Non-Hodgkin Lymphoma (T-cell)

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 T-lymphocytes. T-cell lymphomas are the less common subtype of all lymphomas (including Hodgkin lymphomas), and are usually all aggressive.

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 Lymphoma (T-Cell)

There are several types of T-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.

Precursor T- cell Lymphoblastic Lymphoma

Lymphoblastic lymphomacancers of the lymphatic system (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 T-cell lymphoblastic lymphoma is the most common form of lymphoblastic lymphoma, and develops from immature T-cell lymphocytes. It generally develops from the thymus, or in other organs in the mediastinumthe space between the lungs that holds many important structures, including the heart, trachea and oesophagus. It behaves similarly to T-acute lymphoblastic leukaemiacancer of blood and/or blood forming tissues, but is much less common. While this type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs has a high recurrenceto occur or happen again rate, precursor T-cell lymphoblastic lymphoma can have a good prognosisto predict how a disease/condition may progress and what the outcome might be.

Peripheral T-cell Lymphoma

Peripheral T-cell lymphoma (PTCL) is a rare subtype of NHL that develops from mature T-lymphocytes. There are four broad categories that PTCL can be classified as:

• Nodal T-cell lymphoma (cancer located in the lymph nodes).
  • Peripheral T-cell lymphoma – not otherwise specialised.
  • Angioimmunoblastic T-cell lymphoma.
  • Anaplastica term used to describe abnormal cancer cells that grow uncontrollably in the body and have little or no resemblence to regular cells large cell lymphoma.
• Extranodal T-cell lymphoma (cancer located outside of the lymph nodes).
  • Intestinal T-cell lymphoma.
  • Nasal NK/T-cell lymphoma.
  • Hepatosplenic gamma delta T-cell lymphoma.
• Cutaneous T-cell lymphoma (cancer located in skin tissuea group of cells that work together to perform a function).
• Leukaemic T-cell lymphoma (cancer located in blood and bone marrow).
  • Adult T-cell leukaemia/lymphoma.
  • T-cell lymphoblastic lymphoma.

Peripheral T-cell lymphoma – not otherwise specified (PTCL-NOS)

Peripheral T-cell lymphoma – not otherwise specified (PTCL-NOS) is the most common subtype of PTCL, and refer to a group of cancers that don’t fit into any other type of PTCL. It is usually found in the lymph nodes, however in rare cases it can be extranodal.  While this cancer is aggressive and has a high recurrence rate, PTCL-NOS can have a good prognosis.

Angioimmunoblastic T-cell Lymphoma (AITL)

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of PTCL that is generally found in the lymph nodes. This cancer is aggressive, and often has a high recurrence rate. AITL may not have as good of a prognosis as other NHLs.

Anaplastic Large Cell Lymphoma (ALCL)

Anaplastic large cell lymphoma (ALCL) is a rare, nodal subtype of PTCL that is characterised by large, undeveloped, and abnormal (anaplastic) lymphoma cells. There are four main subtypes of ALCL, which are often classified as either systemic (ALCL in the lymphatic system) or cutaneous (ALCL in the skin).

• Systemic ALCL – ALK positive – the most common subtype.
• Systemic ALCL – ALK negative.
• Breast implant associated ALCL.
• Primary cutaneous ALCL.

Intestinal T-cell Lymphoma

Intestinal T-cell lymphoma is a rare, extranodal subtype of PTCL that develops in the small bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines/intestine. There are two primary types of intestinal T-cell lymphoma.

• Enteropathy-associated T-cell lymphoma (EATL) – most common subtype.
• Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).

Intestinal T-cell lymphoma is often diagnosed at a late stage of disease, and may not have as good of a prognosis as other types of NHL.

Nasal NK/T-cell Lymphoma

Nasal natural killer (NK) T-cell lymphoma is a rare, extranodal subtype of PTCL that develops from natural killer (NK) cells. NK cells are an integral part of the body’s immune system that are produced to kill cancerous cells and/or cells that have been infected by a virus. It generally affects the nose and nasal passages, however in rare cases it can also affect the skin and the gastrointestinal tract. Nasal NK T-cell lymphoma is often diagnosed at a late stage of disease, and may not have as good of a prognosis as other types of NHL.

Hepatosplenic Gamma Delta T-cell Lymphoma (HSGDTCL)

Hepatosplenic gamma delta t-cell lymphoma (HSGDTCL) is a very rare, extranodal subtype of PTCL that is often found in the liver (‘hepato’) and/or the spleen (‘splenic’). Unlike most types of NHL, the average of diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of this disease is 30 years old. HSGDTCL tends to develop from gamma delta T-cells, which play a part in the inflammatory response of the body to foreign pathogensany substance or organism that has the potential to cause disease (e.g. bacteria, viruses, fungi, parasites etc.). It is often diagnosed at a late stage of disease, has a high recurrence rate, and may not have as good of a prognosis as other types of NHL.

Cutaneous T-cell Lymphoma (CTCL)

Cutaneous T-cell lymphoma (CTCL) is a rare subtype of PTCL that is found in the skin. In most cases, these cancers are indolent. There are many types of CTCL:

• Mycosis fungiodes – most common subtype of CTCL.
• Sezary syndrome (aggressive).
• Lymphomatoid papulosis.
• Primary cutaneous anaplastic large-cell lymphoma.
• T-cell skin lymphoma.
• Subcutaneousunder the skin panniculitis-like T-cell lymphoma.

Most types of CTCL have a good prognosis due to their indolent nature.

Adult T-cell Leukaemia/Lymphoma

Adult T-Cell Leukaemia/Lymphoma (ATLL) are a rare, leukaemic PTCL that develops from mature T-cells. It is often found in the blood, lymph nodes, skin, and other areas of the body. There are four primary subtypes of ATLL:

• Acutenew, recent, comes with an urgent or significant sense, is sudden, sharp ATLL (aggressive).
• Lymphomatous ATLL (aggressive, most common).
• Chronica long-lasting disease that changes slowly over time ATLL (indolent).
• Smouldering ATLL (indolent).

ATLL can be aggressive, often has a high recurrence rate, and may not have as good of a prognosis as other types of NHL.

Treatment

If a T-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 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.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

• Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
• Grade II: cancer cells are abnormal and grow faster than grade-I tumours. This is also known as an intermediate grade tumour.
• Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

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 T-cell NHLs may include:

• Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen (only for indolent lymphomas).
• 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 lesions (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 types 1 (HTLV-1) and 2 (HTLV-2).
  • 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 transplanta surgical procedure that involves removing a failing or damaged organ and replacing it with a healthy one from a donor.
• Having celiac disease (only a riskthe possibility that something bad will happen factor for intestinal t-cell lymphoma)
• Having a history of inflammatory bowel disease (only a risk factor for hepatosplenic gamma delta T-cell lymphoma).

Not everyone with these risk 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

Patients with a T -cell NHL may appear asymptomatic in the early stages of disease. As symptoms progress, some of the following symptoms may appear.

General Symptoms

General symptoms of a T-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 Precursor T-cell Lymphoblastic Lymphoma

In addition to the general symptoms listed above, patients with PTCLL may experience the following symptoms:

• Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy (especially in the neck, armpit, or groinarea between the abdomen and thighs).
• Easy bruising.
• Paleness of the skin.
• Dry cough.
• Difficulties recovering from an infection.

Symptoms of Peripheral T-cell Lymphoma – Not otherwise specified

In addition to the general symptoms listed above, patients with PTCL-NOS may experience the following symptoms:

• Abdominal pain and/or discomfort.
• Bloating.
• Itchy, red patches on the skin.
• Chest pain.

Symptoms of Angioimmunoblastic T-cell Lymphoma

In addition to the general symptoms listed above, patients with AITL may experience the following symptoms:

• Skin rash.
• High antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses levels in the blood.
• Painful, swollen joints.
• Inflammation of blood vessels.
• Thyroid problems.
• Swollen liver, which may cause:
  • Bloating.
  • Ascitesa buildup of fluid in the abdomen.
  • Jaundiceyellowing of the skin and the whites of the eyes.
• Swollen spleen, which may cause:
  • Pain behind the rib cage.
  • Feeling full after little food.

Symptoms of Anaplastic Large Cell Lymphoma

In addition to the general symptoms listed above, patients with ALCL may experience the following symptoms:

• Loss of appetite.
• Abdominal discomfort and/or pain.
• Skin rash.
• Bloating.
• Nauseato feel sick or likely to vomit and/or vomiting.

Patients with Breast implant associated ALCL may also experience:

• Build-up of fluid or lump around implant.
• Soreness of implant area.

Symptoms of Enteropathy-associated T-cell Lymphoma

In addition to the general symptoms listed above, patients with EATL may experience the following symptoms:

• Abdominal discomfort and/or pain.
• Diarrhoeafrequent discharge of watery or loose stools from the body.
• Blood in stools.
• Skin rash.

Symptoms of Monomorphic Epitheliotropic Intestinal T-cell Lymphoma

In addition to the general symptoms listed above, patients with MEITL may experience the following symptoms:

• Abdominal discomfort and/or pain.
• Malnutrition.
• Bowel obstructiona complete or partial blockage of the bowel/intestines.
• Intestinal perforations.
• Diarrhoea.
• Blood in stools.

Symptoms of Nasal NK/T-cell Lymphoma

In addition to the general symptoms listed above, patients with nasal NK/T-cell lymphoma may experience the following symptoms:

• Blocked nose.
• Nosebleeds.
• Facial swelling.
• Watery eyes.
• Skin rash.

Symptoms of Hepatosplenic Gamma Delta T-cell Lymphoma

In addition to the general symptoms listed above, patients with HSGDTCL may experience the following symptoms:

• Swollen liver, which may cause:
  • Bloating.
  • Ascites.
  • Jaundice.
• Swollen spleen, which may cause:
  • Pain behind the rib cage.
  • Feeling full after little food.

Symptoms of Cutaneous T-cell Lymphoma

In addition to the general symptoms listed above, patients with CTCL may generally experience the following symptoms:

• Bright red, thickened, swollen and sore skin.
• Peeling skin lesions.
• Hair loss.
• Thickening of the skin on the palms of the hands and/or the soles of the feet.
• Thickening of the nails.
• Drooping of the lower eyelid(s).
• Swollen liver, which may cause:
  • Bloating.
  • Ascites.
  • Jaundice.
• Swollen spleen, which may cause:
  • Pain behind the rib cage.
  • Feeling full after little food.
• Patches of lighter or darker skin.
• Skin swelling (tumours, plaques and/or nodules), which can ulcerate and/or scab.
• Dry and scaley skin.
• Large levels of Sezary cells in the blood (only in patients with Sezary syndrome).
• Deep, persistent muscle aches (only in patients with Subcutaneous panniculitis-like T-cell lymphoma).
• Elevated liver enzymes in the blood (only in patients with Subcutaneous panniculitis-like T-cell lymphoma).

Symptoms of Acute and Lymphomatous Adult T-cell Leukaemia/lymphoma

In addition to the general symptoms listed above, patients with acute and lymphomatous subtypes of ATLL may generally experience the following symptoms:

• Leukocytosishigh levels of white blood cells in the blood.
• Hypercalcaemiaexcess levels of calcium in the blood.
• Irregular heart rhythms.
• Constipationa condition where a person has difficulty passing faeces/stools.
• Skin rash.
• Diarrhoea.
• Headaches.
• Polyuriafrequent urination.
• Polydipsiaabnormal or escessive thirst.

Symptoms of Chronic and Smouldering Adult T-cell Leukaemia/lymphoma

In addition to the general symptoms listed above, patients with chronic and smouldering subtypes of ATLL may generally experience the following symptoms:

• Leukocytosis.
• Skin rash and/or lesions.
• Swollen liver, which may cause:
  • Bloating.
  • Ascites.
  • Jaundice.
• Swollen spleen, which may cause:
  • Pain behind the rib cage.
  • Feeling full after little food.

Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have an NHL, they may order the following tests to confirm the diagnosis 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.

References

• Cancer Council Australia
• Leukaemia Foundation
• Lymphoma Australia