Cutaneous T Cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas of skin homing T cells, with mycosis fungoides (MF) and Sézary syndrome (SS) as the main types.

• Incidence is about 6 to 10 per million per year; median age at diagnosis 55 to 60 years; more frequent in men and in Black patients, who present younger with more advanced disease.
• MF: indolent patch, plaque, and tumour stages, with 10% progressing to advanced disease. SS: erythroderma, lymphadenopathy, and leukaemic involvement with poor prognosis.
• Large cell transformation, CD30+ lymphoproliferative disorders, and infections (Staphylococcus aureus sepsis) are major complications.
• Variants: folliculotropic MF, pagetoid reticulosis, granulomatous slack skin, and hypopigmented MF (common in dark skin and children).

• Patch stage: erythematous, scaly, atrophic patches in sun protected areas (buttocks, thighs, breast), often mistaken for eczema or psoriasis for years.
• Plaque stage: infiltrated, well demarcated plaques; tumour stage: nodules and ulcerating tumours.
• Sézary syndrome: pruritic erythroderma, palmoplantar keratoderma, ectropion, alopecia, lymphadenopathy.
• Itch, pain, and skin infection; systemic involvement of lymph nodes, blood, and viscera in advanced disease.

• Repeated skin biopsies (4 to 6 mm punch from multiple sites, before applying topical steroids): epidermotropism of atypical CD4+ lymphocytes, Pautrier microabscesses, and band like infiltrate.
• Immunophenotype: CD3+, CD4+, loss of CD7 and CD26, CD30 variable; T-cell receptor gene rearrangement (clonality).
• Staging (ISCL/EORTC TNMB): BSA involvement, lymph node examination and ultrasound or CT/PET-CT, blood flow cytometry (Sézary cells: CD4+CD26- over 1000/microL for B2 blood involvement), LDH, and bone marrow biopsy if indicated.
• HTLV-1 serology to exclude adult T-cell leukaemia/lymphoma.
• Exclude atopic dermatitis, psoriasis, lichen planus, drug eruption, and other cutaneous lymphomas.

• Early stage MF (IA to IIA), skin directed therapy:
  • Topical corticosteroids (clobetasol 0.05%).
  • Topical mechlorethamine (nitrogen mustard) gel 0.016% daily.
  • Narrow band UVB (three times weekly) for patch disease, PUVA (twice to three times weekly) for plaques.
  • Topical bexarotene gel 1%.
  • Localised radiotherapy (8 to 12 Gy) for single lesions; total skin electron beam therapy 12 Gy for generalised disease.
• Refractory early or advanced disease (systemic):
  • Bexarotene 300 mg/m2/day (monitor lipids, TSH; give fenofibrate and levothyroxine), interferon alpha 3 to 9 MU three times weekly, low dose methotrexate 5 to 50 mg weekly, extracorporeal photopheresis (SS, erythrodermic MF).
  • Mogamulizumab (anti-CCR4) 1 mg/kg weekly for 4 weeks then every 2 weeks.
  • Brentuximab vedotin 1.8 mg/kg every 3 weeks (CD30+, up to 16 cycles).
  • Histone deacetylase inhibitors: romidepsin 14 mg/m2 on days 1, 8, 15 every 28 days, vorinostat 400 mg daily.
  • Gemcitabine, liposomal doxorubicin, pralatrexate for refractory disease.
• Allogeneic stem cell transplantation for eligible patients with advanced, refractory disease (potentially curative).
• Supportive: itch control (gabapentin, mirtazapine, naltrexone), emollients, antibacterial care (flucloxacillin or doxycycline; dilute bleach baths), and prompt treatment of infection.
• Multidisciplinary follow up every 3 to 6 months and psychosocial support.