Brooke-Spiegler Syndrome

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Brooke-Spiegler Syndrome

• Quyn Sherrod, MD
• Miguel Gutierrez, MD Keith Carlson, MD
• UCLA/WLA VA Division of Dermatology
• David Geffen School of Medicine
• Los Angeles, California

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History

• 39 year-old, healthy, Caucasian male
• Multiple lesions on face and scalp beginning at
  10 years old
• Nonpainful, nonpruritic
• Previous paranasal biopsy consistent with
  trichoepithelioma
• Mother with similar presentation

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Physical Exam
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Physical Exam
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Physical Exam
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Physical Exam
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Histopathology
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HistopathologyScalp cylindroma-spiradenoma
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HistopathologyScalp cylindroma
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HistopathologyScalp spiradeoma
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HistopathologyFace trichoepithelioma
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Brooke-Spiegler Syndrome
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Brooke-Spiegler Syndrome

• Uncommon syndrome with autosomal dominant
  inheritance pattern
• Variable expression and penetrance
• More severe phenotype in women
• Mutiple cutaneous adnexal neoplasms
• Cylindromas, spiradenomas, trichepitheliomas on
  head and neck

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Clinical Presentation

• Begins during second or third decade
• Cylindromas, spiradenomas on scalp
• Turban tumors when numerous
• Trichoepitheliomas more
• common on face
• Progressive increase in size and number

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Genetics

• Autosomal dominant mutation affecting epidermal
  appendages
• CYLD gene on chromosome 16q12-q13
• CYLD functions as a tumor suppresor
• CYLD inhibits NF-?B transcription factor in the
  TNF-a signaling pathway, regulating cell growth

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Differential Diagnosis

• Familial cylindromatosis
• Multiple familial trichoepithelioma
• Rombo syndrome
• Vermicular atrophoderma - Milia
• Basal cell carcinomas - Hypotrichosis
• Peripheral vasodilation/cyanosis -
  Trichoepitheliomas
• Bazex syndrome
• Follicular atrophoderma - Hypotrichosis
• Basal cell carcinomas - Trichoepitheliomas
• Hypohidrosis

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Prognosis

• Psychologic impact due to physical disfigurement
• Rare malignant transformation of
  trichoepitheliomas into basal cell carcinomas
• -Low metastatic potential
• Rare malignant transformation of cylindromas and
  spiradenomas
• -Local infiltration and distant metastases
  reported
• Increased risk for salivary and parotid gland
  adenomas and adenocarcinomas

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Treatment

• Excision
• Dermabrasion
• Electrodessication
• Cryotherapy
• Radiotherapy
• Laser- Argon, erbiumYag, CO2
• Medical therapy with sodium salicylate and
  prostaglandin A1 is under investigation
• -Inhibit NF-?B activiation
• Monitor for clinical signs of malignant
  transformation

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References

• Kakagia D, Lambropoulou M, Alexiadis G.
  Brooke-Spiegler syndrome with parotid gland
  enlargement. Eur J Dermatol. 2004
  May-Jun14(3)139-41.
• Kim C, Kovich OI, Dosik J. Brooke-Spiegler
  syndrome. Dermatol Online J. 2007 Jan
  2713(1)10.
• Zhang GL, Huang YJ, Yan KL et al. Diverse
  phenotype of Brooke-Spiegler syndrome associated
  with a nonsense mutation in the CYLD tumor
  suppressor gene. Exp Dermatol. 2006
  Dec15(12)966-70.
• Ly H, Black MM, Robson A. Case of the
  Brooke-Spiegler syndrome. Australas J Dermatol.
  2004 Nov45(4)220-2.
• Szepietowski JC, Wasik F, Szybejko-Machaj G et
  al. Brooke-Spiegler syndrome. J Eur Acad
  Dermatol Venereol. 2001 Jul15(4)346-9.
• Ralla D, Harland CC. Brooke-Spiegler syndrome
  treatment with laser ablation. Clin Exp
  Dermatol. 2005 Jul30(4)355-7.
• Lee DA, Grossman ME, Schneiderman P et al.
  Genetics of skin appendage neoplasms and related
  syndromes. J Med Genet. 2005 Nov42(11)811-9.