marrow) transplantation.