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1 Review Article pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 췌장낭성병변의평가에서영상검사의역할 박범진 고려대학교안암병원영상의학과 The Role of Imaging in Evaluation: Imaging of Cystic Lesions of the Pancreas Beom Jin Park Department of Radiology, Anam Hospital, College of Medicine, Korea University, Seoul, Korea Pancreatic cystic neoplasms are more increasingly recognized due to the rapid development and widespread use of imaging modalities. It is reported that up to 20% of abdominal cross-sectional images identify incidental asymptomatic pancreatic cysts. Although their accurate differentiation remain difficult because of their overlapping morphologies, proper characterization of pancreatic cystic neoplasm considering imaging finding is important not only to recognize premalignant lesions that will require surgical intervention, but also to allow noninvasive treatment of many cystic neoplasm of the pancreas. Though reliable biomarkers are lacking, imaging plays an important role in directing clinical management and decision making in cases of pancreatic cystic neoplasm. In this topic, a multimodality imaging approach including other cross-sectional imaging studies will be addressed with systemic recognition for morphological subcategory based on imaging morphology of pancreatic cystic neoplasms to avoid unnecessary exposure to invasive treatment. Key words: pancreatic cystic neoplasm, MDCT, MRCP, ultrasonography 서론 1) 단층촬영영상기술의진일보된발전과더불어작은췌장낭성종양의발견율이향상되었다. 그러나임상양상과영상의학적, 그리고병리학적소견이잘알려져있음에도불구하고, 전형적인영상소견을보이는일부를제외하고는술전진단시어려움을겪는경우가많다. 그러므로 MDCT(with multi-planar reformation), MRCP, ERCP 그리고 endoscopic ultrasonography 등과같은여러유용한영상기법을통해추가적인영상정보를얻고, 각각의진단적감별점등에대한숙지를통해정확한진단에접근 Correspongding author. 박범진고려대학교안암병원영상의학과서울특별시성북구안암동5가 Tel: rupture226@daum.net 하도록노력해야한다. 3 cm 미만의작은췌장낭성병변의경우악성의발생빈도는낮으며, 증상이없는환자에서우연히발견된 malignant cystic lesion 은약 3.5% 정도로낮다. 상대적으로낮은유병율이지만다양한췌장의낭성병변들이발견되었을때, 그특징적인영상의학적소견을바탕으로하여추적검사혹은적절한치료의시점에대한기준을인지하고있어야한다. 본론 췌장의낭성종양에대한추적검사와치료기준이세분화되고있으며, 계속적으로가이드라인이제시되고있다. 임상소견을통해감별가능한 pancreatic pseudocyst 를제외하고일반적으로제시되는 pancreatic cystic neoplasm 의추적검사와치료기준은다음과같다. 1) 2 cm( 혹은 3 cm) 이하의 pancreatic cystic lesion이 8

2 췌장낭성병변의평가에서영상검사의역할 9 mural nodule 이나 septation 과같은유의한영상의학적소견을보이지않는경우추적검사로충분하다. 2) 2 cm( 혹은 3 cm) 이상이나영상의학적검사에서 serous cystadenoma 의가능성이높고, 무증상일경우역시추적검사로충분하다. 3) 2 cm( 혹은 3 cm) 이상이며, 진단이불명확한젊은환자의경우는수술적절제를고려하여야한다. 4) 2 cm( 혹은 3 cm) 이상이며, 증상이있거나고령인경우미세침흡인 (fine needle aspiration) 이치료방침의결정에도움이되며, mucin, mucinous epithelium, high CEA level, 악성세포가나온경우수술을고려한다. 상기치료방침을살펴볼때, 낭성병변의크기와함께형태적특성 (internal septation, ductal communication 유무, external morphology) 등영상의학적소견이중요한역할을함을알수있으며, 본론에서는형태학적인분류를중심으로영상의학적, 병리적소견에따른각각의 pancreatic cystic neoplasm 에대한이해를돕고자한다. 1. Classification of Pancreatic Cystic Lesions 췌장낭성병변의감별에는 pseudocyst 와 serous cys- Adapted from Dushyant V. Sahani et al. Radiographics 2005;25 Classification of Cystic Pancreatic Lesions tadenoma 와같은양성병변과 intraductal papillary mucinous neoplasm, mucinous cystic neoplasm (MCN), solid pseudopapillary tumor (SPT) 와같은 potentially malignant lesion, 그리고다른드문낭성질환들이해당된다. 이하의분류표에서 pseudocyst 와 common pancreatic cystic neoplasm 에해당되는질환이전체췌장낭성병변의 90% 를차지한다. 2. Morphologic Classification of Cystic Pancreatic Lesions A. Unilocular Cyst Internal septa, solid component 혹은 central-cyst wall calcification 이없는병변을말한다. Pancreatic pseudocyst 가가장흔하다. 그이외 IPMN, unilocular 한 serous cystadenoma, 그리고 lymphoepithelial cyst가있다. 그중췌관과의연결은 IPMN 과 pseudocyst 에서보일수있으며, 췌장염의병력이나췌관과의연결이없는경우영상의학적소견만으론감별이어렵다. Unilocular cyst가췌장두부에보일 unilocular 한 serous cystadenoma 를고려해야하며, 다수의 unilocular cyst일경우는 pseudocyst나 von Hippel-Lindau disease가감별의대상이된다. B. Microcystic lesion Pseudocyst Common cystic pancreatic neoplasms Serous cystadenoma Mucinous cystic neoplasm IPMN Rare cystic pancreatic neoplasms Solid pseudopapillary tumor Acinar cell cystadenocarcinoma Lymphangioma Hemangioma Paraganglioma Solid pancreatic lesions with cystic degeneration Pancreatic adenocarcinoma Cystic islet cell tumor(insulinoma, glucagonoma, gastrinoma) Metastasis Cystic teratoma Sarcoma True epithelial cysts* *Associated with von Hippel-Lindau disease, autosomal-dominant polycystic kidney disease, and cystic fibrosis. Adapted from Dushyant V. Sahani et al. Radiographics 2005;25

3 박범진 10 많은 chamber 의 cystic compartment 로이루어져있으며각각은 2 cm미만으로 serous cystaden-oma 만해당된다. C. Macrocystic lesion 적은수의 compartment 로이루어져있으며각각의 chamber 가 2 cm 이상일경우로 Mucinous cystic neoplasm 과 IPMN 이이에해당된다. 드물게는 nonfunctioning neuroendocrine tumor나 lymphangioma 와같은 congenital malformation이있다. D. Cyst with a solid component Unilocular 나 multilocular 모두이에해당되며, true cystic tumor(eg, MCN, IPMN) 은물론 cystic component나 degeneration 을보이는고형췌장종양이고, islet cell tumor, SPT, adenocarcinoma 나 metastasis 가에에해당된다. Malignant 나 high malignant potential 일가능성이높으므로외과적절제가고려된다. MR imaging 의 T2WI 나조영증강을통해 mural nodule 을찾는것이중요하며 high resolution endoscopic US 역시민감한진단방법중하나이다. 3. Imaging of Cystic Lesions of the Pancreas (1) Pancreatic Pseudocyst Pseudocyst 이가장흔한 pancreatic cystic neoplasm, 나머지는전체낭성병변의 10-15% 만을차지한다. 만성췌장염환자의 50% 에서췌관의손상등에의해액체의저류가생기는데 4-6주후까지남아있는액체가 organization을하여 fibrotic capsule이생기면서 pseudocyst 가형성된다. 대부분의 pancreatic cystic neoplasm 과달리 epithelial line이없다. 4-5 cm이상일경우에서합병증이동반될수있으며, 주변장기의전위에의한폐색, 복통, 황달을일으킬수있으며, spontaneous rupture 에의한 pancreatic peritonitis, 이차감염에의한농양, 주변혈관의 erosion 에의한대량출혈을유발할수있으므로, 추적검사시유의해야한다. MDCT 상전형적인소견은 internal septa나 intramural nodule 이없이 smooth thin wall이나 uniform thick wall의 unilocular cystic lesion 으로보인다. 내부음영은보통 low fluid density 를보이며, 내부출혈이있는경우상승한다 (45-50HU). 이차감염이생긴경우내부 에 gas가보일수있다. MRI는내부저류액을특성화하는데 CT보다우월하며출혈이나 proteinaceous fluid일때 T1 high signal을보이고, T2WI 상함유된 sold debri 가잘보인다. 그리고췌장의낭성병변에서 internal dependant debri가 pancreatic pseudocyst 의 highly specific MR finding이라는보고가있다. ERCP상췌관과연결성이있을수있으며, pancreatic pseudocyst 가영상소견에서의심되나췌장염, 외상, 그리고수술의병력이없는경우추적검사나미세침흡인이필요하다. Pancreatic pseudocyst 는영상소견상 unilocular macrocystic serous cystadenoma, MCN, 그리고 SPT와유사하게보일수있다. (2) Pancreatic cystic Neoplasm(Non pseudocyst) Pancreatic pseudocyst가아닌다른낭성병변에서급, 만성췌장염을동반하는경우는드물다. 영상소견상이런낭성병변들의형태가서로비슷하여정확한감별은힘들지만, 형태분류에대한이해가감별을좁히고, 나아가치료방침을세우는데도움이된다 A. Serous cystadenoma Serous cystadenoma 는전체췌장종양중 1-2% 만차지하지만, malignant potential 이있는다른낭성종양과는달리양성이므로감별이중요하다. 남녀비는 1:2로여성에서호발하며, mean age는 57세이며, pancreatic head 에잘생긴다. 주로미세낭종형 (microcystic) 과소수낭종형 (oligocystic, 혹은대낭종형 macrocystic) 으로나뉘나 Polycystic(70%), Microcystic honeycomb(30%), Oligocystic pattern(10%) 의 3가지형태와빈도로나누는분석도있다. i. Polycystic pattern Adapted from JY Choi et al.ajr 2009;193

4 췌장낭성병변의평가에서영상검사의역할 11 2 cm 이하의 multiple cyst( 보통 6개이상 ) 이모여있는형태이며, external lobulation 과 central scar가중요한특징이다. 석회화를동반할수있는 scar는 30% 정도에서보이며, 그진단적가치는아주높다. IPMN의 branch duct type이나 MCN이유사하게보일수있다. 췌관과의연결, 췌관확장, phleomorphic cystic shape 은 IPMN에합당한소견이며, smooth surface without lobulation, relative thick enhancing wall, peripheral calcification은 MCN에합당한소견이다. ii. Honeycomb pattern 각각이구분되지않는수밀리미터의수많은 cyst로구성되며, MDCT 영상에서는경계가좋은고형종괴로보인다. MR영상에서 tiny cyst들에의한 T2 high signal intensity 가감별진단에많은도움이된다. 내부괴사에의한 ring enhancement 를보이는 cystic islet cell tumor 나내부에 hemorrhage 를보이는 thick wall의 SPT가감별의대상이된다. iii. Oligocystic pattern 단방형이거나몇개의큰 (>2 cm) cyst로이루어져있으며, 얇은벽과 lobulated contour 가특징이다. MCN, IPMN, pseudocyst 가감별의대상이된다. 특히 MCN과의감별이중요한데, 췌장두부에 septation 을동반한 lobulating cystic lesion은 oligocystic serous cystadenoma 의가능성이높은반면, 체부와미부의부드러운변연 smooth contour의낭종은 MCN의가능성이높다. IPMN 은 phleomorphic or clubbed, fingerlike cyst의형태를보인다. B. Mucinous cystic neoplasm Mucinous cystadenoma는전체 pancreatic cystic neoplasm 의 10% 를차지하며, 대여성 (M:F=1:9) 의체부와미부에호발한다. 병리적으로 mucin-producing columnar epithelium 을가지며, surrounding ovarian-type 의 stroma가특징적이다. 모두 malignant potential 을가지며, 전체적인예후에서 ductal adenocarcinoma 보다는좋다. Unilocular 혹은 multilocular 의 cystic lesion으로보이며, mural nodule 을함유한 irregular thick wall부터 thin wall까지다양하게보일수있으며, peripheral, curvilinear wall calcification을보여 serous cystadenoma 와차이를보인다. 낭종내부는전형적으로 mucin 으로채워져있으나, MR 영상에서주로는 T1 low T2 high signal intensity 를보이며, mucin content 에따라 T1 signal 이증가할수있다. 조영증강이되는 mural nodule이악성을시사하는소견이다. Mucinous cystadenocarcinoma 는 mucinous cyst에 invasive adenomatous element 를함유하는경우에진단되며, 발견당시좀더 older age에호발하므로 cystadenoma 로부터발전하는것으로추정된다. 영상소견상 large complex cystic pancreatic lesion으로보이며대개크기가 4 cm 이상이거나 cyst 내부에 enhancing soft tissue nodularity 를보인다. EUS상 mural nodularity는쉽게인식이가능하므로 SCA의 honeycomb appearance와는쉽게구분되며, EUS guided aspiration에의한 carcinoembryogenic antigen (CEA) 의존재가높은진단율을보인다. C. Intraductal Papillary Mucinous Neoplasm (IPMN) 대에호발하며, 다른췌장의낭성병변들과는달리남성에서발생빈도가약간더높다. 증상을가지는환자의상당수가 serum amylase level이높아췌관폐쇄에의한췌장염을동반하는것으로생각된다. 조직학적으로 pancreatic ductal epithelium의 mucinous transformation 에의한유두상증식과다량의 mucin 분비에의한췌관의확장으로나타난다. 여러정도의 epithelial dysplasia 를보이는 noninvasive neoplasm 으로부터 carcinoma in situ, 그리고 frank invasive adenocarcinoma 까지다양한병리학적스펙트럼을보인다. 형태적으로는주췌관이나분지관의병발여부에따라 main duct type, branch duct type, 그리고 combined type으로나뉜다. Pancreatic cystic neoplasm의감별대상은 branch ductal type으로 main duct type(60-70%) 에비해악성도는낮다 (22%). Branch duct type은영상의학적으로그전형적형태 (pleomorphic cystic shape, clubbed fingerlike cystic shape, grape-like appearance) 와췌관과의연결성에의해다른낭성종양과감별이가능하며, 그연결성을찾는데 MR 영상이나 reformatted MDCT영상이때로 ERCP보다우월하다. ERCP는 thick mucin plug에의해막힌 branch duct의 neck을 cannulation 하기어려울수있기때문이다. EUS 역시 mural nodule 이나벽의두께주변조

5 박범진 12 직침윤등을보는데매우도움이된다. Mural nodule 이나 main pancreatic duct dilatation을수반하지않은 3 cm 이하크기의 branch duct type의 IPMN 이수술적치료없이추적검사만으로충분하다고알려져있으며, branch duct type의경우악성화를시사하는소견으로는 (1) Advanced age, (2) main duct involvement(>10mm), (3) concurrent diabetes or other pancreas related abdominal symptoms, (4) lesion size(>3 cm) and multiplicity, (5) mural nodule이나고형종괴가있을경우이다. 추적검사와치료가이드라인은세분화 ( International consensus guideline 2012 Pancreatology 12(2012) ) 되고있다. D. Solid Pancreatic Tumors with Cystic degeneration i. Ductal adenocarcinoma with cystic features 주로는고형종괴로보이지만약 8% 정도에서 cyst-like feature(cystic degeneration, retention cyst, and attached pseudocyst) 를보일수있다. 원발성암종주변이나내부에 complex cystic area가보이며 pseudocyst, internal necrosis, side-branch ductal obstruction 에의해유발되며, infiltrative pattern 의고형종괴의존재가 mucinous cystadenocarcinoma와 SPT와의감별에도움이된다. ii. Cystic islet cell tumor(neuroendocrine tumor) 주로 pancreatic phase 에서강한조영증강을보이는 small islet cell tumor에반해 large islet cell tumor 는내부에 tumor degernation 에의한 secondary change 를보인다. 내부의 95% 이상이 cystic portion 이 neuroendocrine tumor 인경우, periphery에 arterial phase상 rim-enhancement 가감별에도움이될수있다. iii. Solid and Pseudo papillary tumor (SPT) 젊은여성에서호발하며 (10-30 대, M:F=1:9.5), 나이에따라빈도는증가하는것으로알려져있다. Low malignancy potential 을가지는종양이나 15% 정도는악성종양이며, 성호르몬이종양과관련있어임신중에커질수있다. 종양의변성에의해이차적으로낭성변화가부분적으로생기며, 영상소견은 cystic, solid, 그리고출혈성부위의조성에따라다양하게보일수있다. Thick capsule과내부의출혈이진단에단서가될수있으며, 주변부위의석 회화와 solid portion 이있을수있다. Mucinous cystadenocarcinoma 와영상의학소견이겹치게된다. 결론 췌장낭성종양은형태면에서서로중복된소견이있어영상소견만으로정확한감별진단과특성화가어렵다. 그러나진단적가치가뛰어난발전된 MRCP, MDCT, EUS, ERCP 등다양한영상기법에대한이해를통하여, 향상된발견율과함께위치, 형태, 내부조직의성상, 주변구조물과의관계의면밀한분석은감별을좁히고, 나아가치료방침을세우는데도움이된다 참고문헌 1. Fernandez-del Castillo C, Targarona J, Thayer SP, Rattner DW, Brugge WR, Warshaw AL. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg 2003;138: ; discussion Friedman AC, Lichtenstein JE, Dachman AH. Cystic neoplasms of the pancreas. Radiological-pathological correlation. Radiology 1983;149: Demos TC, Posniak HV, Harmath C, Olson MC, Aranha G. Cystic lesions of the pancreas. AJR Am J Roentgenol 2002;179: Morel A, Marteau V, Chambon E, Gayet B, Zins M. Pancreatic mucinous cystadenoma communicating with the main pancreatic duct on MRI. Br J Radiol 2009; 82:e Sainani NI, Saokar A, Deshpande V, Fernandez-del Castillo C, Hahn P, Sahani DV. Comparative performance of MDCT and MRI with MR cholangiopancreatography in characterizing small pancreatic cysts. AJR Am J Roentgenol 2009;193: Katz DS, Friedel DM, Kho D, Georgiou N, Hines JJ. Relative accuracy of CT and MRI for characterization of cystic pancreatic masses. AJR Am J Roentgenol 2007; 189: Song SJ, Lee JM, Kim YJ, et al. Differentiation of intraductal papillary mucinous neoplasms from other pancreatic cystic masses: comparison of multirow-detector CT and MR imaging using ROC analysis. J Magn Reson Imaging 2007;26: Inan N, Arslan A, Akansel G, Anik Y, Demirci A. Diffusion-weighted imaging in the differential diagnosis

6 췌장낭성병변의평가에서영상검사의역할 13 of cystic lesions of the pancreas. AJR Am J Roentgenol 2008;191: Sahani DV, Kadavigere R, Saokar A, Fernandez-del Castillo C, Brugge WR, Hahn PF. Cystic pancreatic lesions: a simple imaging-based classification system for guiding management. Radiographics 2005;25: Kim YH, Saini S, Sahani D, Hahn PF, Mueller PR, Auh YH. Imaging diagnosis of cystic pancreatic lesions: pseudocyst versus nonpseudocyst. Radiographics 2005; 25: Kalb B, Sarmiento JM, Kooby DA, Adsay NV, Martin DR. MR imaging of cystic lesions of the pancreas. Radiographics 2009;29: Choi JY, Kim MJ, Lee JY, et al. Typical and atypical manifestations of serous cystadenoma of the pancreas: imaging findings with pathologic correlation. AJR Am J Roentgenol 2009;193: Pausawasdi N, Heidt D, Kwon R, Simeone D, Scheiman J. Long-term follow-up of patients with incidentally discovered pancreatic cystic neoplasms evaluated by endoscopic ultrasound. Surgery 2010;147: Kim HJ, Lee DH, Ko YT, Lim JW, Kim HC, Kim KW. CT of serous cystadenoma of the pancreas and mimicking masses. AJR Am J Roentgenol 2008;190: Macari M, Finn ME, Bennett GL, et al. Differentiating pancreatic cystic neoplasms from pancreatic pseudocysts at MR imaging: value of perceived internal debris. Radiology 2009;251: Kim SY, Lee JM, Kim SH, et al. Macrocystic neoplasms of the pancreas: CT differentiation of serous oligocystic adenoma from mucinous cystadenoma and intraductal papillary mucinous tumor. AJR Am J Roentgenol 2006; 187:

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