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1 대한소화기내시경학회지 2007;35: 위누공및위장관출혈을동반한위의위장관기질종양 1 예 메리놀병원내과, * 해부병리과 이진호ㆍ문정윤ㆍ김현정ㆍ허정은ㆍ박종률ㆍ장혜정ㆍ윤지훈ㆍ박승근ㆍ박희욱ㆍ김혜숙 * A Case of a Gastric Gastrointestinal Stromal Tumor with a Fistula and Gastrointestinal Bleeding Jin Ho Lee, M.D., Jung Youn Moon, M.D., Hyun Jung Kim, M.D., Jung Eun Huh, M.D., Jong Ryul Park, M.D., Hye Jung Jang, M.D., Ji Hoon Yoon, M.D., Seung Keun Park, M.D., Hee Ug Park, M.D. and Hye Sook Kim, M.D.* Departments of Internal Medicine and *Pathology, Maryknoll Medical Center, Busan, Korea 위장관기질종양은그기원이나분화및예후에있어지속적논란이있어왔던종양이며, 최근의여러연구들은 c-kit 원발암유전자돌연변이의발견으로이들의기원이 Cajal 간질세포로추정케하였다. 흔한증상으로는복통, 출혈, 종물의촉지등이있으나, 종괴내농양을동반한채위강과교통하는누공을형성한경우는소수에서만보고되었다. 전신쇠약감및발열을주소로내원한 84 세남자에서상부위장관내시경, 전산화단층촬영, 조직및면역조직화학검사를통해중심부누공을통해위강과교통하는광범위괴사를동반한거대위장관기질종양을진단하였기에국내외문헌고찰과함께보고하는바이다. 색인단어 : 위장관기질종양, 위누공 서 위장관기질종양 (gastroinestinal stromal tumor, GIST) 은비상피성종양으로간엽조직에서기원하며전체위장관종양의 1 3% 를차지하는비교적드문종양으로 1 면역조직소견에따라평활근분화성신경세포분화성양극성분화성미분화성으로분류되며, 2 최근 KIT단백발현및 c-kit 유전자돌연변이발견으로이들의기원이위장관평활근의 Cajal cell인것으로추정하고있으며 KIT (CD117) 단백에대한염색양성이 GIST의진단에서강조되고있다. 3-7 GIST 는위, 소장, 대장, 식도의순으로발생빈도가높으며, 7-9 임상양상은종괴의크기및해부학적위치에 론 접수 :2007 년 8 월 29 일, 승인 :2007 년 10 월 25 일연락처 : 박희욱, 부산시중구대청동 4 가 12 우편번호 : , 메리놀병원내과 Tel: , Fax: drhwpark@yahoo.co.kr 따라서차이를보이며, 동통, 복부종물, 위장관출혈이주증상이며, 장관과의누공을형성한경우는흔치않으며, 소수에서보고된바있다 이에저자들은위에출혈및종괴내농양을동반하여위강내로의누공을형성한악성위장관기질종양1예를경험하였기에문헌고찰과함께보고하는바이다 증 84세환자가전신쇠약감및 3개월간지속되는발열및흑색변을주소로응급실로내원하였다. 가족력및과거력상 20여년전의양성전립선비대증으로경요도전립선절제술을받은것외에특이사항은없었다. 내원시시행한신체검사에서활력징후는체온 37.8 o C, 혈압 90/60 mmhg, 맥박수분당 104회, 호흡수분당 20회였으며, 의식은명료하였으며, 극심한결막창백에동반된급만성병색의소견을보였으나, 이외두경부흉부진찰에서특이소견은없었다. 복부진찰시정상장음에압통및종물등의소견은없었으며항문수지검사에 례 337

338 대한소화기내시경학회지 2007;35:337-341 Figure 2. CT scan of the abdomen.

Figure 1. Endoscopic findings. (A) It shows an orifice on the greater curvature side of the high body with small amount of blood clot and mucosal thickening.

(C) It shows the internal surface of the abscess pocket coexisting with multiple fungating masses and pus. mg/dl, creatinin 0.

내원직후시행한상부위장관내시경검사에서위상부의체부대만부위에부종과점막주름의비후를동반한천공이의심되는병변과함께미량의혈괴가관찰되었으며 (Fig.

2 338 대한소화기내시경학회지 2007;35: Figure 2. CT scan of the abdomen. It shows a large lobulating mass (about cm in size) with extensive internal necrotic change and air density in the greater curvature side of the high body. Figure 1. Endoscopic findings. (A) It shows an orifice on the greater curvature side of the high body with small amount of blood clot and mucosal thickening. (B) Endoscope is being passed through the orifice communicating with the abscess pocket of mass. (C) It shows the internal surface of the abscess pocket coexisting with multiple fungating masses and pus. mg/dl, creatinin 0.8 mg/dl, AST 16 IU/L, ALT 20 IU/L, protein 4.8 g/dl, albumin 3.2 g/dl였으며, 혈액응고검사는 PT 13.5초, aptt 36.9초였다. 내원직후시행한상부위장관내시경검사에서위상부의체부대만부위에부종과점막주름의비후를동반한천공이의심되는병변과함께미량의혈괴가관찰되었으며 (Fig. 1A), 말초혈액검사에서심한빈혈소견을보여생검을시행하지않고, 즉시복부전산화단층촬영을시행하여, 위상부의체부대만부에위치하며내부에광범위괴사및공기음영을동반한 cm 크기의거대분엽성종괴를발견하였다 (Fig. 2). 이후위내시경검사를다시시행하였다. 위강과교통하는누공을통해내시경을진입시켜종괴내괴사부위및강내로자라는종괴를관찰하였으며 (Fig. 1B, 1C), 내시경검사로얻은조직검사는급만성의염증소견외특이소견이없었으나, 종괴의크기나성상으로보아악성의가능성을배제할수없어, 초음파유도경피적생검을시행하였으며이를통해얻은조직생검검체를통해점액성의간질에방추세포가엇갈린상태로증식해있는소견 (Fig. 3A) 과함께 CD117 면역조직화학검사상양성반응을확인하였으나특이한유사분열은관찰되지않았다 (Fig. 3B). 이후환자는치료를거부한채퇴원하였다. 서특이소견이없는상태였다. 내원당시시행한말초혈액검사는백혈구 27,300/mm 3, 혈색소 3.9 g/dl, 혈소판 86,000/mm 3 였고, 혈청생화학검사는 BUN 15.7 고 GIST 의기원에관해서는많은논란이있어왔으나 찰

이진호외 : A Case of a Gastric Gastrointestinal Stromal Tumor with a Fistula 339 Figure 3. Microscopic findings. (A) It shows interlacing bundle of spindle cells in the myxoid stroma (H&E staining, 10).

최근에는 Cajal 간질세포가유력한기원세포로인정되고있으며, 이는장관의 myenteric plexus내에존재하며장관운동의조절자역할을하는세포로서장연동운동과평활근세포수축을조절하고신경전달물질을매개한다. 이는장관내에서 tyrosin kinase 수용체 (CD117, c-kit) 및 CD34, vimentin 에유일하게양성인세포이다.

3 이진호외 : A Case of a Gastric Gastrointestinal Stromal Tumor with a Fistula 339 Figure 3. Microscopic findings. (A) It shows interlacing bundle of spindle cells in the myxoid stroma (H&E staining, 10). (B) It shows that most tumor cells are positive for CD117 (immunohistochemical staining, 200). 최근에는 Cajal 간질세포가유력한기원세포로인정되고있으며, 이는장관의 myenteric plexus내에존재하며장관운동의조절자역할을하는세포로서장연동운동과평활근세포수축을조절하고신경전달물질을매개한다. 이는장관내에서 tyrosin kinase 수용체 (CD117, c-kit) 및 CD34, vimentin 에유일하게양성인세포이다. 최근 GIST의 90% 이상에서 CD117 양성소견을보인다는보고들이있어왔고이와연관하여 Cajal 간질세포가그기원세포로주목받고있다. 3-7 GIST는 10만명당 10 20명의발생빈도를보이며, 이중 20 30% 에서악성으로 9 전체위장관악성종양의 1% 미만을차지하며, 13 주로 55 65세사이에호발하며, 성별빈도차는없으며, 위 60 79%, 소장 20 30%, 대장과직장 5%, 식도 5% 미만의발생률을보인다. 9 위에서발생한 GIST의임상증상은종양의크기와관련이있어서크기가작은종양은대부분무증상으로우연히발견되며, 복부종물로촉지되는정도로클경우에는악성일가능성이높으며, 13 미만성복통, 위장관출혈, 종물의촉지순으로흔하나, 11 농양을형성한채위장관내강으로누관을동반한경우는비교적드문상태로, 보고된바가극히드물다. Seidel 등 12 이위벽에농양을형성하고위내로누관을동반한위의평활근육종을보고하였고, Akwari 등 10 은소장의평활근육종환자중 4% 에서고열을관찰하였고모든예에서종양내부의공동안에농양의형성과누관에의한장관과의연결을확인하였으며, 국내에서는김등 11 이다발성농양과위내로누공을형성하고복강으로파열되어복강기종과혈복강을동반한복막염을일으킨위의위장관간질종양 1예를보고한바있다. 종양의중심괴사와농양을형성하는기전으로는큰종양일수록혈관 분포를벗어나서자라기때문에혈액공급의장애에의해중심괴사가초래되며, 또한인접점막의궤양으로인해장관내로천공이일어나며, 형성된누관에의한장관내이차적세균감염이동반되어농양을형성하는것으로알려져있다. 14 본증례는농양으로인한지속적발열및만성위장관출혈으로인한쇠약감등으로인해내원한뒤위의 GIST로확진된경우라하겠다. GIST의진단으로는위장관내시경검사및조영술, 복부초음파및전산화단층촬영등이이용될수있으며, 내시경검사에서중심부에궤양을동반한관강내로돌출한종양이특징적인소견이나, 내시경하생검으로얻은점막조직으로는진단율이 50% 를넘지않아내시경생검만으로종양의악성도를측정하는것은부적합하며, 확진을위해수술이필요하다. 15 GIST는초음파검사에서대부분균질성저에코상을보이나, 크기가큰경우에는내부에괴사나낭종성변화, 출혈이동반되어비균질성상을나타내기도하며, 최근내시경초음파의발달은이러한종양의위치나균질성파악장막및고유근층의침범림프절종대등을파악하는데더높은정확도를나타내게하였다. 16 전산화단층촬영에서는중등도조영증강을보이는균질성연조직종괴로나타나나, 궤양, 괴사, 공동화등이동반될때는비균질성양상을보이기도하며, 종괴의침윤전이범위등을확인할때유용한검사이다. 17 본증례에서는전산화단층촬영상비교적거대하며경계가불명확면서내부에괴사성병변및공기음영을동반한소견을보였으며비균질성조영증강을보였다. GIST는 20 30% 정도에서악성의양태를보여주며, 초기진단시악성의가능성을가늠할수있는분명한조직학적기준이아직은불명확한상태이나현재, 종양

4 340 대한소화기내시경학회지 2007;35: 의크기와유사분열의활성도가가장유용한고려사항으로, 각각 5 cm 이상, 50 HPF당 5 이상의유사분열이보이는경우악성의가능성이좀더높으며, 크기 5 cm 미만이면서 50 HPF당 1 5의유사분열을보이는경우에도전이율이 13% 에이르는것으로보고되어있다. 종괴내괴사소견역시예후불량인자이며 c-kit gene의돌연변이는재발의위험인자로보고되고있다. 종양의해부학적위치에따른예후에관하여는 Emory 등에의하면식도의 GIST가가장높은그리고, 소장의것이가장낮은생존율을보이며, 그러나일부연구에서는병소에위치는생존율과무관하다는보고들도있는상태여서논란의여지가남아있는상태이다. 18 GIST의치료는외과적인근치적광범위절제술이원칙이며수술시의동결절편조직검사를통해선암및악성림프종등과의감별및절제연침습여부를확인해야만한다. 술후가장흔한재발부위는위이며, 간이가장흔한원격전이부위다. 15,19 외에도복막, 폐, 뼈와임파선에도전이가가능하다항암요법은논란이있으나최근 kit 수용체를통해 tyrosine kinase를선택적으로억제하는 STI 571 (imatinib mesylate) 이치료에상당한효과를나타낸다는보고가있다. 1,6,7,15 ABSTRACT There has been much debate on the origin, differentiation and prognosis of gastrointestinal stromal tumors (GIST). Based on recent studies, we consider Cajal interstitial cell as the origin of a GIST. The common symptoms of a GIST are abdominal pain, hemorrhage, and the presence of a mass. However, there are few reported cases of a GIST with abscess pockets that communicate with the lumen of the stomach via a fistula. We report a case of a GIST of the stomach presenting with an abscess and a fistula communicating with the lumen of the stomach. An 84-year-old man presented with continuous fever and general weakness. We were able to diagnose the disease by an endoscopic examination, CT scan, biopsy and by cellular immunohistochemical staining. (Korean J Gastrointest Endosc 2007;35: ) Key Words: GIST, Fistula 참고문헌 1. Choi EY, Kil H, Joen WJ, et al. A case of rectal gastrointestinal stromal tumor (GIST) presenting with hematochezia. The Korean J Gastrointest Endosc 2006;33: Mazur MT, Clark HB. Gastric stromal tumors. reappraisal of histogenesis. Am J Surg Pathol 1983;7: Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH, et al. Intestinal cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 1999;23: Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998;152: Seidal T, Edvardsson H. Expression of c-kit (CD117) and Ki67 provides information about the possible cell of origin and clinical course of gastrointestinal stromal tumours. Histopathology 1999;34: De Silva MV, Reid R. Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expresstion, differentiatial diagnosis and targeted cancer therapy with imatinib. Pathology Oncology Research 2003;9: Kim MK, Lee JK, Park ET, et al. Gastrointestinal stromal tumors: clinical, pathologic features and effectiveness of new diagnostic criteria. Korean J Gastroenterol 2004;43: Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol 1999;23: Miettinen M, Lasota J. Gastrointestinal stromal tumorsdefinition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438: Akwari OE, Dozois RR, Weiland LH, Beahrs OH. Leiomyosarcoma of the small and large bowel. Cancer 1978;42: Kim HJ, Lee HS, Oh HJ, et al. A case of gastrointestinal stromal tumor of the stomach with a gastric fistula. Korean J Gastrointest Endosc 2003;26: Seidel RH Jr, Burdick JS. Gastric leiomyosarcoma presenting as a gastric wall abscess. Am J Gastroenterol 1998;93: Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Omcol 2000;7: Suster S. Gastrointestinal stromal tumors. Semin Diag Pathol 1996;13: Jhu IK, Joo YE, Park GS, et al. A case of duodenal gastrointestinal stromal tumor presenting with gastrointestinal bleeding. Korean J Gastrointest Endosc 2005;31: Palazzo L, Landi B, Cellier C, Cuillerier E, Roseau G, Barbier JP. Endoscopic features predictive of benign and malignant gastrointestinal stromal cell tumors. Gut 2000;46: Burkill GJ, Badran M, Al-Muderis O, et al. Malignant gastro-

5 이진호외 : A Case of a Gastric Gastrointestinal Stromal Tumor with a Fistula 341 intestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology 2003;226: Nowain A, Bhakta H, Pais S, Kanel G, Verma S. Gastrointestinal stromal tumors: clinical profile, pathogenesis, treatment strategies and prognosis. J Gastroenterol Hepatol 2005;20: Conlon KC, Casper ES, Bennan MF. Primary gastrointestinal sarcomas: analysis of prognostic variables. Ann Surg Oncol 1995;2:26-31.

김범수

김범수 Gastrointestinal stromal tumors (GISTs) are rare tumers of the alimentary tract, and these tumors arise from primitive mesenchymal cells. Duodenal GISTs comprise 4-5% of all GISTs. In this article, we