Lymphoma is a family of blood cancers that affect cells from your immune system called lymphocytes. Because these lymphocytes are found in your lymphatic system as well as your blood it is sometimes known as lymphatic cancer.
There are two main types of lymphoma – Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Descriptions of lymphoma are recorded at least as far back as the 17th Century (by the Italian microscopist, Marcel Malpighi). In 1832 a scientific paper was presented by Thomas Hodgkin, a doctor working in London, giving detailed descriptions of patients who had died of a condition involving swollen lymph nodes. Other scientists confirmed that this condition was a form of cancer and named it Hodgkin’s disease, then later, Hodgkin’s lymphoma to recognise the work of the first person to describe it in detail.
Thomas Hodgkin – Source – Wikimedia commons
Scientists studying samples from patients with Hodgin disease noticed that some of the cells looked like popcorn or “owl eyes” once prepared for viewing under the microscope. These are typical of Hodgkin’s lymphoma and are named after the scientists who worked on them, (Dorothy Reed and Carl Sternberg) – Reed Sternberg cells.
Although Hodgkin lymphoma only makes up about a tenth of lymphoma cases, all other forms of lymphoma are in a large group that is named for “not” being the Hodgkin type. This is why most lymphomas are called “Non-Hodgkin lymphoma”, NHL for short. The work to identify and describe the other lymphomas is still going over a hundred years later and has benefited hugely from advances in our understanding of genetics and immunology. There are currently over 80 types of non-Hodgkin lymphoma that have been recognised. Some of the most common or well known are diffuse large B cell lymphoma (DLBCL), follicular lymphoma and Burkitt’s lymphoma. Together there are about 16,300 cases of lymphoma each year, half that of bowel cancer, but individually each type is at most rare and many are extremely rare.
Where does lymphoma come from? - A family of blood cells.
When we are in the early stages of growth as an embryo, we are just a ball of cells of no particular type. These are called stem cells that can change to become all of the different cells that make up a human being. Once we are born only a very few cells keep the ability to do this. The most important of these are found in our bone marrow, the spongy material in the middle of our bones where a single type of stem cell is responsible for producing all the cells that are found in our blood- the oxygen carrying red blood cells, the many types of white blood cells that fight infections and the platelets that help our blood to clot.
The picture below shows the family tree of these blood cells. All of them come from the haematopoietic stem cells (haematopoietic means blood forming). The stem cells will multiply and become more specialised as they develop down the branches of the tree.
Source – wikipedia creative commons
There are two big families within the blood cells. The myeloid cells on the left of the picture and the lymphoid cells on the right.
Blood cancer can develop from any of these cells at different stages of their development and this is reflected in the name given to the cancer. The most well known are the leukaemias which affect cells from both groups that are developing in the bone marrow, and lymphomas that affect lymphocytes, the T-cells, B-cells and NK(natural killer) cells in the lymph nodes.
The lymphatic system
Lymphoma is sometimes called lymphatic cancer as it affects cells that are found in the lymphatic system. The Lymphatic system is a network of tubes (vessels), tissues and organs that connect with your blood circulation at veins near your collarbone. Its job is to collect excess fluid from your tissues and return it to your bloodstream, transporting large molecules from digestion and most importantly here, it is a major part of your immune system.
The lymphatic system includes your bone marrow, where immune cells first develop from stem cells, your spleen, where blood is filtered and red and white blood cells are stored, and about 600 lymph nodes which are where white blood cells are stored until they are needed. Lymph nodes are bean shaped objects, often found in chains throughout the body. The diagram below shows a simplified picture of the lymphatic system, with clusters of lymph nodes and some of the important organs.
Source – CRUK / Wikimedia commons
We can feel lymph nodes close to the surface, such as the neck or armpit, especially when we have an infection and they swell as they fill with extra white blood cells that are preparing to remove the invading organism from your body. They will also swell when they fill with the cells produced by the uncontrolled cell division of a lymphoma.
Symptoms of lymphoma
Swollen lymph nodes are the most common symptom of lymphoma, they are not usually painful unless they are pressing against a nerve or organ. This is more likely when the lymph node affected is deeper in the body.
If the swelling is in your chest or stomach area, there may be breathlessness, a cough or you may feel sick or have a sensation of fullness that makes it difficult to eat.
In HL, one unusual symptom is getting pain in the lymph nodes after drinking alcohol. This might be due to the blood vessels expanding in response to the alcohol. Some people may have bone pain if the bone marrow is affected.
Lymphoma symptoms can also appear in the skin – there may be lumps or rashes as well as itching caused by chemicals released by the cancer cells (this is more common in HL).
There is also a group of symptoms called “B-symptoms”. The “B” comes from a way of categorising the symptoms of lymphoma where “A” means no symptoms and “E” and “S” means extra lymph nodes are affected, or the disease has involved the spleen.
B-symptoms are; having a fever of over 38oC, night sweats that leave you soaked and unintentionally losing more than 10% of your body weight in 6 months.
Diagnosing lymphoma
Blood tests are simple to do, but often can’t give a definitive diagnosis. They will be used to check the numbers of different cells in your blood to confirm your general health and how well organs like your liver are working.
Scans, such as PET and CT scans are useful in diagnosing lymphoma and confirming how many lymph nodes and organs are affected and to confirm the stage of the cancer. MRI scans are used if there is a possibility of the cancer affecting the brain or spinal cord, head, neck or bones as these are harder to see well on CT/PET scans. MRI might also be used if someone can’t have other types of scan. Scans are also essential to help doctors find the best place to take a biopsy which is essential for giving an accurate diagnosis.
A biopsy is a small sample of the lymph node that is removed using a fine needle and then studied under a microscope. The histologist (scientist who studies cells) will use their skill at recognising the cancer from the shape, appearance and growth patterns of the cells as well as using special stains that will colour cells if they have particular features that are typical of certain cancers.
A final test may be to take a bone marrow biopsy to check whether the cancer has spread to the bone marrow.
The biology and treatment of lymphoma
Hodgkin Lymphoma (HL):
The important message about HL is that it is one of the most treatable cancers. Five year survival rates (one of the main ways treatment effectiveness is measured) is up to 90%, meaning that five years after their diagnosis, 90% of patients are still alive.
Although HL affects people of any age after childhood there are two peaks of frequency in young adults and older people, usually in their 70s and it is more common in men, although there is no explanation as to why.
There are no clear avoidable risk factors for developing HL, but there are a few things that are linked with an increased chance of developing it.
There is an association with Epstein Barr virus infection, which usually causes glandular fever. This does not mean that EBV is a significant risk factor for developing HL, as this cancer is very rare and EBV infections are extremely common.
People with immune systems that don’t work well, from HIV infections or taking anti-rejection drugs after a transplant are more likely to get HL as well as other cancers as the immune system is less effective at removing damaged cells before they can multiply.
There is also a slightly increased chance of developing HL if a relative has had blood cancer. Genetic studies have found some hints of genes that might be involved in increasing the risk within individual families, but the link is not strong enough for them to be used as a predictive test.
HL has two main types – classical (cHL) and the much rarer “nodular lymphocyte predominant” (NLPHL) which has a different type of characteristic cell.
Which cells become cancerous in HL was a mystery for a very long time, even though Hodgkin lymphoma was the first lymphoma to be identified.
Genetic analysis of individual cells from both forms of HL found that they were actually transformed B-cells – the ones that usually produce antibodies to fight infection.
Treatment is usually chemotherapy, sometimes a little as two cycles with a combination of drugs for disease caught in the early stages. Radiotherapy will be used to destroy any cancer cells left in the affected lymph nodes . If the cancer is more advanced the chemotherapy given may be for longer, or at a higher dose and the drugs used may be changed if a PET scan shows it is responding well.
If the lymphoma doesn’t respond to treatment (refractory) or comes back (relapses) a stem cell transplant might be offered. In this case a very high dose of chemotherapy is used to destroy all of the cells in the bone marrow which are then replaced by healthy stem cells. Alternatively new targeted drugs might be used that activate the immune system to attack the cancer itself.
Non-Hodgkin Lymphoma:
Any cancer that affects the lymphocytes of the immune system that doesn’t contain the Reed-Sternberg (or rarely LS) cells is a Non-Hodgkin Lymphoma. As this group contains between 60 and 80 different cancers so this article will give an overview.
Although NHL can affect younger people, the incidence increases with age, most people are over 55 when they are diagnosed and the incidence is highest in people over 80. It’s slightly more common in males, although it is not known why that is.
The different types of non-Hodgkin lymphoma can be classed according to their grade – how fast they are growing, or according to the type of lymphocytes they started in. They may be “high grade” which are fast growing or aggressive, or low grade, sometimes called indolent (indolent means lazy) as it is slow growing. Sometimes a low grade lymphoma can “transform” into a higher grade lymphoma. Often it is follicular lymphoma that transforms into diffuse large B-cell lymphoma.
Whilst most cases of NHL can start in B-cells, it can also start in T-cells, although T-cell lymphomas are much less common.
The table below gives some examples of the different types.
High Grade B-Cell
Low Grade B-Cell
Diffuse large B-cell lymphoma (DLBCL)
Intravascular large B-cell lymphoma
Primary mediastinal large B-cell lymphoma (PMBL)
Primary cutaneous diffuse large B-cell lymphoma, leg-type
Burkitt lymphoma
Primary central nervous system lymphoma (primary CNS lymphoma)
Follicular lymphoma
Mantle cell lymphoma
Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) – (this cancer is considered to be a type of NHL)
Lymphoplasmacytic lymphoma (Waldenström’s macroglobulinaemia)
Marginal zone lymphomas:
Extranodal marginal zone lymphoma (also called MALT lymphoma)
Nodal marginal zone lymphoma
Splenic marginal zone lymphoma
Primary cutaneous follicle centre lymphoma
High Grade T-Cell
Low Grade T-Cell
Anaplastic large cell lymphoma (ALCL)
Angioimmunoblastic T-cell lymphoma (AITL)
Enteropathy-associated T-cell lymphoma (EATL)
Adult T-cell leukaemia/lymphoma (ATL)
Extranodal NK/T-cell lymphoma (nasal-type)
Hepatosplenic T-cell lymphoma
Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
Sézary syndrome
(many skin lymphomas are this type)
Mycosis fungoides
Primary cutaneous CD30-positive lymphoproliferative disorders.
Rarer types of T-cell skin lymphoma
The most common NHLs are, in order of frequency:
Diffuse large B-cell lymphoma, chronic lymphocytic leukaemia, marginal zone lymphomas, and follicular lymphoma.
Low grade NHL.
Whilst many people newly diagnosed with a cancer would expect treatment to begin urgently, low grade lymphoma is often approached differently.
For low grade NHL, if you are well and the disease is not actually causing a significant problem, the initial step action is to start “watchful waiting”, or “active monitoring” where your health and the progress of the disease is monitored closely and treatment only starts if it becomes necessary.
Scientists have found that watchful waiting makes no difference to the ability to treat low grade lymphoma. The advantage is that it reduces someone’s exposure to the radiation from additional scans as well as delaying treatment with drugs that can have significant and lasting side-effects.
The main treatment is chemotherapy – there are several combinations that are used depending on the individual alongside a drug called Rituximab. Rituximab works by sticking to a protein that is found on B-cells which then flags them for destruction by the immune system. This treatment will control the cancer, but will not cure it. Low grade NHL will usually come back and need further rounds of treatment. It is often thought of as a chronic (incurable) condition that needs to be managed with occasional treatment.
High Grade NHL.
These more aggressive forms of lymphoma usually need to be treated as soon as they are diagnosed, but will often respond very well to treatment. Many high grade NHLs can be considered cured after treatment. As with low grade lymphomas, the normal treatment is a combination of chemotherapy and immunotherapy that is appropriate for the patient’s age, health and their particular cancer. The most common treatment is a called R-CHOP for short, Rituximab (as for low grade lymphomas) plus cyclophosphamide, doxorubicin and vincristine (was called Onvovin) plus a steroid called prednisolone.
Supportive Treatments:
As well as the disease itself there will sometimes be symptoms or problems caused by the cancer that will also need treating.
Most of these are due to the effect of the disease or the treatments on blood cells. Sometimes the numbers of white or red blood cells will become too low causing anaemia or an increased chance of infections. Blood transfusions are a short term way to increase the number of cells, whilst growth factors can be given that encourage the bone marrow to make more white cells, red cells or platelets.
Anyone with a cancer diagnosis may need support with their mental health and living well during treatment. People who are in the “active monitoring” stage of a low grade lymphoma may need particular support to help them cope with having a cancer that is not being treated.
New treatments:
Research into blood cancers is very active and new discoveries about the causes, nature and treatment of lymphomas are being made all the time.
There are two areas where research is mainly being focussed for the treatment of lymphoma. The first is targeted therapy, drugs that affect the messages that trigger and control cell division. Ibrutinib (Imbruvica) has been approved for several lymphomas recently and other drugs that affect this system are being developed.
The second area is immunotherapy, where a patient’s own immune system is helped to fight the cancer. This can be in the form of drugs that stop the cancer hiding from the immune system – the checkpoint inhibitors. Although some of the ones tried for other cancers are less effective, new ones such as Magrolimab are proving more effective.
The other immunotherapy that often makes the news is CART-T therapy. This is where some of a patient’s own T-cells are removed and sent to a laboratory where they are modified so that they can recognise and attack the cancer cells.
Where can I find lymphoma support groups?
Name
Website
Notes
Blood Cancer UK
UK charity supporting patients and researchers for all blood cancers. Information is clearly presented and there are excellent opportunities to get support or be involved in fundraising.
Lymphoma Action
https://lymphoma-action.org.uk/
Another excellent source of information with many stories from patients, families and volunteers.
Leukaemia and Lymphoma Society
https://www.lls.org/
Major US non-profit organisation dedicated to researching and supporting blood cancers. They have an extensive library of free information about blood cancers as well as other information about new medicines, testing and living with cancer.
Awareness, events, and symbols
The awareness ribbon for all of the lymphomas and leukaemias is orange.
World Lymphoma day is held on 15th September every year.
It is part of blood cancer awareness month.
World blood cancer day is held on May 28th every year.
