Lymphoma
Introduction
Lymphoma is a cancer of the lymphatic system. The lymphatic system is made up of a series of vessels and glands, known as lymph nodes. These are spread throughout your body, much like your blood vessels.
The lymphatic system is part of your immune system. Clear fluid called lymph flows through the lymphatic vessels and contains infection-fighting white blood cells known as lymphocytes.
In lymphoma, these lymphocytes start to multiply in an abnormal way and begin to collect in certain parts of the lymphatic system, such as the lymph nodes. The affected lymphocytes lose their infection-fighting properties, making you more vulnerable to infection.
The most common symptom of lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin (see Lymphoma – symptoms for more information).
There are two main types of lymphoma:
About 80% of all lymphomas diagnosed are non-Hodgkin’s lymphoma. The causes of both types of lymphoma are still unknown.
Non-Hodgkin’s lymphoma
Non-Hodgkin's lymphoma is the most common type of lymphoma. More than 9,700 people in the UK are diagnosed with non-Hodgkin's lymphoma each year.
Non-Hodgkin’s lymphoma refers to any type of lymphoma that does not have the distinctive Reed-Sternberg cell that is present in Hodgkin’s lymphoma (see below).
There are many sub-types of non-Hodgkin’s lymphoma, but they can all be put into one of two broad categories:
- high-grade or aggressive non-Hodgkin’s lymphoma, where the cancer develops quickly and aggressively
- low-grade or indolent non-Hodgkin’s lymphoma, where the cancer develops slowly and you may not have any symptoms for many years
Who is affected
Non-Hodgkin's lymphoma is associated with ageing, as the chances of developing the condition increase as you get older. The average age at diagnosis is around 65.
For reasons that are not understood, the rates of new cases of non-Hodgkin's lymphoma have been slowly but steadily rising for the last 50 years. The rate of increase in the UK is around 4% a year.
If the occurrence of non-Hodgkin's lymphoma continues to rise at the current rate, it is estimated that it will be as common as breast or lung cancer by 2025.
Outlook
Survival rates for non-Hodgkin’s lymphoma vary greatly depending on the exact type, grade and stage of the lymphoma, and the person’s age.
Despite their names, high-grade non-Hodgkin's lymphoma is easier to treat than low-grade non-Hodgkin's lymphoma. Cure rates depend on individual circumstances and the subtype of the lymphoma, but an average of 60% of people with high-grade non-Hodgkin's lymphoma are cured.
The difficulty with low-grade non-Hodgkin's lymphoma is that it does not cause symptoms until it is well advanced, by which time it is often too late to cure. However, it is possible to control symptoms for many years.
Hodgkin’s lymphoma
Hodgkin’s lymphoma is one of the rarer types of lymphoma, but it is one of the most common cancers among younger people. It is named after the doctor who first described the condition in the 19th century.
Hodgkin’s lymphoma is characterised by the presence of a distinctive abnormal cell known as a Reed-Sternberg cell (a B-lymphocyte that has become cancerous)
Nearly 1,500 people are diagnosed with Hodgkin's lymphoma in the UK each year.
Who is affected
Hodgkin's lymphoma mostly affects young adults aged between 15 and 35 and adults over the age of 50. More men than women are affected.
Outlook
Hodgkin’s lymphoma is a relatively aggressive cancer and can quickly spread through the body. Despite this, it is also one of the most easily treated types of cancer.
Almost all young people with Hodgkin's lymphoma will be fully cured. For older people over the age of 50, the cure rate is around 75-80%.
^^ Back to top
Symptoms
The most common symptom of both non-Hodgkin's lymphoma and Hodgkin's lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin. The swelling is caused by an excess of affected lymphocytes collecting in one of your lymph nodes.
Some people may find that the swelling aches.
It should be stressed that swollen nodes or glands are a common response to infection, so do not panic if you have swollen nodes. It is highly unlikely that they are the result of lymphoma.
Other symptoms
Other symptoms will usually only begin once the cancer has spread through most, or all, of your lymphatic system.
This causes the lymphatic system to stop working properly, which weakens your immune response.
Symptoms of advanced lymphoma include:
- unexplained tiredness or fatigue,
- night sweats,
- unexplained weight loss,
- fever,
- trouble getting rid of infections,
- a persistent cough or feeling of breathlessness, and
- persistant itching of the skin all over the body.
Symptoms specific to Hodgkin’s lymphoma
A few people with Hodgkin’s lymphoma have abnormal cells in their bone marrow when they are diagnosed. This can reduce the number of healthy cells in the blood and lead to:
- breathlessness and tiredness
- an increased risk of infection
- excessive bleeding, such as nosebleeds, heavy periods and spots of blood under the skin
In rare cases, people with Hodgkin’s lymphoma may have pain in their affected lymph gland when they drink alcohol.
When to seek medical advice
You should see your GP if you experience any of the additional symptoms listed above. You should also see your GP, if swelling persists in one, or more of your lymph nodes, yet you have no other symptoms of infection.
^^ Back to top
Causes
Lymphoma begins with an alteration to the structure of DNA that is found in the lymphocyte cells (white blood cells in the lymph). This is known as a genetic mutation. The DNA provides the cells with a basic set of instructions, such as when to grow and reproduce.
The mutation in the DNA changes these instructions, so that the cells carry on growing. This causes the cells to multiply in an uncontrollable manner.
How does lymphoma spread?
The abnormal lymphocyte cells usually begin to grow in one, or more, lymph nodes. These lymph nodes are usually confined to one area of the body, such as your neck or groin, but over time it is possible for the lymphoma to spread throughout your lymphatic system, affecting more nodes. The abnormal lymphocyte cells can also spread into other parts of your body, such as your bone marrow, spleen (an organ used to filter out impurities in your blood), liver, skin and lungs.
What triggers lymphoma?
The cause of the initial mutation that triggers lymphoma is unknown. Some experts believe it could be due to a number of related causes.
There are a number of known risk factors for developing lymphoma. These are outlined below.
- Having a medical condition that weakens your immune system - such as HIV, this is known as immunosuppression.
- Having medical treatment that affects your immune system - such as taking immunosuppressant medication (these medicines are often given to people who have undergone an organ donation).
- Epstein-Barr virus (EBV) - people who have previously been exposed to the EBV have a slightly higher chance of developing lymphoma. EBV is a common virus that causes glandular fever, although most people develop immunity to it.
- Human T cell lymphotropic virus (HTLV) - people who have been previously exposed to the HTLV have a slightly higher chance of developing lymphoma. HLTV is quite rare in the UK, with only an average of 50 new cases occurring each year.
- Having a Helicobacter pylori infection, which is a known cause for a type of non-Hodgkin’s lymphoma called MALT lymphoma. H. pylori is a common bacterial infection that usually infects the lining of the stomach and small intestine.
- Chemotherapy or radiotherapy - people who have received chemotherapy or radiotherapy for an earlier, unrelated cancer, have a slightly higher risk of developing lymphoma.
- Having coeliac disease (an allergy to gluten that causes inflammation of the small bowel) – this slightly increases your risk of developing B-cell non-Hodgkin’s lymphoma or a rare type of T-cell lymphoma called enteropathy type T-cell lymphoma (ETTL).
Lymphoma is not infectious and does not run in families. But there is a slightly higher chance of developing the condition if you have an identical twin with lymphoma.
^^ Back to top
Diagnosis
Biopsy
The presence of swollen lymph nodes, and other associated symptoms, can suggest a diagnosis of lymphoma, but the only way to confirm the diagnosis is by carrying out a biopsy.
A biopsy involves removing some, or sometimes all, of an affected lymph node which is then studied in a laboratory. Biopsies can be carried out under a local anaesthetic (where the area is numbed), though there may be some cases where the affected lymph node is not easily accessible, and a general anaesthetic may be required (where you are put to sleep).
A pathologist (an expert in the study of diseased tissue) will then check the tissue sample for the presence of cancerous cells. If they do find cancerous cells, they can also identify exactly which type of lymphoma you have, which is an important factor in planning your treatment.
Confirming a diagnosis
There are two main types of lymphocytes (white blood cells found in lymph):
- B-lymphocytes make antibodies that attack infecting bacteria and viruses
- T-lymphocytes kill cells that have been infected with a virus and cause the immune response to respond faster to an infection the second time round
In Hodgkin’s lymphoma, a cell called the Reed-Sternberg cell (a B-lymphocyte that has become cancerous) is always present.
In non-Hodgkin’s lymphoma, both the B-lymphocytes and T-lymphocytes can be affected.
The treatment and outlook for all subtypes of Hodgkin’s lymphoma is similar. However, treatment for non-Hodgkin’s lymphoma depends on the subtype that you have.
There are more than 20 types of non-Hodgkin’s lymphoma, including:
- diffuse large B-cell lymphoma
- follicular lymphoma
- extranodal marginal zone B-cell (MALT)
- mantle cell lymphoma
- Burkitt lymphoma
- mediastinal large B-cell lymphoma
- nodal marginal zone B-cell lymphoma
- small lymphocytic lymphoma
- lymphoplasmacytic lymphoma (also called Waldenstrom’s macroglobulinaemia)
- peripheral T-cell lymphoma
- skin (cutaneous) lymphomas
- anaplastic large-cell lymphoma
- lymphoblastic lymphoma (mainly T-cell but can be B-cell)
B-cell lymphomas are more common than T-cell lymphomas.
See the Macmillan cancer website for more information on the different kinds of non-Hodgkin’s lymphoma.
Further testing
If a biopsy does reveal the presence of lymphoma, further testing will be required in order to check how far the lymphoma has spread. These tests may include:
- Blood tests – samples of blood will be taken throughout your diagnosis and treatment to check your general health, the levels of red and white cells and platelets in your blood, and how well organs, such as your liver and kidney, are working.
- Bone marrow sample – another biopsy may be carried out to see if the lymphoma has spread to your bone marrow. This involves using a long needle to remove a sample of bone marrow from your pelvis and can be done using a local anaesthetic.
- Chest X-ray – can check whether your lymphoma has spread to your chest or lungs.
- Computerised tomography (CT) scan – takes a series of X-rays that build up a three-dimensional picture of the inside of the body to check the spread of your lymphoma.
- Magnetic resonance imaging (MRI) scan – uses strong magnetic fields instead of X-rays to build up a detailed picture of areas of your body to check the spread of your lymphoma.
- Positron emission tomography (PET) scan – a type of scan that shows how the tissues of the body are working by measuring the activity of cells in different parts of the body. It can check the spread of your lymphoma and the impact of treatment.
- Lumbar puncture – using a thin needle, a sample of spinal fluid is taken and examined to see if it contains any lymphoma cells.
Staging of lymphoma
When the testing is complete, it should be possible to determine the stage of your lymphoma. These stages are explained below.
- Stage 1 - the lymphoma is limited to one group of lymph nodes, such as your neck or groin that are either above or below your diaphragm
- Stage 2 - two lymph node groups are affected, either above or below the diaphragm.
- Stage 3 - the lymphoma has now spread to lymph node groups that are both above and below the diaphragm.
- Stage 4 - the lymphoma has spread through the lymphatic system and is now present in organs and / or bone marrow outside of the lymphatic system.
Stage one, or two, lymphomas can usually be cured. Achieving a cure for a stage three or stage four lymphoma is more challenging, and a remission (where there are no active signs of disease) may only be achievable.
Sometimes, health professionals also use an additional grading system, either 'A' or 'B'. 'A'-type lymphoma means that you are experiencing no additional symptoms other than swollen lymph nodes.
'B'-type lymphoma means you are experiencing additional symptoms, such as weight loss, fever or night sweats.
^^ Back to top
Treatment
Deciding on a treatment plan
Once lymphoma has been diagnosed, you will need to discuss possible treatment plans. It is likely that the discussion will take place with several doctors, and other health professionals, who specialise in different aspects of treating lymphoma. These health professionals make up what is known as a multi-disciplinary team (MDT).
A MDT will often include:
- a oncologist (a specialist in the non-surgical treatment of lymphoma using techniques such as chemotherapy),
- a pathologist (a specialist in the study of cancerous blood cells),
- a pharmacist,
- a social worker,
- a transplant specialist,
- a radiographer (a specialist in radiotherapy)
- a microbiologist (a specialist in infectious diseases)
- a psychologist,
- a specialist cancer nurse (who will serve as the first point of contact between yourself and the members of the MDT), and
- a counsellor.
Treatment for lymphoma may involve a visit to a specialist cancer centre, or hospital. The recommended treatment plan will depend on your general health and your age because many of the treatments can cause serious side effects and complications that can put a tremendous strain on the body.
There are several factors that you will need to take into account when deciding on your treatment. They include:
- your age and general health,
- your symptoms
- the likely progression of your lymphoma,
- the specific sub-type of your lymphoma,
- the stage of your lymphoma, and
- the possible side-effects of treatment.
You should not be rushed into making a decision about your treatment plan and, before deciding, you should feel free to talk to as many people as you want, including friends, family, and your partner.
Chemotherapy
Chemotherapy is a widely used treatment for lymphoma, often combined with radiotherapy. The type of chemotherapy you receive will depend on the type and stage of your lymphoma.
If it is thought that your lymphoma is curable you will normally receive an aggressive treatment regime of chemotherapy injections (intravenous chemotherapy) designed to kill all of the cancerous cells in your body. If however a cure is unlikely, then a more moderate treatment regime involving taking chemotherapy tablets (oral chemotherapy) may be used which can often provide long-term relief from symptoms.
Chemotherapy is usually given over a period of a few months on an out-patient basis, meaning you should not have to stay in hospital over night. But there may be times when your symptoms or the side effects of treatment become particularly troublesome and a longer hospital stay may be needed.
Chemotherapy kills the cancerous cells but it can also damage healthy cells, which can lead to a number of common side effects. These include:
- nausea,
- vomiting,
- diarrhoea,
- loss of appetite,
- mouth ulcers,
- tiredness,
- skin rashes,
- hair loss,
- infertility; this may be temporary or permanent - see the 'complications' section for more details.
Side effects should pass once treatment has finished. Tell your MDT if side effects become particularly troublesome as there are medicines that can help you cope better with some side effects. For example, creams and gels are available for the treatment of mouth ulcers.
Aggressive chemotherapy can also damage your bone marrow. This can interfere with the production of healthy blood cells which can lead to the following symptoms:
- fatigue,
- breathlessness,
- an increased vulnerability to infection, and
- bleeding and bruising more easily.
Treatment may need to be delayed in order for you to produce more healthy blood cells. Growth factor medicines can also help stimulate the production of blood cells.
If the damage to the bone marrow is extensive you may require a stem cell transplantation to replace the damaged bone marrow. See the 'complications' section for more information.
Radiotherapy
Radiotherapy is often used to treat stage 1 and 2 lymphomas, when the cancerous cells are located in only one part of the body. Treatment is normally given daily, Monday to Friday, over the space of 2-6 weeks. You should not have to stay in hospital in-between visits.
The radiographer will need to first carefully plan your treatment. This may involve, one, or several appointments, where the radiographer uses a machine to 'map' out the lymphoma and decide what parts of your body the radiotherapy should be directed at. This may involve making small marks on your skin with a kind of marker pen.
Radiotherapy itself is painless, but it does have a number of common side effects. These can vary, depending on which part of your body is being treated. For example, if the affected lymph nodes are in your throat radiotherapy can lead to a sore throat, while treatment to the head can lead to hair loss. Other common side effects include:
- tiredness,
- nausea,
- vomiting,
- dry mouth, and
- loss of appetite.
Monoclonal antibody therapy
Monoclonal antibody therapy can be used to treat some types of non-Hodgkin's lymphoma. Monoclonal antibodies are special medicines designed to recognise specific cancer cells and then destroy them.
The type of monoclonal antibody therapy used to treat non-Hodgkin's lymphoma is a medicine called rituximab. Rituximab works by attaching itself to the surface of a cancerous cell. It then stimulates the immune system to attack and kill the cell.
Rituximab can be used to treat low grade non-Hodgkin's lymphoma, or combined with chemotherapy to treat high grade non-Hodgkin's lymphoma.
Rituximab is administered directly into your vein over the course of a few hours. The usual recommended dose is once a week, for four weeks.
It is common to experience flu-like symptoms when you are being treated with rituximab. Possible symptoms include:
- headache,
- fever and/or chills,
- fatigue,
- muscle pain.
You may be given additional medication to prevent, or lessen, side effects. Side effects should improve over time as your body gets used to rituximab.
Steroids
Steroids are used to treat some cases of lymphoma, in combination with chemotherapy. Research has shown that using steroids makes the chemotherapy more effective.
Steroids are given intravenously, usually at the same time as your chemotherapy. A short-term course of steroids, lasting no more than a few months, is usually recommended, as this limits the number of side effects you could experience. Common side effects of short-term steroid use include:
- increased appetite - which can lead to weight gain,
- an increase in your energy levels, and
- problems sleeping.
Rarely, it may be necessary for you to take steroids on a long-term basis. Side effects of long-term steroid use include:
- swelling in your hands, feet and eyelids,
- weight gain,
- indigestion,
- raised blood pressure, and
- a slightly higher risk of developing infections.
Treatment for low-grade non-Hodgkin’s lymphoma
Some people with non-Hodgkin’s lyphoma have low-grade lymphomas that grow very slowly. In this case, there is little or no change in the disease for long periods of time.
If your lymphoma is classified as low-grade, treatment may be postponed, and you will just have regular check ups to make sure your lymphoma has not spread any further. This is known as active surveillance or watchful waiting.
The first treatment given for low-grade lymphoma is usually chemotherapy, often in combination with a monoclonal antibody. If your lymphoma is in one group of lymph nodes only, you may be given radiotherapy on that area.
After treatment, many people with low-grade lymphoma have no active signs of the disease. This is known as remission. If the lymphoma returns, it can be treated again with chemotherapy, radiotherapy or monoclonal antibodies. Low-grade non-Hodgkin’s lymphoma can often be controlled in this way for many years.
^^ Back to top
Complications
Stem cell transplant
If you have received an aggressive, high-dose, regime of chemotherapy it can irreversibly damage your bone marrow; specifically special cells found in the bone marrow known as stem cells. Stem cells are important as they have the ability to create other specialised cells, such as red and white blood cells.
If the possibility of bone marrow damage is high, your treatment team will take a small sample of healthy stem cells from your blood. These stem cells can then be kept until your treatment is complete, and then used to stimulate the production of new bone marrow. This procedure is known as an autologous stem cell transplant.
Immunocompromised
Being immunnocompromised (having a weakened immune system) is a common complication of lymphoma. Even if your lymphatic system is restored to normal working order, many of the medications that are used to treat lymphoma have the side-effect of weakening your immune system.
This means that you are more vulnerable to developing infections, and also, there is an increased risk of developing serious complications from infections. You may be advised to take regular doses of antibiotics in order to prevent infections occurring.
You should immediately report any possible symptoms of an infection to your GP, or MDT, because prompt treatment may be required to prevent serious complications.
Symptoms of infection include:
- fever,
- headache,
- aching muscles,
- diarrhoea, and
- tiredness.
You should also ensure that all of your vaccinations are up-to-date. Your GP, or MDT, will be able to advise you about this.
Infertility
Many of the treatments that are used to treat lymphoma can cause infertility. Infertility is often temporary but, in some cases, it may be permanent.
People who are particularly at risk of becoming infertile are those who have received very high doses of chemotherapy and radiotherapy.
Your MDT will be able to provide you with a good estimation of the risk of infertility in your specific circumstances.
It may be possible to take steps to guard against any risk of infertility before beginning treatment. For example, men can have samples of their sperm stored. Similarly, women can have eggs stored, which can be fertilised and placed back into the womb following treatment.
^^ Back to top