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1 아밀라제상승이동반된저분화편평상피세포폐암 1 예 연세대학교의과대학내과학교실 1, 폐질환연구소 2 정현수 1, 박무석 1,2, 김영삼 1,2, 김세규 1,2, 장준 1,2, 김성규 1,2 A Case of Poorly Differentiated Squamous Cell Lung Cancer with Hyperamylasemia Hyun Soo Chung, M.D. 1, Moo Suk Park, M.D. 1,2, Young Sam Kim, M.D. 1,2, Se Kyu Kim, M.D. 1,2, Joon Chang, M.D. 1,2, Sung Kyu Kim, M.D. 1,2 Department of Internal Medicine 1, The Institute of Chest Diseases 2, Yonsei University College of Medicine, Seoul, Korea A 78-year-old man was admitted to our hospital as a result of dyspepsia with a 2-month duration. Upon admission, the laboratory data showed a marked elevation in amylase activity in both the serum and urine. The pancreas and salivary glands were considered unlikely to have any clinical involvement in the hyperamylasemia. The chest PA revealed a right side pleural effusion, and the chest CT showed a heterogeneous enhancing mass on the subcarinal area. The patient was diagnosed bronchoscopically with a poorly differentiated squamous cell carcinoma. The amylase isoenzyme patterns indicated the salivary types, but lung cancer was strongly suspected to be the source. In most cases, lung cancers with hyperamylasemia have been diagnosed as adenocarcinomas. A squamous cell carcinoma is quite rare. We report an interesting case of squamous cell lung cancer with hyperamylasemia (Tuberc Respir Dis 2005; 59: ) Key words : Lung cancer, Squamous cell carcinoma, Hyperamylasemia 서 혈청아밀라제는췌장질환, 타액선질환, 신부전, 종양, 궤양천공, 당뇨병성케톤뇨증, 화상, 박리성대동맥류, 만성간질환, 임신및폐렴등에서상승되는것으로알려져있고, 아밀라제를생성하는종양으로폐암을비롯하여난소암, 자궁암, 결장암, 흉선종등이보고되고있으며, 폐암의경우전체폐암의 1~3% 에서아밀라제를생성하는것으로알려져있다 1-4. 고아밀라제혈증이동반된원발성폐종양은대부분의경우에서그조직형이분화도중등도이상의선암이며, 일부소세포폐암이일본에서 10여례가보고되었으며, 국내에서도 1예보고된바가있으나편평상피세포폐암은국내에보고된바가없다. 저자등은혈청과흉막액아밀라제상승을동반한편평상피세포폐암 1예 론 Address for correspondence : Young Sam Kim, M.D. Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, CPO box 8044, Seoul, Korea Phone : Fax : ysamkim@yumc.yonsei.ac.kr Received : Oct Accepted : Nov 를경험하였기에문헌고찰과함께이를보고하는바이다증례환자 : 박 근, 남자 78세, 농업주소 : 2개월전부터의소화불량, 1개월전부터의기침및노작성호흡곤란현병력 : 환자는 2002년 10월 7일 2개월전부터의식욕부진, 소화불량, 1개월전부터의기침및호흡곤란을주소로내원하여시행한검사상혈청아밀라제의상승소견보여본원소화기내과에내원하여시행한복부초음파검사및복부전산화단층촬영상특이소견없고, 흉부단순촬영상우측흉막액소견보여 (Fig. 1) 호흡기내과로전과되었다. 과거력 : 25년전협심증, 심방세동진단받았으며흡연력은 25갑년, 음주력은 50년간 1주에소주반병이었다. 가족력및사회력 : 특이소견없음. 진찰, 신체검사소견 : 문진상기침, 호흡곤란, 식욕부진을호소하였고, 이학적검사상활력징후는안정적이었고만성병색을보였으며, 의식은명료하였다. 674

Tuberculosis and Respiratory Diseases Vol. 59. No. 6, Dec. 2005 (A) (B) Figure 1. (A) The chest PA showed pleural effusion in the right side.

흉부청진상우측하폐야에서호흡음이감소되어있었고, 복부촉진상압통은없었으며, 간이나비장은촉지되지않았다. 검사실소견 : 말초혈액에서혈색소 12.0 g/dl, 백혈구 7,600 / μl ( 호중구 64.5%, 임파구 20.5%, 단핵구 8.5% 호산구 2.5%, 호염구 1.

9%, 췌장형이 37.1% (Fig. 2) 였고, 24시간소변아밀라제는 272 U/L 였다. 방사선학적소견 : 복부초음파및복부컴퓨터단층촬영, 타액선스캔 (Fig. 3) 상특이소견은보이지않았으며, 흉부컴퓨터단층촬영에서기관용골하부에불균일한조영양상을보이는종괴가관찰되었다 (Fig. 4). Figure 2.

2 Tuberculosis and Respiratory Diseases Vol. 59. No. 6, Dec (A) (B) Figure 1. (A) The chest PA showed pleural effusion in the right side. (B) The right lateral decubitus showed the shifting of pleural effusion in the right side 결막은창백하지않았고, 공막의황달은없었으며, 경부에서임파절은촉지되지않았다. 흉부청진상우측하폐야에서호흡음이감소되어있었고, 복부촉진상압통은없었으며, 간이나비장은촉지되지않았다. 검사실소견 : 말초혈액에서혈색소 12.0 g/dl, 백혈구 7,600 / μl ( 호중구 64.5%, 임파구 20.5%, 단핵구 8.5% 호산구 2.5%, 호염구 1.2%), 혈소판 450,000 / μl이었으며, 혈청생화학검사상아밀라제 590 U/L ( 리파아제 30 U/L) 및종양표지자검사상 CEA 6.07 U/ml으로상승되어있었고. 흉수에서아밀라제 241 U/L, CEA 9.32 U/mL로증가되어있었다. 혈청아밀라제동위효소검사결과타액형이 62.9%, 췌장형이 37.1% (Fig. 2) 였고, 24시간소변아밀라제는 272 U/L 였다. 방사선학적소견 : 복부초음파및복부컴퓨터단층촬영, 타액선스캔 (Fig. 3) 상특이소견은보이지않았으며, 흉부컴퓨터단층촬영에서기관용골하부에불균일한조영양상을보이는종괴가관찰되었다 (Fig. 4). Figure 2. Serum amylase isoenzyme study showed two peaks, the higher peak means salivary type amylase (62.9%), the lower one means pancreatic type amylase (37.1%). Figure 3. Salivary scan showed symmetrically decre ased uptake in both paroid glands and submandibular gland. 675

HS Chung et al. : Squamous cell lung cancer with hyperamlasemia Figure 4.

(H&E stain, x 200) (B) (H&E stain, x400). 병리조직학적소견 : 경기관지폐생검결과저분화편평상피세포폐암으로진단되었다 (Fig. 5).

환자및보호자적극적치료를원치않아입원 12일째퇴원하였으며, 외래추적관찰중진단 3개월후호흡곤란이악화되어응급실에내원하였으며, 내원 2일째사망하였다.

3 HS Chung et al. : Squamous cell lung cancer with hyperamlasemia Figure 4. The chest CT showed heterogeneous enhancing mass at the subcarinal area and 2 nd right main broncheal wall thickening. (A) (B) Figure 5. Pathologic features (A) Microscopic examination of the specimen shows poorly differentiated squamous cell carcinoma (H&E stain, x 200) (B) (H&E stain, x400). 병리조직학적소견 : 경기관지폐생검결과저분화편평상피세포폐암으로진단되었다 (Fig. 5). 입원후경과 : 환자는입원후병기설정및타부위원발성종양의가능성을배제할수없어복부전산화단층촬영, 상부위장관내시경, 전신골주사스캔을시행하였으나, 위궤양외에특이소견은없었다. 환자및보호자적극적치료를원치않아입원 12일째퇴원하였으며, 외래추적관찰중진단 3개월후호흡곤란이악화되어응급실에내원하였으며, 내원 2일째사망하였다. 고찰고아밀라제혈증의원인은, 대부분췌장질환또는 타액선질환이나, 그외에신, 간기능장애, 마크로아밀라제혈증, 종양, 폐결핵등의폐질환, 난소및난관질환, 특발성등이있다 1-4. 혈중, 요중의아밀라제농도가상승되어있는경우에는아밀라제동위효소분획을검사하여췌장형인지타액형인지를조사하는것이필요하다. 그리하여타액선형이우위에있는경우타액선질환이배제된다면아밀라제를생성하는종양또는부종양증후군에의한고아밀라제혈증의가능성에대하여염두에두어야한다 5. 이소성아밀라제를생성하는종양으로는폐암, 난소암, 자궁암, 결장암, 흉선종등이보고되고있으나, 그중에서도폐암이가장많다 6. 고아밀라제혈증을동반한원발성폐암은 1951년 Weiss등에의해보고된이래점점그수가늘어나고있는추세로, 전폐암의 676

4 Tuberculosis and Respiratory Diseases Vol. 59. No. 6, Dec ~3% 까지도보고되고있다 4-6. 일반적으로호르몬을생성하는폐암의대부분은소세포폐암인데반하여, 아밀라제를생성하는폐암은폐포세포형, 유두형등대부분중등도혹은고분화형선암으로, 췌장형이아닌타액선형아밀라제가상승하며 7-9, 평균발병연령이 50세전후로일반적폐암의호발연령보다젊은경향이있고, 남녀비는약 2:1로남성에서호발하는것으로알려져있다 이에대한기전으로성숙폐조직이가지고있는아밀라제생성능이폐조직의악성화로인하여항진되었을가능성을제시하고있는데, 이는우심방혈과좌심방혈의아밀라제활성을측정한결과좌심방혈의아밀라제활성도가높게측정되어정상폐조직이아밀라제생성능을보존하고있을가능성에대하여보고한것에근거하고있다 12. 또한쥐에서태아기에일과성으로아밀라제가상승하는것을보고한바가있는데 13, 이사실로부터폐조직이악성화되면서유약화되는현상에따라아밀라제생성능이출현또는재활성화되었을가능성등을제시하고있으나아직도정확하게규명되지않았다 12. 폐암이아밀라제를생성하는것을증명하기위해서흉수내의종양세포를배양하여배양액의아밀라제활성을측정할수도있으나 11, 최근항인간아밀라제항체를이용한조직효소항체법에의한조직학적진단이나수술중종양세포와가까운폐정맥에서직접혈액을채취하여아밀라제의농도를측정하는방법으로진단하기도한다 본증례에서는아밀라제동위효소분획검사를통하여고아밀라제혈증이타액선형임을확인하였고, 타액선스캔, 복부초음파, 복부전산화단층촬영등을통하여다른원인에의한타액선형고아밀라제혈증의가능성을배제하였다. 종양세포가아밀라제를생성하는것을증명하기위하여항인간아밀라제항체를이용한면역염색을시행하려하였으나현재국내에서염색이불가능하여저분화편평상피세포폐암과동반된고아밀라제혈증으로진단하였다. 기술한바와같이대부분의아밀라제를생성하는폐암은선암이었으며, 일부소세포폐암에서부종양증후군으로고아밀라제혈증을동반한경우가보고되고있으나, 국 내에서편평상피세포폐암과동반된예를보고한바없어이를문헌고찰과함께보고하는바이다. 요 원발성폐암에서아밀라제가증가하는기전은정확히밝혀져있지않으나대부분타액형이며, 조직학적으로거의대부분이선암이었으며, 일부소세포폐암에서부종양증후군으로고아밀라제혈증을동반한경우가보고되고있으나, 편평상피세포폐암과동반된예는국내에서보고된바가없어이를문헌고찰과함께보고하는바이다. 약 참고문헌 1. Nakao M, Kodama T, Sasaki M, Kuroda K. A case of ectopic amylase-producing lung cancer. Kyobu Geka 1996;49: Salt WB 2nd, Schenker S. Amylase: its clinical signi ficance: a review of literature. Medicine 1976;55: Otsuki M, Yuu H, Maeda M, Saeki S, Yamasaki T. Amylase in the lung. Cancer 1977;39: Flood JG, Schuerch C, Dorazio RC, Bowers GN Jr. Marked hyperamylasemia associated with carcinoma of the lung. Clin Chem 1978;24: Nakata Y, Kubota A, Mori Y, Matsumoto A. An auto psied case of an amylase-producing lung cancer. Gan No Rinsho 1988;34: Lenler-Petersen P, Grove A, Brock A, Jelnes R. alpha- Amylase in resectable lung cancer. Eur Respir J 1994; 7: Tsukawaki M, Izawa M, Yoshida M, Araki N, Ha shiba Y, Nakagawa H, et al. A case of amylase pro ducing lung cancer. Intern Med 1992;31: Flood JG, Schuerch C, Dorazio RC, Bowers GN Jr. Marked hyperamylasemia associated with carcinoma of the lung. Clin Chem 1978;24: Lehrner LM, Ward JC, Karn RC, Ehrlich CE, Merritt D. An evaluation of the usefulness of amylase isozyme differentiation in patients with hyperamylasemia. Am J Clin Pathol 1976;66: Martin PC, Sarma DP. Amylase-producing lung cancer. J Surg Oncol 1982;21: Ogawa M, Nakamura Y, Yamamoto T, Nishide T, Emi M, Matsuura N, et al. Production of enzymes and en zyme inhibitors in neoplastic tissues. Gan To Kagaku Ryoho 1986;13:

5 HS Chung et al. : Squamous cell lung cancer with hyperamlasemia 12. Kamio T, Sameshima K, Irie J, Shigematsu K, Kawai K, Tsuchiyama H, et al. Two cases of amylase-pro ducing lung cancer. Gan No Rinsho 1989;35: 山本克己, 武田信英. 高アミラーゼ血症を伴った肺癌の 1 症例. 呼吸 1988;7: Sakai M, Ishikawa S, Yamatoto T, Onizuka M, Saka kibara Y, Noguchi M. A direct measurement of serum amylase levels produced by lung cancer. Ann Thorac Surg 2005;79: Tomita N, Matsuura N, Horii A, Emi M, Mishide T, Ogawa M, et al. Expression of alpha-amylase in human lung cancers. Cancer Res 1988;48:

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<323120C1F5B7CA C0CCB8EDC7F62DBFECC0CEBCF D E687770> 대한내과학회지 : 제 82 권제 4 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.4.507 고아밀라제혈증을보인폐선암 1 예 가톨릭대학교의과대학내과학교실 이명현 고선영 박건우 김정훈 우인숙 한치화 허주연 A Case of Hyperamylasemia Associated with Lung Adenocarcinoma Myung-Hyun