ISSN (print) 1226-8496 ISSN (online) 2288-3819 http://dx.doi.org/10.5933/jkapd.2014.41.1.34 Nevoid Basal Cell Carcinoma Syndrome : A Case Report Yoonjung Lee 1, Jaehong Park 2, Sungchul Choi 2, Sooeon Lee 2, Kwangchul Kim 1 1 Department of Pediatric Dentistry, Kyung Hee University Dental Hospital at Gangdong, 2 Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University Abstract Nevoid basal cell carcinoma syndrome(nbccs) is a autosomal dominant disorder, and its major manifestations are multiple basal cell carcinoma, keratocystic odontogenic tumor, rib anomalies, palmer and plantar pits, calcification of the falx cerebri. Keratocystic odontogenic tumor(kcot) is defined as intraosseous tumor of odontogenic origin with a characteristic lining of parakeratinized stratified squamous epithelium and potential aggressive behavior. We report a case of a 3-year-old patient with nevoid basal cell carcinoma syndrome who initially presented with unilocular keratocystic odontogenic tumor in maxillary canine region. Keratocystic odontogenic tumor was treated by enucleation, and periodic follow-up check will be required for early diagnosis of additional diseases related with this syndrome. Key words : Nevoid basal cell carcinoma syndrome, Keratocystic odontogenic tumor, Enucleation Ⅰ. 서론기저세포모반증후군 (Nevoid basal cell carcinoma syndrome, NBCCS) 은 Golrlin-Goltz 증후군으로도알려져있으며 1894년에 Jarisch 1) 가처음으로이증후군을가진환자를소개하였고, 1960년에 Golrlin과 Goltz 2) 가증후군의특징으로써다발성기저세포암, 악골의다발성각화낭종, 이열늑골의 3대주요증상을보고하였다. 환자들마다증상이매우다양하게나타나는데기저세포모반증후군의임상적, 방사선적진단기준에서적어도 2개의주진단기준이존재하거나 1개의주진단기준과 2개의부진단기준이존재할때진단할수있다 3). 대개상염색체우성으로유전되고 1), 9q22.3-q31 염색체에위치한 PTCH1에서의변이가증후군의원인으로보고되었다 4). 기저세포모반증후군에서호발하는각화낭성치성종양은양성의단방성또는다방성으로나타나는치성기원의골내종양으로 착각화된중층편평상피에의해특징적으로이장되어있고공격적이고침습적인성향을갖는것으로정의된다. 각화낭성치성종양은 1956년 Phillipsen 5) 에의해치성각화낭 (odontogenic keratocyst) 으로보고된이후침습적인성향을띄는종양의특성을반영하여현재는국제보건기구 (World Health Organization) 에의해조직분류가개정되어양성종양의하나로다루게되었다 6,7). 각화낭성치성종양은악골어느부위에서도발생할수있으며하악의후방부와상행지부에서가장빈번히나타나지만상악에서는견치부위에서흔하게발생한다 8). 본증례는감별진단이필요한상악견치부위의단방성의낭종을주소로강동경희대학교병원치과병원소아치과에내원한환아로조직검사를통해각화낭성치성종양으로밝혀진후임상적, 방사선학적검사를통해기저세포모반증후군으로진단되었기에보고하고자한다. Corresponding author : Kwangchul Kim Department of Pediatric Dentistry, Kyung Hee University Dental Hospital at Gangdong, 892, Dongnam-ro, Gandong-gu, Seoul, 134-727, Korea Tel: +82-2-440-7506 / Fax: +82-2-440-7549 / E-mail: juniordent@hanmail.net Received July 10, 2013 / Revised October 24, 2013 / Accepted October 29, 2013 34
Ⅱ. 증례보고 3세 10개월의여아가내원이틀전부터의발열과좌측협측부위에종창을보였으며, 봉와직염이의심되어강동경희대학교병원소아과에입원후약물치료를하였으나종창이안와하방까지더심해져본과에의뢰되었다. 환아는미숙아로태어나서수두증의진단을받았었으나최근의검사를통해대두증에가깝다는재진단을받은바있고언어기능과운동기능에대한발달지연의전신병력이있었으며외상이나치과병력상에는특이사항이없었다. 외관상돌출된이마와함몰된중안모및양안격리증의양상을나타내었다 (Fig. 1). 구외검사를통해좌측협측부위에서구순부에이르는부위의종창으로인한안면비대칭을확인할수있었고, 구내검사시상악좌측유견치의순측치은부에서전정부에이르는종창이있었다 (Fig. 2). 방사선사진을통해상악좌측유견치와상 악좌측유측절치의치근사이에경계가명료한서양배형태의방사선투과성의병소와상악좌측유견치의치근과상악좌측견치치배의변위를확인할수있었다 (Fig. 3, 4). 컴퓨터단층촬영결과상악좌측유측절치와상악좌측유견치사이의순측피질골의파괴가확인되었다 (Fig. 5). 전신마취하에병소는단일조각으로적출되었으며적출된조직에대한조직병리학적검사를통해각화낭성치성종양으로진단되었다 (Fig. 6). 이후, 진단된종양과환아의전신병력및외관상특징과의연관성을통해각화낭성치성종양이동반된기저세포모반증후군이의심되어소아과에의뢰하였다. 흉부방사선사진을재검토한결과이열늑골 (bifid rib) 이관찰되었으며 (Fig. 7), Waters 방사선사진에서대뇌겸의석회화소견은보이지않았다. 이에따라 Kimonis 등 3) 에의한진단기준에서 2개의주요기준과 3 개의부가기준을가지므로소아과와의협진을통해본과에서 Fig. 1. Extraoral photograph showing frontal bossing and hypertelorism. Fig. 2. Initial intraoral photograph showing a swelling on the labial vestibule of maxillary left primary canine. Fig. 3. Initial panoramic view showing well defined radiolucent lesion between roots of maxillary left primary lateral incisor and canine. Fig. 4. Initial periapical view. Fig. 5. Initial CT view showing cortical bone destruction on the labial side, between maxillary left primary lateral incisor and canine. Fig. 6. Histologic finding (x400). 35
Fig. 8. Panorama view at 12-month follow-up showing a radiolucent lesion on left maxilla becoming radiopaque. Fig. 7. Chest PA radiograph showing right fourth bifid rib. Fig. 9. Periapical view at 12-month follow-up. 기저세포모반증후군으로진단하였다. 술후 1년의방사선검사와컴퓨터단층촬영을통해상악의방사선투과상은사라진상태였으며, 상악좌측유견치과상악좌측측절치치배의변위가완화되었고순측피질골은회복되었음을확인할수있었다 (Fig. 8, 9). 임상검사에서는상악좌측유견치의치은퇴축과 1도정도의동요도가관찰되었다 (Fig. 10). 1년의정기검진동안종양의재발은발생하지않았고증후군과관련된추가적인임상증상도발생하지않고있다. Ⅲ. 총괄및고찰 기저세포모반증후군은흔하지않은상염색체우성유전질환으로인종에따라유병률에차이를보이는데한국에서이증후군의유병률은다른나라들에비해매우낮은것으로보고되고있다 9). 기저세포모반증후군은임상적, 방사선적소견의종류와발현시기가매우다양하기때문에조기진단에어려움이있다. 기저세포모반증후군의진단기준은 1993년에 Evans 등 10) 에의해처음으로확립되었고, 이후 1997년에 Kimonis 등 3) 에의해조정되었으며, 적어도 2개의주진단기준이존재하거나 1개의주진단기준과 2개의부진단기준이존재할때기저세포모반증후군으로진단한다 (Table 1). 본증례에서는각화낭성치성종양이먼저확인되었고이후이열늑골까지 2개의주요기준이일치하였으며대두증, 전두부돌출및양안격리증의 3개의부가기준이확인되어기저세포모반증후군으로진단되었다. 각화낭성치성종양은종종증후군의첫번째증상으로나타나본증례에서와같이증후군진단의계기가될수있으며기저세포모반증후군에서의각화낭성치성종양이각화낭성치성종양단독으로존재하는경우보다더어린나이에발생하는경향이있다 3,11). 또한증후군과연관된각화낭성치성종양은일반적으로다발성이지만 2000년에 Bolbaran 등 12) 이단발성의증례를보고하기도하였고, Lo Muzio 등 11) 은어린이에서는단지 Fig. 10. Intraoral photograph at 12-month follow-up. 1개의각화낭성치성종양도기저세포모반증후군의가능성을나타낼수있다고하였다. 본증례에서도상악견치부위에서단방성의단일종양의형태였기때문에초기의잠정적진단시에는증후군을예상하지못하였으나앞서언급되었던것처럼특히어린나이에서는단방성의종양일지라도증후군의가능성을고려하여후속검사가필요할것으로생각된다. 본증례에서와같은상악견치부위에서의단방성의각화낭성치성종양은방사선사진에서함치성낭, 측방치주낭, 비구개관낭, 잔류낭등의다른병소들과유사하게보일수있어감별진단이필요하다. 특히통증, 부종, 삼출등과같은염증성증상들이동반된경우에더욱임상적, 방사선적정보만으로는정확한진단이어렵다 8). 각화낭성치성종양은다른낭종들과뚜렷이구별되는조직학적특징을가지므로조직학적검사가진단을위해필수적이다. 각화낭성치성종양의치료법으로는조대술, 적출술, Carnoy 용액이나냉동요법등을동반한적출술, 변연절제술등이있다 13,14). 본증례에서는환아의나이가매우어린점을고려하여보존적 36
Table 1. Diagnotic criteria in NBCCS Major criteria Multiple(>2) BCCs or 1 younger than 20 years Odontogenic keratocysts of the jaws proven by histopathology Three or more palmer or plantar pits Bilamellar calcification of the falx cerebri Bifid, fused or markedly splayed ribs First-degree relatives with NBCCs Minor criteria Macrocephaly after adjustment for height Congenital malformation: cleft lip or palate, frontal bossing. "coarse face", moderate or severe hypertelorism Other skeletal abnormalities: Sprengel defomity, marked pectus deformity, marked syndactyly of the digits Radiological abnomalities: bridging of sella turcica, vertebral anomalies, such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defecta of the hands and feet, or flame-shaped lucencies of the hands or feet Ovarian fibroma Medulloblastoma Kimonis et al. : Am J Med Genet, 69:299-308, 1997. 인치료법인적출술로치료를진행하였다. 기저세포모반증후군에서의각화낭성치성종양은상피기저세포층안에새로운낭을발생시킬수있는유전적성향으로인하여증후군과관련없는각화낭성치성종양 (28%) 과비교할때증후군에서의각화낭성치성종양은 60% 의높은재발잠재성을가진다 15). 따라서술후첫5년은매년, 그이후에는 2년마다의정기적인검진이추천된다 16). 기저세포모반증후군의주요소견중에서늑골이상은기저세포모반증후군환자의 30~60% 에서보고되고있으며본증례에서나타난것과같이이열늑골이가장흔하게관찰된다 15). 이외에기저세포암, 손과발바닥의소와, 대뇌겸의석회화는본증례에서관찰되지않았다. 그러나기저세포암의경우영아기에나타나는경우도있지만대부분사춘기에서 35세사이에발생하고 15), 손과발바닥의소와는 10세무렵에환아의 30~65% 정도에서나타나며연령이증가할수록더많이나타난다 17). 또한초기병소가관찰된후 23년이지나피부, 골격등증후군의다른증상이추가로나타난보고도있었다 18). 따라서환아의나이가만 3세로매우어린것을고려할때현재관찰되지않은증후군의다른소견들이이후에나타날가능성이매우높을것으로생각된다. 특히주로소아에서호발하는악성침습적배아성뇌종양인수모세포종 (medulloblastoma) 이발병할가능성이있으므로이런질병들에대한조기진단을위해정기적인검진과추적검사가매우중요하고예방을위한교육도필요할것이다. 후속검진을위한지침으로는첫째, 신경학적검사는연 2 회시행해야하며, 둘째, 1~7세사이에매년뇌의 MRI 촬영, 셋째, 8세경부터시작해서 12~18개월마다파노라마촬영, 넷째, 증상에따라매년피부검사와심장검사를시행하는것이다 19). 현재환아는병소의재발과증후군과관련된추가적인임상증상에대한추적검사를진행중이며, 유전성질환임을고려하여가족들에대한유전자검사및상담이예정되어있다. 본증례는이전에보고되었던기저세포모반증후군의증례들 과비교하여환아가매우어렸다는점과일반적으로는증후군과의연관성을놓치기쉬운단방성의각화낭성치성종양을계기로증후군으로진단되었다는점에주목할수있을것이다. 기저세포모반증후군은치과의사에의해처음발견되는경우가많고, 조기진단이중요하다는점에서이질환의임상적, 방사선적인특징들에대한임상가의관심이필요할것이다. Ⅳ. 요약상악견치부위의단방성의낭종을주소로강동경희대학교치과병원소아치과에내원한 3세 10개월의환아가전신마취하에적출술을시행받고조직검사를통해각화낭성치성종양으로진단받은것을계기로기저세포모반증후군으로진단되었다. 단방성의각화낭성치성종양은감별진단이어려우므로반드시조직학적검사가진단을위해필요하고, 각화낭성치성종양의재발여부와기저세포모반증후군과관련된추가적인질환들의조기진단을위하여정기적인검진이중요하다. References 1. Jarish W : Zur lehre von den autgeschwulsten. Archiv Jur Dermatologic und Syphilogic, 28: 163-222, 1894. 2. Gorlin RJ, Goltz RW : Multiple nevoid basal cell epithelioma, jaw cysts and bifid rib syndrome. New Engl J Med, 262:908-12, 1960. 3. Kimonis VE, Goldstein AM, Bale SJ, et al. : Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet, 69:299-308, 1997. 4. Cohen MM Jr : Nevoid basal cell carcinoma syndrome:molecular biology and new hypotheses. Int J 37
of Oral Maxillofac Surg, 28:216-223, 1999. 5. Philipsen HP : Keratocysts in the jaw. Tandlaegeblader, 60:963-80, 1956. 6. Gupta A, Rai B, Nair NA, Bhut MK : Keratocystic odontogenic tumor with impacted maxillary third molar involving the right maxillary antrum: an unusual case report. Indian J Dent Res, 22:157-60, 2011. 7. Madras J, Lapointe H: Keratocystic odontogenic tumour: reclassification of the odontogenic keratocyst from cyst to tumour. J Can Dent Assoc, 74: 165-165, 2008 8. Ali M, Baughman RA : Maxillary odontogenic keratocyst: a common and serious clinical misdiagnosis. J Am Dent Assoc, 134:877-83, 2003. 9. Ahn SG, Lim YS, Yoon JH, et al. : Nevoid basal cell carcinoma syndrome: a retrospective analysis of 33 affected Korean individuals. Int J Oral Maxillofac Surg, 33:458-462, 2004 10. Evans DGR, Ladusans EJ, Farndon PA, et al. : Complication of nevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet, 30:460-4, 1993. 11. Lo Muzio L. Nocini P, Procaccini M, et al. : Early diagnosis of nevoid basal cell carcinoma syndrome. J Am Dent Assoc, 130: 669-74, 1999 12. Bolbaran V, Martinez B, Rojas R : Odontogenic keratocysts. A retrospective study of 285 cases. (II. Histopathological aspects.) Med Oral, 5:338-44, 2000. 13. Stoelinga PJ : Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg, 30:14-25, 2001. 14. Blanas N, Freund B, Schwartz M, Furst IM : Systemic review of the treatment and prognosis of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 90:553-8, 2000. 15. Lo Muzio L : Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis, 3:32, 2008. 16. Manfredi M, Vescovi P, Bonanini M, Porter S : Nevoid basal cell carcinoma syndrome: a review of the literature. Int J Oral Maxillofac Surg, 33:117-24, 2004. 17. Gutierrez MM, Mora RG : Nevoid basal-cell carcinoma. J Am Acad Dermatol, 15:1023-30, 1986. 18. Woolgar JA, Rippin JW, Browne RM : The odontogenic keratocyst and its occurance in the nevoid basal cell carcinoma syndrome. Oral Surd Oral Med Oral Pathol, 64:727-730, 1987. 19. Kim HM, Lee CH, Kim SK, Sung TJ : Basal cell nevus syndrome (Gorlin syndrome) confirmed by PTCH mutations and deletions. Korean J Pediatr, 50:789-793, 2007. 38
국문초록 기저세포모반증후군 : 증례보고 이윤정 1 박재홍 2 최성철 2 이수언 2 김광철 1 1 강동경희대학교병원치과병원소아치과, 2 경희대학교치과대학소아치과학교실 기저세포모반증후군은상염색체우성의유전질환이며주요소견으로는다발성기저세포암, 악골의다발성각화낭종, 늑골이상, 손과발바닥의소와, 대뇌겸의석회화등이있다. 기저세포모반증후군에서호발하는각화낭성치성종양은치성기원의골내종양으로착각화된중층편평상피에의해특징적으로이장되어있고공격적이고침습적인성향을갖는것으로정의된다. 본증례는감별진단이필요한상악견치부위의단방성의낭종을주소로내원한환아가조직검사를통해각화낭성치성종양으로밝혀진후임상적, 방사선학적검사를통해기저세포모반증후군으로진단된경우이다. 종양은적출술로치료되었고증후군과연관된추가적인질환들의조기진단을위해정기적인검진이필요할것이다. 주요어 : 기저세포모반증후군, 각화낭성치성종양, 적출술 39