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 indolent (or slow growing) NHLs that develop from B-lymphocytes. While B-cell lymphomas are the most common subtype of all lymphomas (including Hodgkin lymphomas), indolent lymphomas are less common.
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 (Indolent B-Cell)
There are several types of Indolent B-cell NHL, 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.
Follicular Lymphoma
Follicular lymphomacancers of the lymphatic system is the most common subtype of indolent NHL, and is characterised by the circular or clump-like appearance of cancerous follicular B-cells under the microscope. There are four main subtypes of follicular lymphoma.
Duodenal-type Follicular Lymphoma
Duodenal-type follicular lymphoma, or primary gastrointestinal follicular lymphoma (PGFL), develops in the duodenum, which is the first portion of the small intestinea section of the gastrointestinal tract that recieves food from the stomach and absorbs the nutrients from food, also called small bowel. It is a very-slow growing type of NHL, is usually diagnosed in early stages, and often has an excellent prognosisto predict how a disease/condition may progress and what the outcome might be.
Predominantly Diffuse-appearing Follicular Lymphoma
Predominantly diffuse-appearing follicular lymphoma is characterised by scattered (or diffuse) follicular lymphoma cells spread throughout an area in the body (most commonly in the groinarea between the abdomen and thighs or inguinal area). Despite its diffuse appearance, it often carries a good prognosis.
Paediatric-type Follicular Lymphoma
Paediatric-type follicular lymphoma is a very rare subtype that mostly affects children, but can affect adults up to 40 years of age. It often behaves differently to standard follicular lymphoma, as it behaves more like a benignnot cancerous, can grow but will not spread to other body parts tumour. This subtype rarely metastasises, has a very low recurrenceto occur or happen again rate, and often carries a good prognosis.
Extranodal Follicular Lymphoma
In rare cases, follicular lymphoma can develop outside of the lymph nodes. This is known as an extranodal follicular lymphoma, and is usually found on the skin.
Chronic Lymphocytic Leukemia (CLL) & Small Lymphocytic Lymphoma (SLL)
Chronica long-lasting disease that changes slowly over time lymphocytic leukaemiacancer of blood and/or blood forming tissues (CLL) and small lymphocytic lymphoma (SLL) are often coupled together and expressed as CLL/SLL, as the two diseases are very similar. The main difference between CLL and SLL is the location of the cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. CLL is mostly found in the blood (like a leukaemia), whereas SLL is mostly found in lymph nodes and lymphoid tissuea group of cells that work together to perform a function (like a lymphoma). CLL is also slightly more common than SLL. CLL/SLL can metastasise, and can have a good prognosis.
For more information on CLL/SLL, please refer to the Rare Cancers Australia Chronic Lymphocytic Leukaemia (CLL) page.
Waldenstorm’s Macroglobulinemia (WM)
Waldenstorm’s Macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is a rare subtype of NHL that is generally found in the spleen, which is a blood-filtering organ in the immune system. It is known for causing an overproduction of immunoglobulin macroglobulin (IgM), which is an antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses in the immune system that acts as a primary barrier against pathogensany substance or organism that has the potential to cause disease (e.g. bacteria, viruses, fungi, parasites etc.). WM can be confused with myeloma, however the two diseases are treated differently. WM often has a good prognosis.
Marginal Zone Lymphoma (MZL)
Marginal zone lymphoma (MZL) is a rare subtype of indolent NHL that mainly affects lymphocytes at the edges of lymph nodes and/or lymphoid tissue. Unlike most NHLs, MZL is slightly more common in women. There are three main subtypes of MZL.
Mucosa-associated Lymphoid Tissue (MALT) Marginal Zone Lymphoma
Mucosa-associated lymphoid tissue (MALT) MZL is the most common subtype of MZL, and is classified as an extra-nodal lymphoma (lymphoma developing outside of lymph nodes). The lymphoma is found in the mucosa that lines lymphoid tissue, such as the tonsils, and scattered around the rest of the body.
MALT MZL is often divided into gastric and non-gastric categories, and are treated differently from each other. Gastric MALT MZL is the most common subtype, and develops in the stomach. Non-gastric MALT MZL develops outside of the stomach, and is usually found in the eyes (ocular adnexa), lungs, and salivary glands.
Nodal Marginal Zone Lymphoma
Nodal MZL, also known as monocytoid B-cell lymphoma, is the rarest type of MZL, and is found in the marginal zones surrounding lymph nodes. Unlike most other NHLs, this subtype is slightly more common in women than in men. It is slow growing, unlikely to metastasise, but can recur. Nodal MZL can have a good prognosis.
Splenic Marginal Zone Lymphoma
Splenic MZL is a rare subtype of MALT MZL that develops in the spleen, bone marrow, and blood. It has been linked to people who have autoimmune disorders and/or the hepatitis C virus. Unlike most NHLs, splenic MZL does not cause swollen lymph nodes. It is slow growing, unlikely to metastasise, but can recur. Splenic MZL can have a good prognosis.
Cutaneous B-cell Lymphoma (CBCL)
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.
Primary Cutaneous Follicle Centre Lymphoma (PCFCL)
Primary cutaneous follicle centre lymphoma (PCFCL) is the most common subtype of CBCL. They normally develop on the head, neck or torso of the body, often develop slowly, and usually carry a good prognosis.
Primary Cutaneous Marginal Zone Lymphoma
Primary cutaneous MZL (PCMZL) is the second most common type of CBCL that originates from mucosa-associated lymphoid tissue (MALT). It is normally found on the torso or the arms, and tends to affect men twice as much as women. It develops slowly, has a high recurrence rate, and often carries a good prognosis.
Primary Cutaneous Diffuse Large B-cell Lymphoma
Primary cutaneous diffuse large B-cell lymphoma is an aggressive subtype of CBCL. For more information on this disease, please refer to the Rare Cancers Australia Non-Hodgkin Lymphoma (Aggressive B-Cell) page.
Treatment
If an indolent 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 abdomenstomach, stomach area, belly 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 ‘indolent’, these cancers are all low-grade.
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 indolent B-cell NHLs may include:
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- 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.
- 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.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Bone marrow transplanta procedure that involves replacing unhealthy bone marrow with healthy bone marrow.
- Photodynamic therapya procedure that involves inserting a light-sensitive drug (photosensitiser) to shrink and damage cancer cells when exposed to a light source.
- Splenectomyremoval of the spleen (only required for patients who have a lymphoma in their spleen, such as splenic MZL).
- 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).
- 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.
- Having had a previous organ transplanta surgical procedure that involves removing a failing or damaged organ and replacing it with a healthy one from a donor.
- Infections with certain bacteria, such as helicobacter pylori (H. pylori – known to cause stomach ulcers).
- Having a family history of NHL.
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 indolent B-cell NHL will appear asymptomatic in the early stages of disease. As symptoms progress, some of the following symptoms may appear.
General Symptoms
General symptoms of an indolent 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.
- Recurrent infections.
- 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 Follicular Lymphoma
In addition to the general symptoms listed above, patients with follicular lymphoma 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.
- Haematuriathe presence of blood in urine.
- Feeling of fullness after little food.
- Confusion and/or memory changes.
- Personality changes.
- Seizures.
- Weakness, burning, pins and needles, and/or numbness in limbs.
- Chest pain.
- Dry cough.
- Red/purple looking rash.
- Skin lumps.
- Abdominal pain (more common in duodenal-type follicular lymphoma).
- Heartburn (more common in duodenal-type follicular lymphoma).
- Massa growth of cells that come together to make a lump, may or may not be cancer in groin (more common in predominantly diffuse-appearing follicular lymphoma).
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy in neck and head (more common in paediatric-type follicular lymphoma).
Symptoms of CLL/SLL
In addition to the general symptoms listed above, patients with CLL/SLL may experience the following symptoms:
- Easy bruising and/or bleeding.
- Painless lump in the neck, under arms, groin, and/or other areas.
Symptoms of Waldenstorm’s Macroglobulinemia
In addition to the general symptoms listed above, patients with WM may experience the following symptoms:
- Abnormal bleeding from nose, gums, and/or gastrointestinal tract.
- Headache.
- Peripheral neuropathy.
- Muscle cramps.
- Poor concentration.
- Confusion.
- Hyper-viscosity syndrome.
Symptoms of Marginal Zone Lymphoma
In addition to the general symptoms listed above, patients with MZL may generally experience the following symptoms:
- Lymphadenopathy.
- Easy bruising and/or bleeding.
- Loss of appetite.
- Abdominal pain.
Gastric MALT MZL
- Persistent indigestion.
- Nausea and/or vomiting.
Non-gastric MALT MZL
- Low iron and/or haemoglobin.
- Diarrhoea.
- Constipation.
- Bloating.
- Feeling full after little food.
- Redness of eyes.
- Dark pink lumps on the inside of the eyelid.
- Diplopiaseeing two images of a single object, also known as double vision.
- Droopy eyelids.
- Proptosisbulging or protrusion of one or both of the eyes out of the eye sockets, also known as exophthalmos.
- Cough, which may contain blood.
- Chest pain.
- Lump in the front of the ear, in the mouth, or on the jaw.
- Difficulty swallowing.
- Skin patches (usually pink, red, or purple in colour).
- Skin lumps.
- Hoarse voice.
- Sensitivity to the cold.
- Weight gain.
Nodal MZL
- Pressure on the airway, which may cause difficulties with breathing and/or swallowing.
- Nerve pain.
Splenic MZL
- Splenomegalyenlargement of the spleen.
- Feeling full after little food.
Symptoms of Indolent Cutaneous B-Cell Lymphoma
In addition to the general symptoms listed above, patients with indolent cutaneous B-cell lymphoma may experience the following symptoms:
- 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.
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.
