Cutaneous T-cell lymphoma

What is cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. It is a form of non-Hodgkin lymphoma in which malignant T-cells are initially localised to the skin with no evidence of extracutaneous disease at the time of diagnosis.

Cutaneous T-cell lymphoma

Mycosis fungoides

Sézary syndrome

Who gets cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma comprises 4% of all non-Hodgkin lymphomas and 75-80% of all primary cutaneous lymphomas. It shows a male predominance of 2:1. The incidence of CTCL increases with age, with an average age at diagnosis of 50-60 years.

What causes cutaneous T-cell lymphoma?

The aetiopathogenesis of cutaneous T-cell lymphoma is unknown. Theories include a viral infection (eg, Epstein Barr virus, HTLV-1) causing a chronically heightened immune state, genetic changes (eg, HLA type), or chemical exposure (eg, medications).

Epigenetics regulates gene expression without altering the DNA sequence. Epigenetic studies of CTCL have identified changes in DNA methylation, histone modification, microRNAs and chromatin remodellers. One example is miR-155 which is overexpressed in malignant CTCL cells, especially in advanced stage disease, and treatments inhibiting this are in early clinical trials for tumour-stage mycosis fungoides, Sézary syndrome, and primary cutaneous anaplastic large-cell lymphoma.

What is the classification of cutaneous T-cell lymphomas?

The 2018 WHO-EORTC classification of cutaneous T-cell lymphomas is summarised in the following tables with links to specific DermNet NZ webpages.

Table 1. Indolent forms of cutaneous T-cell lymphoma

Table 2. Aggressive forms of cutaneous T-cell lymphoma

CTCL, cutaneous T-cell lymphoma; EBV, Epstein-Barr Virus; LPD, lymphoproliferative disorders; MF, mycosis fungoides; NDA, no data available; NK, natural killer cell; NOS, not otherwise specified; pcALCL, primary cutaneous anaplastic large-cell lymphoma; * provisional entities.

Adapted from: Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703–14

Primary cutaneous small-medium pleomorphic T-cell lymphoma is an example of a ‘Primary cutaneous peripheral T-cell lymphoma NOS’ with an excellent prognosis.

What are the clinical features of cutaneous T-cell lymphomas?

Cutaneous T-cell lymphomas typically present as patches, papules, nodules, plaques, and/or tumours. Itch is reported by 80% of patients.

Patch stage mycosis fungoides

Plaque stage mycosis fungoides

Tumour stage of CTCL

What are the complications of cutaneous T-cell lymphoma?

The diagnosis of cutaneous T-cell lymphoma is often delayed by months or years due to the indolent course, clinical similarity to inflammatory dermatoses, and subtle changes on histopathology.

Cutaneous T-cell lymphoma papules, nodules, and tumours may ulcerate and become necrotic, healing with varioliform scarring.

Extracutaneous spread affects 10%.

Quality of life can be significantly impacted due the economic burden of a chronic disease, or to symptoms such as itch and pain, psychological effects including anxiety and depression, and visible skin changes including hair loss.

Ulcerated mycosis fungoides, tumour stage

Ulcerated mycosis fungoides, plaque stage

Ulcerated mycosis fungoides, tumour stage

How is cutaneous T-cell lymphoma diagnosed?

Diagnosis of cutaneous T-cell lymphoma involves careful clinicopathological correlation. Multiple skin biopsies are often required to detect the characteristic histopathology changes, especially in the early patch stages. Further investigations may be performed on skin biopsy specimens including immunohistochemistry.

EBV, T-cell receptor (TCR) gene rearrangements, ALK, DUSP22-IRF4, and TP63 gene studies may be performed to confirm the diagnosis and predict the clinical course.

Enlarged lymph nodes may also be biopsied. Cutaneous T-cell lymphoma can cause harmless swelling, known as reactive or dermopathic lymphadenopathy, or malignant growth in the lymph nodes.

The blood count is normal in most patients with CTCL. An elevated white cell count is characteristic of Sézary syndrome and confirmed on flow cytometry. Some patients may require bone marrow biopsy.

Patients with advanced cutaneous T-cell lymphoma may undergo CT or MRI scans to determine whether the disease has affected internal organs.

Formal TNMB staging is recommended in some forms of CTCL.

What is the differential diagnosis for cutaneous T-cell lymphoma?

• Patch stage – dermatitis, psoriasis, and other inflammatory dermatoses
• Cutaneous pseudolymphoma
• Pityriasis lichenoides

What is the treatment for cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma is regarded as treatable, not curable. Treatments considered will depend on the individual patient, specific type of CTCL, stage of disease, local expertise, and available drugs and equipment. There are no global consensus guidelines for treating CTCL.

Topical treatment

Skin-directed topical treatments are the mainstay of early disease.

• Topical steroids
• Topical nitrogen mustard
• Topical bexarotene gel

Procedural treatment

• Surgical excision of solitary or small numbers of lesions
• Phototherapy
• Localised radiotherapy or electron beam therapy

Systemic treatment

• Chemotherapy
• Retinoids and rexinoids
• Extracorporeal photophoresis
• Brentuximab vedotin (anti-CD30 monoclonal antibody linked to monomethyl auristatin W) for CD30+ CTCL

What is the outcome for cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma typically follows a long slow course remaining confined to the skin, progressing over many years, and not usually life-threatening.

Some forms of CTCL progress more rapidly with a minority developing advanced disease including tumour formation, extracutaneous spread (10%), and progression to systemic lymphoma.