Resident Physician D Ryan Skinner DO PGY - PDF document

Brooke - Spiegler Syndrome Resident Physician: D. Ryan Skinner DO, PGY - 4 Program Director: Daniel S. Hurd DO, FAOCD History • A 28 year - old female presented to the clinic with multiple facial papules that have been present since around the time of puberty. • She had been previously diagnosed as having “ milia ”͘ • There

is no family history of similar skin lesions. • She had recently become pregnant and thought that since becoming pregnant she was getting more spots. • She wished to have them “extracted” like her previous dermatologist in North Carolina had done. • On further examination she also had a few small scattered papules on her scalp

Differential Diagnosis • Multiple facial papules • Brooke - Spiegler syndrome • Multiple familial trichoepitheliomas • Familial cylindromatosis • Cowden syndrome • Birt - Hogg - Dube • Tuberous sclerosis • Rombo syndrome • Bazex syndrome • Muir – Torre syndrome Brooke - Spiegler Syndrome • :ow did = get it ? No one

in my family has anything like this͙ • Is it dangerous? Are these spots cancer, will they turn to cancer? • Are other areas of my body going to be affected ? • Other organs ? • How much worse are these going to get? • I googled Brooke Spiegler syndrome and the pictures = saw͙is that going to be me ? • Is my unborn daughter

going to get this? • What are the chances? • W hen will we know if she has it? • If she gets it, how bad will it be͙like mine? • Like the pictures on google?? • I felt like these got worse during pregnancy, did I imagine that or do hormones influence these lesions ? • Most importantly͙how do = get rid of these spots

and stop new ones from growing ? I HATE them !!! Brooke - Spiegler Syndrome • Features: • Trichoepithelioma • Cylindroma • Spiradenoma • CYLD mutation on 16q12 - q13 • Familial Cylindromatosis • Multiple Familial Trichoepitheliomas • Malignant counterparts • Cylindrocarcinoma • Spiradenocarcinoma • Basal cell carcinom

a • Rarely associated • Basal cell adenomas and adenocarcinomas of the parotid glands and minor salivary glands Genetics • Autosomal Dominant condition • Women affected more severely than men • Variable phenotypical expression • Drastically different presentations within the same family • What causes the second hit that leads

to loss of heterozygosity? • UV radiation • Cylindromas occur largely in sun exposed areas • Hormones • Androgen dependent areas of scalp / pubic area • Onset after adrenarche • Follicular neoplasms • One other case reported with worsening of lesions during pregnancy Blake PW, Toro JR. 2009. Update of cylindromatosis gene (CY

LD) mutations in Brooke - Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum. Mutat . 30:1025 – 1036. 10.1002/humu.21024 Blake PW, Toro JR. 2009. Update of cylindromatosis gene (CYLD) mutations in Brooke - Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. H

um. Mutat . 30:1025 – 1036. 10.1002/humu.21024 CYLD JNK NF - κB CYLD JNK NF - κB NF - kB Cell survival through inhibition of apoptosis Angiogenesis Spermatogenesis Cell differentiation Immune response and Inflammation Osteoclastognesis and bone homeostasis. Bubici C, Papa S (2014) JNK signalling in cancer: in need of new, smarte

r therapeutic targets. Br J Pharmacol 171: 24 – 37 JNK Cell transformation Cell death Inflammation Cell survival Proliferation Zhang JY, Selim MA. The role of the c - Jun N - terminal Kinase signaling pathway in skin cancer. Am J Cancer Res. 2012;2:691 – 698 Treatment • Characteristic lesions of Brooke - Spiegler are considered beni

gn, medical treatment is not necessary. • Treatment for cosmetic reasons. • Commonly reported treatments • Excision • Electrosurgery • Dermabrasion , • CO2 laser resurfacing, • C ryotherapy • R adiotherapy • Potential for scarring/adverse side effects. Future/Emerging Treatments • NF - kB inhibitors • Nearly 800

compounds/drugs are inhibitors of NF - kB • ASA, TNF - alpha, cantharidin • Topical Salycylic Acid used on 17 cylindromas • Two showed complete remission • JNK inhibitors • Tanzisertib (CC - 930) • Bentamapimod • SP600125 References 1. Carlson, Ryan M., Lori Haddad, and John C. Pui ,. "Brooke Spiegler Syndrome with Associat

ed Pegged Teeth." Cutis 82 (2008): 345 - 49. Web. 9 May 2014. 2. Bowen, Sarah, Melissa Gill, David A. Lee, Galen Fisher, and Roy G. Geronemus . "Mutations in the CYLD gene in Brooke – Spiegler Syndrome, Familial Cylindromatosis , and Multiple Familial Trichoepithelioma: Lack of Genotype – Phenotype Correlation." Journal of Investigative

Dermatology 124 (20 05): 919 - 20. Web. 13 May 2014. 3. Trufant , Joshua; Robinson, Maria; & Patel, Rishi. (2012). Brooke - Spiegler syndrome. Dermatology Online Journal, 18(12). Retrieved from: http://escholarship.org/uc/item/4b04h9p3 4. Scinska , Justyna , Adriana Rakowska , Joanna Czuwara - Ladykowska , Andrzej Mroz , Marcin Lipins

ki, Anna Nasierowska - Guttmejer , Jolanta Sikorska , Katarzyna Sklinda , Monika Slowinska , Elzbieta Kowalska - Oledzka , Irena Walecka , Jerzy Walecki , and Lidia Rudnicka . " Cylindroma transforming into basal cell carcinoma in a patient with Brooke - Spiegler syndrome." Journal of Dermatological Case Reports 1.1 (2007): 4 - 9. We

b. 16 May 2014. 5. Glodny , Bradley, and Joshua Zeichner . Acneiform Eruptions in Dermatology: A Differential Diagnosis. New York: Springer, 2014. 191 - 94. Print. 6. Ruiz, Ramon G., Altea E. Martinez, Anna A. Mejias , Juan Corell , and Victor A. De Miquel . "Old Syndromes, New Perspectives: Brooke - Spiegler Syndrome." Journal of the

American Academy of Dermatology 64.2 (2011): AB86. Print. 7. Bolognia , Jean L., Joseph L. Jorizzo , and Julie V. Schaffer. Dermatology. Third ed. Vol. 1. N.p .: Saunders Elsevier, 2012. Print. 8. Rathi , Monika, Seema Awasthi , Satish K. Budania , Faiyaz Ahmad, Shyamoli Dutta, and Ashutosh Kumar. "Brooke - Spiegler Syndrome: A Rare

Entity." Case Reports in Pathology 2014 (2014). Web. 13 May 2014. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC392091倀6/. 9. Uede , Koji, Yuki Yamamato , and Fukumi Furukawa. "Brooke - Spiegler syndrome associated with cylindroma , trichoepithelioma, spiradenoma , and syringoma ." The Journal of Dermatology 31 (2004): 32 - 38. Web. 11

May 2014. 10. Oosterkamp , H.M., Neering , H., Nijman , S.M.B., Dirac, A.M.G., Mooi , W.J., Bernards , R. and Brummelkamp , T.R. (2006), An evaluation of the efficacy of topical application of salicylic acid for the treatment of familial cylindromatosis . British Journal of Dermatology, 155: 182 – 185. 11. Johnson, Hillary; Robles,

Mirin ; Kamino , Hideko; Walters, Ruth F; Lee, Arnold; & Sanchez, Miguel. (2008). Trichoepithelioma. Dermatology Online Journal, 14(10). Retrieved from: http://escholarship.org/uc/item/862492p4 12. Samaka RM, Bakry OA, Seleit I, Abdelwahed MM, Hassan RA. Multiple familial trichoepithelioma with malignant transformation. Indian J Derm

atol 2013;58:409 13. Bercin , Sami, Ahmet Kutluhan , Ahmet Metin , and Dinc Suren. "Malignant eccrine spiradenoma on the lateral margin of nose as an infrequent localization." Indian Journal of Dermatology 54.2 (2009): 173 - 175. Print 14. Cunha, Rafael A., Caroline B. Batista, Fabricio M. Pinto, Maria C. Issa , Mayra C. Rochael , an

d Sandra M. Barbosa Duraes ͘ “ Cylindroma : Typical presentation of uncommon tumor” Hournal of the American Academy of Dermatology ͕ Volume 68 ͕ =ssue 4 ͕ AB160 15. Smith, Scott A., Anita C. Gilliam, and Paradi Mirmirani . "Familial Cylindromatosis : A Case Report" Journal of the American Osteopathic College of Dermatology 4.1 (2

005): 12 - 14. Print. 16. Goette CK͕ McConnell CA͕ Fowler MR͘ “ Cylindroma and Eccrine Spiradenoma Coexistent in the Same Lesion” Arch Dermatol . 1982;118(4):273 - 274. 17. Gerretsen AL, van der Putte Sc , Deenstra W, van Vloten WA͘ “Cutaneous cylindroma with malignant transformation͘” Cancer͘1993 Sep1͖72(5)͗1618 - 23.