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1 대한내과학회지 : 제 86 권제 4 호 선천성낭성선종양기형에서발견된악성변화 1 예 충남대학교의학전문대학원 1 내과학교실, 2 병리학교실 최재우 1 송승택 1 박연희 1 박동일 1 정재욱 1 이충식 2 정성수 1 A Case of Malignant Transformation in a Congenital Cystic Adenomatoid Malformation Jae Woo Choi 1, Seung Taek Song 1, Yeon Hee Park 1, Dong Il Park 1, Chae Uk Chung 1, Choong Sik Lee 2, and Sung Soo Jung 1 Departments of 1 Internal Medicine and 2 Pathology, Chungnam National University School of Medicine, Daejeon, Korea Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare condition with the potential for malignant transformation. Several cases that presented with malignant changes have been reported worldwide. However, no report about a malignant transformation case in a CCAM in Korea has been published. We report the first patient who had a malignant change in a CCAM. A 32-year-old female underwent a bilobectomy for a cystic lung lesion that was a type 1 CCAM associated with malignant transformation. A biopsy specimen from the resected cystic lesion showed foci of adenocarcinoma. (Korean J Med 2014; 86: ) Keywords: Cystic adenomatoid malformation of lung, congenital; Adenocarcinoma 서론선천성낭성선종양기형 (congenital cystic adenomatoid malformation, CCAM) 은드문종말호흡기구조의발생학적이상으로종말세기관지의다낭성병변이특징이며발생률은 10,000출생에서 35,000출생당한명으로추정된다 [1]. 임상증상으로는무증상에서부터기침, 발열, 급성호흡곤란, 폐농양, 기흉, 혈흉등이있을수있다. 성인에서선천성낭성선종양기형은보통무증상이다가우연히흉부방사선사진에서발견되고나중에같은엽에서반복적인폐렴을일으킨다. Stocker 등 [2] 은선천성낭성선종양기형을임상적특징과육안적그리고조직학적특징에따라서세가지아형으로분류하였다. 하지만악성변화는제1형에서주로관찰되고있으며보고된악성변화는거의대부분점액기관지폐포암종이었다 [3]. 전세계에서 31명의선암종이동반된선천성낭성선종양기형환자들이보고되었지만 [4-6] 국내에서는보고된적이없었다. 저자들은반복적인폐렴으로내원한 32세여자환자에서전산화단층촬영및조직학적검사를통해선암종이동반된선천성낭성선종양기형으로진단된 1예를국내처음으로경험하였기에문헌고찰과함께보고하는바이다. Received: Revised: Accepted: Correspondence to Sung Soo Jung, M.D., Ph.D. Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon , Korea Tel: , Fax: , jss24@cnuh.co.kr Copyright c 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Jae Woo Choi, et al. Malignant transformation in a CCAM - 증례환자 : 여자, 32세주소 : 1주일전부터지속되는기침및객담, 3일전부터동반된오른쪽흉막염통증현병력 : 4일전기침과객담으로인근의원에서대증치료를받았지만증상의호전은없었다. 3일전부터발열및오른쪽흉막염통증이동반되며증상악화되어인근의원에다시내원하여촬영한단순흉부사진에서오른쪽하엽에폐농양이동반된양측성폐렴이관찰되어본원으로전원되었다. 과거력 : 4-8년전타병원에서세차례폐렴으로입원치료를받은적이있었다. 사회력 : 음주및흡연력없음. 직업력및가족력 : 특이사항없음. 진찰소견 : 혈압은 110/80 mmhg, 맥박수 95회 / 분, 호흡수 20회 / 분, 체온 37.0 로안정적이었다. 환자는급성병색을띠고있었으나의식은명료하였으며흉부진찰에서오른쪽하부에호흡음이감소되었으며양쪽폐야에서수포음이청진되었다. 그외기타두경부검사및복부진찰에서는이상소견없었으며신경학적검사에서도특이소견은없었다. 검사실소견 : 입원하면서시행한말초혈액검사에서백혈구 /ul ( 호중구 68.2%, 호산구 3.1%), 혈색소 11.9 g/dl, 적혈구용적률 34.3%, 혈소판 /ul였다. 생화학적검사에서는총단백질 6.8 g/dl, 알부민 3.8 g/dl, 총빌리루빈 0.50 mg/dl, 콜레스테롤 187 mg/dl, AST 11 IU/L, ALT 12 IU/L, ALP 62 IU/L, LDH 245 IU/L, BUN 8.7 mg/dl, Creatinine 0.45 mg/dl, Glucose 147 mg/dl, Na meq/l, K 3.50 meq/l 였다. 그외검사는 CRP mg/dl, ESR 120 mm/h 이었고객담세균과결핵균도말및배양검사는음성이었다. 폐기능검사에서는노력성폐활량 (forced vital capacity, FVC) 이 2.50 L로예측치의 74%, 1초간노력성호기량 (forced expiratory volume in 1 second, FEV1) 이 2.18 L로예측치의 81%, FEV1/FVC가 87% 였다. 기관지내시경검사에서기관지내병변은관찰되지않았다. 방사선검사소견 : 4년전본원첫내원당시촬영한흉부고해상전산화단층촬영에서는오른쪽아래엽에직경이 0.4 cm에서 3 cm로다양한크기의다낭종병터가관찰되고주위에젖빛유리혼탁이동반되어있었다 (Fig. 1). 하지만 4년후증상이재발하여촬영한단순흉부사진에서는양측폐야에음영이증가되어있고오른쪽아래엽부위에공기액체층이있는공동성병터가관찰되었다 (Fig. 2). 그리고흉부고해상 Figure 1. Computed tomography scan of the chest taken in 2009 showing multiple cystic changes in the right lower lobe of the lung. Figure 2. Chest radiography on admission showing a cavitary lesion with air-fluid level, increased haziness in the right middle and lower lung zone, and multiple patches of opacity in the left middle lung zone

3 - 대한내과학회지 : 제 86 권제 4 호통권제 644 호 A B Figure 3. Computed tomography scan of the chest taken on admission showing multiple cystic lesions with inner air-fluid level in lateral and posterior basal segments of the right lower lobe and consolidation with ground glass opacity in the right medial, right lower, and left upper lobes of the lung. 전산화단층촬영에서는오른쪽가운데엽과아래엽, 그리고왼쪽위엽에경화가산재되어있었으며오른쪽하엽에공기액체층이있는 8 cm 크기의낭성덩이와함께다낭종병터가보이는악화된소견이관찰되었다 (Fig. 3). 조직검사소견 : 가슴절개술을통해서오른쪽아래엽은낭종변형이관찰되고오른쪽가운데엽은다수의백색반이관찰되어양엽절제술을시행하였다. 육안적으로절제된오른쪽아래엽은 8 4 cm 크기의큰낭종공간주위에직경이 0.8 cm에서 5 cm 정도되는다양한크기의다낭종병터가관찰되었다 (Fig. 4A). 조직검사에서큰낭종공간은정상으로보이는호흡상피와역형성세포로피복되어있었지만 (Fig. 4B) 다낭종병터부위에서는정상원주세포가암세포로의악성변이를보이고있다 (Fig. 4C). 그리고오른쪽가운데엽은샘을형성하는원주모양의점액분비악성세포들이산재되어있었다 (Fig. 4D). 치료및임상경과 : 환자는폐렴에대해항생제주사치료를 2주간받으며기침, 가래및흉막염통증등의증상은호전되었다. 선천성낭성선종양기형에대하여수술적치료를시행하였으며수술후조직검사에서선암종이관찰되었다. 선암종의전이및잔류종양여부를평가하기위해양전자방출단층촬영및흉부고해상전산화단층촬영을시행하였 으며검사결과특이소견은없었다. 수술후합병증관찰되지않아퇴원후외래추적관찰중이다. 고찰선천성낭성선종양기형 (congenital cystic adenomatoid malformation, CCAM) 은 1949년에처음으로기술된하기도의드문과오종성비유전적발달이상이다 [7]. 대부분의 CCAM은정기산전초음파검사에서진단되거나신생아기에진단되며성인에서나타나는경우는극히드물다. 1975년에 Stocker 등 [2] 이 CCAM을임상적특징과육안적그리고조직학적특징에따라서세가지아형으로분류한후부터그분류법이널리사용되었다. Type I은 50-70% 정도로가장흔하며직경 2 cm 넘는단일또는다수의큰낭종으로원주상피로피복되어있다. Type II는 40% 정도에서관찰되며직경 2 cm 미만의작은다낭종이특징으로입방상피와원주상피로피복되어있다. Type III는 3% 정도에서관찰되는드문형태로입방상피로피복된세기관지양구조들의고형모양이특징이다. 방사선학적소견은 CCAM을진단하는데도움이되지만단순흉부사진은비특이적이어서엽성폐렴, 폐농양및공

4 - 최재우외 6 인. 선천낭성선종양의악성변화 - A B C D Figure 4. (A) Cut surface of the right lower lobe of the lung. One side shows large cystic change consisting of multiple small and large cysts. (B) Histological finding of the congenital cystic adenomatoid malformation. A normal bronchus is seen at the left, and the lesions are on the right. There is a nest of adenocarcinoma at the top [hematoxylin and eosin (H&E) stain, 40]. (C) Malignant transformation of the congenital cystic adenomatoid malformation. The normal pseudostratified ciliated columnar epithelium changed to columnar adenocarcinoma cells (H&E stain, 200). (D) Mucinous adenocarcinoma area in the right middle lobe of the lung (H&E stain, 200). 기낭종과구분이되지않으며때로는단순흉부사진에서관찰되지않을수있다. 따라서 CCAM 병터를확인하기위해서는흉부고해상전산화단층촬영이가장좋은방법이다. 하지만 CCAM이영상의학적으로다양한소견을보이며수술전정확한진단을하기힘들기때문에조직학적확진이필요하다. 본증례는수술후조직학적검사에서거짓중층섬모원주상피로피복된큰다낭종인 type I CCAM 과같은자리에서악성변이를보인선암종이관찰된경우이다. 임상적으로성인에서 CCAM 증상은반복적또는지속적인호흡기감염이가장흔하다. 다른합병증및증상들로는 기흉, 혈흉, 농흉, 객혈, 호흡곤란, 또는만성기침들이있으며단순흉부사진에서우연히발견되는경우들이있다. 또한 CCAM은일반적으로종양발생과연관이있다고알려져있다 [3]. CCAM의치료는보통연관된부위의폐를완전히절제하는것이다 [8]. CCAM 에서암이발견된환자를치료했던대부분의의사들은낭종병터를조기절제하였다면종양을예방할수있었을것으로생각한다 [9]. 본증례또한 CCAM 환자들에서악성변형에대한위험성측면에서해부학적폐절제의중요성을보여준다

5 - The Korean Journal of Medicine: Vol. 86, No. 4, 요 폐에서발생한 CCAM은전형적으로신생아에서나타나는드문선천성기형이다. 성인에서는 type I CCAM 이다른호흡기이상들과관련하여극히드물게보고되고있다. 하지만만성기침과같이서서히발생하는증상들이있거나영상의학검사에서낭종병터가있는경우에는악성변형가능성이있는선천성이상병터일수있기때문에추가적인검사가필요하다. 이러한병터의진단과치료를위해서전산화단층촬영과수술적생검이고려되어야한다. 저자들은수술적절제한 CCAM에서국내처음으로악성변형을관찰하였기에문헌고찰과함께보고하는바이다. 약 중심단어 : 선천성낭성선종양기형 ; 선암종 REFERENCES 1. Laberge JM, Flageole H, Pugash D, et al. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther 2001;16: Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum. Human Pathol 1977;8: West D, Nicholson AG, Colquhoun I, Pollock J. Bronchioloalveolar carcinoma in congenital cystic adenomatoid malformation of lung. Ann Thorac Surg 2007;83: Lantuejoul S, Ferretti GR, Goldstraw P, Hansell DM, Brambilla E, Nicholson AG. Metastases from bronchioloalveolar carcinomas associated with long-standing type 1 congenital cystic adenomatoid malformations: a report of two cases. Histopathology 2006;48: Summers RJ, Shehata BM, Bleacher JC, Stockwell C, Rapkin L. Mucinous adenocarcinoma of the lung in association with congenital pulmonary airway malformation. J Pediatr Surg 2010;45: McDonough RJ, Niven AS, Havenstrite KA. Congenital pulmonary airway malformation: a case report and review of the literature. Respir Care 2012;57: Ch'In KY, Tang MY. Congenital adenomatoid malformation of one lobe of a lung with general anasarca. Arch Pathol (Chic) 1949;48: Oh BJ, Lee JS, Kim JS, Lim CM, Koh Y. Congenital cystic adenomatoid malformation of the lung in adults: clinical and CT evaluation of seven patients. Respirology 2006;11: Granata C, Gambini C, Balducci T, et al. Bronchioloalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: a case report and review on malignancies originating in congenital cystic adenomatoid malformation. Pediatr Pulmonol 1998;25:

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