Nevus Sebaceous, Epidermal Nevi, and Epidermal Nevus Syndrome

Nevus Sebaceous, EpidermalNevi, and Epidermal NevusSyndrome9 th Sainte-Justine Pediatric Dermatology DayNovember 18, 2011Moise L. Levy, M.D.‘Specially for ChildrenDell Children’s Medical CenterAustin, TX

Potential Conflicts of Interest‣ Investigator, Consultant, or Speaker for:-Stiefel/GSK-Galderma-Topaz-Coria-Pierre-Fabre‣ None should apply for this presentation

Nevus Sebaceous‣ Congenital… some said to develop later‣ Growth around puberty‣ 0.3 % - 0.4 %‣ Malignant risk ???-Trichoblastoma, Syringocystadenomapapilliferum, other adnexal tumors

Nevus Sebaceous –Malignant Risk‣ 0-2.7 %; 0.8 % ; 2.2% BCC‣ SCCA‣ Sebaceous CA‣ PTCH deletions found in some NS lesionsPediatr Dermatol 2009;26:676; Dermatol Surg 2004;30:1546; EurAcad Derm Venereol 2002;16:319; Pediatr Clin N Am2010;57:1177

Nevus Sebaceous –Malignancy‣ Some publications w/o any BCC inexcised NS‣ 18 yr retrospective of excised lesions‣ 651 lesions/631 patients‣ 0.8% BCC‣ 1.1% Syringocystadenoma papilliferumPediatr Dermatol 2009;26:676

Nevus Sebaceous –Malignancy‣ Retrospective study of excised NS x 20yrs‣ Included pts with Epidermal NevusSyndrome (Schimmelpenning)‣ 226 pts- 5 with BCC, 2.2 %‣ Recommendation for clinical f/uEur Acad Dermatol Venereol 2002;16:319

Nevus Sebaceous - Malignancy‣ 4,923 cases NS (1932-2010)‣ 16% benign tumors‣ 8% malignant (0-22); no determination ofmis.diagnosis‣ Suggestion of discussion withfamily/patient regarding excisionPediatr Dermatol 2011 Oct 13.doi:10.1111/j.1525-1470.2011.01562.x.

Nevus Sebaceous –Management‣ Discussion of low malignant risk withparents, patients‣ Excision (? Indication)-General anesthesia-Local anesthesia-Size, Location‣ Clinical f/u

Epidermal and Sebaceous Nevi‣ “Organoid” nevi‣ Epidermal with differentiationtoward “epidermal” structures(primarily)‣ Sebaceous with differentiation toward“sebaceous” structures (primarily)

Epidermal Nevi‣ Usually congenital; may appear later‣ Growth/Extension during childhood, puberty‣ Most occur without concern forassociated findings‣ Histology usually non.specific-Like seborrheic keratosis-Approx 1/3 with FGFR3 mutations-May see epidermolysis ( risk ofEpidermolytic ichthyosis)‣ Variants; ILVEN, Nevus comedonicus, others

Epidermal Nevus Syndrome‣ Epidermal nevi and other organ systeminvolvement-Neurologic-Ophthalmologic-Skeletal (15%-70%; Craniofacial 30%)-Cardiac-Renal-Hypophosphatemic Vit D Resistant Rickets‣ Many variants; Proteus, CLOVE,Phakomatosis Pigmentokeratotica, others

Case History‣ 10 y/o female seen for evaluation of congenital skinlesions‣ Sickle-thal trait‣ Prior diagnosis of IP‣ On 1, 25 (OH) 2 D 3 for “rickets”‣ Contralateral mandibular cysts‣ PHEX (-); Mutation assoc w/hypophosphatemic Vit DResistant Rickets (Phosphate Endopeptidase Homologon X-chromosome)‣ FGF-23 elevated

Am J Med Genet 2005;139A:67

Epidermal Nevus Syndrome& Rickets‣ ?Tumor-induced osteomalacia (TIO)‣ Usually associated with benign lesions and renal wasting of P andlow calcitriol-Reports of reversal with removal of tumors‣ Elevated FGF-23 in hypophosphatemic rickets w/o focal bonedisease (blunts Vit D synthesis and P resorption)-elevated in pt reported w/focal disease*-@ high levels, cross reacts w/ FGFR 2 (bone), 3 (renal tubules)(craniosynostosis)**Am J Med Genet 2005;139A:67*J Craniofac Surg 2009;20:439**

Proteus Syndrome‣ Epidermal Nevus‣ Progressive/Asymmetric limb overgrowth‣ Vascular malformation, usu CM‣ Fatty overgrowth or Atrophy (ellatoproteus)

Proteus Syndrome‣ NIH diagnostic criteria‣ Lipomas, Vascular malformations, Plantar cerebriformconn tiss nevi, Epid nevi, Lipohypoplasia, Dermalhypoplasia‣ PTEN association does not apply‣ 26/29 with AKT1 somatic mutation-oncogene encoding AKT1 kinase (cellproliferation/apoptosis (NEJM 2011;365:611)

CLOVE Syndrome‣ Congenital Lipomatous Overgrowth,Vascular Malformation, Epidermal Nevi‣ Proportionate overgrowth‣ Risk of central/thoracic phlebectasia andpulmonary embolism (PE)-12 pts with CLOVE; 11/12 with phlebect.-2/11 with perioperative PE; one deathJ Thor Cardiovasc Surg 2010;140:459

Epidermal Nevus –Evaluation‣ None if pt is clinically w/o other systeminvolvement; Not clear that extent impt.‣ Neurologic, Ophthalmologic examinations‣ Skeletal survey‣ Serum/urine Ca/P‣ PTH‣ ?FGF23, FGF2R‣ Consider preop eval and prophylaxis(CLOVE)

Epidermal Nevi –Management‣ None‣ Emollients‣ Topical retinoids, Ammonium lactate‣ 5-FU; alone or in combination w/ retinoid‣ Excision‣ LaserPediatr Clin N Amer 2010;57:1177; JAAD1994;30:287; JAAD 2000;43:129; Ann PlastSurg 2001;47:285

Sebaceous/Epidermal Nevi –What I do‣ Consider association with other findings, ifany (? Relation to extent… )‣ Discuss low malignant risk with either‣ Ask family members/patients‣ Most NS excised for cosmetic reasons‣ For EN; emollients, topical retinoids,rarely systemic retinoids, selectiveexcision, or laser