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1 대한내과학회지 : 제 77 권부록 2 호 2009 증례 삼제복합항암요법에반응을보인간전이를동반한췌장의원발성편평상피세포암 1예 울산대학교의과대학서울아산병원내과 천윤희 최원정 노세희 김동회 이성숙 김태원 이재련 A case of primary squamous cell carcinoma of the pancreas responding to gemcitabine, capecitabine, and cisplatin chemotherapy Yoon Hee Chun, M.D., Won Jung Choi, M.D., Se Hui Noh, M.D., Dong Hoi Kim, M.D., Sung Sook Lee, M.D., Tae Won Kim, M.D., and Jae-Lyun Lee, M.D. Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Primary squamous cell carcinoma of the pancreas is a very rare form of pancreatic cancer; the incidence is approximately 0.5~ 3.5% of all pancreatic malignancies. Although squamous metaplasia of the ductal columnar cells can be observed during periods of inflammation, the histogenesis of primary squamous cell carcinoma of the pancreas is uncertain. The cancer has been reported to be poorly responsive to chemotherapy or radiation. We report an unusual case of primary squamous cell carcinoma of the pancreas with multiple liver metastases, which responded favorably to gemcitabine, capecitabine, and cisplatin combination chemotherapy. We also present a brief review of the literature. (Korean J Med 77:S425-S429, 2009) Key Words: Squamous cell carcinoma; Pancreatic cancer 서론췌장의원발성편평세포암은관상피에서발생하는매우드문형태의암으로보고에따라다르지만그빈도는약 0.5~3.5% 이다 1). 췌장의편평세포암도췌장암의흔한조직형인선암과비슷한특징을가지는것으로알려져있으나선암에비해좀더고령에서발생하는경향이있고진단당시전이병변이흔하며, 항암치료나방사선치료에잘반응하지않으며짧은생존기간을보인다 1,2). 매우낮은발생률로인 해췌장의진행성원발성편평상피세포암의치료에있어항암치료의효과에대한보고는극히제한적이다 1-5). 저자등은간전이가있는췌장의원발성편평세포암에서 gemcitabine, capecitabine, cisplatin 복합항암치료후부분반응을보인 1예를경험하였기에문헌고찰과함께보고한다. 증례환자 : 62세, 남자 Received: Accepted: Correspondence to Jae-Lyun Lee, M.D., Departments of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Pungnap-2dong, Songpa-gu, Seoul , Korea jaelyun@amc.seoul.kr - S 425 -

- The Korean Journal of Medicine: Vol. 77, Suppl.

결과간전이가동반된췌장암으로진단하여췌장병변과간전이병변에대해조직검사를시행후본원으로전원되었다. 과거력및가족력 : 과거력으로특이사항없었고, 가족력으로아버지와남동생에게위암의병력이있었다. 이학적소견 : 상복부압통이나반발통없었고, 복부에만져지는종괴없었다. 검사실소견 : 말초혈액검사상백혈구 8,600/mm 3, 혈색소는 13.

4 mg/dl이었고, amylase는 113 U/L (30-110 U/L), lipase는 33 U/L (22~51 U/L) 이었다. 전해질검사와소변검사는정상이었고, 종양표지자인 CA 19-9는 73.4 U/mL, CEA 는 6.8 ng/ml로상승되어있었다.

6 cm의여러중격으로나뉘어진낭종성병변이있었다. 양전자방출단층촬영 (PET) 에서췌장과간병변이외에는대사가증가된다른병변은없었다. 내시경소견 : 위내시경결과만성표재성위염이외특이소견없었다. 병리조직학적소견 : 췌장병변과간병변조직모두중등도의분화도를보이는편평세포암이었다.

2 - The Korean Journal of Medicine: Vol. 77, Suppl. 2, 주소 : 심와부통증현병력 : 내원 3개월전부터식후에발생하는쥐어짜는양상의심와부통증을주소로타원내원하여위내시경, 대장내시경시행한결과만성위염이외에특이소견발견되지않아위염에준해약물치료받았으나증상호전없어복부전산화단층촬영시행하였고, 결과간전이가동반된췌장암으로진단하여췌장병변과간전이병변에대해조직검사를시행후본원으로전원되었다. 과거력및가족력 : 과거력으로특이사항없었고, 가족력으로아버지와남동생에게위암의병력이있었다. 이학적소견 : 상복부압통이나반발통없었고, 복부에만져지는종괴없었다. 검사실소견 : 말초혈액검사상백혈구 8,600/mm 3, 혈색소는 13.3 g/dl, 혈소판 295,000/mm 3 이었고, 간기능검사상 AST 44 IU/L, ALT 33 IU/L, ALP 102 IU/L, total bilirubin 1.3 mg/dl, direct bilirubin 0.4 mg/dl이었고, amylase는 113 U/L ( U/L), lipase는 33 U/L (22~51 U/L) 이었다. 전해질검사와소변검사는정상이었고, 종양표지자인 CA 19-9는 73.4 U/mL, CEA 는 6.8 ng/ml로상승되어있었다. 방사선검사소견 : 흉부 X-선검사는정상이었고, 복부전산화단층촬영에서췌장두부에 2.8 cm 정도의종괴와다발성간전이소견, 복강내소량의복수와함께 1 cm 정도의 nodule 소견이발견되었다 ( 그림 1). 자기공명담췌관조영술 (MRCP) 에서는췌장두부에 3.5 cm의종괴가주췌관을에워싸고있으며그아래로 1.6 cm의여러중격으로나뉘어진낭종성병변이있었다. 양전자방출단층촬영 (PET) 에서췌장과간병변이외에는대사가증가된다른병변은없었다. 내시경소견 : 위내시경결과만성표재성위염이외특이소견없었다. 병리조직학적소견 : 췌장병변과간병변조직모두중등도의분화도를보이는편평세포암이었다. 췌장의편평세포암의조직학적특징인상피세포내불규칙한모양의 cord 와 nest 양상의편평세포군집과케라틴펄, 세포사이다리 (intercellular bridge) 소견도관찰되었다 ( 그림 2). 임상경과 : 환자의경우췌장, 간모두에서편평상피세포암을보였고, 흉부전산화단층촬영및전신양전자방출단층 A B Figure 1. (A) Initial abdominal CT showed multiple liver metastases and a 2.8-cm mass in the pancreas head. (B) Abdominal CT after chemotherapy showed a decrease in the size of the multiple liver metastases and pancreatic head mass after gemcitabine, capecitabine, and cisplatin combination chemotherapy. - S 426 -

- Yoon Hee Chun, et al. Primary squamous cell carcinoma of the pancreas responding to chemotherapy - A B Figure 2. (A) Microscopic view of pancreatic mass (H&E, 400).

The arrow shows an intercellular bridge, which is characteristic of squamous cell carcinoma.

3 - Yoon Hee Chun, et al. Primary squamous cell carcinoma of the pancreas responding to chemotherapy - A B Figure 2. (A) Microscopic view of pancreatic mass (H&E, 400). Irregular nest of malignant cells showed features compatible with squamous cell carcinoma. The arrow shows the keratin pearl. (B) Microscopic view of liver metastasis (H&E, 400). The arrow shows an intercellular bridge, which is characteristic of squamous cell carcinoma. 촬영 (PET) 에서다른원발성병변이없어췌장의원발성편평상피세포암으로진단하고 gemcitabine (1,000 mg/m 2 IV, D1,8), capecitabine (650 mg/m 2 PO bid, D1-14), cisplatin (60 mg/m 2 IV, D1) 을 3주간격으로투여하는삼제복합항암치료를시작하였다. 2회시행후복부전산화단층촬영에서췌장의두부의종괴 (2.8 cm 2.0 cm) 및다발성간전이 ( 가장큰병변의경우 3.7 cm 3.0 cm) 모두그크기가감소하여부분반응을보였으며, 4회시행후추적복부전산화단층촬영에서부분반응을재확인할수있었다. 현재환자는중등도이상의부작용없이총 6회의항암치료종료후외래에서 5개월째경과관찰중이다. 고찰췌장에는정상적으로편평상피세포가존재하지않으나췌장염과같은염증이있는동안에는관상피의편평화생이관찰될수있다. 편평화생은췌장의 9~64% 에서발견될수있는데이렇게편평화생이상대적으로흔함에도불구하고췌장의원발성편평세포암은매우드물다 2). 췌장의원발성편평세포암의발생에대해서는정확한기전이밝혀져있지않으며다음과같은가설이제기되었다. 1) 편평세포와선세포로모두분화할수있는미분화세포로부터암이발생할수있다 2) 이미존재하는선암이편평세포로이형화한다 3) 췌관상피의편평화생으로부터암이발생한다 4) 이소성의편평세포가존재하고여기에서암이 발생한다는가설등을들수있다 1,6). 이환자의경우에는이전췌장염의과거력이나췌장염을일으킬만한위험인자를가지고있지않고, 조직학적소견에서도암근처관상피의편평화생의증거나편평상피세포안에선종성변화 (adenomatous change) 가발견되지않았기때문에미분화세포나이소성의편평세포에서암이발생했을것이라고추론할수있다. 췌장의원발성편평세포암은예후가매우불량하여근치적절제수술을시행한환자는평균생존기간이 7개월정도이고근치적절제수술을시행하지못한환자는평균생존기간이 3개월이다 7,8). 절제하지못하는경우에는항암치료를시행하는경우가있는데이역시예후가불량하다. 대부분의경우 cisplatin과 5-fluorouracil 로 1,5,9) 치료하였고, 한예에서 cisplatin과 etoposide로 3), 한예에서 cisplatin과 vinblastine으로 5), 한예에서 gemcitabine과 5-fluorouracil 로 4) 치료하였다. Itani 등이보고한바에따르면 cisplatin과 5-fluorouracil 로치료하였던 2명중 1명은 1개월후사망하였고, 다른 1명은 1.5개월후사망하였다 5). cisplatin과 vinblastine으로치료한 1명은 7개월후사망하였다 5). 본증례에서는간전이가있는췌장의원발성편평세포암에서 gemcitabine, capecitabine, cisplatin 복합항암치료 2번시행후복부전산화단층촬영에서간전이와췌장암의크기가감소하는부분반응을보였고, 4번시행후간전이병변이더감소하는반응을보였다. 진행성췌장선암의주된항암 - S 427 -

4 - 대한내과학회지 : 제 77 권부록 2 호 화학요법은 gemcitabine이다. 대규모 3상연구나메타분석에의하면 gemcitabine에 capecitabine이나 platinum 제재를추가하면 gemcitabine 단독에비해반응률및생존율을증가시킬수있고 10-15) 이러한효능은특히활동능이우수한환자에서보다더효과적이라고밝혀져있다 12,14,15). 또한경구용 capecitabine 은대장암과위암에서정맥주사용 5-FU를대체할수있으며안정성측면에서더욱우수한것으로알려져있다 16,17). 이러한 capecitabine 과 cisplatin의복합항암화학요법은편평상피세포암 ( 두경부, 자궁경부암 ) 에효과적인것으로알려져있다 18,19). 저자들은이러한각각의제재의췌장암및편평상피세포암의효과및본원에서시행된 gemcitabine, capecitabine, cisplatin 복합항암화학요법의 2상연구를근거로본증례환자에게투여하였으며확인된부분반응을획득하였다 20). 이러한삼제복합항암화학요법의효과에대한결론을내기위해서는좀더많은환자를대상으로하는연구가필요할것으로사료된다. 요 저자들은간전이가있는췌장의원발성편평세포암에서 gemcitabine, capecitabine, cisplatin 복합항암화학요법시행후간전이와췌장암크기가감소하는부분반응을보인증례를경험하였기에보고한다. 약 중심단어 : 편평세포암 ; 췌장 ; 췌장암 REFERENCES 1) Beyer KL, Marshall JB, Metzler MH, Poulter JS, Seger RM, Diaz- Arias AA. Squamous cell carcinoma of the pancreas: report of an unusual case and review of the literature. Dig Dis Sci 37: , ) Anagnostopoulos GK, Aithal GP, Ragunath K, Kaye P, Rowlands BJ. Squamous cell carcinoma of the pancreas: report of a case and review of the literature. JOP 7:47-50, ) Bringel RW, Souza CP, Araujo SE, Lopasso FP, Gama-Rodrigues J, Pinotti HW, Laudanna AA. Squamous cell carcinoma of the pancreas with gastric metastasis: case report. Rev Hosp Clin Fac Med Sao Paulo 51: , ) Colarian J, Fowler D, Schor J, Poolos S. Squamous cell carcinoma of the pancreas with cystic degeneration. South Med J 93: , ) Itani KM, Karni A, Green L. Squamous cell carcinoma of the pancreas. J Gastrointest Surg 3: , ) Nakashima H, Hayakawa T, Hoshino M, Kamiya Y, Ohara H, Yamada T, Mizuno K, Inagaki T, Nakazawa T, Yamada H. Squamous cell carcinoma of the pancreas with massive invasion of the retroperitoneum. Intern Med 34:61-64, ) Mulkeen AL, Yoo PS, Cha C. Less common neoplasms of the pancreas. World J Gastroenterol 12: , ) Brown HA, Dotto J, Robert M, Salem RR. Squamous cell carcinoma of the pancreas. J Clin Gastroenterol 39: , ) Fajardo LL, Yoshino MT, Chernin MM. Computed tomography findings in squamous cell carcinoma of the pancreas. J Comput Tomogr 12: , ) Scheithauer W, Schull B, Ulrich-Pur H, Schmid K, Raderer M, Haider K, Kwasny W, Depisch D, Schneeweiss B, Lang F, Kornek GV. Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial. Ann Oncol 14:97-104, ) Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Metaanalysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 8:82, ) Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25: , ) Poplin E, Levy DE, Berlin J, Rothenberg ML, O'Dwyer PJ, Cella D, Mitchell E, Alberts S, Benson A. Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion [FDR]) versus gemcitabine + oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201) [Abstract] [Internet]. J Clin Oncol 24:LBA4004, 2006 Cited 2006 Jun. Available from: 14) Louvet C, Hincke A, Labianca R, Heinemann V. Increased survival using platinum analog combined with gemcitabine as compared to gemcitabine single agent in advanced pancreatic cancer (APC): pooled analysis of two randomised trials, the GERCOR/ GISCAD Intergroup Study and a German Multicenter Study [Abstract] [Internet]. J Clin Oncol 24:4003, 2006 Cited 2006 Jun. Available from: 15) Cunningham D, Chau I, Stocken DD. Phase III randomized comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer [Abstract] [Internet]. Eur J Cancer 3:3, 2005 Cited Available from: S 428 -

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy