Mycosis fungoides/Sézary syndrome

Mycosis fungoides and Sézary syndrome are indolent types of cutaneous T-cell lymphomas that primarily affect the skin.

Mycosis fungoides and Sézary syndrome arise from clonal proliferation of malignant T-cells, primarily CD4+ memory T-cells. In mycosis fungoides, these cells infiltrate the skin, causing characteristic patches, plaques, and potential tumor formation, while in Sézary syndrome, the malignant cells circulate in the blood, leading to erythroderma and lymphadenopathy. Molecular mechanisms implicated in these diseases include genetic and epigenetic alterations that disrupt normal T-cell signaling pathways. Mutations in genes such as STAT3, TNFRSF1B, STAT5B, and PLCG1 affect the JAK/STAT and T-cell receptor pathways, promoting uncontrolled cell growth. Additionally, alterations in chromatin-modifying genes, such as TET2 and DNMT3A, contribute to epigenetic dysregulation. Aberrant expression of certain molecules (such as PD-1, CTLA-4), chemokine receptors (such as CCR4, CCR7), and dysregulation of microRNAs also play roles in disease progression and dissemination.

Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. The incidence of cutaneous T-cell lymphomas in the US is estimated at 6.4-9.6 per 1,000,000 person-year. The incidence of classic Sézary syndrome in Europe is estimated at 5 per 1,000,000 person-year.

Mycosis fungoides typically presents with skin lesions that progress through distinct stages. Initially, patients develop flat, scaly, red patches, often on sun-protected areas such as the buttocks and thighs. These patches can evolve into thicker, raised plaques and eventually form tumors that may ulcerate. Sézary syndrome, on the other hand, is characterized by a triad of generalized erythroderma, lymphadenopathy, and the presence of malignant Sézary cells in the blood. Patients with Sézary syndrome often experience severe pruritus, scaling, alopecia, and nail abnormalities. Both mycosis fungoides and Sézary syndrome have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies.

Both mycosis fungoides and Sézary syndrome have a chronic, relapsing course, and patients frequently undergo multiple consecutive therapies. Mycosis fungoides typically presents in early-stage disease, which may progress to advanced disease over years. The 5-year overall survival in patients with stage IIB-IV mycosis fungoides/Sézary syndrome is estimated at 39-52%.