What is the leukemia phase of cutaneous T-cell lymphoma, mycosis fungoides, called?

Sézary Syndrome: The Leukemic Phase of Mycosis Fungoides

The leukemic phase of cutaneous T-cell lymphoma, mycosis fungoides, is called Sézary syndrome (answer D). 1

Definition and Classification

Sézary syndrome (SS) represents the leukemic variant of mycosis fungoides (MF), characterized by:

• Erythroderma (generalized redness of the skin)
• Presence of neoplastic T cells (Sézary cells) in peripheral blood
• Lymphadenopathy
• Significant blood involvement (B2 classification in staging) 1

Distinguishing Features Between MF and SS

While MF and SS are both forms of cutaneous T-cell lymphoma (CTCL), they have important distinctions:

• Mycosis Fungoides:

  • Primarily involves the skin with patches, plaques, and tumors
  • Usually follows an indolent course in early stages
  • May progress to involve lymph nodes, blood, and visceral organs

• Sézary Syndrome:

  • Presents with generalized erythroderma
  • Has significant blood involvement from onset
  • More aggressive clinical course
  • Classified as stage IVA1 in the TNMB staging system 1, 2

Diagnostic Criteria

The diagnosis of SS requires:

• Erythroderma
• Peripheral blood involvement with Sézary cells
• Matching T-cell clone in skin and blood
• B2 blood involvement criteria including:
  • Elevated absolute Sézary cell count
  • CD4/CD8 ratio > 10
  • Loss of T-cell markers
  • Demonstration of T-cell clonality 1

Clinical Significance and Prognosis

SS carries a significantly worse prognosis compared to early-stage MF:

• 5-year overall survival: 15-40% for stage IVA disease (which includes SS)
• 10-year overall survival: 0-20% for stage IVA disease 1

Treatment Approach

Treatment for SS differs from early-stage MF:

• Early-stage MF: Skin-directed therapies (topical corticosteroids, PUVA, radiation)
• Sézary syndrome: Requires systemic approaches including:
  • Extracorporeal photopheresis
  • Systemic retinoids (bexarotene)
  • Interferon-α
  • Histone deacetylase inhibitors
  • Monoclonal antibody therapies
  • Allogeneic stem cell transplantation in selected cases 1, 3, 4

Genetic Differences

Recent oncogenomic analysis has revealed major differences between MF and SS:

• MF shows recurrent chromosomal alterations including gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21
• SS demonstrates a different pattern of chromosomal alterations
• These genomic differences suggest distinct molecular pathogenesis and potentially different therapeutic requirements 5

Clinical Pearls

• SS should be suspected in any patient with erythroderma and lymphadenopathy
• Diagnosis requires integration of clinical, histopathologic, and molecular data
• Poor prognostic factors include advanced age, elevated LDH, and large cell transformation
• Patients require close monitoring for infectious complications due to compromised skin barrier and immune dysfunction 3, 4

The distinction between MF and SS is critical for proper staging, treatment selection, and prognostication in patients with cutaneous T-cell lymphoma.