Cutaneous T-cell lymphoma

What are cutaneous T-cell lymphomas?

Lymphomas are tumours of the lymph nodes and lymphatic system. Extranodal lymphomas are tumours that occur in organs or tissues outside of the lymphatic system. When lymphomas occur in the skin with no evidence of disease anywhere else at the time of diagnosis, they are called ‘primary’ cutaneous lymphomas. There are many different types of primary cutaneous lymphomas but they can be broadly divided into two categories, cutaneous T-cell lymphomas and cutaneous B-cell lymphomas. Of all primary cutaneous lymphomas, 65% are of the T-cell type.

Cutaneous T-cell lymphomas (CTCL) refer to a serious but uncommon skin condition in which there is an abnormal neoplastic proliferation of lymphocytes with a ´T´ subtype (thymus-derived). The diagnosis is made by skin biopsy.

Classification of cutaneous T-cell lymphomas

Recently the World Health Organisation (WHO) and European Organization for Research and Treatment of Cancer Classification (EORTC) reached a consensus classification for cutaneous lymphomas1. Cutaneous T-cell lymphomas are broken down into the following classifications.

Indolent (low-grade/slow growing) clinical behaviour	Aggressive clinical behaviour
Mycosis fungoides (MF) MF variants and subtypes Folliculotropic MF Pagetoid reticulosis Granulomatous slack skin Primary cutaneous CD30+ lymphoproliferative disorders Primary cutaneous anaplastic large cell lymphoma Lymphomatoid papulosis Subcutaneous panniculitis-like T-cell lymphoma (histiocytic cytophagic panniculitis) Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma	Sézary syndrome Adult T-cell leukaemia/lymphoma Extranodal NK/T-cell lymphoma, nasal type Primary cutaneous peripheral T-cell lymphoma, unspecified Primary cutaneous aggressive CD8+ T-cell lymphoma Cutaneous γ/δ T-cell lymphoma

Mycosis fungoides is the most common type of CTCL and accounts for almost 50% of all primary cutaneous lymphomas. The second most common group of CTCL is primary cutaneous CD30+ lymphoproliferative disorders.

Mycosis fungoides

Mycosis fungoides is a condition in which the skin is infiltrated by patches or lumps composed of white cells called lymphocytes. It is more common in men than women and is very rare in children. Its cause is unknown but in some patients it is associated with a pre-existing contact allergic dermatitis or infection with a retrovirus.

Mycosis fungoides has an indolent (low-grade) clinical course, which means that it may persist in one stage or over years or sometimes decades, slowly progress to another stage (from patches to thicker plaques and eventually to tumours).

Patch stage

In patch stage mycosis fungoides, the skin lesions are flat. Most often there are oval or ring-shaped (annular) pink dry patches on covered skin. They may spontaneously disappear, remain the same size, or slowly enlarge. The skin may be atrophic (thinned), and may or may not itch. The patch stage of mycosis fungoides can be difficult to distinguish from psoriasis, discoid eczema or parapsoriasis.

Patch stage mycosis fungoides

Poikiloderma atrophicans vasculare

Poikiloderma atrophicans vasculare is an unusual variant in which the skin shows areas of thinning, pigmentary change and dilation of the capillaries (telangiectasia).

Poikiloderma vasculare atrophicans

Plaque stage

In plaque stage mycosis fungoides, the patches become thickened and may resemble psoriasis. They are usually itchy.

Plaque stage mycosis fungoides

Tumour stage

In tumour stage mycosis fungoides, large irregular lumps develop from plaques, or de novo. They may ulcerate. At this stage, spread to other organs is more likely than in earlier stages.

Tumour stage mycosis fungoides

MF variants and subtypes

There are a number of variants and subtypes of mycosis fungoides. Most follow the same clinical and pathological features as MF but some have distinctive features as described below.

Variant/subtype	Clinical/pathological features
Folliculotropic MF (follicular cell lymphoma)	Localised form of cutaneous T-cell lymphoma in which there is a slowly enlarging solitary patch, plaque or tumour in which biopsy shows characteristic lymphomatous change around hair follicles. Most commonly found in the head and neck area. Skin lesions are often associated with alopecia, and sometimes with mucinorrhea (see alopecia mucinosa).
Pagetoid reticulosis	Localised patches or plaques with an intraepidermal growth of neoplastic T cells. Presents as a solitary psoriasis-like or hyperkeratotic patch or plaque, usually on the extremities.
Granulomatous slack skin	Extremely rare subtype characterised by slow development of folds of lax skin in the major skin folds. Skin folds show a granulomatous infiltrate with clonal T cells. Occurs most commonly in the groin and underarm regions.

Primary cutaneous CD30+ lymphoproliferative disorders

This is the second most common group of CTCL and account for about 30% of all CTCL cases. This group includes primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis.

Primary cutaneous anaplastic large cell lymphoma	Lymphomatoid papulosis
Usually solitary or localised nodules or tumours, often with ulceration Multifocal lesions seen in about 20% of patients Lesions may show partial or complete spontaneous regression Regional lymph nodes may become involved in 10% of patients Prognosis is generally favourable	Chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease Lesions occur predominantly on the trunk and limbs Lesions clear spontaneously within 3-12 weeks, and may leave behind superficial scars Recurrences occur throughout the disease duration which may be from several months to more than 40 years

CD30+ lymphoproliferative disorders

Anaplastic large cell lymphoma

Lymphomatoid papulosis

Lymphomatoid papulosis

Sézary syndrome

Sézary syndrome is the name given when T-cell lymphoma affects the skin of the entire body. It is also known as the red man syndrome because the skin is bright red. The skin is also thickened, dry or scaly and usually very itchy. Examination usually reveals the presence of neoplastic T cells (Sézary cells) in skin, lymph nodes, and peripheral blood. The prognosis of Sézary syndrome is generally poor with a median survival between 2 and 4 years. Most patients die of opportunistic infections that are due to immunosuppression.

Sézary syndrome

Adult T-cell leukaemia/lymphoma

Adult T-cell leukaemia/lymphoma (ATLL), is a serious blood disease in which there are large numbers of circulating atypical cells. It is caused by a retrovirus infection with human T-lymphotropic virus (HTLV I). The condition can be divided into acute and chronic types. Acute ATLL is characterised by skin lesions similar to those found in mycosis fungoides or Sézary syndrome, enlarged lymph glands, high levels of calcium in the blood and bone lesions. Prognosis is poor for this type with survival ranging from 2 weeks to more than 1 year. Chronic ATLL present with skin lesions only and have a longer clinical course and survival, however this may transform into an acute phase with an aggressive course.

Investigations

The diagnosis of cutaneous T-cell lymphoma is made by a dermatopathologist as there are characteristic microscopic changes seen on skin biopsy. The diagnosis is often delayed for months or years and may require several biopsies, as early cutaneous T-cell lymphoma can be difficult to tell apart from other skin conditions, particularly eczema.

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

The blood count is normal in most patients with cutaneous T-cell lymphoma, but an elevated white cell count is characteristic of Sézary syndrome.

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

Treatment

Treatment of individual patients varies, and depends on the stage, local expertise and available drugs and equipment. The following may be useful.

• Topical steroids
• UVB Phototherapy
• PUVA Photochemotherapy
• Topical nitrogen mustard
• Chemotherapy
• Localised radiotherapy
• Electron beam radiotherapy
• Interferons
• Oral retinoids
• Photopheresis.

Prognosis

Cutaneous T-cell lymphoma may remain confined to the skin for many years, but the abnormal cells may eventually infiltrate other tissues including blood, lymph nodes, lungs, heart, liver and spleen.

Unlike some other lymphomas, the outlook is generally good. Symptoms can usually be controlled with treatment. However treatment is not curative.