What are the similarities and differences between classic mycosis fungoides, folliculotropic mycosis fungoides (MF), and syringotropic mycosis fungoides (MF)?

Similarities and Differences Between Classic Mycosis Fungoides, Folliculotropic MF, and Syringotropic MF

Classic mycosis fungoides (MF), folliculotropic MF, and syringotropic MF are distinct variants of cutaneous T-cell lymphoma with important clinical, histopathological, and prognostic differences that impact therapeutic management.

Common Features Across All Three Variants

• Pathogenesis: All are cutaneous T-cell lymphomas (CTCLs), representing malignant proliferation of T lymphocytes with primary cutaneous involvement 1
• Classification: All are variants of mycosis fungoides, the most common form of CTCL 1, 2
• Diagnostic Approach: All require:
  • Skin biopsies (elliptical preferred over punch) 1
  • Immunophenotypical studies (CD2, CD3, CD4, CD8, CD20, CD30) 1
  • T-cell receptor gene rearrangement analysis when possible 1
• Staging System: All use the TNMB (tumor-node-metastasis-blood) staging system 1, 2

Classic Mycosis Fungoides

Clinical Features

• Presents with patches and plaques, later developing tumors 1
• Predilection for non-sun-exposed areas 3
• Typically affects older adults
• Slow progression through patch, plaque, and tumor stages

Histopathology

• Superficial infiltrates of small to medium-sized atypical T cells 4
• Epidermotropism (atypical lymphocytes in epidermis)
• Characteristic Pautrier microabscesses
• Typically CD3+, CD4+, CD45R0+, CD8- phenotype 1

Prognosis and Treatment

• Generally indolent course with good prognosis in early stages
• Early stages (IA/IB): 5-year survival 73-100% 1
• Treatment: Skin-directed therapies (topical steroids, PUVA, narrow-band UVB, topical cytostatic agents) 1

Folliculotropic Mycosis Fungoides

Clinical Features

• Follicular papules, acneiform lesions, and cystic lesions 5
• Comedo-like and hidradenitis suppurativa-like lesions 5
• Predilection for head and neck region
• Associated with follicular mucinosis and alopecia 1
• Generalized involvement with loss of body hair 5
• Significant pruritus 5

Histopathology

• Atypical T cells with preferential infiltration around and within hair follicles
• Folliculotropism rather than epidermotropism
• Often associated with follicular mucinosis
• Similar immunophenotype to classic MF 1

Prognosis and Treatment

• More aggressive clinical course than classic MF
• 5-year disease-specific survival for stage IB: 36% (vs 83% for classic MF) 1
• 10-year disease-specific survival: 81% for stage IB 1
• More resistant to skin-directed therapies due to deeper follicular involvement 6
• Often requires combined modalities or systemic approaches earlier 1

Syringotropic Mycosis Fungoides

Clinical Features

• Erythematous papules and plaques 6
• Can present with studded papules 6
• May have clinical overlap with folliculotropic MF
• Can cause hypohidrosis due to eccrine gland involvement 5

Histopathology

• Atypical lymphocytes with preferential infiltration around and within eccrine sweat glands 6
• Concentration of abnormal lymphocytes around eccrine structures 6
• May or may not coexist with folliculotropism 5

Prognosis and Treatment

• Better prognosis than folliculotropic MF 6
• More indolent course than folliculotropic MF, but still more resistant to therapy than classic MF 5, 6
• Increased disease-specific survival compared to folliculotropic MF 6
• More resistant to standard skin-directed therapies due to deeper adnexal involvement 6

Key Differences

Tissue Tropism

• Classic MF: Epidermotropic (atypical cells in epidermis)
• Folliculotropic MF: Folliculotropic (atypical cells around and within hair follicles)
• Syringotropic MF: Syringotropic (atypical cells around and within eccrine sweat glands)

Prognosis (From Best to Worst)

1. Classic MF: Most favorable prognosis in early stages
2. Syringotropic MF: Intermediate prognosis, better than folliculotropic 6
3. Folliculotropic MF: Worst prognosis among the three variants 1, 6

Treatment Response

• Classic MF: Responds well to skin-directed therapies in early stages
• Folliculotropic and Syringotropic MF: More resistant to skin-directed therapies due to deeper adnexal infiltration 6
• Folliculotropic MF: May require more aggressive systemic approaches earlier in the disease course

Clinical Implications

• Deep biopsies containing adnexal structures are essential for diagnosing folliculotropic and syringotropic variants 5
• Distinguishing between folliculotropic and syringotropic MF is crucial for prognostication and treatment planning 6
• The presence of folliculotropism in patients with infiltrated plaques and tumors in the head and neck region is associated with poorer prognosis 2
• Aggressive treatment may not be necessary in cases of syringotropic MF with indolent course 5