What Is Peripheral T-Cell Lymphoma

Overview

Lymphoma is a cancer that starts in the lymphatic system, a part of the body's immune system. It is broadly categorized into two main types: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

Peripheral T-cell lymphoma (PTCL) falls under the non-Hodgkin lymphoma category, specifically within the subgroup of T-cell lymphoma, and it is relatively rare and aggressive. T-cell lymphomas, including PTCL, develop from abnormal T-cells and differ from B-cell lymphomas, which originate from B-cells, another type of white blood cell.

PTCL specifically originates in mature T-cells and natural killer cells. PTCLs are a heterogeneous group of diseases, meaning they have diverse subtypes, each with distinct clinical and pathological features.¹ 

Understanding PTCL is crucial due to its aggressive behaviour, rapid progression, and limited treatment options, particularly since it is often linked with a serious prognosis.² PTCLs often do not respond well to standard chemotherapy used for other lymphomas, posing significant challenges in finding effective treatment strategies.² Research into targeted therapies and immunotherapies is essential to improving outcomes.

Understanding lymphoma 

Lymphoma is a type of cancer that originates in the lymphatic system, a vital part of the body's immune system.³ The lymphatic system includes lymph nodes, spleen, tonsils, and bone marrow, among other components. Lymphomas occur when lymphocytes, a type of white blood cell involved in the immune response, become malignant and form tumours.³ These tumours can develop in lymph nodes or other lymphatic tissues, disrupting the normal functioning of the immune system.³

Hodgkin lymphoma (HL)

• Distinctive cells - HL is characterised by the presence of Hodgkin Reed-Sternberg cells, large abnormal cells of B-cell origin
• Subtypes - HL has four specific subtypes based on the characteristics of Hodgkin Reed-Sternberg cells
• Prognosis - HL often has a better prognosis and is considered more curable than many types of non-Hodgkin lymphomas

Non-hodgkin lymphoma (NHL)

• Diverse types - NHL includes a wide range of lymphomas that do not have Reed-Sternberg cells and are more diverse in terms of cell types and behaviours
• High heterogeneity - NHL is highly heterogeneous meaning that patients with this cancer may have various compositions of cancerous cells. It has various subtypes, each having distinct clinical, pathological, and genetic features
• Prognosis - prognosis in NHL varies significantly based on the specific subtype, stage at diagnosis, and response to treatment

T-cell lymphomas are a subset of non-Hodgkin lymphomas that originate from T-cells, a type of lymphocyte involved in cell-mediated immunity. They can affect lymph nodes and other organs, similar to B-cell lymphomas.³

Causes and risk factors

Genetic factors

• Somatic mutations (mutations within non-reproductive cells) - PTCL development is often associated with specific genetic mutations in T-cell receptor genes and signalling pathways, leading to inflammation and uncontrolled cell growth⁴
• Genetic predisposition - certain genetic predispositions, such as chromosomal variations may increase susceptibility to PTCL, although specific genes involved are still under investigation⁴

Environmental factors

• Infections - Epstein-Barr virus (EBV) infection has been linked to some PTCL subtypes, alongside acquired immune deficiency syndrome (AIDS), human herpes virus, and Helicobacter pylori⁴
• Autoimmune diseases - certain autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis and coeliac disease, are linked to a greater occurrence of various NHL types⁴
• Immunosuppression - populations with a suppressed immune system, such as those on immunosuppressive medications, or following an organ transplant, are more likely to develop PTCL⁴
• Chemical exposure - exposure to certain chemicals and toxins, such as pesticides, benzene, and organic solvents, may increase the risk of PTCL development. Individuals working in industries where they are often exposed to chemicals, such as agriculture, may be at higher risk⁴
• Lifestyle - smoking and obesity are linked with an increased risk of PTCL development⁴

Symptoms and diagnosis

Symptoms

Symptoms of PTCL are broad and dependent on disease subtype and stage. Below are some common symptom groups.

Generalised lymphadenopathy - enlarged lymph nodes, often painless, in various parts of the body, sometimes causing limb swelling⁵

Skin involvement: 

• Rash 
• Ulcers
• Itchy skin

Respiratory symptoms: 

• Persistent cough 
• Difficulty breathing
• Chest pain

Digestive issues: 

• Abdominal pain 
• Nausea 
• Vomiting
• Diarrhoea

Neurological symptoms: 

• Headaches
• Seizures
• Other neurological symptoms within the central nervous system

Diagnosis

Diagnosis of PTCL is confirmed by biopsy, a procedure during which a piece of tissue is removed for examination. This sample is usually taken from a lymph node; however, bone marrow biopsies can be useful in determining the presence of cancerous cells in the bone marrow.³

Further evaluation could include imaging studies, such as CT, PET, and MRI scans. Blood tests are also a significant assessor of PTCL and disease progression. A complete blood count measures the number and types of blood cells, revealing abnormalities associated with lymphoma, whereas other blood composition tests could evaluate organ function and detect anomalies that may indicate lymphoma-related complications.³ 

Additionally, in some high-risk cases, diagnosis may be supplemented with cerebrospinal fluid testing, which is a useful tool for predicting relapse or progression when the nervous system is affected.³

Treatment approaches

Early-stage PTCL can usually be monitored or treated with skin-directed treatments, such as topical medications, ultraviolet therapy or involved-field radiotherapy. On the other hand, aggressive PTCLs would require chemotherapy with multiple agents used or radiation therapy. Chemotherapy is the standard first-line treatment, and it involves the administration of a range of drugs such as cyclophosphamide, doxorubicin, vincristine, and prednisone (collectively called CHOP).³

For eligible patients, high-dose chemotherapy followed by autologous stem cell transplantation may be considered for secondary treatment or relapse cases.² Antibody medications like Brentuximab vedotin may also be used, targeting specific markers on lymphoma cells. This prevents further tumour growth and causes cell death, contributing to higher remission rates and better survival outcomes.⁶

There is a wide range of other therapeutic options being researched to provide a better prognosis for patients with highly aggressive forms of cancer and to decrease the chances of remission. One of these includes the use of CAR-T therapies, which is when immune cells are modified to target tumours.⁶ 

Despite this, lymphoma treatments come with an array of disadvantages and a wide range of side effects. Some treatments, such as radiotherapy, may slightly increase the risk of developing secondary cancers later in life. Certain chemotherapy agents may impact heart and lung function, requiring long-term monitoring. PTCL treatments may also affect fertility, and treatment may not always be effective.³

Prognosis and survival rates

Factors influencing prognosis:^1,3

• Stage at diagnosis - staging helps determine the extent of cancer spread and guides treatment decisions, and early-stage diagnosis often leads to more favourable outcomes
• Response to treatment - a positive response to initial treatment is a crucial indicator of prognosis; hence patients achieving complete remission or partial remission have better outcomes
• Subtype - different PTCL subtypes have varied levels of aggression and some respond better to certain treatments, influencing prognosis
• Age and overall health - younger, healthier patients often tolerate intensive treatments better, leading to improved prognosis; patients who do not smoke, are not exposed to organic solvents and have a healthy diet are more likely to react better to treatments

Summary

Peripheral T-cell lymphoma is a rare and aggressive non-Hodgkin lymphoma originating from T-cells. There are several diverse subtypes with distinct clinical and pathological features. PTCL can be diagnosed through biopsies, imaging studies, and blood tests; however, it poses some challenges due to tumour diversity, which often requires specialised testing for accurate classification. 

Treatment options include chemotherapy, immunotherapy, radiation therapy, and, in some cases, stem cell transplantation. Common side effects and long-term considerations include potential impact on fertility, secondary cancers, and issues concerning the heart and lungs. Prognosis is influenced by factors such as diagnosis stage, treatment response, subtype, age, and overall health.

Understanding PTCL is vital in advancing cancer research and treatment, especially considering its rarity, aggressive nature, and unique challenges in finding suitable therapies. By delving into the complexities of PTCL, researchers and clinicians can work towards more targeted and effective treatments, ultimately improving the prognosis and quality of life for patients diagnosed with this aggressive form of lymphoma. 

Continued research, awareness, and innovative therapies offer promising avenues for improved outcomes for PTCL patients. Collaboration among researchers, healthcare providers, and advocacy groups is essential in driving progress and providing hope for a brighter future for individuals diagnosed with this challenging disease.