Mycosis Fungoides (Cutaneous T-Cell Lymphoma)

Mycosis fungoides (MF) accounts for 50-70% of all cutaneous T-cell lymphomas (CTCL) with annual incidence of 6 per million, predominantly affecting middle-aged to older adults (median age 55-60 years), with male-to-female ratio of 1.6-2:1, and slightly higher incidence in African Americans. The disease was first described by Jean-Louis-Marc Alibert in 1806 as 'mushroom-like' tumors. Pathogenesis involves clonal proliferation of mature CD4+ T-helper cells expressing skin-homing markers (CCR4, CLA), with predominantly Th2 cytokine pattern, complex genetic alterations, and possible roles for chronic antigen stimulation, infections, and environmental factors.

Clinical course typically progresses through stages over many years: early patch stage (flat, scaly, atrophic, often photoexposure-spared, mimicking eczema or psoriasis), plaque stage (raised, infiltrated, indurated lesions), tumor stage (raised nodular masses with possible ulceration), and erythrodermic stage (Sezary-like, with generalized erythroderma). TNMB staging considers tumor (skin involvement), nodes (lymphadenopathy), metastasis (visceral), and blood (Sezary cells). Variants include folliculotropic MF, pagetoid reticulosis (Woringer-Kolopp disease), granulomatous slack skin syndrome, and CD8+ MF. Sezary syndrome is the leukemic variant with erythroderma, lymphadenopathy, and circulating atypical lymphocytes (Sezary cells with hyperconvoluted nuclei).

Diagnosis can be challenging in early stages and requires multiple skin biopsies over time, characteristic histology with epidermotropism, Pautrier microabscesses, atypical lymphocytes with cerebriform nuclei, immunohistochemistry (CD3+, CD4+, CD8-, CD7- aberrant pattern, T-cell receptor clonality), molecular studies for T-cell receptor gene rearrangement, peripheral blood flow cytometry for Sezary cell quantification, and staging imaging. Treatment depends on stage: skin-directed therapies for early stages (topical corticosteroids, topical retinoids, topical mechlorethamine, topical imiquimod, phototherapy with PUVA or UVB-NB, total skin electron beam therapy), systemic therapies for advanced disease (oral retinoids, interferon alpha, methotrexate, gemcitabine, doxorubicin, brentuximab vedotin, mogamulizumab), and stem cell transplantation for selected refractory cases. Outcomes are excellent in early stages (10-year survival >85%) but decline in advanced disease.