1. 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

2. 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

3. Physical Exam

7. Histopathology

8. Histopathology Scalp cylindroma-spiradenoma

9. Histopathology Scalp cylindroma

10. Histopathology Scalp spiradeoma

11. Histopathology Face trichoepithelioma

12. Brooke-Spiegler Syndrome

13.  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

14. 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

15. Genetics  Autosomal dominant mutation affecting epidermal appendages  CYLD gene on chromosome 16q12-q13  CYLD functions as a tumor suppresor  CYLD inhibits NF-κB transcription factor in the TNF-α signaling pathway, regulating cell growth

16. 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

17. 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

18. Treatment  Excision  Dermabrasion  Electrodessication  Cryotherapy  Radiotherapy  Laser- Argon, erbium:Yag, CO 2  Medical therapy with sodium salicylate and prostaglandin A1 is under investigation – -Inhibit NF-κB activiation  Monitor for clinical signs of malignant transformation

19. References  Kakagia D, Lambropoulou M, Alexiadis G. Brooke-Spiegler syndrome with parotid gland enlargement. Eur J Dermatol. 2004 May-Jun;14(3):139-41.  Kim C, Kovich OI, Dosik J. Brooke-Spiegler syndrome. Dermatol Online J. 2007 Jan 27;13(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 Dec;15(12):966-70.  Ly H, Black MM, Robson A. Case of the Brooke-Spiegler syndrome. Australas J Dermatol. 2004 Nov;45(4):220-2.  Szepietowski JC, Wasik F, Szybejko-Machaj G et al. Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol. 2001 Jul;15(4):346-9.  Ralla D, Harland CC. Brooke-Spiegler syndrome: treatment with laser ablation. Clin Exp Dermatol. 2005 Jul;30(4):355-7.  Lee DA, Grossman ME, Schneiderman P et al. Genetics of skin appendage neoplasms and related syndromes. J Med Genet. 2005 Nov;42(11):811-9.