Mucin-Hypersecreting Bile Duct Tumor Characterized hy the Striking Homology with an Intraductal Papillary Mucinous Tumor (IPMT) of the Pancreas
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1 대한춰 l 담도연구회지 1999; 4: Mucin-Hypersecreting Bile Duct Tumor Characterized hy the Striking Homology with an Intraductal Papillary Mucinous Tumor (IPMT) of the Pancreas Hong Ja Kim, M.D., Myung Hwan Kim, M.D., Sung Koo Lee, M.D. Kyo Sang Yoo, M.D., Eun Tack Park, M.D., Byeong Cheol Lim, M.D. Dong Wan Seo, M.D. and Young 11 Min, M.D. Department 01 Internal Medicine, Asan Medical Center, University 01 Ulsan College 01 Medicine, Seoul, Korea = 국문초록 = 훼장의접액과분비성유두상종양과유사한담관내점액과분비성유두상종양 울산대학교의과대학서울중앙병원내과학교실김홍자 김명환 이성구 유교상박은택 임병철 서동완 민영일 연구배경및목적 : 혜장의정액과분비성유두상종양과유사한담관내점액과분비성종양에대해보고된예는드물다. 저자들은지난 4년간본교실에서경험한 9예의담관내점액과분비성종양을분석하여이들의임상병리학적특정을알아보고자하였다대상및방법 1995 년부터 1998 년까지담관내점액과분비성종양으로진단된 9명의환자 ( 남자 4, 여자 5, 평균연령 54세 ) 를대상으로하였다. 결과 대부분의환자에서내원당시담도성동통또는급성담도염을주소로하거나또는내원전에이러한증상이반복적 로발생한병력이있었다넓게개구된유두입구로부터점액의유줄이모든환자에서관찰되었다담도조영상관찰되는담도내유동성의충만결손을동반한전반적인간내및간외담도의확장이특징적인소견이었는데담도경소견상정액이찬담도내에유두상으로자라고있는종괴나, 또는미미한점막의과립상변화가관찰되었다 9명중 8 명에서근치적절제술을시행하였다조직검사상과형성, 선종화를보이는담도점막에서군데군데악성화의소견이관찰되었다. 결론 : 당관내점액과분비성종양은보고된예는드무나춰l장의점액과분비성유두상종양과유사하여예후가좋고내시경적쉐담관역행성조영술의보편화로점차발견율이높아질것으로추정되어세밀한관심이필요하다하겠다. 핵심단어 혜장의점액과분비성유두상종양, 담관내정액과분비성유두상종양 연락처검영환, 서울시송파구풍납동 388-1, 서울중앙병원소화기내과, 우편번호 \ Tel: , Fax , mhkim@ 116
2 Hong Ja Kim, et al : Mucin-Hypersecreting Bile Duct Tumor 117 INTRODUCTION Intraductal papillary mucinous tumor (IPMT) of the pancreas is increasingly recognized and is accepted all over the world as a distinct disease entityl - 6 Its unique features are primarily attributable to the excessive amounts of mucin secreted by the tumor. Recently we observed bile duct tumor that c10sely resemb1ed IPMT of the pancreas. However, contraη to IPMT of the pancreas, there were only anecdotal reports regarding this biliary tumory In the present study, we report on our experience of nine patients with the mucin-hypersecreting bile duct tumor and analyze the cases to elucidate its c1inicopathologic characteristics. MATERIALS AND METHODS Among 4,570 cases of the endoscopic retrograde cholangiopancreato graphy (ERCP) from 1995 to 1998, nine cases which were diagnosed as a mucin-hypersecreting bile duct tumor were inc1uded and analyzed retrospectively. The mucin-hypersecreting bile duct tumor was initially suspected by findings during ERCP, which inc1uded mucin extrusions from the papi11ary orifice, mucinous filling defects in dilated bile duct, and dilated intra- and extrahepatic bile ducts in the absence of obstructing ductal strictures, and was finally confirmed by the pathology of surgical specimen. All patients underwent operation and their c1inical, radiological and pathological features were reviewed. complained of biliary pain. Acute cholangitis and obstructive jaundice were noted in other four patients. A past history of recurrent cholangitis or episodic biliary pain was elicited in four out of these eight patients. In one patient, the lesion was incidentally found during a general check-up. The median duration of symptoms before diagnosis was 8 months (1 week - 24 months). Elevation of serum AST and ALT ( > 40 IU/L) was noted in four patients (AST: range IU/L, mean 97.3 IU/L; ALT: range IU/L, mean IU/L). The elevated alkaline phosphatase (> 250 IU/L) was noted in six (range IU/L, mean IU/L) and increased level of bilirubin ( > 3 mg/dl) was documented in two patients (range mg/dl, mean 4.9 mg/dl). More than 37 IU/L of CA 19-9 was demonstrated in four patients (range IU/L, mean IU/L). Clonorchiasis infestation evaluated by stool and bile examination was confirmed in one patient. There was no patient with RESULTS 1. Clinical features at presentation The mean age of the nine patients (women 5, men Fig. 1. Endoscopic view of the ampulla of Vater during 4) was 54 (range: 38-72). At admission, four patients ERCP; mucin is seen protruding from the papil1a.
3 118 대한혜담도연구회지제 4 권제 2 호 1999 primary sclerosing ch이 angitis or history of inflammatory bowel disease 2. Radiologic features Diffuse intra- and extrahepatic duct dilatation with internal, low attenuation was the most common finding in CT of these patients. During ERCP, a widely open ampulla of Vater with the extrusion of mucoid material was observed in all patients (Fig. 1). On their cholangiograms, extremely dilated intra- and extrahepatic bile ducts with amorphous filling defects were demonstrated (Fig. 2A). Table 1 summarized the characteristics of the patients. In patients 4 and 5 who showed intrahepatic cystic lesion on the CT scan, the cyst and contiguous peripheral dilated duct became visible after continuous forceful injection of contrast medium, indicating that the main lesion is a dilated duct rather than an extraductal cavity. Fig. 2. Case 6 A) Cholangiographic finding; diffuse duct dilatation and intraductal amorphous filling defects corresponding to mucin plugs are noted. B) Cholangioscopic finding; thick mucin fills the bile duct. Papillary mass is found after washing the bile duct. C) Gross finding; in hilar area, papillaη mass with glistening surface is documented It is confined to this area. D) Microscopic finding; a well-differentiated adenocarcinoma is documented in the background of hyperplasia and adenoma.
4 Hong Ja Kim, el al : Mucin-Hypersecreling Bile Duct Tumor Cholangioscopic features Cholagnioscopic examination was perfonned in five patients. Papillary growing mass was found in four patients (Fig. 2B) and minute mucosal change like a c1uster of frog-spawn was noted in one patient. The mass was soft and was covered with glistening mucin. Pathologic lesions were demonstrated at intrahepatic duct in four patients and at hilar area in one patient In three patients, lesions were confined in focal area. In two patients, they widespread along the unilateral intrahepatic duct and extrahepatic bile duct appeared nonna1. They were successfully resected by extended lobectomy. 4. Treatment and follow-up Nine patients were referred to an operation and curative resection was perforrned in eight patients. The extent of disease could be predicted in three patients showing mass-shadow or localized cystic dilatation on CT or ERCP. However, the pathologic area could not be localized and a proper surgical plan could not be detennined by conventional radiological study in five patients. In these patients, cholangioscopic examination provided an additional infonnation on the extent of disease, and curative resection was successfully perfonned. Explolaparotomy and biopsy were carried out in one patient with peritoneal seeding. After the c1inical follow-up ranging from 8 months to 42 months, seven patients are stil1 alive and well, but tumor recurred in one patient 18 months after resection. One patient who initially had had peritoneal seeding died due to the septic cholangitis. S. Pathologic features Macroscopically the cut sections of eight patients with curative resection revealed the dilated intra- and extrahepatic bile ducts containing papillary masses (Fig. 2C). Histologically, the Iining epithelium of the dilated duct showed various degrees of cellular atypias. Eight patients demonstrated well-differentiated adenocarcinoma (Fig. 2D) in the background of benign hyperplasia and adenoma. Pure adenoma was documented in one patient. DISCUSSION Pancreaticobiliary neoplasms usually produce mucin, however, most of them only retain the mucin in the tumor cell or in the cyst. Exceptionally, intraductal papillary mucinous tumor (IPMT) of the pancreas excretes excessive mucin direc t1y into the pancreatic duct and the mucin leads to the characteristic features 1-6 of the IPMT.' - v In bile duct, the tumor excreting mucin into the bile duct, like an IPMT of the pancreas, may also exist theoretically because of the same embriologic origin of the two duct systems. 9 Actually, there are a few reports on the so called mucin-hypersecreting bile duct tumor,7,8,10 but the nomenclature and concept have not been established, yet. We have experienced nine cases of this tumor since We think that our series are the largest among the series of these tumor reported in a single institution. In this study, it was not c1ear that geographical and/or environmental factor played roles in tumor occurrence. However, since the first case of this tumor was diagnosed about 4 years ago, we have begun to be concemed about this rare disease. In addition, percutaneous transhepatic c h 이 angioscopic examination has been actively perfonned in recent years. Furthermore, our hospital is a third-referral center and the largest hospital in Korea with about 2,000 beds. We believe that we could detect so many cases of this tumor in recent years for these reasons. This tumor showed unique c1inical, radiological and pathological features distinct from those of ordinary bile duct carcinoma. Clinically, they secrete large quantities of viscous mucin into the duct lumen, lead-
5 120 대한쉐담도연구회지 : 제 4 권제 2 호 1999 ing to interrnittent blockage of the bile duct system and thereby causing ductal dilatation and various biliary symptoms. In our study, most of our patients presented biliary pain and acute ch이 angitis at admission, or had suffered from episodic attacks of biliary pain and recurrent cholangitis before admission. Those symptoms are unusual for common bile duct tumor and may be considered as the characteristic c1inical features different from those of usual bile duct tumor. 10 In case of this tumor, bile duct dilatation can occur not only in the bile duct distal to the main pathologic lesion but also in the bile duct proximal to the 1esion, due to the partial obstruction by mucin. In addition, it is often confused weather an intraductal filling defect is caused by mucin or by a neoplastic mass. Therefore, the virtual extent of pathologic lesion can not be proposed exactly on the base of conventional radiological study. In our study, cholangioscopic examination could provide detailed inforrnation on the extent of disease and the surgical treatment appropriate to individual patients could be decided. We speculate that preoperative direct observation of bile duct may be indispensable for deterrnining a best management plan Under the cholangioscopic examination, majority of patients showed distinct papillaη mass. Minute frog spawn- like mucosal change was also observed. Such endoscopic finding c10sely resembled that of the IPMT of the pancreas 11,12 Microscopically, the tumor was often accompanied by a wide range of histology, such as hyperplasia, adenoma, in situ carcinoma, and invasive carcinoma. This result suggests that the pathogenesis of tumor be in the sequence of hyperplasiaadenoma -carcinoma. 2 In usual ch 이 angiocarcinoma, resection is seldom 13,14 possible and survival rate is discouraging:~'" However, in our study, initial curative resection was perforrned in 85% (8/9) of patients and 87% of them are still alive after follow-up of 8-42 months. These high resectability and long survival may be attributed to early detection of the tumor due to the acute biliary symptoms caused by the mucin, in addition to the slow-growing biological behavior of the tumor. In summary, mucin-hypersecreting bile duct tumor may be characterized by striking homology with IPMT of the pancreas in c1inical, radiological and pathological features. If mucin from the ampulla is observed during ERCP, a thorough evaluation should be made for the early detection of mucin-hypersecreting bile duct tumor. SUMMARY Background/ Aims: Mucin-hypersecreting bile duct tumor, which c10sely resembles intraductal papillaη mucinous tumor (lpmt) of the pancreas, is rare and its c1inical features are not well known. We report our experience of nine patients with the tumor and analyze the cases to elucidate its clinicopathologic characteristics. Methods: Between 1995 and 1998, nine consecutive patients (4 men and 5 women, mean age 54 years) who were diagnosed as a mucin-hypersecreting bile duct tumor were enrolled in this study, Results: Recent or previous attacks of biliarγ pain and acute cholangitis were elicited in most of the patients. A widely open ampulla of Vater with extrusion of mucin and an diffuse dilated intra- and extrahepatic bile duct with amorphous filling defects on cholangiogram were characteristic. On cholangioscopic examination, papillary mass or minute mucosal lesion was found in the dilated bile duct containing thick viscid mucin. Nine patients were referred to an operation and curative resection was perforrned in eight patients. Histologically, well-differentiated adenocarcinoma in the background of benign hyperplasia and adenoma was documented in all patients except one, who showed pure adenoma. Conc\usion: Mucin-hypersecreting bile duct
6 Hong Ja Kim, et al : Mucin-Hypersecreting Bile Duct Tumor 121 tumor may be characterized by striking homology with IPMT of the pancreas in clinical, radiological and pathological features. Key Words: Intraductal papillary mucinous tumor (IP~π') tumor of pancreas, Mucin-hypersecreting bile duct REFERENCES 1. 0 삐 llis hl K, Murakimi Y, Maruyama M, et al: Four cases of mucous secreting pancreatic cancer. Prog Dig Endosc 1982; 20: Obara T, Maguchl H, Saitoh Y, et al: Mucin producing tumor of the pancr, 않s: natural hlstory and serial pancreatogram changes. Am J Gastroenterol 1993; Loftus EV, Olivarres-pakzad BA, Batts KP, et al: Intraductal papillary mucinous tumors of the pancreas: c1inicopathologic features, outcome, and nomenclature. Gastroenterol 1996; 110: Nickl NJ, Lawson JM, Cotton PB: Mucinous pancreatic tumors: ERCP findings. Gastrointest Endosc 1991; 37: Tenner S, Carr-Locke DL, Banks PA, et al: Intraductal mucin hypersecreting neoplasm mucinous ductal ectasia: endoscopic recognition and management. Am J Gatroenerol 1996; 91: Kimura W, Sasahlra N, Yoshikawa T, et al: Duct ectatic type of mucin producing tumor of the pancr않s- new concept of pancreatic neoplasia. Hepatogastroenterol 1996; 43: Chow LTC, Ahuja AT, Kwong KH, et al: Mucinous cholangiocarcinoma: an unusual complication of hepatolithlasis and recurrent pyogenic cholangitis. Histopathology 1997; 30: Isogai M, Nimura Y, Hayakawa N, et al: A case of mucus producing ch 이 angiocarcinoma with s 때 erficial spread. Jpn J Gastroenterol Surg 1986; 19: Sadler TW: Langmans medical embriology. Ba\timore, Williams & Wilkins Kokubo T, Itai Y, Ohtomo K, et al: Mucin hypersecreting intrahepatic biliary neoplasm. Radiology 1988; 168: Seo DW, Kim MH, Lee SK, et al: The value of pancreatoscopy in patients with mucinous ductal ectasia Endoscopy 1997; 29: Myung SJ, Kim MH, Kim HJ, et al: Magnetic resonance ch 이 angiopancreatography is insufficient for the detection of flat lesion in mucinous ductal ectasia; pancreatoscopy may be needed additionally. Am J Gastroenterol 1998; 93: Okuda K, Kubo Y, Okazaki N, et al: Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma. Cancer 1977; 39: Shigeki AR: Surgical treatrnent for intrahepatic bile duct carcinoma. Kan Tan Sui 1995; 30: (In Japanese).
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