Ki Yeol Lee : Intraductal Mucin-Hypersecreting Neoplasm of Pancreas describe in detail the imaging findings of five IMHN and to discuss their differen

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J Korean Radiol Soc 1997; 37 : 265-27 1 Intraductal Mucin-Hypersecreting Neoplasm of the Pancreas : US, CT and ERP Findings 1 Ki Yeol Lee, M.D. Purpose: To eva1uate US, CT and endoscopic retrograde pancreatography (ERP) findings ofintrad ucta1 mucin-hypersecreting neop1asm (IMHN). MateriaJs and Methods : We categorized an IMHN as be10nging to a group of disease that can be clinica11y detected by the pooling ofmucus prod uced by tumors inside the main duct or branch ducts ofthe pancreas, thus causing di1atation ofthese ducts. We retrospective1y reviewed the US, CT and ERP findings offive patients(hyperp1asia, 4 ; adenocarcinoma, 1). ResuJts : On US and/or CT, diffuse di1atation of the main pancreatic duct was demonstrated in five patients. In two cystic 1esions corresponding to cystic dilatation of branch ducts were noted at the pancreatic head(n= 1) and neck(n= 1). In one patient, mu1tip1e cystic 1esions were seen on CT a10ng the entire pancreas, but these were not detected on US. In a11 patients, dilatation ofthe main duct and/or its branch ducts was seen on ERP. Filling defects resulting from mucin in the main duct or branch ducts were noted in a11 cases. Lymphadenopathy was not seen on US or CT, but carcinoma peritonei was found in the adenocarcinoma patient at the time of operation. ConcJ usion : IMHN usually shows smooth, diffuse di1atation ofthe main duct, and on US or CT, dilated branch ducts are occasionally noted. ERP findings are the most characteristic and conclusive; di1atation of the main duct and/or branch ducts is noted, with a filling defect corresponding to mucin. If overlooked during diagnosis, an IMHN might be interpreted simp1y as chronic pancreatitis, and so the recognition of this neop1asm is important. Jndex Words : Pancreas, radiography Pancreas, CT Pancreas, neop1asms In 1982, Ohhashi et a1. (1) described a patient with hypersecretion ofmucin from the pancreas caused by a ducta1 neop1asm and since then, similar tumors have been reported in the literature, particu1arly by Japanese authors. They were given various names: mucin-producing tumors, mucin-hypersecreting car cinoma, ductectatic mucinous cystadenoma, cystadenocarcinoma, and intraducta1 papillary mucinous neop1asms of the pancreas associated with mucinous 'Department ofdiagnostic Radiology, College ofmedicine, Korea University Received January 6, 1997; Accepted May 29, 1997 Address reprint requests to : Ki Yeol Lee, M.D., Department of Diagnostic Radiology, College of Medicine, Korea University HospitaL # 126-1. 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul1 36-705, Korea Te l. 82-2-920-5579 Fax.82-2-929-3796 % duct ectasia(2-7). These entities are characterized by mar ked di1atation of the entire or segmental main duct associated with fi11ing defects during endoscopic retrograde pancreatography(hereafter, ERP), and by the excretion of mucin through the patu10us orifice of the en1arged papilla ofvater (major duodena1 papilla) during endoscopy(2-4, 8). The disease was found to include not on1y malignant but also benign cases including hyperp1asia and adenoma(s). It a1so was found that, in some cases, the tumors did not deve10p on1y in the main duct, but a1so in branch ducts(4). Increasing attention is being paid to the morphology of this tumor, its prognosis, and its re1ationship with intraducta1 papillary neoplasms. This study aims to

Ki Yeol Lee : Intraductal Mucin-Hypersecreting Neoplasm of Pancreas describe in detail the imaging findings of five IMHN and to discuss their differential diagnosis Materials and Methods We categorized IMHN as belonging to a group of diseases that can be clinically detected by the pooling of mucus produced by tumors inside the main or branch ducts of the pancreas, thus causing dilatation of these ducts, and between 1989 and 1996, studied five such cases. A review ofultrasound(us), computed tomography (CT) and ERP files disclosed five patients with diffuse dilatation and filling defects of the main duct and/or cystic dilatation and filling defects of branch ducts Two of five patients had undergone partial panreatectomy, and the remaining three had undergone pancreaticoduodenectomy, opening and closure (due to carcinoma peritonei), and brush cytology respectively. On histologic examination, four cases of hyperplasia and one of adenocarcinoma ofthe pancreas were identified. Three ofthese patients were men, and two were women, and they were aged between 40 and 70(mean, 56) years. Radiologic findings of this IMHN, including US, CT, and ERP were reviewed, as was the clinical data. The radiologic and clinical data relating to four histologically-proven cases of classic mucinous cystadenoma (n=3) or cystadenocarcinoma (n=l) of the pancreas were also reviewed. Results On US, dilatation of the main duct(fig. 1) was detected in five patients, and hypoechoic round or ovoid lesions were seen in two; one of these was located at the pancreatic head, and one at its neck. On CT scans, diffuse dilatation of the main pancreatic duct was seen in five patients(fig. 1, 2). In one, multiple cystic lesions were seen at the head, bodyand tail and the intrahepatic and extrahepatic bile ducts were dilated by invasion of the adenocarcinoma(fig. 1) Septum-like structures were detected in two patients, and were due to clustering of the cysts, but mural nodules, a thickened cyst wall and calcification were not present(fig. 2). The rest of the pancreas was normal in three patients and atrophied in two patients (Fig. 2); there were no enlarged lymph nodes or obvious metastases in the peripancreatic tissue, but during surgery, carcinoma peritonei was found in the cystadenocarcinoma patient. On CT or US scans, the mucin was not detected. In four patients, dilatation of the main and branch ducts was seen on ERP and in one, the main duct was dilated with multiple filling defects, without dilatation of the branch ducts(fig. 2). The maximum diameter of the main duct ranged from 6 to 25(mean, 9.5mm); in three cases, it had a smooth contour(fig. 2) and in two, its appearance was tortuous(fig. 1). In all patients, filling defects of varying sizes were noted in the main pancreatic duct(figs. 1, 2) or cystic lesions, the filling defects corresponded to a mucoid substance that was observed endoscopically at the patulous orifice of the papilla ofvater. The level of serum amylase was not elevated in all patients and diabetes mellitus was detected in two patients. The radiologic and clinical findings of these five cases are presented in Table 1. Descussion A primary characteristic of a mucin-producing tumor is that it is present in the dilated main or branch ducts ofthe pancreas. Histologically, the cystic pancre atic duct that contains viscous mucin is lined by tall columnar cells, which often form papillary projections and encroach on secondary ducts. According to the classification of atypicality in the epithelium, this tumor is classified as either hyperplasia without atypia, atypical hyperplasia, adenoma, or adenocarcinoma. Although gross inspection revealed no polypoid or elevated tumor in the main duct or cystic lesions, histologic examination showed neoplastic columnar mucinous epithelium with prominent papillary growth(2). Itai et al. (9) described ductectatic cystadenoma or adenocarcinoma ofthe pancreas which is characterized by localized cystic dilatation of branch ducts and the presence of tumor cells, and spreads along the main duct and produces excessive amounts of mucin. According to that report, US and CT demonstrated small cystic lesions, with lobulated or irregular margins located preferentially in the uncinate process, and the main pancreatic duct was dilated. On ERP, localized, prominent cystic dilatation of a branch duct of the main pancreatic duct was seen, and there were grape like clusters or pear-shaped pools of contrast material associated with filling defects of various sizes. In three of patients, cystic lesions were located at the head, neck and entire pancreas, respectively. Itai et al. also reported five cases of mucin-producing" carcinoma of the pancreàs, which was characterized by smooth, diffuse dihtation of the main duct associated with filling defects on ERP. In contrast to their findings, our - 266 -

? ιj Korean Radiol Soc 1997; 37 : 265-271 case of mucinous cystadenocarcinoma showed, on ERP, irregular dilatation of the main duct with mul tiple cysts communicating with this duct along the en tire pancreas, and filling defects. Mucinous obstruction of the biliary tree may de velop. A fistulous communication from the cystic lesion to the common bile duct continued to drain copious amounts of mucinous material and invasion of the bile duct and obstruction by a tumor, rather than by the mucinous material may cause biliary obstruction(2, 10). In addition, one of our patients developed biliary dilatation because of carcinomatous invasion of the distal common bile duct. Pancreatic insufficiency may ensue when the lesion further expands in the duct sys- A B C D

KiYe 이 Lee: Intraductal Mucin 쉬 ypersecreting Neoplasm of Pancreas A B c D E F Fig. 2. A and B. CT scan shows dilatation ofthe main duct(small black arrows) and clustered cysts-like lesions in the body of the pancreas(large black arrows). c. ERP shows extreme dilatation ofthe main duct with filling defects (open arrows) correspond to the mucin plugs. D. Pancreaticoduodenectomy specimen with IMHN. Cut surface shows dilated main pancreatic duct(asterisks). D; duodenal mucosa E. Photomicrograph(H&E; original magnification, X 40이 of the histologic specimen shows papillary hyperplasia featuring paphlary projections of tall columnar epithelium. Arrowheads indicate atypical hyperplasia showing pseudostratification of epithelium with pelomorphic and dense nuclei. F. Follow-up CT scan, 2 months after pancreaticoduodenectomy shows remained pancreatic body and tail with still dilated pancreatic duct ω@

μj Korean Radiol Soc 1997 ;37:265-271 Table 1. Clinical and Radiologic Findings in 5 Patients with IMHN Patient Age(yrll C o Laboratory Symptoms ERP Findings Number Sex Findings 4 찌a 따뼈맥따s Operation Histology 58 /F lndigestion Am ylase N lrregular dilatation of MPD ~ lrregu lar dilatation ofmpd Open & Closure due to Adenocarcinoma Abdominal Glu cose 1 ** with c1ustered cysts in the head, with c1 ustered cysts(not carcinoma peritonei body and ta il oft he pancreas. seen on usl Dilatation of intra- and extrahepatic bile ducts 40/M Epigastric Normal Dilatation of MPD and branch Smooth dilatation of MPD Pyloric preserving Hyperplasia ducts with fìl 1ing defects 58 /F RUQ pain Normal Dilatation ofmpd and branch ducts with filling defects 53 /M RUQ pain Normal Dilatation of MPD with filling defects 70 /M RUQ pai n Glucose 1 Dilatation ofmpdand branch Jaundice Amylase N ducts with fi lli ng defects with c1 ustered cysts in pancreaticoduodenectomy with atypia the neck Smooth dilatation of MPD Partial pancreatectomy Hyperplasia without atypia Smooth dilatation of MPD Partial pancreatectomy Hyperplasia with c1 ustered cysts in the head Smooth dilatation of MPD Brush cytology without atypia Hyperplasia without aty pi * Normal serum level ** Increased serum level @ Alkaline phosphastase a ι1ain Pancreatic Duct tem(2). Two of our patients developed pancreatic insufficiency with diabetes, but the level of serum amylase was n ot elevated. This then increases the amount of mucin to such as extent that it cannot be washed out by normal pancreatic secretion, resulting in permanent duct occlusion with its sequelae, acinar atrophy, pancreatic fibrosis, and exocrine as well as endocrine insufficiency(2). Because of the well-known malignant potential of the classic ty pe of mucinous cystic neoplasm(mucinous cystadenoma-cystadenocarcinoma), this and IMHN must be clearly distinguished. In contrast to IMHN, which shows no sex predilection, a mucinous cystic n eoplasm mainly affects middle aged women(ii). It presents as a cystic abdominal mass, preferably located in the tail of the pancreas, and does not usually com municate with the duct system. There have been spor adic case reports of classic cystadenoma or adenocarcinoma in which the lesion commuincates with the pancreatic duct, common bile duct, or duodenum(12) In these rare cases, the size of the communicating orifice is, however, small and a solid portion of the cystadenocarcinoma is detected by means of CT or US (2, 3, 5, 9, 10, 13, 14). An IMHN and a mucinous cystic n eoplasm may be difficult to distinguished by ERP, and a resected specimen may be required(2). In the four cases of classic cystadenoma or cystadenocarcinoma, there was no communication between the cystic lesion and the duct system. Chronic pancreatitis can mimic this entity both radiologically and clinically. Common findings include m diffuse, corkscrew dilatation of the main duct and branch ducts, with or without filling defects resulting from stones(15, 16). Figure 2 shows a case of hyperplasia with atypia where dilatation of the main duct was smooth on ERP with filling defect ; this was different from the finding in chronic pancreatitis. Dilatation in the adenocarcinoma case was seen on US to be beaded, however, and this appearance is also seen in cases of chronic pancreatitis. Another condition in which findings include marked dilatation of the entire main pancreatic duct is carcinoma of the papilla of Vater, in which the common bile duct is also markedly dilated. Hypotonic duodenography and/or ERP is necessary for differential diagnosis. It is known that an IMHN has a low potential for malignancy(2, 4, 8, 9); these tumors are clearly distiguished from malignant lesions of the pancreas, such as ductal cell adenocarcinoma, by the absence ofinvasive tumors or metastasis, medical histories that cover many years, and the fact that patients who undergone an operation live for many years after surgery without evidence of tumor recurrence(2, 3). Yamada et al. (4), however, r eported 12 malignant cases in a series of 22 mucin-producing tumors ofthe pancreas, and our case of mucinous cystadenocarcinoma showed tumoral infiltration of the parenchyma; the bile duct was invaded, and peritoneal seeding occurred. Because the reported number of these tumors is so far very smal!, however, a larger series of cases is needed if the risk of malignancy is to be indicated more precisely

KiYe 이 Lee: Intraductal Mucin-Hypersecreting Neoplasm of Pancreas In conclu sion, US and/or CT scans ofimhn usually demonstrate smooth, diffuse dilatation of the main duc t, and dilated branch ducts are occasionally noted Endoscopic observation is useful for diagnosis ; en largement of the papilla and its patulous orifice, and excretion of muc in are see n in about 90 % of patients. ERP findings are the most characteristic and conclu sive ; dilatation of the main duct and/or branch ducts is n oted. Filling defects on ERP are another feature ofthis entity, and they corrspond to mucin or, occasionally, to polypoid tumors. ERP is therefore valuable in differentiating cystic lesions of the pancreas and leads to enables a definitive diagnosis o fimhn. References 1. Ohhash i K, Murakami F, Takekoshi T. et al. Four cases of mu cin-prod uci ng" cancer of the pancreas on specifìc findings of the papi lla of Vater, (abstr). Prog Dig Endosc 1982; 20: 348 2. Rickaert F, Cremer M, Dev iere j, et al. Intraductal mucin hypersecreting neoplasms of the pancreas. Gaslroenlerolo 와 l 1991; 101: 512-519 3. Itai Y, Kokubo T, AlOmi Y, Kuroda A, Haraguchi y, Terano A Mucin-hypersecreting carci nom a of the pancreas. Radiology 1987; 165 :5 1-55 4. Yamada M, Kozuka 5, Yamao K, et al. Mucin-producing tumor ofthe pancreas. Cancer 1991 ;68: 159-168 5. Gaze lle GS, Muell er PR, Raafat N, Halpern EF, Cardensa G, Warshaw A. Cystic neoplasms of the pancreas: evaluation with endoscopic retrograde pancreatography. Radiology 1993; 188 633-636 6. Nagai E, Ueki T, Chijiiwa K, et al. In traductal papillary mucin- ous neoplasms of the pancreas associated with so-ca lled mucinous duct ectasia: Histochemical and immunohistochemical anal ysis of 29 cases, (abstr). Am J Surg Patholo 1995; 19 576-589 7. Freeny PS, 5tevcnson GW. Margulis and Burhenne' s elemenlary tracl radiology. 5th ed. 51. Louis: Mosby, 1994: 1132-1149 8. Morohoshi T, Kanda M, Asanuma K, KI ppel G. Intraductal pa il lary neoplasms of the pancreas: a cli ni copathologic stud y of six patients. Cancer 1989; 15: 1329-1335 9. Itai Y, Ohhashi K, Nagai H, et al Ductectatic" mu ci nous cystadenoma and cystadenocarcinoma of the pancreas. Radi 010 gy 1986; 161: 697-700 10. Ito y, Brackstone MO, Frank PH, 5kinner DB. Mucinous biliary obstruction associated with a cystic adenocarcinoma of pancreas. GastroenteroLogy 1977;73: 1410-1412 11 Compagno J, Oertel JE. Mucinous cystic neoplasms of the pancreas with overt and laten t malignancy(cystadenocarcinoma and cystadenoma). A c1inicopathologic study of 41 cases. Am J Clin pathol 1978, 69 : 573-580 12. Cross MR. Mucinous cystadenoma 0 1' the pancreas. Endoscopy as an aid to diagnosis. Gaslroelllerology 1980; 19: 944-947 13. Vahlensiek M, Vogel J, Kreft ß, Reisen M. Mucinous cystadenoma of the pancreas tail with ductal commun ica tion. J Comput Assit Tomogr 1993; 17: 502-503 14. Cohen SA, 5urapaneni RK, Kasmin FE, Siegel JH. Communication between the main pancreatic duct and cystic cavity in patients with cystic neoplasms of thc pan creas. Radiology 1994; 194:582 15. Robbins AH, Messian RA, Widrich Wc. et al. Endoscopic pan creatography : an analys is of the radio logic fìndings in pancreatitis. Radiology 1974; 1 13 : 293-296 16. Zimmon DS, Falkenstein Dß, Abrams RM, Selinger G, Kessl er RE. Endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic inflammatory disease. Radiology 1974; 113 : 287-292 m

J Korean Radiol Soc 1997 ; 37 : 265-271 [H 한빙시선의학회지 1997 ; 37: 265-271 훼장의관내점액과분비성종양 : US, CT 와 ERP 소견 l l 고려대학교의과대학진단방사선과학교실 이기열 목적 : 춰 1 장의관내점액과분비종양 (I ntraducta l Mucin Hypersecreting Neop l asm [IMHN ] ) 의초음파, 전산화단층촬영과내시경적역행성춰 l 장관조영술의소견을알아보고자하였다. 대상및방법 : 저자틀은 IMHN 을주혜장관 (main pancreatic duct) 혹은분지관 (br anch duct) 내의종양에의 하여점액저류 (muc i n pooi) 가형성되고이것에의하여취l 장관이확장되는질환으로분류하고이러한환자 5명 (hyperplasia : 4, adenocarcinoma ; 1) 을대상으로하여초음파, 전산화단층촬영과내시경적역행성훼장관조 영술의소견을후향적으로분석하였다. 결과초음파나전산화단층촬영에서주훼장관의확장이 5 명에서관찰되었고, 초음파에서분지관의냥성확 장에해당하는저에코의낭성병변을 2 명의환자에서각각훼장의두부와경부에서관찰되였으며, CT 에서는위 의 2 명외에 1 명에서훼장의전장에걸친낭성병변을관찰할수있었다.5 명의환자모두에서내시경적역행성 춰 l 장관조영술상주취 l 장관의확장을보였고, 모든예에서주춰 l 장관혹은분지관에서점액에해당하는충만결손 (filling defect) 을관찰할수있었다. 서수술시복막으로의전이를확인하였다. 결 럼프절전이는초음파나전산화단층촬영에서는안보였으나선암의예에 론 :IMHN 은초음파나전산화단층촬영에서주훼장관의미만성확장혹은국한성의낭성병변으로보이 며, 역행성춰 l 장관조영술에서는주춰 l 장관혹은분지관의확장과함께점액에해당하는충만결손을보인다. IMHN 은진단당시간과하여단순한만성훼장염으로진단될가능성이많기때문에방사선학적으로인지하는 것이중요하다고사료된다. m

아시아지역방사선과의사의국내수련병원 Fellowship 안내 새로운국제질서가만들어지고급변하는국제관계속에아시아태평앙시대의구조적역할을하는현재의우리니라는경제, 사호 등모든분야에그위상이크게달라져있습니다. 그중의학학술분야에서는어느선진국못지않은세계적인수준이라자부할수있으며이제는배우는나라에서배움을주는 l-f라로발전하였습니다. 이에대한방사선의학회에서는중국을포함한아시아각국방사선과의학도들을선발하여학문적수준과시설이나은우리나라연수기관에서 6개월에서 1 년동안수련시켜우리나라방사선의학의수준을세계여러나라에과시하고나아가아시아국가간협력과우호증진및학술교류에도기여하고자합니다. 이에소요되는제반비용은삼성 GE의료기기의후원으로이루어집니다. 여러수련병원에서는학회에서주관하는이프로젝트에적극참여하시어대한밤사선의학회의국 제화노력에협조하여주시기바랍니다. 참여희망신청 본학회사무국또는대한방사선의학회국제협력위원회 문의사항 : 대한밤사선의학회국제협력위원회 ( 위원장 : 오용호, 간사 : 윤종현 ) 전호 f: (02)224-4362. FAX : (02)476-4719. E-mail : Chyoon @amc.ulsan.ac.kr 낀