Peripheral T-cell lymphomas (PTCLs) are rare, aggressive lymphomas that affect mature T cells. “Peripheral” means the cancer developed from lymphoid tissue outside the thymus.

This cancer is a subtype of non-Hodgkin lymphoma (NHL) and accounts for 6–10% of all NHL cases. PTCL can affect anyone, although it is slightly more common in males ages 60 years and over.

This article discusses PTCL, its signs and symptoms, causes, diagnosis, stages, treatment options, and outlook.

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Most often, symptoms of PTCL are nonspecific and may overlap other conditions. The disease process usually appears late and in aggressive stages.

While PTCL can have a wide range of signs and symptoms, it usually affects lymph nodes. A common sign of PTCL is a painless, enlarged lymph node located in one of the following areas:

  • on either side of the neck
  • the armpit
  • the groin
  • on the back of the knees
  • near the ears
  • on the elbows

These are not the same as reactive lymph nodes, which increase in size due to infection. Aside from lymph nodes, PTCL can affect organs such as the skin, liver, spleen, and stomach, which may cause:

Some people may experience the three “B symptoms,” which are drenching night sweats, fevers that come and go, sometimes for weeks, and unexplained weight loss.

The cause of PTCL is unknown. However, research from 2020 mentions that changes in the DNA’s structure causing abnormal gene expression (epigenetic alterations) have an essential role in the development of certain types of PTCL.

Certain conditions may cause alterations in the DNA of lymphocytes or increase the chances for mutations to occur. These conditions include long-term, viral, and bacterial infections.

For example, an infection with the human T-cell lymphotropic virus type 1 (HTLV-1) can cause adult T-cell lymphoma/leukemia (ATLL). A 2020 study found that HTLV-1 has specific mRNA viral genes involved in the development of ATLL from people infected with the virus.

The Epstein-Barr virus causes lymphomas, including Burkitt lymphoma and diffuse large B-cell lymphoma. A 2021 in-vitro study stated that it is also associated with over 80% of angioimmunoblastic T-cell lymphoma (AITL).

A 2014 review found that individuals with a family history of blood cancers, eczema, psoriasis, and celiac disease are at risk of developing PTCL, as well as the following groups:

  • people who have smoked for over 40 years
  • textile workers
  • electrical fitters

To make a diagnosis, a doctor conducts a medical history and a physical examination, paying close attention to a person’s clinical information. If a doctor suspects a person has lymphoma, they will request a lymph node biopsy, where a healthcare professional removes part or the entire lymph node for lab analysis.

Sometimes, a doctor may also ask for other samples, such as a bone marrow biopsy and a cerebrospinal fluid analysis, also known as a spinal tap.

Specialists may request additional tests to identify the type of PTCL a person has. These include:

  • Flow cytometry and immunophenotyping. This test looks for specific proteins or markers in cells that can identify the type of lymphocyte and how mature the lymphocyte is.
  • Chromosome tests. Cytogenetic studies, fluorescent in situ hybridization, and polymerase chain reaction tests detect genetic and chromosomal changes in cells.

Doctors may also order imaging tests, such as chest X-rays, CT scans, PET scans, and MRIs to find the extent of the lymphoma.

Blood tests, including a complete blood count, metabolic panel, and serum lactate dehydrogenase, can also help determine lymphoma and monitor its progression.

Experts developed a staging system that helps healthcare professionals know the extent of cancer spread. The Lugano classification consists of four stages, indicated as Roman numerals I–IV. When the lymphoma has affected an organ outside the lymphatic system (extralymphatic organ), an E is added to the stage, for example, IIE.

Stage I

  • I: The cancer is limited to one lymph node or lymphoid organ.
  • IE: The cancer is only in one area of a single organ outside the lymph system.

Stage II

  • II: The cancer is in two or more lymph nodes in the region of the diaphragm (above or below).
  • IIE: The cancer is in one organ and its regional lymph nodes. It may or may not affect other groups of lymph nodes on the same side of the diaphragm.

Stage III

  • The cancer is in the lymph node areas on both sides of the diaphragm (above and below).
  • The cancer is in the lymph nodes found above the diaphragm and in the spleen.

Stage IV

  • The cancer has spread throughout the body outside the lymph system, commonly in the liver, lungs, or bone marrow.

Stages I and II and stage II non-bulky are under limited or localized diseases, while stages III and IV are considered advanced.

The general practice is to treat the disease whether it is limited or advanced. For stage II bulky lymphomas, doctors need to consider other prognostic factors to determine if it is limited or advanced.

Treatment for limited stages involves a short course of chemotherapy and a targeted drug, with or without radiotherapy, also known as radiation therapy. Healthcare professionals treat advanced stages with a more intensive chemotherapy treatment that combines three or four drugs.

Drug combinations

While PTCL has no standard of care, most subtypes receive an initial treatment of a combination chemotherapy regimen. The regimens are most commonly CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) or other multidrug combinations such as CHOEP (CHOP plus etoposide) and EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone).

Many other combinations are available and currently under study.

For example, a 2019 animal study found that combining tyrosine kinase inhibitor dasatinib with CHOEP helped reduce cancer growth in mice.

Stem cell transplants

Doctors may recommend that fit individuals who responded well to initial intensive chemotherapy treatments undergo a stem cell transplant, which studies suggest may improve outcomes and lead to longer remissions.

Other therapies

Doctors may give antiviral drugs to people with PTCL caused by viruses in addition to a chemotherapy regimen. Those with localized PTCL, such as extranodal NK/T-cell lymphoma and angioimmunoblastic T-cell lymphoma, may benefit from radiation therapy. Some may also benefit from chemotherapy with radiation (chemoradiation).

Clinical trials

Since these standard treatment options are only based on small trials and lack randomized trials, response to these treatments is usually unsatisfactory. Doctors may recommend that people participate in clinical trials that involve new drugs or drug combinations.

The outcome of PTCL is generally poor except for anaplastic large cell lymphoma and anaplastic lymphoma kinase. Treatment outcomes with conventional therapy have also been poor.

However, advances in genetic and molecular testing techniques and a greater understanding of PTCL have led to the development of new drugs that are currently under study and trial.

Doctors use the International Prognostic Index (IPI) to help them determine the outlook and overall survival in individuals with aggressive lymphomas, such as PTCL. It can also help them decide on the appropriate care and predict the risk of relapse. The IPI includes five factors:

  • a person’s age
  • lymphoma stage
  • presence of lymphoma in organs outside the lymph system (extralymphatic organ)
  • performance status, or a person’s ability to function in everyday activities
  • levels of lactate dehydrogenase in the blood, which increase according to the amount of lymphoma in the body

PTCL is a group of rare, aggressive diseases that affect mature T cells. Since PTCL can appear in different areas of the body, it may cause varying symptoms in individuals. Similarly, a person’s treatment varies depending on multiple factors.

While outcomes for PTCL are generally poor because of its rarity, advances in techniques are assisting experts in developing new drugs that may help treat PTCL.