Mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. Due to its nonspecific features, mycosis fungoides is often initially mistaken for other skin conditions. Patients commonly present with pruritic cutaneous plaques and patches, which can progress to nodular tumors and/or systemic involvement in advanced disease. Histopathological findings can be difficult to detect. Characteristic findings on skin punch biopsy include atypical lymphocytes in the upper dermis or aggregates in the epidermis (Pautrier microabscesses). Most cases do not progress beyond early-stage disease. In early stages, several options, including topical corticosteroids and phototherapy, can improve symptoms. In advanced disease, a combination of systemic therapy and skin-directed treatment can provide palliative relief.

• Incidence ^[1][2]
  • Approx. 4% of non-Hodgkin lymphoma cases
  • Mycosis fungoides and Sézary syndrome are the two most common cutaneous T-cell lymphomas (CTCL).
• Age: mostly middle-aged or older adults
• Sex: ♂ > ♀

Epidemiological data refers to the US, unless otherwise specified.

• Cutaneous lesions: variable presentation, often accompanied by severe pruritus ^[3]
  • Erythematous cutaneous plaques and patches in non-sun-exposed areas, which may be hyperpigmented or hypopigmented ^[4]
  • Nodular tumors: often discolored and can ulcerate ^[5]
  • Diffuse erythroderma
• Extracutaneous involvement: lymphadenopathy, hepatosplenomegaly, and involvement of other extracutaneous sites in advanced disease ^[3]

Loss of the skin barrier can result in skin and soft tissue infections, which can lead to systemic infection.

Consider mycosis fungoides in patients with persistent and/or progressive clinical features, especially if treatment for an alternative diagnosis was unsuccessful. Refer to dermatology for diagnostic testing. ^[3]

• Punch biopsies of skin lesions: for diagnostic confirmation based on histopathology, immunohistochemistry, and genetic testing ^[4]
• Laboratory studies
  • CBC with differential, CMP, LDH: to rule out other lymphoproliferative disorders and establish a baseline before treatment ^[6]
  • Consider peripheral blood flow cytometry, e.g., to evaluate for Sézary syndrome.
• Imaging studies ^[3]
  • To evaluate for extracutaneous disease as part of staging
  • May include CT neck, chest, abdomen, and pelvis ± FDG-PET scan
• Lymph node biopsy: Perform an excisional biopsy of enlarged lymph nodes to evaluate for infiltration. ^[6]

Initial misdiagnosis is common because mycosis fungoides has varied and nonspecific features.

• Histopathology ^[4]
  • Atypical T cells with cerebriform nuclei infiltrating the dermis and epidermis ^[5]
  • Pautrier microabscesses: aggregates of atypical CD4+ T cells within the epidermis that are indicative of mycosis fungoides ^[7]
• Immunohistochemistry: Mycosis fungoides tumor cells are often CD4+ and CD8- and frequently lose expression of other pan-T-cell antigens. ^[3]

• Eczema
• Psoriasis
• Cutaneous drug reactions
• Other T-cell lymphoproliferative disorders
  • Sézary syndrome
  • Adult T-cell leukemia-lymphoma

Sézary syndrome

• Definition: a cutaneous T-cell lymphoma with leukemic dissemination of mutated T cells
• Epidemiology ^[8]
  • Exact prevalence unknown
  • Can be an advanced form of mycosis fungoides or arise de novo
• Clinical features
  • Systemic skin lesions
    • Erythroderma accompanied by palmar and plantar hyperkeratosis
    • Intense pruritus
  • Generalized lymphadenopathy
• Diagnostics: : based on the characteristic triad of pruritic erythroderma, lymphadenopathy, and atypical T cells (Sézary cells) on peripheral blood smear ^[9]

The leukemic dissemination present in Sézary syndrome distinguishes it from mycosis fungoides.

Adult T-cell leukemia-lymphoma (ATLL) ^[10]

• Definition: a non-Hodgkin lymphoma associated with infection with the human T-cell lymphotropic virus I (HTLV-I)
• Epidemiology
  • Rare in the US; most commonly seen in Japan, West Africa, and the Caribbean
  • Associated with IV drug use
• Clinical features
  • Generalized lymphadenopathy
  • Hepatosplenomegaly
  • Skin lesions: may be similar to those seen in mycosis fungoides
  • Lytic bone lesions
• Diagnostics
  • Peripheral blood smear: lymphocytes with condensed chromatin and hyperlobulated nuclei that resemble clover leaves
  • Laboratory tests: hypercalcemia, ↑ LDH
  • Immunophenotype: stain positive for CD2, CD4, CD5, CD29, and CD45RO

The differential diagnoses listed here are not exhaustive.

Treatment is guided by disease stage, patient preference, and performance status and is typically managed by specialists.

• Expectant management: for very early disease, e.g., < 10% of body surface area affected ^[3]
• UV phototherapy: for early or advanced disease ^[4]
• Topical pharmacological therapy: for early or advanced disease ^[4]
  • First line: topical corticosteroids, e.g., clobetasol propionate
  • Second line: topical nitrogen mustard OR topical bexarotene ^[5]
• Systemic chemotherapy or immune therapy: for advanced disease (generally, alongside topical therapy) ^[4]
  • Oral bexarotene
  • OR interferon alpha
  • OR vorinostat
  • OR brentuximab vedotin ^[5]
• Radiation therapy
  • Local skin-directed radiotherapy: for early localized disease (potentially curative) ^[4][6]
  • Total skin electron beam therapy: for advanced disease (typically used in combination with systemic therapy) ^[3][5]

Topical therapy (pharmacological or UV phototherapy) is generally used for disease limited to skin patches or plaques. More advanced disease is treated with a combination of topical (pharmacological or radiation therapy) and systemic therapy. ^[3][4]