Cutaneous T-Cell Lymphoma - Clinical Features, Diagnosis and Treatment

What Is Cutaneous T-Cell Lymphoma?

A cutaneous T-cell lymphoma is a heterogeneous group of extranodal non-Hodgkin lymphomas. Adults aged 55 to 60 years are usually affected by cutaneous T-cell lymphoma. Mycosis fungoides, sézary syndrome, and primary cutaneous peripheral T-cell lymphomas are the most significant variants.

Incidence of Cutaneous T-Cell Lymphoma

Extranodal locations are involved in 25 % to 40 % of non-Hodgkin's lymphoma patients. The gastrointestinal system and the skin are most frequently affected. About 0.5 per 100,000 people are concerned with cutaneous T-cell lymphoma annually, and men are more likely to be affected than women. Adults with a median age of 55 to 60 years are commonly affected.

What Is the Classification of Cutaneous T-Cell Lymphoma?

There are three major types of cutaneous T-cell lymphomas (CTCLs). They are as below:

1. Primary cutaneous peripheral T-cell lymphomas.

2. Sézary syndrome (SS) (leukemic variant).

3. Mycosis fungoides.

What Is the Etiology of Cutaneous T-Cell Lymphoma?

The actual cause and development mechanisms of this illness are still unknown. However, the following are some etiological factors for cutaneous T-cell lymphoma:

• Gene and signaling pathway dysregulation.

• Chromosome 10 alterations.

• Ectopic expression of cancer-testis genes.

• Apoptosis inhibition.

• Resistance to a variety of treatment approaches.

• Oncogenesis is accelerated by targeting tumor suppressor genes such as p53 and p21.

• Inadequate expression or function of negative regulators.

• Jak-3 or STAT pathway dysregulation and interleukin (IL)-independent proliferation of cancerous T-cells.

What Are the Clinical Features of Cutaneous T-Cell Lymphoma?

In its early stages, cutaneous T-cell lymphoma is frequently misinterpreted as a benign skin disorder.

Mycosis Fungoides - is the most common kind of cutaneous T-cell lymphoma, accounting for 44 % to 62 % of the cases. Mycosis fungoides limited to the skin progress slowly from the macule and patch stages to the infiltrated plaque and tumor stages.

Sézary Syndrome (SS) (leukemic variant) - is a leukemic type of mycosis fungoides clinically distinguished by redness of the skin (erythroderma) and widespread inflammation and swelling of the lymph nodes (lymphadenopathy).

Primary Cutaneous Peripheral T-cell Lymphomas - appear with a single red-violet nodule, which may be scattered multifocal or diffuse nodules that may accompany any area of the body. These nodules might become ulcerated and infected. Other essential characteristics of this primary cutaneous peripheral T-cell lymphoma class include rapid cutaneous spread and systemic involvement.

What Are the Histological Features of Cutaneous T-Cell Lymphoma?

The histologic features of cutaneous T-cells are subtle, so differentiating these disorders from benign inflammatory diseases is difficult. However, some histologic features are

• Lymphocytes with a halo.

• Exocytosis.

• Epidermotropism.

• Microabscess of Pautrier.

• Largely entangled.

• Hyperchromatic lymphocytes in the epidermis.

How Is Cutaneous T-Cell Lymphoma Diagnosed?

The following methods are used to diagnose cutaneous T-cell lymphoma:

1. Observation.

2. Biopsy.

3. Dermatopathology.

4. Immunohistochemistry.

5. Molecular analysis.

Observation and palpation of the skin is the standard method for staging cutaneous T-cell lymphoma. However, the morphologic and clinical characteristics of cutaneous T-cell lymphoma are heterogeneous, and information acquired from a single biopsy might lead to misinterpretation. Thus, numerous biopsies are frequently necessary to make a conclusive diagnosis.

Identifying malignant cells in cutaneous T-cell lymphoma peripheral blood is crucial for diagnosing Sézary syndrome (SS) (leukemic variant) early on and evaluating prognosis. The absence of cell surface markers such as CD26, CD27, and CD7 on malignant T-cells aids in diagnosing cutaneous T-cell lymphoma. On the other hand, CD164 overexpression on CD4+ T cells is a definitive diagnosis of cutaneous T-cell lymphoma.

What Is the Treatment for Cutaneous T-Cell Lymphoma?

There is no known cure for Sézary syndrome (SS) (leukemic variant) and mycosis fungoides. Thus, the therapeutic choices for Sézary syndrome (SS) (leukemic variant) and mycosis fungoides are primarily palliative. Multi-drug treatment regimens are contraindicated for cutaneous T-cell lymphoma because of the significant risk of infection in individuals with a weak skin barrier. The treatment choices are divided into two categories:

Skin-Directed Treatments - These are the preferred option for treating the early stages of sickness (IA to IIA) when they impact less than 20 % of the body surface.

Systemic Medicines -These are utilized to treat refractory patients in their early and mature phases (stage IIB). Corticosteroids, including topical and systemic, are beneficial in treating cutaneous T-cell lymphoma. However, corticosteroids are more prone to cause relapse.

Retinoids - These are effective in treating cutaneous T-cell lymphoma due to their anti-proliferative and apoptosis-inducing properties — the retinoid acid receptor two gene functions as a tumor suppressor. The US Food and Drug Administration (FDA) has approved Bexarotene, also known as Targretin, as a topical retinoid for the treatment of stage I mycosis fungoides and relapsed refractory cutaneous T-cell lymphoma. However, Bexarotene causes reversible, dose-dependent adverse effects such as severe mixed hyperlipidemia with a significant decrease in high-density lipoprotein cholesterol levels and central hypothyroidism.

Histone Deacetylase Inhibitors (HDACI) - These are antineoplastic agents that are the new therapeutic options for treating cutaneous T-cell lymphoma. These agents destroy the transformed cells over normal cells. Vorinostat and Romidepsin are two drugs in this class. Histone deacetylase inhibitors (HDAC) are generally well tolerated. However, these agents have been associated with minor side effects such as fatigue, gastrointestinal discomfort, thrombocytopenia, neutropenia, anemia, and dehydration.

Imiquimod- It is a TLR7 agonist that is effective in treating mycosis fungoides. It works by causing plasmacytoid dendritic cells, which are found in inflamed and malignant skin lesions, to produce interferon-alpha (IFN-), TNF-, IL-1 (interleukin - 1), IL-6 (interleukin - 6), and IL-8 (interleukin - 8). Topical Resiquimod, an Imidazoquinoline with TLR7- and TLR8-stimulating activity, is also effective in treating early-stage cutaneous T-cell lymphomas.

Denileukin Diftitox- It is a recombinant fusion protein made up of diphtheria toxin, and IL-2 is also used for the treatment of cutaneous T-cell lymphomas.

What Is the Differential Diagnosis for Cutaneous T-Cell Lymphoma?

The differential diagnosis for Cutaneous T-Cell Lymphoma are:

• Adverse drug reactions.

• Parapsoriasis.

• All kinds of dermatitis and eczema.

• Psoriasis.

• Panniculitis.

• Morphea.

• Pityriasis lichenoides chronica.

• Folliculitis.

• Lichen planus.

• Pigmented purpuric dermatoses.

• Pityriasis lichenoides et varioliformis acuta.

• Lymphomatoid papulosis.

• Vitiligo.

Conclusion:

Cutaneous T-cell lymphoma is a lifelong disorder that recurs after therapy is stopped, even in cases where the disease does not progress. Despite introducing several therapeutic options for treatment, the malignant cells still infiltrate lymph nodes and peripheral blood vessels; as a result, they move and become resistant to treatment. Skin lesions are severe in cutaneous T-cell lymphoma cases with visceral involvement, and the risk of skin infection is high. The therapy aims to include symptom relief, remission induction, and progression postponement while minimizing significant adverse effects.