Case Report pissn / eissn J Korean Soc Radiol 2017;76(3): Squamous Cell Carcinom
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1 Case Report pissn / eissn J Korean Soc Radiol 2017;76(3): Squamous Cell Carcinomas of the Lung Which Presented as Numerous Polypoid Nodules in the Tracheobronchial Tree: A Case Report 기관기관지의다발성폴립결절로나타난편평상피세포폐암 : 증례보고 Hyun Gyu Lee, MD 1, Yo Won Choi, MD 1 *, Hyun Jung Yoon, MD 1, Seung Sam Paik, MD 2 Departments of 1 Radiology, 2 Pathology, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea We report a case of squamous cell carcinomas of the lung, which presented as numerous polypoid nodules in the tracheobronchial tree. They occurred at two years and 7 months after resection of squamous cell carcinoma, which presented as a lung nodule in the left lower lobe, and at 7 months after resection of tracheal squamous cell carcinoma. Index terms Lung Neoplasms Neoplasms, Second Primary Carcinoma, Squamous Cell Received July 15, 2016 Revised August 9, 2016 Accepted August 13, 2016 *Corresponding author: Yo Won Choi, MD Department of Radiology, Hanyang University Hospital, Hanyang University College of Medicine, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. Tel Fax ywchoi@hanyang.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 증례보고 기관기관지의다발성폴립모양 (polypoid) 병변은일반적으로후두기관의유두종증 (papillmatosis) 기관기관지골연골증식증 (tracheobronchopathia osteochondroplastica) 을시사하고 (1), 드물게양성의섬유상피성폴립 (fibroepithelilal polyp)(2), Bronchus-associated lymphoid tissue 에서기원한악성림프종 (3) 도이런소견을보일수있다고알려져있다. 한편폐암, 특히편평상피세포암은여러개의폴립으로발현하였다는보고는있지만 (4, 5), 많은수의다발성폴립으로발현하였다는보고는없다. 저자들은두차례에걸쳐폐와기관에이시성 (metachronous) 편평상피세포암이나타난환자에서마지막으로기관기관지의다발성폴립모양병변으로나타난편평상피세포암을보고한다. 61 세남자환자가 3개월간지속된기침, 가래를주소로내원하였다. 환자는 50갑년의흡연력을가진과거흡연자 (ex-smoker) 였고전립선암으로호르몬치료를받고있었다. 혈액검사상전립선특이항원이 8.88 ng/ml( 정상수치 < 4.5 ng/ml) 로증가해있었다. 2주전타원에서시행한흉부조영증강전산화단층촬영 (computed tomography; 이하 CT) 에서좌하엽에벌집폐 (honeycomb lung) 낭종에둘러싸인약 2 cm의결절이있었다 (Fig. 1A). 5번흉추에는골용해성의병변이있었는데, 전립선암의골전이는보통골경화 (osteosclerotic) 소견을보이기때문에폐암의전이로생각하였다. 커져있는림프절이나기관기관지의이상소견은없었다. 본원내원 2일째좌하엽의결절에대해세침흡인세포검사가시행되어편평상피세포암세포가검출되었다. Positron emission tomography ( 이하 PET) 에서 CT 에발견된폐결절과흉추병변부위에섭취증가가있어악성병 Copyrights 2017 The Korean Society of Radiology 211
2 기관기관지의다발성폴립결절로나타난편평상피세포폐암 변을시사하였고다른부위에는섭취증가가없었다. 골전이가있어폐암 4기였지만환자가강력히수술을원하여 2개월후좌하엽의쐐기절제술이시행되었다. 수술전기관지내시경은시행되지않았다. 절제한표본에서장측흉막을침습하는 1.5 cm의결절이있었고중등도분화편평상피세포암으로진단되었 으며임파선전이는없었다. 면역조직화학염색에서 p53에 33% 의양성률을, Ki-67에 28% 의양성률을보였다 ( 면역조직화학염색양성률은 field 에서양성을보이는종양세포의백분율을의미 ). 환자는수술후 gemcitabine 과 cisplatin 조합의보조항암요법을 5차례받았다. 수술 3개월후 CT에서 A B C D E Fig. 1. A case of squamous cell carcinomas of the lung, which presented as multiple tracheobronchial polyps in a 61-year-old male. A. Initial CT without enhancement axial image mediastinal window shows a 2 cm-sized nodule in the left lower lobe, which was confirmed to be moderately differentiated squamous cell carcinoma by histopathologic examination through wedge resection (arrow). B, C. Follow-up CT without enhancement axial and coronal image mediastinal windows obtained two years after wedge resection show a 1.5-cm-sized mural nodule along the left side of the trachea with adjacent focal tracheal wall thickening. After tracheal resection, moderately differentiated squamous cell carcinoma was detected by histopathologic examination (arrow). D, E. CT was obtained seven months after resection of the tracheal lesion, and the coronal lung window images show innumerable polypoid nodules along the trachea, both main bronchi, and the right bronchus intermedius. Squamous cell carcinoma in situ was diagnosed by histopathologic examination through bronchoscopic biopsy. 212 대한영상의학회지 2017;76(3): jksronline.org
3 이현규외 흉추의병변은골경화성으로변했고재발소견은없었다. 수술 4개월후의전신 PET-CT에서섭취증가부위는보이지않았다. 수술 2년후추적 CT에기관의중부에약 1.5 cm의편심성결절과근처의벽비후병변이발견되었고 (Fig. 1B, C), 이전의수술전후 CT에서는다시보아도이부위의이상소견은없었다. 기관지내시경검사및생검에서기관분기부상방 4.5 cm 기도의폴립모양결절에서편평상피세포암이확인되었다. 내시경검사때기도병변의조직검사후출혈때문에기관분기부이하의기관지는검사하지못하였다. 전신 PET-CT에서기관의결절에만섭취가항진되어있었다. 기도결절부위의기관절제술과단단문합술 (end-to-end anastomosis) 이시행되었다. 절제한표본에서 1.6 cm의결절은중등도분화의편평상피세포암으로진단되었고, 면역조직화학염색에서 p53 에 17% 의양성률을, Ki-67 에 15% 의양성률을보여, 좌하엽의원발종양과양성률이달랐기때문에기관전이보다는이시성이차원발편평상피세포암으로생각되었다 (6). 환자는 paclitaxel 과 carboplatin 조합의고식적항암요법을시작하였다. 4차항암치료를완료한후외래에서추적관찰중에, 기관절제술을받은지 7개월후의추적 CT에서무수히많은폴립모양결절이기관, 양측주기관지, 우측중간기관지 (bronchus intermedius) 에보였다 (Fig. 1D, E). 기관지내시경검사에서도전에관찰되지않던, 비정상점막으로덮인많은폴립들이기관기관지에보여 3개의병변에서생검이시행되었다. 세병변모두편평상피세포내암 (squamous cell carcinoma in situ ) 으로확인되어이시성이차원발편평상피세포암을시사하였다 (7). 면역조직화학염색에서도 p53에 11% 의양성률을, Ki-67에 21% 의양성률을보여, 이전병변의양성률과는달라원발병변을시사하였다. 항암요법제제를 docetaxel 로바꾸었고 3개월후의 CT와기관지내시경검사에서무수히많던기관-기관지의폴립모양결절들은모두사라졌다. 처음에골용해성으로보인 5번흉추의병변은골경화성으로바뀐후변화가없었다. 그로부터 3개월이지날때까지환자는재발의증거가없었다. 고찰 본증례의가장큰특이점은편평상피세포폐암이기관기관지의다발성폴립으로나타났다는것이고이들병변은 7개월전시행한 CT와기관지내시경검사에서는없었다. 환자는유두종증과거력이없었다. 본증례에서이와같은기관기관지의다발성폴립모양으로나타난편평상피세포암은최초병변이아니었다. 처음좌하엽의폐결절의편평상피세포암이발견되어수술로제거후추적관찰중기관에편평상피세포암이또나타났고, 이것역시수술로제거후항암제치료중나타난세번째의편평상피세포암이었다. 따라서두번째와세번째로나타난병변들이이시성원발폐암 (metachronous cancer) 인지전이폐암인지문제가되며, 이들의구분은치료와예후가다르기때문에, 정확한감별진단이필요하다. 다발성원발폐암의진단에있어가장널리사용되고실용적인기준 (criteria) 은 1975 년에소개된 Martini 와 Melamed (7) 의임상병리학적기준이다. Martini 와 Melamed (7) 기준에서이시성원발폐암의진단에대한내용만소개해보면이시성원발폐암은일차원발폐암과다른조직형이면쉽게진단할수있지만, 본증례처럼일차원발폐암과같은조직형이라면무병기간 (disease free interval) 이 2년이상이면서이시성폐암이상피내암으로부터의기원함이확인되고일차원발폐암과이시성원발폐암이서로다른엽 (lobe) 에위치해야하며임파선전이나폐외전이는없어야한다. 하지만다수의폐결절을가진환자가항상 Martini 와 Melamed 의기준에정확하게들어맞게분류되지않고, 이기준에의해분류된다발성원발폐암의생존율에는보고자마다주목할만한차이가발견되고있다 (6). 이는 Martini 와 Melamed 기준의다소임의적인성격과분자생물학적기초의부재에의한것으로생각된다. 한코호트연구에따르면 Martini 와 Melamed 기준은오직 68% 에서만분자생물학적분류와일치한다고한다 (8). 한편다발성원발폐암은각각의종양이독립적인클론에서기원하고전이폐암은각각의종양표본이같은클론에서기원하는것을이용하여, 최근에는둘의감별을위해분자생물학기술이활발히이용되고있다. van Rens 등 (9) 은 p53 유전자분석이다발성원발폐암과전이폐암을구분하는데유용한도구가될수있다고보고하였다. 한편 Okita 등 (6) 은서로다른 p53, Ki-67 의면역조직화학염색양성률을보이는 3개의동시성편평세포폐암의증례를보고한바있다. 본증례도시간적간격을둔세번의편평세포암표본이서로매우다른 p53, Ki-67 면역조직화학염색양성률을보였고, 세번째병변으로기관기관지의다발성폴립이생겼을때기관지내시경생검한세개의표본모두에서상피내암이확인되었으며일차원발폐암과다른해부학적위치에서발생하여서 Martini 와 Melamed 기준도어느정도만족하였기때문에, 세번에걸쳐나타난이시성이차원발폐암이적절한진단으로생각한다. 하지만 Martini 와 Melamed 의기준과는달리둘째와셋째병변이나타났을때무병기간이 2년이안되고, 또기관기관지에나타난다발성폴립의조직검사소견이모두상피내암이지만전이가아니라면다발성병변이어떻게동시에생겼을까하는의문점도있어전이성병변의가능성도완전히배제하기 jksronline.org 대한영상의학회지 2017;76(3):
4 기관기관지의다발성폴립결절로나타난편평상피세포폐암 어렵다. Hwang 등 (10) 에따르면기관지잘린끝 (stump) 근처에서임파선을통해도약전이 (skipped endobronchial metastasis) 가생길수있는데, 본증례에서는기관기관지전체에서동시에다발성으로생겼기때문에도약전이의가능성은떨어져보인다. 요약하면본증례에서는세번에걸쳐폐결절, 기관결절, 다발성의기관기관지폴립등의다양한형태로편평상피세포암이발생했다. 이들세번결절들이모두서로다른 p53, Ki-67 면역조직화학염색양성률을보이고, 세번째병변의일부에서편평상피세포내암을보여, 전이폐암보다는이시성원발폐암을시사하였지만전이폐암도완전히배제되지는않는다. 특히세번째병변은기관기관지의다발성폴립모양을보였고역시폐암으로확진되었다. 골초환자 (heavy smoker) 에서 CT상기관이나기관지에다발성폴립형태의병변이보이는경우폐암, 특히편평상피세포암을감별에고려해볼수있겠다. REFERENCES 1. Obusez EC, Jamjoom L, Kirsch J, Gildea T, Mohammed TL. Computed tomography correlation of airway disease with bronchoscopy: part I--nonneoplastic large airway diseases. Curr Probl Diagn Radiol 2014;43: Ling IT, Mulrennan SA, Phillips MJ. Multiple endobronchial polyps. J Bronchology Interv Pulmonol 2011;18: Yoon RG, Kim MY, Song JW, Chae EJ, Choi CM, Jang S. Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings in 7 patients. Korean J Radiol 2013;14: Burke G, McCaughan B, Glanville A. Metachronous tracheal squamous cell carcinoma treated with Nd: YAG laser. Respirol Case Rep 2015;3: Youn HC, Kim YH, Lee YK, Kim GY. Multiple endotracheal and endobronchial metastases after pneumonectomy for a primary lung cancer: a case report. Thorac Cancer 2013; 4: Okita R, Shimizu K, Mimura T, Miyata Y, Okada M, Arihiro K. Suggestive synchronous triple squamous cell carcinoma of the lung in the same lobe. Gen Thorac Cardiovasc Surg 2010;58: Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975;70: Girard N, Deshpande C, Lau C, Finley D, Rusch V, Pao W, et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol 2009;33: van Rens MT, Eijken EJ, Elbers JR, Lammers JW, Tilanus MG, Slootweg PJ. p53 mutation analysis for definite diagnosis of multiple primary lung carcinoma. Cancer 2002;94: Hwang HJ, Kim MY, Kim SS, Choi CM. CT Characteristic of early local recurrence after resection of the squamous cell carcinoma: comparison with CT characteristics of stump deformity or granulation tissue at stump site. Medicine (Baltimore) 2015;94:e 대한영상의학회지 2017;76(3): jksronline.org
5 이현규외 기관기관지의다발성폴립결절로나타난편평상피세포폐암 : 증례보고 이현규 1 최요원 1 * 윤현정 1 백승삼 2 저자들은 61 세남자환자에서기관과기관지의무수한폴립모양결절로나타난편평상피세포폐암의증례를보고하고자 한다. 폴립모양결절들은좌하엽의편평상피세포폐암을절제한지 2 년 7 개월후와기관의편평상피세포폐암을절제한지 7 개월후에발생하였다. 한양대학교의과대학한양대학교병원 1 영상의학과, 2 병리과 jksronline.org 대한영상의학회지 2017;76(3):
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