Peripheral T-Cell Lymphoma - An Overview

What Is Peripheral T-Cell Lymphoma?

Peripheral T-cell lymphoma (PTCL) is an uncommon, heterogeneous tumor of T cells classified as non-Hodgkin lymphoma (NHL). It is a diverse category of lymphomas that accounts for 5 % to 15 % of all non-Hodgkin lymphomas (NHL). Peripheral T-cell lymphoma (PTCL) has peripheral (systemic) and cutaneous versions derived from T-cells and natural killer (NK) cells and are frequently aggressive clinically.

What Is the Etiology of Peripheral T-Cell Lymphoma?

• The etiology of peripheral T-Cell lymphoma remains unknown. However, a family history of hematologic malignancies, eczema, psoriasis, celiac disease, heavy smoking, and specific employment is related to a high risk of peripheral T-cell lymphoma (PTCL).

• Molecular analysis revealed that the tyrosine kinase receptor ALK gene (2p23) is overexpressed due to a t(2;5)(p23;q35) translocation.

• Environmental factors, immunological changes, infections, and other cancers are potential causes of peripheral T-Cell lymphomas.

• Given that the people afflicted by these illnesses have a familial susceptibility to malignancies, genetic factors appear to be more implicated in the onset of mycosis fungoides (MF) than other lymphomas.

How Is Peripheral T-Cell Lymphoma Classified?

Peripheral T-cell lymphoma (PTCL) is classified as:

1. Angioimmunoblastic T-cell lymphoma (AITL).

2. Mycosis fungoides (MF).

3. Primary cutaneous anaplastic large cell lymphoma (PCALCL).

Angioimmunoblastic T-cell Lymphoma (AITL)- is currently recognized as a distinct subtype of peripheral T-cell lymphoma (PTCL). According to molecular investigations, the follicular T helper cell is the cell of origin for angioimmunoblastic T cell lymphoma (AITL).

Primary Cutaneous Anaplastic Large Cell Lymphoma (PCALCL)- is non-Hodgkin lymphoma (NHL) that appears in the skin when no extracutaneous signs are present at the diagnosis. Cutaneous lymphomas account for up to four-fifths of all primary cutaneous lymphomas and are further split into cutaneous B-cell lymphoma (CBCL) and cutaneous T-cell lymphoma (CTCL).

Mycosis Fungoides (MF)- also known as 'Alibert-Bazin syndrome' or 'granuloma fungoides,' is the most frequent kind of cutaneous T-cell lymphoma (CTCL) and a rare variety of non-Hodgkin lymphoma (NHL).

What Are the Signs and Symptoms of Peripheral T-Cell Lymphoma?

Peripheral T-cell lymphoma (PTCL) frequently appears with chronic dermatitis, which is resistant to treatment and is commonly misinterpreted as chronic nonspecific dermatoses. In addition, lesions caused by mycosis fungoides (MF) can proceed from patch to tumor.

A patch is a flat lesion with different degrees of erythroderma, whereas a plaque is a raised, elevated lesion with well-demarcated lesions smaller than 0.4 inches. The clinical stage dictates the distribution of lesions, with early-stage lesions preferentially affecting folds and places not exposed to light.

Lesions are often pruritic, with severity reported influencing the quality of life. For example, the aggressive leukemic type of cutaneous T-cell lymphoma (CTCL), Sezary syndrome, is distinguished by pruritic erythroderma, widespread lymphadenopathy, and anemia.

The other common clinical characteristics of peripheral T-cell lymphoma (PTCL) are:

• Drenching night sweats.

• Fever.

• Weight loss.

• Lymphadenopathy.

• Enlargement of the liver and spleen.

• Rashes (first symptom in 20 % to 50 % of people).

• Brownish to violaceous nodule (solitary or widespread in location).

What Is the Staging for Peripheral T-Cell Lymphoma?

A staging system assists healthcare practitioners in determining the amount of cancer metastasis. The Lugano categorization is divided into four phases, denoted by Roman numbers I-IV. When lymphoma affects an organ other than the lymphatic system (different lymphatic organs), an E is added to the stage, such as IIE.

Stage I-

I: The malignancy is contained within a single lymph node or lymphoid organ.

IE: The cancer is limited to a single organ outside the lymph system.

Stage 2-

II: The malignancy has spread to two or more lymph nodes in the diaphragm area.

IIE: Cancer has spread to one organ and its surrounding lymph nodes. Other groupings of lymph nodes on the same side of the diaphragm may or may not be affected.

Stage 3- The malignancy has spread to the lymph nodes on both sides of the diaphragm and the spleen.

Stage 4- Cancer has spread throughout the body, most usually to the liver, lungs, or bone marrow.

Stages I and II are classified as localized disorders, whereas stages III and IV are classified as progressed.

How Is Peripheral T-Cell Lymphoma Diagnosed?

The initial evaluation consists of:

1. Physical examination.

2. Complete blood count.

3. Comprehensive metabolic panel.

4. Systemic imaging includes computed tomography, chest scans, abdomen or pelvis with contrast or positron emission tomographic (PET) scan, bone marrow evaluation, and an echocardiogram (before anthracycline therapy).

5. Histopathologic aspects.

6. Immunophenotyping.

7. Molecular tests.

8. Hematology.

Immunophenotyping and Molecular Investigations - Malignant cells are CD3+, CD4+, and CD10+, according to immunophenotyping. CXCL13, universally expressed in neoplastic cells, is diagnostically significant, whereas CD30+, seen in around 20 % of all peripheral T-Cell lymphoma, is therapeutically effective.

What Is the Treatment for Peripheral T-Cell Lymphoma?

CHOP(Cyclophosphamide, Daunorubicin, Vincristine, Prednisone) Treatment:

It is the most commonly used therapy in the initial phase. CHOP (Cyclophosphamide, Daunorubicin, Vincristine, Prednisone) for six cycles every three weeks is considered standard therapy for people over 60.

CHOP Plus Etoposide (CHOEP)Treatment:

CHOEP (CHOP plus Etoposide) enables deeper remission, ensuring that the person obtains a transplant.

Transplantation of Stem Cells:

People who reacted well to the first intense chemotherapy treatments may be recommended to have a stem cell transplant, which results in more prolonged remissions.

What Is Treatment in Case of a Relapse?

Divergent therapy patterns have emerged if people are transplant eligible but did not receive it during the first treatment. These include short-course combination regimens adapted from relapsed, aggressive B-cell lymphomas such as ICE (Ifosfamide, Carboplatin, Etoposide) and DHAP (Dexamethasone, Cisplatin, Cytarabine).

Continuous treatment, which includes histone deacetylase (HDAC) inhibitors such as Romidepsin and Belinostat, can reduce cancer risk by up to 70 %. Romidepsin had a 30 % overall response rate, but Belinostat had a 45 % rate. Therefore, continued treatment is an option for transplant-ineligible persons with relapsed peripheral T-Cell lymphoma.

What Are the Complications of Peripheral T-Cell Lymphoma?

The most prevalent cause of mortality is infection. It is responsible for nearly half of the deaths in these individuals. The other general reasons are septicemia and bacterial pneumonia. Herpes virus infection affects about 10 % of those with advanced mycosis fungoides (MF). The most common cause of mortality after the disease appears to be organ failure.

Conclusion:

Apart from bone marrow transplantation, there is no cure for peripheral T-cell lymphoma (PTCL). Therefore, it is critical to include a specialized hematologist to select the best chemotherapy regimen to induce a complete or partial transplant-eligible person. In transplant-ineligible people, the aim should be to choose the best possible regimen to improve progression-free survival. Before commencing treatment, a doctor should educate persons on the kind of cancer, its prognosis, treatment choices, and potential adverse effects.