ASPECTE CLINICE ªI HISTOPATOLOGICE ÎNTR-UN CAZDE NEV SEBACEU ASOCIAT CU UN KERATOACANTOM

KERATOACANTHOMA ARISING WITHIN A NEVUSSEBACEOUS

FLOAREA SÃRAC, ILARIE BRIHAN, SIMONA FRÃÞILÃ*

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* Universitatea din Oradea, Facultatea de Medicinã ºi Farmacie,Disciplina Dermatologie.University of Oradea, Faculty of Medicine and Pharmacy, Department of Dermatology.

CAZURI CLINICECLINICAL CASES

Rezumat

Nevul sebaceu este un hamartom caracterizat prinhiperplazia glandelor sebacee la nivelul dermului superior,fãrã componentã nevocelularã ºi apare cel mai frecvent de lanaºtere sau în primele sãptãmâni de viaþã.

Aspectul clinic cel mai frecvent întâlnit este cel al uneiplãci alopecice situate la nivelul scalpului, bine delimitatã,rotund-ovalarã, cu dimensiuni între 1 ºi 4 cm, supra-denivelatã, de culoare gãlbuie sau roz-brunã, cu suprafaþanetedã, mamelonatã, comedonianã sau verucoasã.

Transformarea malignã a unui nev sebaceu este foarterarã. Totuºi, în literaturã sunt descrise cazuri excepþionalede nev sebaceu pe care s-au dezvoltat diverse carcinoame.

Unele hamartoame sebacee localizate în pielea pãroasãa capului ºi în special la nivelul feþei (unde dezvoltareaembrionarã a craniului facial este mai complexã) prezintãpe lângã hiperplazia sebacee variate malformaþii epidermicesau anexiale care pot da naºtere unor tumori complexe.Descriem un caz de nev sebaceu prezent de la naºtere pecare s-a dezvoltat dupã 25 ani de evoluþie un keratoacantomconfirmat clinic ºi histopatologic.

Cuvinte-cheie: hamartom, trichoblastom, nev sebaceuJadassohn, keratoacanthom.

Summary

Nevus sebaceous of Jadassohn is a hamartoma that

appears at birth or in the first weeks of life and is

characterized by the hyperplasia of sebaceous glands at the

level of superior dermis, without nevocellular component.

The most frequent clinical presentation is a well delimited,

round-oval, yellowish or pink-brown alopecic plaque,

measuring 1-4 cm, with smooth or papilomatous, verrucous

or comedonian surface, on the scalp. The malignant

transformation of the nevus sebaceous is very rare, though

different carcinoma developing in nevus sebaceus have been

described in the literature. Among the sebaceous

hyperplasia some sebaceus hamartoma located on the scalp

and especially on the face present different epidermic or

adnexal malformations with possible tumoral trans-

formation. We describe a case of keratoacanthoma at the age

of 26 developing on a nevus sebaceous that appeared from

birth.

Keywords: hamartoma, trichoblastoma, nevus seba-

ceous of Jadassohn, keratoacanthoma.

Intrat în redacþie: 10.12.2015

Acceptat: 23.01.2016

Received: 10.12.2015

Accepted: 23.01.2016

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Introducere

Nevul sebaceu descris de Jadasson în 1895este o displazie epidermicã congenitalã rarã ce semanifestã de la naºtere, sau în perioada copilãrieiºi mai rar în adolescenþã [7].

În cele mai multe cazuri se manifestãsporadic, dar sunt descrise în literatura despecialitate ºi cazuri familiale [22].

Clinic se dezvoltã cel mai frecvent la nivelulscalpului (regiunea temporalã ºi în jurulurechilor), mai rar la nivelul feþei sau trunchiului.Leziunile sunt unice, rareori multiple, cu aspectulunor papule sau plãci imprecis delimitate, deculoare galben-portocalie, ceroasã. Histopato-logic se caracterizeazã prin prezenþa glandelorsebacee imature ºi a foliculilor piloºi la copil ºiprezenþa glandelor sebacee mature, foliculi piloºimici sau absenþi la adult.[16]

NSJ este un hamartom complex în care pot sãaparã variate tipuri de proliferãri secundareneoplazice sau hiperplazice: malformaþii epider-mice sau anexiale asociate hiperplaziei sebacee(structurã folicularã primitivã, glande apocrine ºiecrine ectopice) [2,4]. Sunt citate în literaturãasocierea hamartomului sebaceu cu: tricho-lemomul, siringocistadenoame papilifere, cist-adenoame apocrine, trichoblastoame ca de altfelºi tumori benigne dificil de clasificat. (Izumi,2008, Kazakow, 2007) [13,14] . Incidenþa ºi risculde transformare malignã al NSJ este necunoscut.

Prezentãm cazul unui keratoacantom dez-voltat pe un nev sebaceu Jadassohn.

Caz clinic

Este vorba despre un pacient, de sexmasculin, în vârstã de 26 ani, care acuzã prezenþaunei excrescenþe tumorale apãrutã de o lunã,dezvoltatã pe o leziune preexistentã în pieleapãroasã a capului (anamnestic de la naºtere, cucreºtere progresivã).

Antecedentele heredocolaterale sunt ne-semnificative, neexistând istoric familial deleziuni asemãnãtoare.

Examenul local pune în evidenþã în regiuneatemporo-parietalã dreaptã a pielii pãroase acapului o placã alopecicã, ovalarã, cu contur binedelimitat de 2,5–3 cm, de culoare roz-brunã,proeminentã, cu suprafaþa papilomatoasã ºi oformaþiune tumoralã exofiticã centralã, hiper-

Introduction

Nevus sebaceous described by Jadassohn in1895 is a rare congenital skin malformation thatusually appears at birth or in early childhood. [7]Most cases are sporadic but family related caseshave been also described.[22]

It develops most frequently in the scalp area(temporal, pre- and retroauricular), and rarely onthe face or trunk. The lesion is unique, rarelymultiple, with a poor defined, yellow to orangecolor, waxy papule or plaque aspect.

Histopathological findings include immaturesebaceous glands and hair follicles in childrenand mature sebaceous glands and no or smallhair follicles in adults. [16]

Nevus sebaceous of Jadassohn (NSJ) is acomplex hamartoma characterized by epithelialhyperplasia that can develop various types ofsecondary neoplastic or hyperplastic prolifera-tions: epidermic or adnexal malformationsassociated to sebaceous hyperplasia (primitivefollicular structures, ectopic apocrine and eccrineglands).[2,4] Trichilemmoma, syringocystade-noma papilliferum, syringocystadenocarcinomapapilliferum apocrine cystadenoma, tricho-blastoma, tricholemmona, desmoplastic trichi-lemmona were described in association with NSJ(Izumi,2008, Kazakow, 2007). [13,14] Theincidence and the lifetime risk of malignantpotential of NSJ is unknown.

We present a case of a keratoacanthomaarising on a nevus sebaceous of Jadassohn.

Clinical Case

A 26-year-old male patient reported atumoral lesion with a history of 1 monthdeveloping in a preexisting scalp lesion that hadbeen present from birth. The patient had noprevious personal and family history ofmalignancy.

Local examination revealed a well delimitedpink-brownish alopecic plaque measuring 2.5–3 cm, in the temporo-parietal area, with apapilomatous surface. For a month a firm,hemispheric nodular tumor of 0.5 cm diameterwith a central exofitic hyperkeratosis of 1 cmlength appeared (Fig. 1).

General clinical examination was negativeand biologic investigations were within normal

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keratozicã, pediculatã, cu diametrul de 0,5/1cm(aspect de corn cutanat). (Fig. 1)

Examenul clinic general nu a evidenþiat nimicpatologic, iar investigaþiile biologice au fost înlimite normale. Examenul clinic orienteazãdiagnosticul spre un nev sebaceu Jadasson,nodulul exofitic dezvoltat pe suprafaþa plãciinevice fiind susceptibil de o degenerare malignã(epiteliom bazocelular, epiteliom spinocelular)(Fig. 2).

Terapeutic s-a optat pentru excizia chirur-gicalã a întregii leziuni cu margine de siguranþãoncologicã. Dehiscenþa cutanatã a fost acoperitãprin rotaþie de lambou (Fig. 3).

Examenul histopatologic efectuat din leziu-nea excizatã în totalitate confirmã diagnosticul denev sebaceu (hiperplazie sebacee importantã careintereseazã dermul în întregime) ºi o hiperplazieepiteliomatoasã accentuatã dezvoltatã în zonacentralã a leziunii, care prezintã un crater umplutde þesut hiperkeratozic orto ºi parakeratozic,aspect histopatologic caracteristic keratoacanto-mului (Fig. 5).

Studierea la lupã a tumorii a dat impresiaunui keratoacantom (Fig. 4).

Discuþii

Apariþia unui keratoacantom pe un nevsebaceu este foarte rarã (8 cazuri au fost raportateîn literaturã: Ujiie H -1caz [20], Corbett ºi colab-1

values. The clinical examination suggests aneoplastic tumor (basal or squamous cellcarcinoma) arising on a sebaceous nevusJadassohn. Complete excision of the entire plaquewas performed and the defect covered with arotational flap. (Fig. 2).

Histopathological examination confirms thediagnosis of sebaceous nevus, showingpapillomatosis and important dermal sebaceoushyperplasia. (Fig. 3).

The central exophytic proliferation showswell differentiated squamous epithelium with acentral core of ortho- and parakeratotic hyper-keratosis. The periphery of squamous prolife-ration was smooth, regular, and well demarcated.(Fig. 5).

The aspect was consistent with the diagnosisof keratoacanthoma. (Fig. 4).

Discussion

Occurrence of keratoacanthoma within asebaceous nevus is very rare. There were 8 casesreported in the literature: Ujiie H -1case [20],Corbett et al-1 case [6], Szyszymar andGwoezdinski-1 case, Mehregan and Pinkus–4cases, Oehlschlaegel and Rakoski-1 case. [17]

Fig. 1. Keratoacantom dezvoltat pe un nev sebaceuJadassohn la nivelul scalpului.

Fig. 1. Keratoacanthoma developed within a nevussebaceous of Jadassohn, located on the scalp.

Fig. 2. Excizia formaþiunii tumorale ºi acoperirea defectuluiprintr-un lambou rotat.

Fig. 2. The excision of tumor and the coverage of defectwith a rotation flap.

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caz [6], Szyszymar ºi Gwoezdinski-1 caz,Mehregan ºi Pinkus – 4 cazuri, Oehlschlaegel ºiRakoski -1 caz [17]. Nu sunt rare în cadrulaceluiaºi hamartom sebaceu, 2 sau 3 tumoridiferite (ultimii 2 autori descriu dezvoltarea dinacelaºi nev sebaceu a unui KA, siringocista-denom ºi trichoepiteliom).

Creºterea nevului la pubertate a sugerat oposibilã implicare hormonalã. Studiile imuno-histochimice efectuate în 18 cazuri de copii ºiadulþi de cãtre Hamilton KS, Johnson S ºi SmollerBR – Departament of Pathology, VanderbiltUniversity Medical Center, Nashville, Tenesse,USA.au constatat receptori androgeni pozitivi întoate componentele epiteliale ale nevului sebaceu: glande sebacee, glande apocrine, glande ecrineºi keratinocite, fãrã schimbãri în perioadapubertãþii. [12]

În tratatele clasice este menþionatã posi-bilitatea relativ frecventã a degenerescenþeimaligne a NS la vârsta adultã. Potenþialul malignraportat este între 0,8 ºi 50%. Epiteliomulbazocelular este asociat cu 5% din cazuri.Michalowski raporteazã 22% din 160 de cazuriiar Wilson 23 de cazuri din 140, autorii pledândpentru introducerea lui în leziunile precanceroaseºi pentru excizia chirurgicalã timpurie în ideeapreîntâmpinãrii dezvoltãrii unui carcinombazocelular dupã pubertate. Degenerescenþa

There are frequent cases of 2 or 3 differenttumors within the same sebaceous hamartoma(the last 2 authors describe the development ofKA, siringocystadenoma and trichoepitheliomawithin the same NS).

The growth of the sebaceous nevus atpuberty suggested hormonal implication.

Fig. 3. Imagine H-P a nevului sebaceu. Se observãimportanta hiperplazie sebacee, ce intereseazã dermul

aproape în întregimeFig. 3. The H-P image of nevus sebaceous. It can be noticedthe importance of sebaceous hyperplasia, that interests the

dermis almost entirely.ed on the scalp.

Fig. 4. Imagine la lupã a preparatului histopatologic. Seobservã masa cornoasã ortokeratozicã din keratoacantom.

Fig. 4. Image magnifier of the histopathological piece. It canbe noticed the orthokeratosis horny mass within

keratoacanthoma.

Fig. 5. Imagine H-P cu evidenþierea hiperplazieiepiteliomatoase caracteristice keratoacantomului ºi prezenþade glande sebacee bine dezvoltate mature specifice nevului

sebaceu JadassohnFig. 5. The H-P image highlighting the epitheliomatoushyperplasia, characteristic to keratoacanthoma, and thepresence of well-developed, mature, sebaceous glands -

specific to nevus sebaceus of Jadassohn.

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hamartoamelor sebacee în carcinoame bazo-celulare este mult mai rara decât lasã sã seînþeleagã datele clasice din literaturã.

Exista controverse cu privire la natura acestorneoplasme (carcinoamele bazocelulare diagnosti-cate anterior ar putea fi , de fapt, trichoblastoame,care sunt tumori benigne (Cribier, 2000). [8]

Astfel Merrot, Cotten, Piette ºi colab. re-analizând din punct de vedere anatomopatologic80 de NSJ excizaþi în perioada 1982-1990 înServiciul de Chirurgie plasticã ºi reconstructivãdin Lille, au confirmat diagnosticul de carcinombazocelular în 2 cazuri (faþã de 19) ºi detricoblastom pigmentat în 17 cazuri. [15]

Trichoblastomul este cea mai frecventãtumoare bazaloidã dezvoltatã în cadrul NSJ .

Muñoz Pérez – et al. (2002 ) au descoperitîntr-un studiu pe 226 pacienþi cã papilliferumsyringocystadenomul papilifer ºi trichoblastomulau fost cele mai frecvente tumori care apar la SN,în timp ce epiteliomul bazo-celular a fost gãsitdoar la 5 pacienþi (3,5%) .[16]

Tumorile în curs de dezvoltare în NS par sãmanifeste caracteristici clinicopatologice diferitecomparativ cu carcinoamele sebacee de novo(Izumi , 2008) [13] , cu un comportament clinic alunui carcinom de calitate inferioarã (Kazakow,2007) [14] .

Un studiu efectuat de Departamentul deDermatologie al Univ. de Medicinã din Tokio aurmãrit incidenþa celulelor care exprimãcitokeratina 20 în 49 de cazuri de NSJ cuproliferãri secundare hiperplazice ºi neoplazice.Cazurile au fost analizate clinic, histopatologic ºiimunohistochimic utilizând 10 anticorpi mono-clonali îndreptaþi împotriva involucrinei ºi acitokeratinei. 15 din cele 49 de cazuri aveaumodificãri de proliferare-structurã folicularãprimitivã (SFP) iar 6 cazuri erau asociate cu SFPºi leziuni neoplazice secundare (2 bazalioame, 2 siringoame papilifere, 1 trichilemom, 1 tricho-blastom). Incidenþa celulelor care exprimã CK afost similarã în NSJ cu cea din tegumentulnormal. În schimb expresia citokinei 20 a fost maimare în cazurile cu SFP. În cazurile cu EBC CK20nu s-a exprimat. Din analiza statisticã rezultã cãexistenþa SFP este asociatã cu un potenþial maimare de dezvoltare a leziunilor neoplazicesecundare. Absenþa celulelor care exprimã CK20(celulele Merkel provenite din creasta neuralã)

Immunohistochemical studies on 18 cases ofsebaceous nevus in children and adults showedpositive androgen receptors in all epithelialcomponents of the sebaceous nevus: sebaceumglands, apocrine glands, eccrine glands andkeratinocytes (Hamilton KS, Johnson S ºi SmollerBR – Departament of Pathology, VanderbiltUniversity Medical Center, Nashville, Tenesse,USA). [12]

Malignant transformation of NSJ at adult ageis reported as frequent in classical dermatologybooks, ranging from 0.8 to 50%. Basal cellcarcinoma is associated to 5% of the cases.Michalowski reports 22% of cases, from 160, andWilson 16% (23/140 cases), the authors con-sidering NSJ a premalignant lesion that should beexcised early to prevent the development of basalcell carcinoma after puberty.

There are controversies on the nature of theseneoplasms as previously diagnosed basal cellcarcinoma could be in fact trichoblastoma, whichare beingn tumors (Cribier, 2000).[8] Merrot,Cotten, Piette et al reanalized the pathologyaspects in 80 NSJ excised between 1982-1990 andconfirmed the diagnosis of basal cell carcinoma inonly two cases (19 before), while 17 cases werepigmented trichoblastoma.[15] Trichoblastoma isthe most frequent bazaloid tumor developedwithin NSJ. Muñoz-Pérez et al (2002) found in astudy on 226 patients that syringocystadenomapapilliferum and trichoblastoma were the mostfrequent tumours arising on SN, while basal cellepithelioma was found only in 5 patients (3.5%).[16]

The tumors developing in NS seem tomanifest different clinicopathological featurescompared to de novo sebaceous carcinoma(Izumi, 2008) [13], with clinical behaviour of alow-grade carcinoma (Kazakow, 2007) [14].

Citokeratin 20 was studied in 49 cases of NSJwith secondary hyperplastic and neoplasticproliferations, using 10 monoclonal antibodiesagainst involucrin and citokeratin. Fifteen out of49 cases had changes of PFS (primitive follicularstructure) and 6 cases had PFS and secondaryneoplastic changes (4 basal cell carcinoma, 2siringoma, 1 trichilemmoma). The citokeratinexpression was similar in normal epidermis andNSJ, but citokeratin 20 was expressed in caseswith PFSs and not with basal cell carcinoma. The

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din structurile analizate se pare cã prezicedezvoltarea carcinomului bazocelular. [18,20]

Existã totuºi tumori maligne autenticedezvoltate pe aceste hamartoame din care unelecu evoluþie mortalã doveditã. [9] Aceste cazurisunt extrem de rare în literaturã: este de faptvorba de carcinoame apocrine, de carcinoamespinocelulare, de carcinoame sebacee saucarcinoame mai mult sau mai puþin binediferenþiate, dificil de clasat. Aceste leziuni sedezvoltã pe hamartoame ºi pot fi considerate maidegrabã complicaþii decât ca o asociere pato-logicã.[1,3,4,7]

Tratamentul clasic constã în exciziechirurgicalã, de preferat înainte de maturitate.Datoritã faptului cã incidenþa malignitãþiiprovenite din nev sebaceu e foarte micã, uniiautori, afirmã cã intervenþia chirurgicalãprofilacticã la copii nu este recomandatã. Alþiirecomandã excizia chirurgicalã în timpulcopilãriei datoritã elasticitãþii mai bune ategumentelor (în mod special pe scalp unde estede altfel mai frecvent localizat). [5,11]

Concluzii

Un nev sebaceu se poate complica prinhiperplazii tumorale ale unor zone (cu tumori)nevoide suborganoide ºi organoide ale anexelorcutanate inclusiv cu keratoacantoame.

Observaþia noastrã cu privire la dezvoltareaunui KA pe un nev sebaceu este importantãdatoritã raritãþii acesteia (8 cazuri au fostraportate în literaturã).

Cazul nu prezenta din punct de vedere clinicºi histopatologic semne de transformare malignã.

Am optat pentru excizia chirurgicalã atâtpentru prevenirea transformãrii acestuia înepiteliom spinocelular cât ºi în scop estetic.

conclusion shows that the presence of PFSindicates potency to develop secondary neo-plasms, while the absence of citokeratin 20expressed cells (Merkel cells) within the analysedstructured predicts the development of BCC inthe future. [18, 20].

There are true malignant tumors, some ofthem fatal, developed within these hamar-toma.[9] These cases are rarely described in theliterature as apocrine carcinoma, squamous cellcarcinoma, sebaceous carcinoma or other more orless differentiated carcinoma that are un-classified. They can be considered complications,rather than pathologic association [1,3,4,7].

The classical treatment consists of surgicalexcision, better done before puberty. Because theincidence of malignancy arising within the NS isvery low, some authors do not recommend theprophylactic excision in children. Othersrecommend surgical excision to prevent thedevelopment of malignant neoplasia or at leastclose clinical surveillance of adult patients. [5,11].

Conclusions

Sebaceous nevus may complicate by neo-plastic hyperplasia of some infraorganoid andorganoid nevoid areas of the cutaneousappendages, including keratoacanthoma. Ourobservation of keratoacanthoma arising withinsebaceous nevus is important because its rarity(only other 8 cases reported in the literature).

There were no clinical and histopathologicalsigns of malignant transformation in thepresented case. Surgical excision was performedto prevent malignant transformation and also toimprove the aesthetic aspect.

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