Cutaneous T-Cell Lymphoma (CTCL)

Cutaneous T-cell lymphoma (CTCL) is not a single disease but a group of non-Hodgkin lymphomas that arise from mature T lymphocytes and primarily affect the skin.

The two most common forms are mycosis fungoides (MF) and Sézary syndrome (SS).

MF often begins with patches or plaques on the skin and may remain stable for many years. In some patients, it can progress to skin tumors or involve the lymph nodes, blood, or internal organs.

SS usually causes widespread skin redness and severe itching, together with abnormal T cells in the blood and often lymph node involvement.

Early-stage MF usually follows a slow course, while advanced MF and SS generally require more systemic treatment.

The exact cause of CTCL is not known.

The disease is thought to develop through genetic and molecular changes that accumulate in T lymphocytes. These changes can affect cell growth, survival, and immune regulation, allowing abnormal T cells to migrate to, accumulate in, and infiltrate the skin.

No specific lifestyle factor has been established as a direct cause of CTCL.

Symptoms of CTCL depend on the subtype and stage of disease. Early skin changes can resemble eczema, psoriasis, or other chronic skin conditions.

Common signs and symptoms include:

• Persistent red, dry, or scaly patches or plaques

• Significant itching

• Areas of darker or lighter skin

• Nodules or tumors on the skin

• Ulceration or secondary infection of skin tumors

• Enlarged lymph nodes

• Hair loss

• Thickened skin on the palms and soles

MF often progresses from patches to plaques and, in some patients, skin tumors, although not everyone follows this pattern.

SS more commonly causes widespread skin redness, severe itching, scaling, thickening of the palms and soles, hair loss, and enlarged lymph nodes. Some patients may also develop fever, drenching night sweats, or unexplained weight loss as the disease advances.

Diagnosis of CTCL usually combines clinical skin findings with tissue biopsy, pathology, and immunophenotyping. Additional testing may be needed to determine whether the blood, lymph nodes, or other organs are involved.

A skin biopsy is central to diagnosing MF and other forms of CTCL. Because early MF can be difficult to distinguish from benign skin conditions, repeat biopsies from different lesions may sometimes be needed before the diagnosis becomes clear.

Blood tests may include a complete blood count, peripheral blood smear, and flow cytometry. In patients with suspected SS or blood involvement, testing focuses on identifying abnormal T cells and Sézary cells in the blood.

T-cell receptor clonality testing may also be used in selected cases to support the diagnosis.

If lymph nodes are significantly enlarged, a lymph node biopsy may be recommended.

CT or PET/CT is mainly used in patients with advanced disease or suspected lymph node or internal organ involvement and is not required for every patient with early-stage MF.

Bone marrow testing is also not routine for all patients and is generally reserved for selected patients with abnormal blood findings, advanced disease, or suspected marrow involvement.

Skin-Directed Therapy

For early-stage MF that is mainly limited to the skin, treatment usually begins with skin-directed therapies such as topical corticosteroids, topical anticancer medications, and phototherapy.

Phototherapy commonly includes narrowband UVB (NB-UVB) and psoralen plus UVA (PUVA).

Radiation Therapy

CTCL is generally sensitive to radiation therapy.

Localized plaques or skin tumors can be treated with local radiation, while selected patients with widespread skin involvement may receive total skin electron beam therapy (TSEBT).

Systemic Therapy

Patients with advanced MF, SS, or disease that does not respond adequately to skin-directed treatment may need systemic therapy.

Options may include retinoids, interferon, low-dose methotrexate, and other immunomodulatory treatments.

Targeted treatments are also available for selected patients. For example, brentuximab vedotin may be used in some patients with CD30-positive disease, while mogamulizumab is an important option for some patients with MF or SS, particularly when there is significant blood involvement.

Chemotherapy may still be used for selected patients with advanced, rapidly progressing, or refractory disease, but multi-agent chemotherapy is generally not a routine treatment for early-stage MF.

Extracorporeal Photopheresis

Extracorporeal photopheresis (ECP) is an important treatment for SS and for some patients with significant blood involvement.

During ECP, white blood cells are collected from the patient's blood, treated with a photosensitizing agent and UVA light outside the body, and then returned to the patient.

Its effect is more complex than simply using ultraviolet light to kill lymphoma cells. ECP alters treated lymphocytes and helps regulate the immune response against the disease. It may be used alone or in combination with other treatments.

Allogeneic Hematopoietic Stem Cell Transplantation

For selected younger, medically fit patients with progressive MF or SS that remains difficult to control after multiple treatments, allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered.

Allogeneic transplantation is one of the few treatments with curative potential in CTCL, but it also carries significant treatment-related risks and is not appropriate for everyone.

The decision and timing depend on disease stage, treatment response, age, overall health, and donor availability.

Clinical Trials

CTCL is a relatively rare lymphoma, and new treatments targeting different molecular and immune pathways continue to be studied.

Patients with advanced, relapsed, or refractory disease may wish to discuss appropriate clinical trials with their healthcare team.