Non-Hodgkin lymphomas (NHLs) are malignancies that arise from white bloodthe red bodily fluid that transports oxygen and other nutrients around the body cellsthe basic structural and functional unit of all living things in the lymphatic systema network of tissues and organs that help our bodies fight infection and disease. More specifically, they develop from B-lymphocytic and T-lymphocytic cells, which are more commonly known as white blood cells. Unlike Hodgkin lymphomas, non-Hodgkin lymphomas do not have Reed-Sternberg cells present.
The lymphatic system is a network of tissues and organs that help our bodies fight infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease. It is composed of lymph vesselsa network/chain of thin tubes that moves lymph fluid around the body, lymph fluida clear watery fluid that carries nutrients around the body and removes unwanted bacteria/viruses and lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid/glands. Some of the most well-known lymph tissues include the bone marrowsoft, spongy tissue found in bones that makes blood cells, the spleen, and the tonsils.
This page will focus on aggressive NHLs that develop from B-lymphocytes. B-cell lymphomas are the most common subtype of all lymphomas (including Hodgkin lymphomas), and aggressive lymphomas tend to be more common than indolent (or slow-growing) lymphomas.
In general, NHLs are more commonly found in men, and are generally diagnosed after the age of 60. However, anyone can develop this disease.
Types of Non-Hodgkin Lymphomas (Aggressive B-cell)
There are several types of aggressive B-cell NHLs, which are often categorised based on cellular appearance under the microscope, tumoura tissue mass that forms from groups of unhealthy cells behaviour, and/or location of disease.
Diffuse Large B-cell Lymphoma (DLBCL)
Diffuse large B-cell lymphomacancers of the lymphatic system (DLBCL) is the most common subtype of all NHLs, and has many different subtypes.
Primary Mediastinal B-cell Lymphoma (PMBCL)
Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of DLBCL that develops from the thymus gland in the mediastinumthe space between the lungs that holds many important structures, including the heart, trachea and oesophagus. Unlike most NHLs, it mainly occurs in adults between the ages of 25-40, and is more common in women. While PMBCL can metastasise, it often has a good prognosisto predict how a disease/condition may progress and what the outcome might be.
T-Cell/Histiocyte rich B-cell Lymphoma (T/HRBCL)
T-cell/histiocyte rich B-cell lymphoma (T/HRBCL) is a rare subtype of DLBCL that is characterised by the presence of excess T-lymphocytes, excess histiocytes (a type of immune cell), and cancerous B-lymphocytes. This type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs is often difficult to diagnose, as it can resemble Hodgkin’s lymphoma and peripheral T-cell lymphoma. As it is often diagnosed at a late stage, T/HRBCL may not have as good of a prognosis as other types of NHL.
Primary Central Nervous System Lymphoma (PCNSL)
Primary central nervous system lymphoma (PCNSL) is a rare subtype of DLBCL that often originates in the central nervous system (CNS). The CNS is responsible for all sensory and motor functions in the body, and is composed of the brain and the spinal cord. While it is most commonly found in the brain, it can also develop in the spinal cord, eye(s), and leptomeninges (the inner membranes surrounding the brain and spinal cord). Unfortunately, due to the delicate locations of the disease, the prognosis for PCNSL may be poor.
Cutaneous B-cell Lymphoma
Cutaneous B-cell lymphoma (CBCL) is a rare subtype of NHL that usually begins in the skin. There are two types of indolent CBCL, and one aggressive type called primary cutaneous diffuse B-cell lymphoma, leg type (PCDLBL-LT).
PCDLBL-LT is very rare, and is generally found in the lymphatic nodules in the legs. It is commonly found in patients over 70 years old and unlike most NHLs, is significantly more common in women than men. PCDLBL-LT can have a good prognosis when caught early.
For more information on the indolent forms of CBCL, please refer to the Rare Cancers Australia Non-Hodgkin Lymphoma (Indolent B-Cell) page.
Plasmablastic Lymphoma
Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of NHL that is associated with having a weakened immune system, most commonly from an infection with the human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and/or post organ transplanta surgical procedure that involves removing a failing or damaged organ and replacing it with a healthy one from a donor. Unlike most other forms of NHL, plasmablastic lymphoma tends to be diagnosed in patients between the ages of 40-50, but is still slightly more common in males. It is most commonly found in the oral cavity and the gastrointestinal tract, however it has also been found in the head and neck region, skin, and bone. This disease is often diagnosed at a late stage, is often aggressive, and may not have as good of a prognosis as other NHL subtypes.
Rare Types of DLBCL
These types of DLBCL are considered very rare:
- Intravascular large B-cell lymphoma.
- EBV-positive DLBCL not otherwise specified.
- Double hit lymphoma (DHL).
- Triple hit lymphoma (THL).
- ALK-positive large B-cell lymphoma.
Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a rare subtype of NHL that develops from the ‘mantle zone’ (outer edge) of the lymph nodes. While this type of cancer is usually aggressive, it can behave like an indolent (slow growing) cancer in rare instances. MCL often has a high recurrenceto occur or happen again rate, but can have a good prognosis when caught early.
Grey Zone Lymphoma
Grey zone lymphoma (GZL) is a very rare subtype of NHL that often develops in the mediastinum. It has characteristics of both classical Hodgkin lymphoma, and a subtype of DLBCL called primary mediastinal B-cell lymphoma (PMBCL). Although it is often difficult to diagnose, GZL can have a good prognosis when caught early.
Burkitt Lymphoma
Burkitt lymphoma (BL) is a rare subtype of NHL that affects both children (between the ages of 5-10) and, rarely, adults (between the ages of 30-50). It has often been associated with viral infections, such as the Epstein-Barr virus (EBV) and the Human-immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). There are three main subtypes of BL.
Endemic (African) Burkitt Lymphoma
Endemic BL is most commonly found in children of African descent, who are between four to seven years old. It is strongly associated with EPV and chronica long-lasting disease that changes slowly over time malaria infections, and is rarely found outside of Africa. In both adult and paediatric cases, it is usually found in the jaw and facial bones, and can have a good prognosis.
Sporadic (non-African) Burkitt Lymphoma
Sporadic BL is found throughout the world, and is most commonly found in the abdomenstomach, stomach area, belly. It is commonly found in children, but can also be found in adults. Sporadic BL can be associated with an EPV infection, and can have a good prognosis.
Immunodeficiency-associated Burkitt Lymphoma
Immunodeficiency-associated BL is also found throughout the world, and most commonly affects people with the Human-immunodeficiency virus and/or acquired immunodeficiency syndrome (HIV/AIDS). It can also occur in people with inherited immunodeficiency syndromes, or patients who take immunosuppressive medications after an organ transplant. Immunodeficiency-associated BL can have a good prognosis when caught early.
AIDS-Related Lymphoma
AIDS-related lymphoma is when a patient with AIDS is diagnosed with a lymphoma (in most cases, a NHL). The two primary types of AIDS-related lymphomas include:
- Diffuse large B-cell lymphoma.
- Burkitt lymphoma.
Precursor B-cell Lymphoblastic Lymphoma
Lymphoblastic lymphoma (LL) is a rare subtype of NHL that is commonly diagnosed around 20 years of age. It most commonly develops from T-lymphocytes, but can rarely develop from B-lymphocytes.
Precursor B-cell lymphoblastic lymphoma develops from immature B-cell lymphocytes, generally in the lymph nodes. It behaves similarly to B-acute lymphoblastic leukaemiacancer of blood and/or blood forming tissues, but is much less common. While this type of cancer has a high recurrence rate, precursor B-cell lymphoblastic lymphoma can have a good prognosis.
Treatment
If an aggressive B-cell NHL is detected, it will be staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you.
All NHLs are staged using the Lugano classification system, which may also be referred to as a modification of the Ann Arbor staging system. In this system, NHLs are assigned numerical values, from stage I-IV:
- Stage I: cancer cells are confined to a single lymph nodea small lump or mass of tissue in your body area, either above or below the diaphragm (large muscle separating the abdomen from the chest). This stage is also known as early-stage cancer.
- Stage II: cancer cells have spread to two or more lymph node areas on the same side of the diaphragm. This is also known as localisedaffecting only one area of body cancer.
- Stage III: the cancer has become larger and affected lymph node areas on both sides of the diaphragm. This is also known as localised cancer.
- Stage IV: Lymphoma is in multiple lymph node areas and may be present in other parts of the body, such as bone marrow, liver, and/or lungs. This is also known as advancedat a late stage, far along or metastatic cancer.
In addition to the numerical system, your doctor may also stage your cancer with a letter, which gives more information about your symptoms and how your body is being affected by the disease. These letters include:
- A – You feel well and have no B-symptoms of lymphoma.
- B – You have some or all of the B-symptoms of lymphoma.
- E – You have NHL in an organ that is not a part of the lymphatic system (such as lungs, skin, bladdera hollow, muscular sac in the pelvis that stores urine etc.).
- X – You have a tumour that is greater than 10cm in size. This is also called ‘bulky disease’.
- S – You have a lymphoma in your spleen.
As all cancers discussed on this page are classified as ‘aggressive’, these cancers are usually all high gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells.
Once your tumour has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, age, stage of disease and overall health.
Treatment options for aggressive B-cell NHLs may include:
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer, potentially including:
- CAR T-cell therapya type of immunotherapy where a patients T-cells (a type of white blood cell in the immune system) are re-engineered to target cancer cells; also known as chimeric antigen receptor T-cell therapy.
- Rituximab.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Targeted therapymedication that targets specific molecular features of cancer cells, potentially including monoclonal antibodies.
- Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells, potentially including:
- Autologous transplant (stem cells removed from your own blood and later reinfused into your body).
- Allogenic transplant (stem cells are collected from another person).
- Photodynamic therapya procedure that involves inserting a light-sensitive drug (photosensitiser) to shrink and damage cancer cells when exposed to a light source.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove skin lesion (only in patients with a lymphoma of the skin).
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
While the cause of all NHLs remains unknown, the following factors may increase the likelihood of developing the disease:
- Previous infections with viruses, including:
- Epstein-Barr virus (EBV).
- Human immunodeficiency virus (HIV).
- Acquired immunodeficiency syndrome (AIDS).
- Human T-lymphotropic virus type 1 (HTLV-1).
- Hepatitis C (Hep C).
- Human herpesvirus-8 (HHV-8)
- Chemical exposure to pesticides, fertilisers, and/or solvents.
- Having an autoimmune disease, such as:
- Rheumatoid arthritis.
- Scleroderma.
- Sjögren’s syndrome.
- Infections with certain bacteria, such as helicobacter pylori (H. pylori – known to cause stomach ulcers).
- Having a family history of lymphoma.
- Obesity (past or present).
- Taking immunosuppressant medication, such as after an organ transplant.
Not everyone with these riskthe possibility that something bad will happen factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Symptoms
Most patients with an aggressive B-cell NHL will appear asymptomatic in the early stages of disease. As the cancer progresses, some of the following symptoms may appear.
General Symptoms
General symptoms of an aggressive B-cell NHL may include:
- B-symptoms, which include:
- Drenching night sweats.
- Unexplained weight loss.
- Persistent fevers over 37.5°C.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Itchy skin.
- Dyspneadifficulty breathing, shortness of breath.
- Cytopenialow levels of red blood cells, white blood cells or platelets in the blood; one or more blood cell type can be affected, potentially including anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection, thrombocytopenialow levels of platelets in the blood, and/or neutropeniaa condition where there are low levels of neutrophils (a type of white blood cell) in the body, which may cause the following symptoms:
- Dyspnea.
- Fatigue.
- Dizziness.
- Confusion.
- Difficulty concentrating.
- Paleness.
- Abnormal protein levels, which may cause the following symptoms:
- Poor circulation (causing blue fingers and/or toes, numbness and/or tingling in fingers and toes etc.).
- Confusion.
- Headaches.
- Nosebleeds.
- Blurred vision.
Symptoms of diffuse large B-cell lymphoma
In addition to the general symptoms listed above, patients with DLBCL may experience the following symptoms:
- Nauseato feel sick or likely to vomit and/or vomiting.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Constipationa condition where a person has difficulty passing faeces/stools.
- Blood in urine and/or stoolwaste product from the bowel sent to the anus for removal; also known as faeces or poo.
- Feeling full after little food.
- Chest pain.
- Dry cough.
- Recurrent infections.
- Easy bruising and/or bleeding.
- Red/purple rash.
- Skin lumps and bumps.
Primary mediastinal B-cell lymphoma
In addition to general DLBCL symptoms, patients with PMBCL may also experience:
- Pains/aches in the chest.
- Voice hoarseness.
- Swelling of the neck and/or face.
- Dizziness.
- Headaches, which are worse when bending forward.
- More visible chest veins.
T-cell/histiocyte rich B-cell lymphoma
In addition to general DLBCL symptoms, patients with T/HRBCL may also experience:
- Swelling of the liver and/or spleen.
- General feeling of unwellness.
- Abdominal swelling/discomfort.
Primary Central Nervous System Lymphoma
In addition to general DLBCL symptoms, patients with PCNSL may also experience:
- Confusion.
- Memory changes.
- Personality changes.
- Seizures.
- Weakness, numbness, burning and/or pins and needles in the arms and/or legs.
Cutaneous B-cell Lymphoma
In addition to general DLBCL symptoms, patients with CBCL may also experience:
- Small, raised, solid lumps on the skin called papules (look like pimples).
- Thickened, flat, larger lumps.
- Nodules that are red or pink in colour.
- Ulcerations, which may occur with an infection.
Plasmablastic Lymphoma
In addition to general DLBCL symptoms, patients with PBL may also experience:
- A lump or sore in the mouth that may or may not bleed.
- Gastrointestinal symptoms, such as:
- Abdominal pain.
- Diarrhoea.
- Blood in stool.
- Nose bleeds.
- Frequent runny noses.
- Sinus inflammation.
- Lump in the skin.
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy.
Symptoms of Mantle Cell Lymphoma
In addition to the general symptoms listed above, patients with MCL may experience the following symptoms:
- Lymphadenopathy (especially in the neck, armpit, and groinarea between the abdomen and thighs).
- Diarrhoea.
- Blood in stool.
- Iron deficiency.
- Abdominal bloating.
- Loss of appetite.
Symptoms of Grey Zone Lymphoma
In addition to the general symptoms listed above, patients with GZL may experience the following symptoms:
- Dry cough.
- Lymphadenopathy (especially in the neck, armpit, and groin).
- Loss of appetite.
Symptoms of Burkitt Lymphoma
Adult
In addition to the general symptoms listed above, adult patients with BL may experience the following symptoms:
- Abdominal swelling.
- Abdominal pain.
- One or more lumps (clustering of lymphoma cells).
- Bleeding from the bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines.
- Bowel obstructiona complete or partial blockage of the bowel/intestines.
- Loss of appetite.
- Nausea.
- Diarrhoea.
Childhood
In addition to the general symptoms listed above, children with BL may experience the following symptoms:
- Recurrent infections.
- Lymphadenopathy (especially in the neck, armpit, or groin).
- Dry cough.
- Difficulty recurring from infection.
Precursor B-cell Lymphoblastic Lymphoma
In addition to the general symptoms listed above, patients with PBCLL may experience the following symptoms:
- Lymphadenopathy (especially in the neck, armpit, or groin).
- Easy bruising.
- Paleness of the skin.
- Dry cough.
- Difficulties recovering from an infection.
Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.
Diagnosis
If your doctor suspects you have an NHL, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests (if the cancer is thought to have spread beyond blood and bone marrow), potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- Lumbar puncturea procedure that involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis.
- Exploratory surgeryan exploratory surgical procedure used for conditions that cannot be confirmed by scans and tests alone.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Biopsyremoval of a section of tissue to analyse for cancer cells.
