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1 성인에서진단된선천성낭포성유선종폐기형 6 예 인제대학교의과대학 1 호흡기내과학교실, 2 흉부외과학교실, 3 영상의학교실, 4 진단병리학교실, 5 대동병원내과박영진 1, 정훈 1, 박이내 1, 최상봉 1, 허진원 1, 이혁표 1, 염호기 1, 최수전 1, 구호석 1, 이양행 2, 최석진 3, 정수진 4, 이현경 1, 김애란 5 Congenital Cystic Adenomatoid Malformation of Lung in Adults: Clinical, Pathologic and Radiologic Evaluation of Six Patients Young Jin Park, M.D. 1, Hoon Jung, M.D. 1, I-Nae Park, M.D. 1, Sang Bong Choi, M.D. 1, Jin-Won Hur, M.D. 1, Hyuk Pyo Lee, M.D. 1, Ho-Kee Yum, M.D. 1, Soo Jeon Choi, M.D. 1, Ho-Seok Koo, M.D. 1, Yang-Haeng Lee, M.D. 2, Suk-Jin Choi, M.D. 3, Soo-Jin Jung, M.D. 4, Hyun-Kyung Lee, M.D. 1, Ae Ran Kim, M.D. 5 Departments of 1 Internal Medicine, 2 Thoracic Surgery, 3 Radiology and 4 Pathology, College of Medicine, Inje University, 5 Department of Internal Medicine, Daedong Hospital, Busan, Korea Background: Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital developmental anomaly of the lower respiratory tract. Most cases are diagnosed within the first 2 years of life, so adult presentation of CCAM is rare. We describe here six adult cases of CCAM and the patients underwent surgical resection, and all these patients were seen during a five and a half year period. The purpose of this study was to analyze the clinical, radiological and histological characteristics of adult patients with CCAM. Methods: Through medical records analysis, we retrospectively reviewed the clinical characteristics, the chest pictures (X-ray and CT) and the histological characteristics. Results: Four patients were women and the mean age at diagnosis was 23.5 years (range: years). The major clinical presentations were lower respiratory tract infection, hemoptysis and pneumothorax. According to the chest CT scan, 5 patients had multiseptated cystic lesions with air fluid levels and one patient had multiple cavitary lesions with air fluid levels, and these lesions were surrounded by poorly defined opacities at the right upper lobe. All the patients were treated with surgical resection. 5 patients underwent open lobectomy and one patient underwent VATS lobectomy. On the pathological examination, 3 were found to be CCAM type I and 3 patients were CCAM type II, according to Stocker s classification. There was no associated malignancy on the histological studies of the surgical specimens. Conclusion: As CCAM can cause various respiratory complications and malignant changes, and the risks associated with surgery are extremely low, those patients who are suspected of having or who are diagnosed with CCAM should go through surgical treatment for making the correct diagnosis and administering appropriate treatment. (Tuberc Respir Dis 2008;65: ) Key Words: Adult, Congenital cystic adenomatoid malformation, Surgery 서 선천성낭포성유선종폐기형 (Congenital cystic adenomatoid malformation of lung, CCAM) 은드문하부호 Address for correspondence: Hyun-Kyung Lee, M.D. Department of Internal Medicine, Pusan Paik Hospital, Inje University College of Medicine, , Gae-gum 2-dong, Jin-gu, Busan , Korea Phone: , Fax: goodoc@gmail.com Received: Jun. 17, 2008 Accepted: Jul. 24, 2008 론 흡기의선천성발달기형이다. CCAM 은정상폐포대신에낭종을형성하는세기관지의선종성증식을특징으로한다. CCAM 환자는비정상적인폐조직의증식때문에폐가제기능을할수없어, 호흡부전으로신생아기에발견되는경우가흔하고 1,2, 유아기에진단되는경우도종종보고된다. CCAM 환자의 90% 이상은생후 2년내에진단되는것으로보고되고있다 1,2. 그러나드물게는성인기에반복적인하부호흡기감염등의호흡기합병증이생기거나무증상인채로우연히진단된다. 최근에는산전초음파등의진단기술발전으로점차태아기에진단되는경우가많아지고있다 3,4. 110

2 Tuberculosis and Respiratory Diseases Vol , Aug CCAM 은흔치는않지만악성화나다양한호흡기합병증과연관될수있기때문에잠정적으로생명을위협할수있는호흡기기형이다. CCAM 과연관된악성화로는소아에서횡문근육종 (rhabdomyosarcoma), 폐모세포종 (pulmonary blastoma), 세기관지폐포암종 (bronchioloalveolar carcinoma) 과성인에서세기관지폐포암종이보고된바있다 5-8. 현재까지무증상일지라도앞서언급한악성화나다양한호흡기합병증이생길수있기때문에수술적제거가가장좋은치료법으로고려되고있다 9. 저자들은성인기에진단되어수술을통해조직학적으로확진된 6명의 CCAM 환자의임상적, 방사선학적및조직학적특성을분석하여보고한다. 대상및방법저자들은 2001년 8월부터 2007년 2월까지인제대학교의과대학백병원에서수술을통해조직학적소견으로확진된 17명의 CCAM 환자를확인하였다. 그중성인기에진단된 6명의환자를대상으로하여전화면담과의무기록검토를통해그들의인구학적및임상적특성, 흉부방사선학적자료 ( 흉부 X선검사, 흉부전산화단층촬영 ), 수술후합병증및치료, 그리고조직학적특성을후향적으로분석하였다. 모든환자들은수술전방사선학적검사 ( 흉부 X선검사, 흉부전산화단층촬영 ) 를시행받았다. 대부분환자에서 CCAM 이의심되어확진및완치를위해그리고일부에서는다른호흡기질환의감별진단및치료를위해선택적수술을받았다. 각각의환자들의주요한특징을 Table 1에나타내었다. 수술후얻은검체는육안적및조직학적소견을바탕으로 Stocker 씨분류법에따라분류하였고동반된악성화또는다른기형동반유무에대해서도평가되었다. 결과 6명의 CCAM 환자중 4명이여자였고, 진단당시의평균나이는 23.5 세 ( 범위 세 ) 였다. 기존에다른질환이나선천성기형이동반된경우는없었고선천성기형에대한가족력및흡연력도없었다. 병원방문시주요증상은 3명의환자에서발열과화농성객담을동반한기침, 1명에서심한피로감, 1명의환자에서객혈, 그리고 1명의환자에서는흉통이었다. 1명의환자는 2년전만성부비동염으로수술을위해시행한단순흉부 X선및흉부전산화단층촬영에서 CCAM 을진단받았으나증상이없어 2년간경과관찰하던중발열과화농성객담을동반한기침이생겨병원을다시방문하였다. 흉부전산화단층촬영에서 5명의환자는공기액체층을동반한다발성격막을가진낭종성병변을가지고있었고, 나머지 1명에서는우상엽에공기액체층을동반한다발성 Table 1. Clinical and histologic data for six adult patients with congenital cystic adenomatoid malformation of lung Case. Age/ Sex Age at diagnosis Clinical presentation Involved lobe Histologic types Treatment Smoking Hx. Family Hx. 1 27/F 20 Hemoptysis RUL 2 RUL lobectomy 2 43/F 39 Pneumothorax RUL 1 RUL lobectomy 3 22/M 21 Lung abscess LLL 1 LLL lobectomy esophageal diverticulectomy 4 21/M 18 Pneumonia LLL 2 LLL lobectomy 5 23/F 22 Pneumonia RLL 1 RLL lobectomy 6 23/F 21 Pneumonia RLL 1 RLL lobectomy (VATS) VATS: video assisted thoracoscopic surgery. 111

3 YJ Park et al: Congenital cystic adenomatoid malformation of lung Figure 1. There are multiple cystic lesions, about 6 7 cm in diameter in the left middle lung field. Pneumonic consolidations and air fluid levels are in and around the cystic lesions (A). At the level of the left inferior pulmonary vein, the lesion contains about 4.5 cm in diameter cystic space (B). The CT scan at the level of left main bronchus reveals innumerable fine cystic lesions in the superior segment of the left lower lobe (C). Figure 2. Chest PA shows a cystic lesion with air fluid level and pericystic pneumonic infiltration in right lower lobe on admission (A). Chest CT scan on admission reveals a thin walled multicystic lesion with fluid collection mimics a pulmonary abscess in RLL (B). 공동성병변과주위에다발성침윤성병변을가지고있었다. 병변의위치는 2명의환자에서우상엽, 다른 2명에서는우하엽그리고나머지 2명의환자에서는좌하엽에병변이있었다 (Figure 1, 2). 1명의환자 (Case 1) 는객혈과우상엽의다발성공동성병변을가진특징적방사선소견이있어 6.5 년전폐결핵으로항결핵제를 1년간투여받고그이후추적관찰을받았다. 수술전임상적소견및방사선학적검사를통해 6명중 5명은 CCAM 진단을받았고수술후조직학적소견으로확진을받았다. 나머지 1명의환자에서는폐결핵으로장기간치료를받아오다객혈이생겨진단및치료목적으로수술을하였기에수술전에는 CCAM 을의심하지못했 고수술후조직학적검사결과가나온후에야 CCAM 으로진단받았다. CCAM 은성인기에진단되는경우가매우드물고다양한임상양상으로나타났기에처음증상이생겨서 CCAM 으로확진되는데평균 4.3년이소요되었다. 모든환자는폐엽절제수술을받았는데 5명은개흉술을통한폐엽절제술을그리고 1명은흉강경을이용한폐엽절제술을시행받았다. 조직학적검사결과 Stocker 씨분류법에따라 3명의환자는 1형그리고나머지 3명은 2형으로분류되었다 (Figure 3, 4). 모든환자의검체에서동반된악성종양의증거는없었다. 1명의환자에서식도게실이동반된것이외에다른기 112

4 Tuberculosis and Respiratory Diseases Vol , Aug 형은 동반되지 않았다. 수술 후 회복기간 동안 1명에서 유미흉이 있어 장기간 흉관 배액술을 시행하였던 것 외에 다른 수술 후 합병증은 없었다. 그리고 수술 후 외래 추적 관찰하는 동안 1명의 환자에서 폐렴이 있었지만 증상이 경미하여 경구 항생제만으로 금방 호전되었다. 그 외에 추적 관찰 기간 동안 다른 합병증이나 악성화 소견은 없었 다(평균 2.94년, 범위 년). Figure 3. Gross finding of a resected right lower lobe in Case 6 shows one large cystic lesion and small variable sized cysts surrounding by bronchial like structures, accompanied with grayish pneumonic consolidation. 고 찰 CCAM은 1949년 Ch in 등에 의해 처음으로 보고 된 드 10 문 선천성 과오종성 폐 병변이다. 태생 3주경 호흡기 계 통의 발달이 시작이 된다. 이 과정에 이상이 생기면 CCAM, 폐분리증(pulmonary sequestration), 영아 폐엽 공기증(infantile lobar emphysema) 등의 기관지 폐의 앞 창자 기형(bronchopulmonary foregut malformations)으 로 불리는 구조적 이상이 발생한다. 그 중 CCAM은 태생 7주 이전에 비정상적 발생에 의해 종말 세기관지의 선종 성 증식과 폐 실질의 낭종성 변화를 일으키는 것으로 생각 되고 있다. 성인기에 CCAM이 진단된 경우는 매우 드물기 때문에 대부분 증례보고를 통해 보고되고 있다. 성인기에 진단된 CCAM의 예후는 조직학적 특성, 감염 그리고 악성화의 가 3 능성에 달려 있다. CCAM의 전형적 방사선학적 소견은 공기 액체층 또는 액체가 찬 다발성 낭성 병변이다. 하지만 다양한 소견으 로 나타날 수 있기 때문에 방사선적 검사만으로 진단이 쉽지 않다. 전산화 단층촬영은 폐의 낭종성 및 공동성 병 변의 형태학적 평가를 하는 데 유용할 지라도 CCAM과 비슷한 방사선학적 특징을 가진 다른 낭종성 폐 질환을 감별하는 데 충분하지 않다11. 다른 낭종성 폐 질환, 특히 단순 낭종은 거의 악성화와 호흡기의 합병증 발생과 관련 이 없다. 하지만 악성화와 호흡기 합병증이 흔히 CCAM에 서 발생할 수 있기 때문에 CCAM을 다른 낭종성 폐 질환 Figure 4. The mass is composed of multiple, variable sized cysts in Case 3 (CCAM Type 1) (A, H&E stain, 40). The cysts are lined by ciliated pseudostratified columnar epithelium with frequent mucus producing cells. The wall of the cysts contains cartilage (B, H&E stain, 200). 113

5 YJ Park et al: Congenital cystic adenomatoid malformation of lung 과의감별진단하는것은필수적이다 11. 방사선학적검사가감별진단에도움이될수있지만확진은발생학적이상 (embryonic abnormalities) 의조직학적확인없이이루어질수없다. 본연구에서 1명의환자는임상적및방사선소견으로폐결핵을의심하여 1년간항결핵약물치료를받았고, 그이후 6.5년간추적관찰을받았다. 하지만증상및흉부 X선사진의호전이없어수술을시행했고, 조직검사결과가나온후에야 CCAM 으로진단할수있었다. 이는임상적소견과방사선학적검사만으로는 CCAM 을진단하기에는불충분하다는것을보여주었다. 이제까지문헌을고찰했을때 CCAM 은거의대부분일측성으로발생되었고, 남녀비율이나종족간의차이는없었다 1. 그리고호발부위도큰차이없이고르게분포되었다. 가장흔한임상양상은하부호흡기감염이었고가장흔한방사선학적특징은공기액체층또는액체가찬다발성낭성병변이었다. 본연구에서는총 6명중 4명이여자였고병변의위치는 2명에서우하엽, 또다른 2명에서우상엽그리고나머지 2명에서좌하엽으로고르게발생되었다. 방사선학적소견역시 5명에서는공기액체층을동반한다발성격막을가진낭종성병변으로특징적소견을나타냈지만나머지 1명에서는우상엽에공기액체층을동반한공동과주위에다발성침윤을동반한병변이었다. 본연구에서도이전문헌보고의특징과유사함을보여주었다. 최근 2년동안국내 2곳의대학병원에서본연구와비슷한연구결과가발표되었다. 본연구와비교해볼때임상적, 방사선학적및조직학적특성은전반적으로큰차이가없었다. 흉부방사선적으로가장흔히다발성낭종성병변이있어대다수에서수술전 CCAM 을의심해수술적치료를시행하였고조직검사결과모든환자에서 I형과 II형이었고 III형은없었고동반된악성화소견이나가족력모두없었다. 단지차이점으로는 Oh 등 9 의연구대상환자들중상당수 (3/7) 가 50세이상의연령층이었다는것이고이는장기간무증상으로지냈거나정확한진단이지연되었음을유추해볼수있다. 그리고 Kwon 등 15 의연구대상환자 9명중 3명에서특징적방사선소견이없어수술전진단이어려운경우가많았다. 하지만결론적으로는본연구결과를통해이전국내및국외문헌보고의인구학적, 임상적, 방사선학적및조직학적결과들을다시한번지지할수있었다. 비록보고된환자수가적어서치료가이드라인은명확히정립되어있지는않지만일반적으로수술적제거가가장좋은치료법으로고려되고있다 9. 왜냐하면무증상일지라도 악성화나반복적감염등의합병증이생길수있고 3,12,13, 수술과관련된합병증이거의없었기때문이다. 본연구에서 1명의환자는무증상으로 2년간경과관찰중결국내과적치료에반응하지않는중증폐렴이생겨수술적치료를함으로써증상이호전되었다. 일반적으로개흉술을통한폐엽절제술이표준수술방법으로알려져있다. 최근들어수술후통증조절이쉽고미용적인면에서의우수성, 그리고입원기간단축등의장점이있어점차비디오흉강경을이용한수술 (VATS) 이중요한위치를차지하고있다 14,15. 최근 Kwon 등은 CCAM 으로진단받은 9명의성인환자들을대상으로하여개흉수술과 VATS 를비교함으로써 VATS 의유용성과안전성에대해보고한바있다 15. 증상이없는 CCAM 환자를경과관찰을할것인지수술을할것인지에대해서는아직도논란이있다. 하지만여러문헌고찰과본연구를통해서무증상일지라도 CCAM 이하부호흡기감염, 기흉, 객혈등의다양한호흡기합병증과악성화를일으킬가능성이있고수술적치료와연관된합병증이거의없기때문에 CCAM 으로의심되거나확실치않은폐의낭종성혹은공동성병변이있을때지체없이정확한진단과적절한치료를위해서반드시수술적치료가필요할것으로생각된다 16,17. 요약연구배경 : CCAM 은드문하부호흡기의선천성발달기형으로대부분은생후 2년내에진단되는것으로보고되고있다. 그리고매우드물게성인이되어서호흡기합병증이생기거나무증상인채로우연히진단된증례들이보고되었다. 우리는본원에서수술을통해조직학적소견으로확진된 6명의성인 CCAM 환자들을기술하였고이들의임상적, 방사선학적및조직학적특성을분석하고자하였다. 방법 : 2001 년 8월부터 2007 년 2월까지본원에서성인기에수술을통한조직학적소견으로확진된 6명의 CCAM 환자를확인하였다. 의무기록검토를통해그들의인구학적및임상적특성, 흉부방사선자료그리고조직학적특성을후향적으로분석하였다. 결과 : 6명의 CCAM 환자중 4명이여자였고진단당시의평균나이는 23.5세 ( 범위 18 39세 ) 였다. 내원당시주요임상양상은하부호흡기감염, 객혈, 그리고기흉이었다. 흉부전산화단층촬영을보면 5명의환자는공기 114

6 Tuberculosis and Respiratory Diseases Vol , Aug 액체층을동반한다발성격막을가진낭종성병변을가지고있었고나머지 1명에서는우상엽에공기액체층을동반한다발성공동성병변과주위에다발성침윤성병변을가지고있었다. 모든환자는폐엽절제수술을받았는데 5명은개흉술을통한폐엽절제술을그리고 1명은흉강경을이용한폐엽절제술을시행받았다. 조직학적검사결과 Stocker 씨분류법에따라 3명의환자는 1형그리고나머지 3명은 2형으로분류되었다. 모든환자의검체에서동반된악성종양의증거는없었다. 결론 : CCAM 이하부호흡기감염, 기흉, 객혈등의다양한호흡기합병증과악성화를일으킬가능성이있고수술적치료와연관된합병증이거의없기때문에 CCAM 으로의심되거나확실치않은폐의낭종성혹은공동성병변이있을때정확한진단과적절한치료를위해서반드시수술적치료가필요하다. 참고문헌 1. Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum. Hum Pathol 1977;8: Rosado-de-Christenson ML, Stocker JT. Congenital cystic adenomatoid malformation. Radiographics 1991;11: Luján M, Bosque M, Mirapeix RM, Marco MT, Asensio O, Domingo C. Late-onset congenital cystic adenomatoid malformation of the lung: embryology, clinical symptomatology, diagnostic procedures, therapeutic approach and clinical follow-up. Respiration 2002;69: Laberge JM, Flageole H, Pugash D, Khalife S, Blair G, Filiatrault D, et al. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther 2001;16: d'agostino S, Bonoldi E, Dante S, Meli S, Cappellari F, Musi L. Embryonal rhabdomyosarcoma of the lung arising in cystic adenomatoid malformation: case report and review of the literature. J Pediatr Surg 1997;32: Federici S, Domenichelli V, Tani G, Sciutti R, Burnelli R, Zanetti G, et al. Pleuropulmonary blastoma in congenital cystic adenomatoid malformation: report of a case. Eur J Pediatr Surg 2001;11: Kaslovsky RA, Purdy S, Dangman BC, McKenna BJ, Brien T, Ilves R. Bronchioloalveolar carcinoma in a child with congenital cystic adenomatoid malformation. Chest 1997;112: Ribet ME, Copin MC, Soots JG, Gosselin BH. Bronchioloalveolar carcinoma and congenital cystic adenomatoid malformation. Ann Thorac Surg 1995;60: 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: Ch in KY, Tang MY. Congenital adenomatoid malformation of one lobe of a lung with general anasarca. Arch Pathol (Chic) 1949;48: Morelli L, Piscioli I, Licci S, Donato S, Catalucci A, Del nno F. Pulmonary congenital cystic adenomatoid malformation, type I, presenting as a single cyst of the middle lobe in an adult: case report. Diagn Pathol 2007;2: MacSweeney F, Papagiannopoulos K, Goldstraw P, Sheppard MN, Corrin B, Nicholson AG. An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol 2003;27: Lantuejoul S, Ferretti GR, Goldstraw P, Hansell DM, Brambilla E, Nicholson AG. Metastases from bronchioloalveolar carcinomas associated with longstanding type 1 congenital cystic adenomatoid malformations: a report of two cases. Histopathology 2006;48: Weatherford DA, Stephenson JE, Taylor SM, Blackhurst D. Thoracoscopy versus thoracotomy: indications and advantages. Am Surg 1995;61: Kwon YS, Koh WJ, Han J, Choi YS, Kim K, Kim J, et al. Clinical characteristics and feasibility of thoracoscopic approach for congenital cystic adenomatoid malformation in adults. Eur J Cardiothorac Surg 2007;31: Allan BT, Day DL, Dehner LP. Primary pulmonary rhabdomyosarcoma of the lung in children: report of two cases presenting with spontaneous pneumothorax. Cancer 1987;59: Granata C, Gambini C, Balducci T, Toma P, Michelazzi A, Conte M, et al. Bronchioalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: a case report and review of malignancies originating in congenital cystic adenomatoid malformation. Pediatr Pulmonol 1998;25:

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