Radiation Oncology/Mycosis fungoides

For B-cell lymphomas, see Cutaneous B-cell lymphoma

Epidemiology

• More common in blacks than whites
• More common in males than females (1.6:1)
• Median age at presentation is 55-60

Presentation

• Generally presents in patients with long history of skin plaques, rash, plaques, pruritis, erythroderma
• 5% present as Sezary Syndrome (defined historically by the triad of erythroderma, generalized lymphadenopathy, and presence of Sezary cells in skin, nodes, and peripheral blood)

Histology

• Typical cells are lymphocytes with cerebriform and sometimes hyperchromatic nuclei, and mostly confined to the epidermis.
• Sezary cells are enlarged atypical lymphocytes with convoluted nuclei

Pathogenesis

• PMID 15128898, 2004 — "The pathogenesis of mycosis fungoides." Girardi M, Heald PW, Wilson LD. 2004 May 6;350:1978-88.

WHO-EORTC Classification

During recent consensus meetings, the WHO and EORTC agreed upon a new classification system for cutaneous lymphomas which is now called the WHO-EORTC Classification. PMID: 15692063

• Indolent cutaneous T-cell lymphomas - includes mycosis fungoides, lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma. These entities have 5-year disease specific survival of approximately 80-100%
• Aggressive cutaneous T-cell lymphomas - includes Sezary syndrome, primary cutaneous peripheral T-cell lymphoma. These entities have 5-year disease specific survival of <25%

Prognosis

• 97% 10-year disease specific survival with limited patch/plaque disease
• 83% 10-year disease specific survival with generalized patch/plaque disease
• 42% 10-year disease specific survival with tumor stage disease
• 20% 10-year disease specific survival with lymph node involvement

Staging

2009 AJCC Staging (7th edition)

T Stage

• T1 - Limited patch/plaque (<10% total skin surface)
  • T1a - Patch only
  • T1b - Plaque +/- patch
• T2 - Generalized patch/plaque (>10% total skin surface)
  • T2a - Patch only
  • T2b - Plaque +/- patch
• T3 - One or more tumors (≥ 1cm diameter)
• T4 - Confluence of erythema covering 80% or more of body surface area

N Stage

• N0 - Nodes clinically uninvolved
• N1 - Nodes clinicall abnormal, histopathology Dutch grade 1 or NCI LN0-2
  • N1a - Clone negative
  • N1b - Clone positive
• N2 - Nodes clinically abnormal, histopathology Dutch grade 2 or NCI LN3
  • N2a - Clone negative
  • N2b - Clone positive
• N3 - Nodes clinically abnormal, histopathology Dutch grade 3-4 or NCI LN4

M Stage

• M0 - No visceral involvement
• M1 - Visceral involvement (must have pathology or imaging confirmation)

B Stage (Blood)

• B0 - No circulating Sezary cells (<5% of lymphocytes)
  • B0a - Clone negative
  • B0b - Clone positive
• B1 - Circulating Sezary cells (≥5% of lymphocytes)
  • B1a - Clone negative
  • B1b - Clone positive
• B2 - High blood tumor burden (≥ 1000/uL Sezary cells with positive clone)

Notes:

• Patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted
• Plaque indicates any size skin lesion that is elevated or indurated. Presence/absence of scale, crusting, and/or poikiloderma should be noted
• Tumor indicates at least one 1-cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest size lesion, and region of body involved
• Abnormal node indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or 1.5 cm or larger in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes are not currently considered in the nodal classification, unless used to establish N3 histopathologically
• T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene
• For viseceral spread, spleen and liver may be diagnosed by imaging criteria
• For blood, Sezary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei

Treatment

• NCI Randomized Trial PMID 2594037 comparing combination electron beam radiation + chemotherapy to topical therapy
  • 103 patients
  • Xrt arm treated to 30 Gy to total skin + CTX, doxorubicin, etoposide, vincristine. Topical treatment arm treated patients with sequential topical therapies.
  • Patients in combined arm had higher rate of complete response (38% vs 18%), but also higher rate of acute toxicity. There was no difference in overall survival.
  • Median duration of complete response in combined-modality for advanced disease was less than 2 years
  • Authors' conclusion was that aggressive therapy did not improve prognosis as compared to conservative treatment beginning with sequential topical therapies