Cutaneous T-cell lymphoma
Mycosis fungoides (MF); Sézary syndrome; primary cutaneous T-cell lymphoma; CTCL
Mycosis fungoides is the commonest primary cutaneous lymphoma — an indolent, often patch- or plaque-stage T-cell lymphoma that can progress to tumours, erythroderma or visceral involvement over years. Sézary syndrome is the leukaemic variant. Management is stage-driven, multidisciplinary and centred on UK supraregional CTCL services.
Epidemiology
UK incidence of MF is approximately 0.4–0.7 per 100,000 per year. Median age at diagnosis is in the sixth decade; men are affected approximately twice as often as women. Diagnostic delay is common — 4–6 years from first symptom to diagnosis is typical, particularly with patch-stage disease misdiagnosed as eczema or psoriasis.
Classification
The current authoritative taxonomies are WHO Classification of Haematolymphoid Tumours, 5th edition (WHO-HAEM5, 2022) and the parallel International Consensus Classification (ICC) 2022; both update and largely supersede the WHO-EORTC 2018 4th-edition framing. The principal cutaneous-relevant entities are:
Cutaneous T-cell lymphomas (most common, ~75% of CTCLs)
- Mycosis fungoides and variants (folliculotropic, pagetoid reticulosis, granulomatous slack skin).
- Sézary syndrome — leukaemic variant with erythroderma, lymphadenopathy and circulating clonal T-cells (≥1000/µL Sézary cells in blood; B2).
- Primary cutaneous CD30+ lymphoproliferative disorders — primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis.
- Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (LPD; reclassified from "lymphoma" in WHO-EORTC 2018 and retained as LPD in WHO-HAEM5 2022) — indolent solitary lesions, see dedicated page.
- Subcutaneous panniculitis-like T-cell lymphoma; primary cutaneous γδ T-cell lymphoma.
- Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma — remains a provisional entity in WHO-HAEM5 / ICC 2022, see dedicated page.
Cutaneous B-cell lymphomas
- Primary cutaneous marginal zone lymphoma (indolent).
- Primary cutaneous follicle centre lymphoma (indolent).
- Primary cutaneous diffuse large B-cell lymphoma, leg type (aggressive).
Histiocytic / dendritic-cell neoplasms with cutaneous presentation
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN) — placed under plasmacytoid dendritic cell neoplasms / histiocytic-dendritic cell neoplasms in WHO-HAEM5 2022 (revised from its earlier home under "myeloid neoplasms and acute leukaemia" in WHO 2017). See dedicated page.
Clinical features
The classical evolution of mycosis fungoides is patch → plaque → tumour, but stages may co-exist or be skipped.
- Patches — erythematous, scaly, ill-defined, often on sun-protected sites (buttocks, breasts, inner thighs); may itch.
- Plaques — raised, infiltrated patches with sharper borders.
- Tumours — ulcerated, often on face or scalp; high transformation risk.
- Erythroderma — Sézary syndrome: >80% body surface area, intense pruritus, palmoplantar keratoderma, ectropion.
Folliculotropic MF
Acneiform, alopecic or follicular plaques — typically head and neck. More aggressive than classical MF; treatment-resistant.
Diagnosis
Multiple deep skin biopsies (≥4 mm punch from indurated areas) are recommended; ideally repeat sampling at intervals if early disease. Histology shows epidermotropic infiltrate of atypical lymphocytes with cerebriform nuclei and Pautrier microabscesses (intraepidermal collections). Immunohistochemistry: CD2+, CD3+, CD4+, CD45RO+, CD8 variable, frequent loss of CD7, CD26.
T-cell receptor gene rearrangement on PCR helps confirm clonality; identical clones across separate biopsies strongly support CTCL.
For suspected Sézary syndrome: peripheral blood flow cytometry for circulating CD4+CD7– / CD4+CD26– clones, Sézary cell count, TCR clonality.
Staging — ISCL/EORTC TNMB (Olsen 2007; updated 2011)
Used for mycosis fungoides and Sézary syndrome. T1/T2 are subdivided into a/b (patch only vs patch + plaque) because patch-only disease carries materially better prognosis.
| T (skin) | Definition |
|---|---|
| T1 | Limited patches / plaques < 10% BSA — T1a = patch only; T1b = patch + plaque |
| T2 | Patches / plaques ≥ 10% BSA — T2a = patch only; T2b = patch + plaque |
| T3 | One or more cutaneous tumours (≥ 1 cm) |
| T4 | Confluent erythema ≥ 80% BSA |
| B (blood) | Definition |
|---|---|
| B0 | Absent / minimal blood involvement: < 250 Sézary cells/µL (or < 5% of lymphocytes) |
| B1 | Low blood tumour burden: 250–999 Sézary cells/µL |
| B2 | High blood tumour burden: ≥ 1000 Sézary cells/µL, OR CD4:CD8 ratio ≥ 10, OR ≥ 40% CD4+CD7− cells, OR ≥ 30% CD4+CD26− cells, plus a positive blood clone matching the skin |
N (nodes), M (visceral) and B (blood Sézary burden) complete the stage. B2 forces stage IVA1 regardless of T — B2 with erythroderma (T4) defines Sézary syndrome. Stage groupings IA (T1 N0 M0 B0/B1) through IVB (T1–4 N0–3 M1) determine prognosis: 5-year disease-specific survival ~95–98% (IA, Agar 2010 / Scarisbrick PROCLIPI cohort) declining to ~10–18% (IVB).
Investigations by stage
- Stage IA–IIA: clinical examination, blood film and flow cytometry.
- Stage IIB+: CT thorax/abdomen/pelvis ± bone marrow biopsy if blood involvement.
- Sézary syndrome: PET-CT may identify nodal disease for biopsy.
Management by stage
Stage IA–IIA (skin-limited)
- Skin-directed therapy: potent topical corticosteroids; topical mechlorethamine / chlormethine gel (NICE TA720) for adults with early-stage stage IA, IB or IIA mycosis fungoides-type CTCL.
- Phototherapy: narrowband UVB for patch-stage; PUVA for thicker plaques.
- Localised radiotherapy for resistant tumour or unilesional disease.
Stage IIB (tumour-stage)
- Localised radiotherapy.
- Total skin electron beam therapy (TSEB) for diffuse skin involvement — supraregional centres only.
- Bexarotene, low-dose methotrexate, interferon-α (off-label use).
- Brentuximab vedotin for CD30+ relapsed/refractory disease (NICE TA577).
Stage III–IV (Sézary, advanced)
- Extracorporeal photopheresis (ECP) for Sézary syndrome.
- Mogamulizumab — anti-CCR4 monoclonal antibody (NICE TA754) for relapsed/refractory MF/SS.
- Allogeneic stem cell transplantation in selected younger patients with advanced disease.
- Symptom control: emollients, antihistamines, gabapentin / pregabalin for pruritus.
UK NHS commissioning identifies supraregional cutaneous lymphoma multidisciplinary teams (currently at major centres). Discuss every confirmed or strongly suspected CTCL with these services for diagnostic confirmation and treatment planning.
Follow-up
- Stage IA–IIA: 6–12 monthly clinical review; blood tests if symptomatic change.
- Stage IIB+: 3–6 monthly with imaging on symptoms or as per MDT.
- Photoprotection counselling — long-term phototherapy carries skin cancer risk.
- Watch for second primary cutaneous malignancies (BCC, cSCC, melanoma).
References
- Gilson D et al. British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas. Br J Dermatol; 2019;180:496–526.
- Olsen EA et al. Revisions to the staging and classification of mycosis fungoides and Sézary syndrome. Blood; 2007;110:1713–22.
- WHO Classification of Haematolymphoid Tumours, 5th edition (WHO-HAEM5); 2022. International Consensus Classification of Mature Lymphoid Neoplasms; 2022.
- NICE. Brentuximab vedotin for treating CD30-positive cutaneous T-cell lymphoma (TA577). 2019.
- NICE. Mogamulizumab for treating mycosis fungoides and Sézary syndrome (TA754). 2021.
- Willemze R et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood; 2019;133:1703–14.
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