Peripheral T-cell lymphoma (PTCL) is a rare and aggressive type of non-Hodgkin lymphoma (NHL). It develops in the T-cells, which are the mature white blood cells, and also in the NK (natural killer) cells.
There are various types of cancer which are known as NHL. These cancers start in lymphocyte cells, and they help the body fight against infections. There are three major types of lymphocytes such as B lymphocytes or B-cells, T lymphocytes or T-cells, and natural killer cells (NK cells). NHLs can be slow growing (indolent) or fast-growing (aggressive).
In this blog, we will cover peripheral T-cell lymphoma in detail, discussing its symptoms, treatment options, and other related information.
How Common Is Peripheral T-Cell Lymphoma?
About 10-15% of NHL patients develop a T-cell lymphoma subtype. People over 60 years old are usually the ones who get affected by this type of cancer. Diagnosis of this cancer is more common in men than women. But, it does not imply that young adults, or even children, for that matter, can not develop peripheral T-cell lymphoma. However slim the chances may be.
As we already mentioned, it is rarely the case when we come across a patient with this medical condition in the US. Even across the world, the disease is not common; however, the disease is comparatively more common in countries like Asia, Africa, and The Caribbean. It is possibly because of exposure to viruses like Epstein-Barr virus (EBV) and human T-cell leukemia virus-1.
Types Of Peripheral T-Cell Lymphoma?
There are various subtypes of peripheral T-cell lymphoma, such as AITL (angioimmunoblastic T-cell lymphoma), PCALCL (primary cutaneous anaplastic large cell lymphoma), and MF (mycosis fungoides). These are the most frequent subtypes of PTCL. Let’s have a look at all types of PTCL.
Angioimmunoblastic T-Cell Lymphoma (AITL)
About 2% of all NHL (non-Hodgkin lymphoma) cases are attributed to AITL. This subtype is usually aggressive (fast-growing), but, at times, it can have a spontaneous regression. It commonly occurs in the lymph nodes and can affect the patient’s liver or spleen.
Primary Cutaneous Anaplastic Large Cell Lymphoma (PCALCL)
PCALCL usually affects the skin and falls in the group of slow-growing (indolent) lymphoma. Even with a good prognosis, it is ALK-negative.
Nasal, Natural Killer (NK)/T-Cell Lymphoma
This lymphoma subtype affects the nasal area and some areas behind the nose and cheeks, which are the paranasal sinus areas. Although, it does not mean that it can only occur in those areas. Its occurrence can also be in the skin, testes, and gastrointestinal tract. Less than 1.5% of all NHL cases in the US come from this subtype, making it a rare disease.
Peripheral T-Cell Lymphoma, Not Otherwise Stated (PTCL-NOS)
It is the most common type of PTCL, containing a group of diseases that can not fit into any other PTCL subtype. In PTCL-NOS there are nodal as well as extranodal sites. The subtype is aggressive in nature most of the time.
Anaplastic Large Cell Lymphoma
This subtype is also pretty rare in adults, with a constitution of 3% of all NHL cases. The percentage of cases in children is much higher, making it more common in children. It can be further divided into ALK-positive and ALK-negative. The division is due to the absence or presence of anaplastic lymphoma kinase (ALK), which is a protein.
Blastic NK-Cell Lymphoma
Blastic NK-cell lymphoma is a subtype of PTCL which is hard to treat, rare, and grows very fast. Often, the patients in this category take part in clinical trials after discussing it with their medical team.
Precursor T-Cell Acute Lymphoblastic Lymphoma Or Leukemia
This condition can be diagnosed as leukemia or lymphoma, or even both of them. You can find this subtype more commonly in adolescents and male adults. However, it can also exist in children and other adults.
Enteropathy-Associated Lymphoma
Celiac disease is usually associated with this subtype. Celiac disease is a chronic disorder caused in the intestine due to being hypersensitive to gluten proteins. The common symptoms of enteropathy-associated lymphoma are weight loss, stomach pain, gastrointestinal bleeding, etc.
Hepatosplenic Lymphoma
It is an extremely aggressive and rare disease. You can find it commonly in young adults under 30 years. The patients of this subtype experience it first in their spleen or liver.
Subcutaneous Panniculitis-Like Lymphoma
This subtype is the rarest and is also the worst when it comes to well-defined lymphomas. It occurs in the subcutaneous fat tissues and forms nodules. Some of its symptoms include fever, weight loss, chills, and oral mucosal ulcers. They can be either aggressive or indolent.
Adult T-Cell Acute Lymphoblastic Lymphoma Or Leukemia
This type is more common in Japan and the Caribbean and is associated with the HTLV-1 virus. The transmission of HTLV-1 (Human T-cell Leukemia Virus-1) can be through blood transfusions, sexual intercourse, childbirth, breast milk, etc.
Apart from these subtypes, there are categories of PTCL that the WHO recognizes. Even though PTCL is already a type of cancer with subtypes, it also has these categories.
- Nodal
- Extranodal
- Leukemic
The WHO also added two groups into the T-cell lymphomas, which are: Aggressive (fast-growing) and Indolent (slow-growing).
How Is Peripheral T-Cell Lymphoma Different?
Peripheral T-cell lymphoma is different from B-cell lymphomas. It is because PTCL is a rare occurrence which makes it difficult to understand the functioning of this disease. It is only recently that some developments on the subtypes of PTCL were made. That is why there are no established treatment plans, whether it is for a newly diagnosed patient or relapsed or refractory patient.
There may also be some level of skin involvement; however, it is not like cutaneous t-cell lymphomas. In the case of cutaneous T-cell lymphomas, the origination is from the skin itself instead of the involvement.
Traditional chemotherapy treatments have been ineffective as well. There has been a recent development of new drugs that target the cancer type. It was only possible due to the recent understanding of peripheral T-cell lymphoma, new molecular testing techniques, and new genetic studies of T-cells.
It is safe to say that there has been development in the area of treatment. However, there is still a lot to discover, and we may get more treatment options in the near future. Many human trials are still in the process of finding better treatment options for the medical condition.
One other thing that you should note is that the research on PTCL is still not common, which is why you must rely on a specialized medical center for diagnosis and treatment.
Signs And Symptoms Of Peripheral T-cell Lymphoma
The first signs of peripheral T-cell lymphoma can vary based on the subtype of the disease because of the involvement of lymph nodes. Also, it is quite common to confuse the symptoms with other diseases as they tend to overlap. The discovery is usually at the later stages of the disease when cancer gets into its aggressive stage.
A painless, enlarged lymph node located in some areas of the body is a common sign of peripheral T-cell lymphoma. These areas include either side of the neck, armpits, back of the knees, groin, elbows, and ears.
These parts are not like reactive lymph nodes, as there is an increase in size due to infection. Peripheral t-cell lymphoma can also affect other organs such as the liver, stomach, and spleen, resulting in extreme levels of exhaustion, painful & enlarged belly, chest pain, infections, coughs, difficulty in breathing, nausea or vomiting, etc. Some of the other symptoms include:
- Night Sweats
- Fever
- Weight loss
- Rashes
Diagnosis
A biopsy or a small sample of an enlarged lymph node is used for the diagnosis of the majority of peripheral T-cell lymphoma. The next step is the examination of those cells under the microscope. The lymph node or some part of it undergoes the process of surgical removal. The removed nodes are used later by the hematopathologist** for a detailed diagnosis.
Sometimes, additional tests become an essential requirement for a precise diagnosis. It can help in avoiding confusion that arises from similarities in the cells of subtypes of PTCL. These additional tests can include positron emission tomography (PET), blood tests, computerized axial tomography (CT), magnetic resonance imaging (MRI), and bone marrow biopsy.
Some other tests to identify the subtypes of PTCL in a patient are flow cytometry and immunophenotyping, and chromosome tests. Tests like flow cytometry and immunophenotyping identify the type and maturity of the lymphocyte by looking for specific proteins or markers in cells. In contrast, tests like cytogenetic studies, polymerase chain reaction, and fluorescent in situ hybridization detect chromosomal and genetic changes in cells to identify the type of PTCL.
An accurate diagnosis can help with determining appropriate treatment approaches. We would advise you to consult an experienced hematopathologist to analyze your biopsy samples. A second opinion is also a good choice if there is any doubt related to the diagnosis.
**A hematopathologist is a doctor specializing in the interpretation and diagnosis of the physical changes that occur in blood and marrow diseases.
Different Stages Of Peripheral T-Cell Lymphoma
There are several stages of peripheral T-cell lymphoma, and understanding these stages can help your healthcare provider determine the most effective treatment course for you. The most common staging system for the classification of every NHL subtype is the Ann Arbor Staging System. It divides the system into four stages and uses the location of the disease in the body. These are the four stages:
- Stage 1: In the first stage of this cancer, the cancer occurs in a single lymph node or a region of the lymph node. The cancer can also be on a site other than a lymph node which is often called extranodal. However, it is limited to these nodes only and does not spread to other organs or lymph nodes.
- Stage 2: In this stage, the cancer spreads to two lymph and can spread even more in the lymph node regions. The spread is usually on one side of the diaphragm.
- Stage 3: Cancer spreads to both sides of the diaphragm, and there may also be partial involvement of extranodal organs or sites on either top or below the diaphragm.
- Stage 4: This is the final stage of peripheral T-cell lymphoma, where cancer spreads to multiple nodes and organs. You can also find the involvement of single or multiple extranodal sites, including the bone marrow.
The first two stages of cancer involving peripheral T-cell lymphoma are usually limited, and the more advanced stages of the cancer are 3rd and 4th. There are several treatment plans which differ on the type of diagnosis of the patient.
Peripheral T-Cell Lymphoma Prognosis
There are several scoring systems that are used to predict survivability and make treatment decisions. These systems are IPI (International prognostic index) and PIT (prognostic Index for PTCL).
The International Prognostic Index
The IPI, or International Prognostic Index, is a known scoring system. The information it provides helps medical experts to determine the suitable treatment plan for patients with aggressive types of lymphomas, predicting the risk of relapse. The scoring system assigns one point for the following risk factors.
- More than 60 years of age
- Disease at stage 3 or 4
- Involvement of more than one lymph node
- Performance status, which rates the ability of the individual to perform menial daily tasks without needing any help.
- Elevated serum LDH (lactate dehydrogenase)
The number of IPI factors determines the risk group of a person. It helps in predicting the risk of relapse. Every subsequent point increases the risk of recurrence of the disease. The categorization of the risk is as follows:
- 0-1 points are in the low-risk range
- 2 points fall in the low-intermediate range
- 3 points are in high-intermediate risk
- The highest risk is for the patients who have 4-5 points
This risk categorization is for patients older than 60 years of age. It is different for patients younger than 60 years. 0 points (low risk), 1 point (low-intermediate risk), 2 points (high-intermediate risk), and 3 points (high risk).
The Prognostic Index For PTCL (PIT)
This Index is more common for the prognosis of peripheral T-cell lymphoma, specifically. It separates the not otherwise specified (PTCL-NOS) patients, making them into more specific prognostic groups than the IPI. There are four risk factors in PIT: performance status, age, serum lactate dehydrogenase, and bone marrow involvement.
Using these risk factors instead of the IPI risk factors makes it a better choice for predicting PTCL-NOS. Once the prognosis is complete, the patients can refer to their doctor to receive appropriate treatment options.
Also Read: A Brief Guide On Invasive Ductal Breast Cancer/Carcinoma (IDC)
Treatment Option For Patient (Newly Diagnosed)
This section will cover the treatment plans that are available to newly diagnosed patients. Anthracycline-based chemotherapy regimes are common for treating these patients of peripheral t-cell lymphoma.
The other treatment options available for these patients are:
- CHOP (cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone).
- CHOP (cyclophosphamide, hydroxy doxorubicin, oncovin, etoposide, prednisone).
- EPOCH (etoposide, prednisone, oncovin, cyclophosphamide, hydroxy doxorubicin).
- Hyper-CVAD (cyclophosphamide, oncovin, Adriamycin, dexamethasone).
The term “hyper” in the Hyper-CVAD refers to the hypofractionation of the dose, which implies that chemotherapy provision is in small and frequent doses. The reason for providing small doses is to reduce the side effects of the dosage.
There is also a preference for clinical trials having new chemotherapy combinations. However, there is one thing that you must realize, which is that the rate of cure is very low, with only a few exceptions, such as ALK-positive anaplastic large-cell lymphoma and localized extranodal NK/T-cell lymphoma.
Treatment Options For Relapsed Or Refractory PTCL Patients
There is no common standard for the care of relapsed or refractory peripheral T-cell lymphoma. However, FDA has given approval to some drugs for the treatment of relapsed or refractory PTCL. These drugs are:
- Pralatrexate (Folotyn) is a metabolic inhibitor that is given through an IV. It is capable of reducing the size of the tumor.
- Belinostat (Beleodaq) is a histone deacetylase inhibitor and is also given by IV.
- Romidepsin (Istodax) is another histone deacetylase inhibitor given Intravenously. Istodax is approved for treating patients with prior therapy experience.
There are also some chemotherapy regimes that are used on relapsed or refractory PTCL patients. These regimens are:
- ICE (ifosfamide, carboplatin, etoposide)
- GND (gemcitabine, navelbine, dexamethasone) or similar regimens that contain gemcitabine.
- DHAP (dexamethasone, high-dose cytarabine [ara-C], cisplatin [platinol*-AQ])
- ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin)
Stem Cell Transplant For Relapsing PTCL
Peripheral T-cell lymphoma has a history of high relapse rates. In such cases, consolidative high-dose chemotherapy is followed by a stem cell transplant (SCT). It is usually a recommendation for first-time emission** patients. However, patients with a low risk of relapse and ALK-positive anaplastic large-cell lymphoma patients are exceptions for this treatment. It is because of their usually good prognosis and good response to certain chemotherapy combinations.
Broadly, two types of stem cell transplants are there, which are autologous and allogeneic. In autologous SCT, the patients are given their own stem cells. On the contrary, there is an allogeneic, where a patient receives the stem cells from another donor who matches the stem cells of the receiver.
Both of these types are common for treating PTCL patients. There are various studies going on to find out the best option for treating individual patients. Also, the use of stem cell transplantation alongside high-dose chemotherapy causes severe side effects and complications. Bone marrow suppression is one such complication. It also causes infections which is why stem cell transplants are not considered for treating every PTCL patient.
To determine whether the patient is capable of handling the treatment, the medical expert will consider many things, such as:
- General Health
- Medical history
- Stage of cancer
- Age
- Previous treatment response
An alternative to high-dose chemotherapy is the use of reduced-intensity conditioning (RIC) before a stem cell transplant. It is good for PTCL patients who are at high risk for developing toxicity with the use of high-dose chemotherapy. But, there is still a need to study RIC in PTCL patients to test its effectiveness.
**First-time emission refers to the situation where there was no evidence of disease using standardized tests.
Peripheral T-Cell Lymphoma ICD 10
The ICD-10-CM C84.48 is a specific code that indicates a diagnosis for the purpose of reimbursement. This code was revised on 1 October 2022 and is the American version of C84.48. The international versions of the code may differ from the American ones.
What Is The Survival Rate In Peripheral T-Cell Lymphoma?
About 10% of all lymphoma cases refer to the PTCL in North America. Chemotherapy is a potential cure for PTCL. However, there is no certainty of a complete cure. The median PFS or progression-free survival is around 1 year after the CHOP chemotherapy. The rate of survival is in the range of 20-30%. The patients in this survival range live disease-free for 5 years after getting the treatment.
The 5-year overall survival is 74% for low-risk IPI patients. The patients in the intermediate range of risk have survival rates of 49% and 21%, respectively, for the low-intermediate and high-intermediate risks. The rate drops further to 6% for high-risk IPI patients.
The rates are different for PIT-scored patients. The following table describes the 5 and 10-year overall survival (OS) rate.
| PIT Score | 5 year OS | 10 year OS |
|---|---|---|
| 0 | 62% | 55% |
| 1 | 53% | 39% |
| 2 | 33% | 18% |
| 3-4 | 18% | 12% |
While there is some level of overlap in the IPI and PIT standard survival rates, there is no clear standard, and most clinicians refer to the IPI standards to refer to PTCL survival rates.
Conditions Similar To Peripheral T-Cell Lymphoma
There are many similar conditions that are often confusing but vary from peripheral T-cell lymphoma. PTCL cutaneous involvement may suggest a dermatologic or rheumatologic process at the beginning. However, it can become even more confusing with the presence of a clonal T cell population in the lymph nodes. It can also be present in the patient’s peripheral blood making infectious or rheumatologic diseases difficult to distinguish.
PTCL can also be misdiagnosed in healthy patients over 60 years old due to the clonal T-cell population in the peripheral blood. A lack of empirical evidence of infection is one of the major reasons why it becomes easier to exclude similar lymphoma conditions when diagnosing rheumatologic disease.
PTCL is commonly an aggressive disease and even follows a subacute path. The initial lymph node sample may show signs of atypical lymphocytes but does not conclusively demonstrate peripheral T-cell lymphoma. To conclusively diagnose PTCL, there is a need for evaluation using multiple biopsy sites.
Conclusion
Peripheral T-cell lymphoma is a type of cancer that is usually an aggressive disease and has a low rate of occurrence. The disease is more common in older adults, usually over the age of 60 years old. The lack of studies and research on the PTCL is what makes it peculiar. It is also why one should only refer to a recognized healthcare provider.
