CTCL

• 70% of all cutaneous lymphomas.
• MF and SS are the most common CTCL subtypes worldwide, constituting 54% of the CTCLs and an annual incidence of approximately four cases per million people.
• The malignant cells are typically CD3+, CD4+ , CD45RO+, CD8+, and CD30+ by immunohistochemical analysis. CD7 is not expressed by cells from the early disease stages.
  • CD7 is a T-cell marker expressed in early differentiation, but usually absent in T-cell homing to the skin.
• More aggressive variants and advanced forms of CTCL may have cells with multiple pan–T-cell antigen deletions, especially CD2, CD5, and even CD4.
• TCR genes are clonally rearranged.
• Elevated serum LDH and β2 microglobulin.
• Eosinophilia and hypergammaglobulinemia are occasionally observed in advanced SS.

MF

• The characteristic patch lesion is typically well demarcated with fading edges, lightly erythematous, and scaly, with a predilection for sun-protected areas, such as the lower abdomen or buttocks.
• Plaque lesions are more indurated, have fairly well-demarcated margins, and some scaling.
• Tumor lesions tend to appear in advanced cases, frequently associated with previous patches or plaques, and are commonly associated with histologic evidence and large-cell transformation. They can be located on any part of the body. Ulceration of these lesions is common, and secondary infection is a major cause of morbidity. Tumors may be the initial presentation in a small percentage of patients (d'emblée presentation).

Early cutaneous T-cell lymphoma (CTCL): mechanisms of epidermotropism

The release of interferon (IFN)-γ by early, reactive CD8-cytotoxic T cells or NK cells leads to increased keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) and release of the C-X-C chemokine IP-10, which binds to the CXCR3 receptor, and may lead to nesting of CTCL cells within the epidermis.

Late cutaneous T-cell lymphoma (CTCL): loss of epidermotropism

As the clonal population of CTCL cells expands, more IL-4 is released, which drives autocrineinduced proliferation of the CTCL cells and inhibition of CD8-cytotoxic T cells and NK cells. The impaired release of interferon (IFN)-γ may lead to less intercellular adhesion molecule-1 (ICAM-1) expression and decreased keratinocyte-CTCL cell adhesion.

SS

• Present with generalized desquamative erythroderma, pruritus, and circulating malignant cells.
• Peripheral blood usually shows a significant number or percentage of hyperconvoluted atypical lymphocytes.
• In its most advanced form, patients with SS suffer from alopecia, ectropion, leonine facies, hyperkeratosis, nail dystrophy, fissuring of the palms and soles, and severe pruritus and cutaneous pain.