Mycosis Fungoides: Definition and Clinical Overview
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by malignant skin-homing CD4+ T cells that infiltrate the skin, typically presenting with progressive patches, plaques, and potentially tumors, with an indolent clinical behavior in early stages. 1
Classification and Epidemiology
Mycosis fungoides represents approximately 60-70% of all primary cutaneous lymphomas and is classified as an indolent cutaneous T-cell lymphoma in the WHO-EORTC classification system 1, 2
The annual incidence is 0.7 per 100,000 population in the U.K., with a significantly higher male predominance (1.6:1.0 ratio) and peak age between 50-74 years 1
Approximately 20% of patients are diagnosed between ages 25-49 years, and mycosis fungoides may rarely present in childhood 1
Clinical Presentation and Disease Stages
The disease progresses through three distinct clinical stages:
Patch stage: Flat, erythematous, scaly lesions that commonly mimic eczema or psoriasis, most frequently appearing on the buttocks, trunk, and breast 2, 3
Plaque stage: Raised, infiltrated lesions that develop from patches or appear de novo 4, 2
Tumor stage: Nodular lesions that may ulcerate, indicating more advanced disease 4, 5
Erythroderma (generalized redness affecting >80% body surface area) can occur and is associated with worse prognosis 4, 5
Immunophenotype and Diagnosis
The classic immunophenotype is CD3+, CD4+, CD45RO+ (memory T-cell marker), and CD8-negative, though rare CD8+ variants exist 6
Essential diagnostic markers on paraffin-embedded tissue include: CD2, CD3, CD4, CD8, CD20 (to exclude B-cell lymphoma), and CD30 (to exclude CD30+ lymphoproliferative disorders) 1, 6
Histology shows characteristic epidermotropic infiltrates of small-to-medium lymphocytes with Pautrier microabscesses 6, 2
Multiple ellipse skin biopsies targeting different lesional areas are required, as diagnosis remains challenging especially in early patch stage 6, 3
T-cell receptor (TCR) gene rearrangement analysis is strongly recommended to detect clonality, ideally on fresh tissue 6
HTLV-1 serology must be checked in all patients to exclude adult T-cell leukemia/lymphoma, which can mimic CTCL, particularly in endemic areas 1
Prognosis by Stage
Prognosis is strongly determined by extent and type of skin involvement:
Stage IA: 96-100% 5-year survival with median survival exceeding 32 years; most patients die from causes other than mycosis fungoides 6, 5
Stage IB/IIA: Median survival greater than 11 years, with 24% likelihood of disease progression 5
Stage IIB (tumor stage): Median survival of 3 years, with 30-40% developing extracutaneous dissemination 5
Stage III (erythroderma): Median survival of 4.5 years 5
Stage IVB (visceral involvement): 0-15% 5-year survival with median survival of 13 months 6, 5
Increasing age is a poor prognostic factor, while younger patients typically present with early-stage disease and have excellent outcomes 1
Relationship to Sézary Syndrome
Mycosis fungoides and Sézary syndrome are closely related both clinically and pathogenetically but are classified separately, with Sézary syndrome representing an aggressive leukemic variant characterized by erythroderma, peripheral blood involvement with malignant Sézary cells, and lymphadenopathy 1, 7
Critical Diagnostic Pitfalls
The nonspecific skin presentation in early stages frequently mimics common inflammatory dermatoses such as eczema and psoriasis, making diagnosis challenging and often requiring multiple biopsies over time 2, 3
Folliculotropic variant has worse prognosis (36% disease-specific survival at 5 years for stage IB) and requires recognition on histology 6
Large cell transformation (often CD30+) can develop in plaque-type or erythrodermic mycosis fungoides and is associated with less favorable outcome 5