Mycosis fungoides is the most common primary cutaneous T‑cell lymphoma (CTCL), typically an indolent CD4+ epidermotropic malignancy presenting with patches and plaques on sun-protected sites. Disease course is heterogeneous; early stages are skin-limited with excellent survival, while tumor, erythrodermic, or extracutaneous involvement carries worse prognosis. Diagnosis requires clinicopathologic correlation with repeat biopsies and T‑cell receptor (TCR) clonality testing in equivocal cases. Management is stage-based: skin-directed therapies for early disease and systemic therapy for advanced or refractory stages, ideally within a multidisciplinary CTCL center.
Epidemiology and Risk Factors
- Median age at diagnosis ~55–60; male predominance; all skin types affected.
- Risk factors are not well defined; chronic antigenic stimulation and genetic/epigenetic alterations implicated.
Clinical Features
- Patch stage: well-demarcated, scaly, erythematous patches/薄 plaques on trunk, buttocks, and proximal thighs; often in “bathing-suit” distribution, with poikiloderma (atrophy, telangiectasia, mottled pigment).
- Plaque stage: thicker infiltrated plaques; may be pruritic.
- Tumor stage: nodules/tumors that can ulcerate.
- Folliculotropic MF: follicular-based papules/plaques, acneiform lesions, alopecia of eyebrows/scalp; often more recalcitrant.
- Erythrodermic MF vs Sézary syndrome: generalized erythema and scaling; pruritus.
- Lymph node and visceral involvement in advanced disease.
Differential Diagnosis
- Chronic eczema/psoriasis, parapsoriasis (small/large plaque), drug eruptions, tinea corporis, pityriasis lichenoides chronica, lichen planus, lupus, atopic dermatitis, nummular dermatitis.
Diagnosis
- Multiple, deep shave or punch biopsies from representative untreated lesions; avoid recently treated sites.
- Histopathology: epidermotropism of atypical cerebriform lymphocytes, Pautrier microabscesses (classic), interface changes.
- Immunophenotype: CD3+, CD4+ predominant, loss of pan–T markers (CD7/CD26), TCR clonality by PCR; flow cytometry for blood involvement (Sézary cells).
- Staging (ISCL/EORTC TNMB): T (skin), N (nodes), M (viscera), B (blood).
Management (Stage-Adapted)
- Early-stage (IA–IIA; patches/plaques)
- Skin-directed therapies:
- Topical corticosteroids (class I–II) for patches/plaques.
- Topical mechlorethamine (nitrogen mustard) 0.016% gel/ointment; monitor for dermatitis.
- Topical bexarotene or carmustine in select settings.
- Phototherapy: NB-UVB (patch stage) or PUVA (thicker plaques, skin of color); maintenance to reduce relapse.
- Local radiotherapy for solitary/plural lesions.
- Observation for very limited, asymptomatic disease may be reasonable.
- Refractory early-stage or advanced-stage (IIB–IV)
- Systemic options (often combined with skin-directed therapy):
- Retinoids: bexarotene (monitor lipids/thyroid), acitretin.
- Interferon-α.
- Histone deacetylase inhibitors: vorinostat, romidepsin.
- Antibody therapies: mogamulizumab (anti-CCR4; effective for blood/skin), brentuximab vedotin (CD30+ MF), alemtuzumab in select refractory cases.
- Methotrexate (low-dose) or pralatrexate.
- Immune checkpoint inhibitors (nivolumab/pembrolizumab) in trials/selected cases.
- Total skin electron beam therapy (TSEBT) for diffuse skin disease (low-dose or standard).
- Extracorporeal photopheresis (ECP) especially with blood involvement/erythroderma.
- Local/field radiation for bulky tumors or symptomatic lesions.
- Allogeneic stem cell transplantation: only curative option; consider in fit patients with advanced/refractory MF.
Supportive Care and Follow-up
- Pruritus control, skin barrier repair, infection prevention (Staph decolonization if recurrent).
- Regular staging assessments; monitor for transformation to large cell lymphoma (rapid growth, ulceration, rising LDH).
- Psychosocial support and patient education.
Prognosis
- Excellent in IA (>90% 10-year survival), worse with higher T stage, node/viscera involvement, folliculotropic subtype, elevated LDH, and LCT transformation.
References (recent guidelines and key reviews)
- ISCL/EORTC staging and management updates, 2021–2024.
- Trials of brentuximab vedotin, mogamulizumab, and HDAC inhibitors in MF, 2021–2024.
- TSEBT and combined-modality approaches, 2022–2024.