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Intraductal oncocytic papillary neoplasm of the bile duct: ultrasonography and CT findings with pathological correlations
Clinical Radiology (2009) 64, 841e844
CASE REPORT
Intraductal oncocytic papillary neoplasm of the bile duct: ultrasonography and CT findings with pathological correlations S. Leea, Y.-S. Kima,*, W.J. Leea, K.-T. Jangb a
Department of Radiology and Center for Imaging Science, and bDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Received 20 November 2008; received in revised form 2 February 2009; accepted 13 February 2009
Introduction
Case reports
Papillary tumours of the bile ducts are characterized by an intraluminal papillary mass in association with bile duct obstruction and dilatation.1,2 Some of these tumours secrete an excessive amount of mucin, which may disturb bile flow and cause severe ductal dilatation.3 The condition currently is most commonly described as intraductal papillary mucinous tumour or neoplasm (IPMN) of the bile ducts.4 In 1996, Adsay et al.5 proposed the term, intraductal oncocytic papillary neoplasm (IOPN) for a distinctive cystic intraductal tumour with oncocytic features and mucin production as a subtype of IPMN of the pancreas. However, oncocytic (i.e., eosinophilic) changes are extremely rare in the biliary system. To our knowledge, fewer than 10 cases of IOPN of the liver have been reported previously. As the diagnostic concept of IOPN of the biliary system is a relatively recent introduction and the frequency of this diagnosis is increasing, radiologists need to be familiar with this entity. In this report, two cases of IOPN of the bile duct, comprising a unilocular cystic mass with mural nodules, are presented. The radiological features on ultrasonography (US) and computed tomography (CT) are illustrated and correlated with the pathological findings.
Case 1
* Guarantor and correspondent: Y.-S. Kim, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: þ82 2 3410 2518; fax: þ82 2 3410 2559. E-mail address: [email protected] (Y.-S. Kim).
A 57-year-old woman was referred to our hospital for the evaluation of a hepatic mass. Ten years before, a 2.8 cm cystic lesion in the liver had been detected on routine abdominal US incidentally. On follow-up US, 3 years before the visit to our hospital, the mass measured 3.1 cm, and the solid component inside the cystic mass had newly appeared. The patient refused biopsy of the mass. Recently, she presented with chronic fatigue and mild right upper quadrant pain of 3 months. At physical examination, no abnormalities were noted. Liver function tests were also normal. Hepatitis B and C serology tests were negative. Tumour markers, including carcinoembryonic antigen, carbohydrate antigen 19-9, and a-fetoprotein, were normal. On CT there was a 4 cm, well-demarcated, cystic mass with two mural nodules in segment IV of the liver. The mass did not contain calcification. On arterial and portal venous-phase images, a thin capsule and mural nodules showed contrast enhancement. US revealed a unilocular cystic mass with two mural nodules. Colour Doppler US failed to demonstrate the vascularity of the mural nodules (Fig. 1). Laparotomy was performed under the tentative diagnosis of atypical biliary cystadenocarcinoma. The mass separated from the liver parenchyma easily. However, it appeared as a mass originating from the extrahepatic bile duct because it was firmly attached. Operative cholangiography did not show any communication between the bile duct and
0009-9260/$ - see front matter ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.02.017
842
S. Lee et al.
Figure 1 An intraductal oncocytic neoplasm involving the extrahepatic duct in a 57-year-old woman who presented with an incidentally detected cystic mass. (a) Contrast-enhanced CT image shows a 4 3.3 cm, well-demarcated, hypoattenuating mass with enhancing two mural nodules and a thin capsule in the left lobe of the liver (arrows). (b) US demonstrated a unilocular cystic mass with two mural nodules (arrows) showing a paucity of intramural vascularity. (c) Intraoperative cholangiogram did not show a connection between the cystic mass and the extrahepatic duct. Arrows indicate the presumed location of the cystic mass to the duct, which is displaced by the mass. (d) The photograph of the cut surface of the cyst shows multiple papillary fronds with mucin, which measured up to 2.5 2 cm (arrowheads). (e) At low magnification, from the area of mural nodule, complex papillary fronds with fibrovascular core (arrows) were noted [haematoxylin and eosin (H&E) staining, 40]. (f) At high magnification, the papillary tumour cells disclosed oncocytic cytoplasm (asterisks; H&E staining, 200). Based on these histopathological findings, the mass was diagnosed as intraductal oncocytic papillary neoplasm (carcinoma).
the cystic mass. En-block resection of the mass with the common bile duct was performed. On gross examination, the cut section showed a thickwalled, unilocular cyst that measured 4 4 cm. The inner surface of the cyst was covered with mucoid material and multiple papillary excrescences measuring up to 2.5 cm. On histopathological examination, the tumour had thick, branching, complex papillary fronds with a fibrovascular papillary core. In some areas, the papillae become confluent to form solid aggregates of cells. The tumour cells were homogeneous, eosinophilic, with abundant, granular cytoplasm. The histopathological diagnosis was intraductal oncocytic papillary carcinoma. The patient has survived over 1 year after the surgery without recurrent disease.
Case 2 A 51-year-old man presented with an increasing cystic mass with small mural nodules in the liver,
which had been previously detected incidentally on US. The size of the mass had measured 8.8 cm initially. CT was performed 6 years after the initial detection of the mass. Hepatitis B and C serology tests were negative. Liver function tests and tumour markers, including carcinoembryonic antigen, carbohydrate antigen 19-9, and a-fetoprotein, were normal. At CT, there was a 17 12 cm, wellcircumscribed, cystic mass with an ill-defined mural nodule. The mass was replacing the left hepatic lobe. There was no abnormal calcification on the unenhanced images. US showed similar features without any internal septa (Fig. 2). Left hemihepatectomy was performed under the preoperative diagnosis of biliary cystic neoplasm. During surgery, about 2000 ml of fluid was aspirated from the mass. On gross examination, the cut section revealed a large cyst with a small polyp with mucoid material on its surface. On histological examination, the lining epithelium showed slight papillary growth of epithelial cells
Intraductal oncocytic papillary neoplasm of the bile duct
with oncocytic cytoplasm. The histopathological diagnosis was intraductal oncocytic papillary neoplasm with low-grade malignancy. The patient has survived over 4 years after the surgery without recurrent disease.
Discussion The unified term IPMN was proposed in 1994 for pancreatic tumours characterized by the presence of a mucin-producing tumour and dilation of the branch or main ducts,6 and the term IOPN in 1996 as a subtype of IPMN. Recently, there was consensus regarding the nomenclature and criteria for classifying variants as distinctive IPMN subtypes, including gastric, intestinal, pancreato-biliary, and oncocytic type.7 Because of the shared origins of the biliary tract and pancreas, the two systems may exhibit the same pathological conditions. There have been several reports revealing close
843
similarities between the clinical, pathological, and radiological characteristics of biliary papillary tumours and IPMN of the pancreas.3,8e10 Oncocytic change is described in many different tumours in variable locations, but this change is extremely rare in the biliary system. In the hepatobiliary system, oncocytic variants of hepatocellular carcinoma and cholangiocarcinoma have been described.11 There have been two previous reports of oncocyctic papillary cystadenocarcinoma of the liver, in which both patients died of metastatic disease after 20 and 25 months, respectively.12,13 However, Sudo et al.12 reported that oncocytic papillary cystadenocarcinoma of the liver is more closely related to intraductal mucin-producing papillary cholangiocarcinoma than to hepatobiliary mucinous cystadenoma. Intraductal papillary neoplasms of the extrapancreatic biliary tree are rare tumours, and there are only a few reports of the oncocytic variant.14e16 Martin et al.15 described three cases of IOPN of the liver, predominantly found in men who
Figure 2 An intraductal oncocytic neoplasm in the left lobe of the liver in a 51-year-old man who presented with an incidentally detected cystic mass. (a) Contrast-enhanced CT image shows a 17 12 cm, well-circumscribed, lowattenuating mass with several enhancing, ill-defined, mural nodules (arrows) and a thin capsule. (b) US showed a huge unilocular cystic mass with several mural nodules (arrow). (c) A photograph of the surgical specimen showed an outgrowing unilocular cystic mass nearly replacing the left lobe of the liver (arrowheads). (d) Microscopically, the papillary epithelial cells revealed oncocytic cytoplasm (asterisks; H&E, 200). The histologic diagnosis was intraductal oncocytic papillary neoplasm, low-grade malignancy with marked cystic change.
844
presented with large (5 cm) mucinous, cystic lesions of the bile duct. A predominantly non-invasive pattern was seen and long-term survival was achieved with complete resection. Spector et al.16 reported a case of IOPN of the extrahepatic biliary tree with complex papillae, several layers of oncocytic cells, and mucin production. In the report of four cases of biliary IOPN by Rouzbahman et al.,14 the age range of the patients was 52e81 years, and symptoms were abdominal fullness/pain, chest pain, or transient jaundice, and dark urine. Two cases showed cystic mass lesions, and two cases showed the lesion confined to the intraluminal bile duct.14 In the present cases, the masses were detected incidentally without specific symptoms. However, one patient diagnosed with carcinoma complained of chronic fatigue and mild right upper quadrant pain, which was caused by unilocular cystic masses with mural nodules showing contrast enhancement. There were neither internal septa, nor calcifications, and no significant bile duct dilatation was evident. The initial radiological diagnosis was biliary cystic neoplasm. However, the pathology results indicated biliary IOPNs. According to Lim and colleagues,17 biliary cystic IPMN can be differentiated from biliary cystadenoma/carcinoma on CT images based on the presence of mural nodules and dilatation of the bile ducts distal to the cystic tumour. Based on their study, the present cases can be classified as biliary cystic IPMN morphologically because of the presence of mural nodules; however, significant bile duct dilatation was not present. To the best of the authors’ knowledge, there have been no reports of the clinical and radiological findings of biliary IOPN. The present study provides clinical and radiological findings of two cases of biliary IOPN presenting as incidentally-detected unilocular cystic masses with mural nodules.
References 1. Lee JW, Han JK, Kim TK, et al. CT features of intraductal intrahepatic cholangiocarcinoma. AJR Am J Roentgenol 2000;175:721e5.
S. Lee et al.
2. Yoon KH, Ha HK, Kim CG, et al. Malignant papillary neoplasms of the intrahepatic bile ducts: CT and histopathologic features. AJR Am J Roentgenol 2000;175:1135e9. 3. Kim HJ, Kim MH, Lee SK, et al. Mucin-hypersecreting bile duct tumor characterized by a striking homology with an intraductal papillary mucinous tumor (IPMT) of the pancreas. Endoscopy 2000;32:389e93. 4. Lim JH, Yoon KH, Kim SH, et al. Intraductal papillary mucinous tumor of the bile ducts. RadioGraphics 2004;24:53e66 [discussion -7]. 5. Adsay NV, Adair CF, Heffess CS, et al. Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol 1996;20:980e94. 6. Sessa F, Solcia E, Capella C, et al. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch 1994;425:357e67. 7. Furukawa T, Kloppel G, Volkan Adsay N, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch 2005;447: 794e9. 8. Lim JH, Yi CA, Lim HK, et al. Radiological spectrum of intraductal papillary tumors of the bile ducts. Korean J Radiol 2002;3:57e63. 9. Abraham SC, Lee JH, Hruban RH, et al. Molecular and immunohistochemical analysis of intraductal papillary neoplasms of the biliary tract. Hum Pathol 2003;34:902e10. 10. Shibahara H, Tamada S, Goto M, et al. Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms. Am J Surg Pathol 2004;28: 327e38. 11. Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors. Pathol Annu 1992;27(Pt 1):263e304. 12. Sudo Y, Harada K, Tsuneyama K, et al. Oncocytic biliary cystadenocarcinoma is a form of intraductal oncocytic papillary neoplasm of the liver. Mod Pathol 2001;14:1304e9. 13. Wolf HK, Garcia JA, Bossen EH. Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma. Mod Pathol 1992; 5:665e8. 14. Rouzbahman M, Serra S, Adsay NV, et al. Oncocytic papillary neoplasms of the biliary tract: a clinicopathological, mucin core and Wnt pathway protein analysis of four cases. Pathology 2007;39:413e8. 15. Martin RC, Klimstra DS, Schwartz L, et al. Hepatic intraductal oncocytic papillary carcinoma. Cancer 2002;95:2180e7. 16. Spector SA, Bejarano PA, Amortegui JD, et al. Intraductal oncocytic papillary neoplasm of the extrahepatic biliary tree: first report. Am Surg 2004;70:55e8. 17. Lim JH, Jang KT, Rhim H, et al. Biliary cystic intraductal papillary mucinous tumor and cystadenoma/cystadenocarcinoma: differentiation by CT. Abdom Imaging 2007;32: 644e51.
CASE REPORT
Intraductal oncocytic papillary neoplasm of the bile duct: ultrasonography and CT findings with pathological correlations S. Leea, Y.-S. Kima,*, W.J. Leea, K.-T. Jangb a
Department of Radiology and Center for Imaging Science, and bDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Received 20 November 2008; received in revised form 2 February 2009; accepted 13 February 2009
Introduction
Case reports
Papillary tumours of the bile ducts are characterized by an intraluminal papillary mass in association with bile duct obstruction and dilatation.1,2 Some of these tumours secrete an excessive amount of mucin, which may disturb bile flow and cause severe ductal dilatation.3 The condition currently is most commonly described as intraductal papillary mucinous tumour or neoplasm (IPMN) of the bile ducts.4 In 1996, Adsay et al.5 proposed the term, intraductal oncocytic papillary neoplasm (IOPN) for a distinctive cystic intraductal tumour with oncocytic features and mucin production as a subtype of IPMN of the pancreas. However, oncocytic (i.e., eosinophilic) changes are extremely rare in the biliary system. To our knowledge, fewer than 10 cases of IOPN of the liver have been reported previously. As the diagnostic concept of IOPN of the biliary system is a relatively recent introduction and the frequency of this diagnosis is increasing, radiologists need to be familiar with this entity. In this report, two cases of IOPN of the bile duct, comprising a unilocular cystic mass with mural nodules, are presented. The radiological features on ultrasonography (US) and computed tomography (CT) are illustrated and correlated with the pathological findings.
Case 1
* Guarantor and correspondent: Y.-S. Kim, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: þ82 2 3410 2518; fax: þ82 2 3410 2559. E-mail address: [email protected] (Y.-S. Kim).
A 57-year-old woman was referred to our hospital for the evaluation of a hepatic mass. Ten years before, a 2.8 cm cystic lesion in the liver had been detected on routine abdominal US incidentally. On follow-up US, 3 years before the visit to our hospital, the mass measured 3.1 cm, and the solid component inside the cystic mass had newly appeared. The patient refused biopsy of the mass. Recently, she presented with chronic fatigue and mild right upper quadrant pain of 3 months. At physical examination, no abnormalities were noted. Liver function tests were also normal. Hepatitis B and C serology tests were negative. Tumour markers, including carcinoembryonic antigen, carbohydrate antigen 19-9, and a-fetoprotein, were normal. On CT there was a 4 cm, well-demarcated, cystic mass with two mural nodules in segment IV of the liver. The mass did not contain calcification. On arterial and portal venous-phase images, a thin capsule and mural nodules showed contrast enhancement. US revealed a unilocular cystic mass with two mural nodules. Colour Doppler US failed to demonstrate the vascularity of the mural nodules (Fig. 1). Laparotomy was performed under the tentative diagnosis of atypical biliary cystadenocarcinoma. The mass separated from the liver parenchyma easily. However, it appeared as a mass originating from the extrahepatic bile duct because it was firmly attached. Operative cholangiography did not show any communication between the bile duct and
0009-9260/$ - see front matter ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.02.017
842
S. Lee et al.
Figure 1 An intraductal oncocytic neoplasm involving the extrahepatic duct in a 57-year-old woman who presented with an incidentally detected cystic mass. (a) Contrast-enhanced CT image shows a 4 3.3 cm, well-demarcated, hypoattenuating mass with enhancing two mural nodules and a thin capsule in the left lobe of the liver (arrows). (b) US demonstrated a unilocular cystic mass with two mural nodules (arrows) showing a paucity of intramural vascularity. (c) Intraoperative cholangiogram did not show a connection between the cystic mass and the extrahepatic duct. Arrows indicate the presumed location of the cystic mass to the duct, which is displaced by the mass. (d) The photograph of the cut surface of the cyst shows multiple papillary fronds with mucin, which measured up to 2.5 2 cm (arrowheads). (e) At low magnification, from the area of mural nodule, complex papillary fronds with fibrovascular core (arrows) were noted [haematoxylin and eosin (H&E) staining, 40]. (f) At high magnification, the papillary tumour cells disclosed oncocytic cytoplasm (asterisks; H&E staining, 200). Based on these histopathological findings, the mass was diagnosed as intraductal oncocytic papillary neoplasm (carcinoma).
the cystic mass. En-block resection of the mass with the common bile duct was performed. On gross examination, the cut section showed a thickwalled, unilocular cyst that measured 4 4 cm. The inner surface of the cyst was covered with mucoid material and multiple papillary excrescences measuring up to 2.5 cm. On histopathological examination, the tumour had thick, branching, complex papillary fronds with a fibrovascular papillary core. In some areas, the papillae become confluent to form solid aggregates of cells. The tumour cells were homogeneous, eosinophilic, with abundant, granular cytoplasm. The histopathological diagnosis was intraductal oncocytic papillary carcinoma. The patient has survived over 1 year after the surgery without recurrent disease.
Case 2 A 51-year-old man presented with an increasing cystic mass with small mural nodules in the liver,
which had been previously detected incidentally on US. The size of the mass had measured 8.8 cm initially. CT was performed 6 years after the initial detection of the mass. Hepatitis B and C serology tests were negative. Liver function tests and tumour markers, including carcinoembryonic antigen, carbohydrate antigen 19-9, and a-fetoprotein, were normal. At CT, there was a 17 12 cm, wellcircumscribed, cystic mass with an ill-defined mural nodule. The mass was replacing the left hepatic lobe. There was no abnormal calcification on the unenhanced images. US showed similar features without any internal septa (Fig. 2). Left hemihepatectomy was performed under the preoperative diagnosis of biliary cystic neoplasm. During surgery, about 2000 ml of fluid was aspirated from the mass. On gross examination, the cut section revealed a large cyst with a small polyp with mucoid material on its surface. On histological examination, the lining epithelium showed slight papillary growth of epithelial cells
Intraductal oncocytic papillary neoplasm of the bile duct
with oncocytic cytoplasm. The histopathological diagnosis was intraductal oncocytic papillary neoplasm with low-grade malignancy. The patient has survived over 4 years after the surgery without recurrent disease.
Discussion The unified term IPMN was proposed in 1994 for pancreatic tumours characterized by the presence of a mucin-producing tumour and dilation of the branch or main ducts,6 and the term IOPN in 1996 as a subtype of IPMN. Recently, there was consensus regarding the nomenclature and criteria for classifying variants as distinctive IPMN subtypes, including gastric, intestinal, pancreato-biliary, and oncocytic type.7 Because of the shared origins of the biliary tract and pancreas, the two systems may exhibit the same pathological conditions. There have been several reports revealing close
843
similarities between the clinical, pathological, and radiological characteristics of biliary papillary tumours and IPMN of the pancreas.3,8e10 Oncocytic change is described in many different tumours in variable locations, but this change is extremely rare in the biliary system. In the hepatobiliary system, oncocytic variants of hepatocellular carcinoma and cholangiocarcinoma have been described.11 There have been two previous reports of oncocyctic papillary cystadenocarcinoma of the liver, in which both patients died of metastatic disease after 20 and 25 months, respectively.12,13 However, Sudo et al.12 reported that oncocytic papillary cystadenocarcinoma of the liver is more closely related to intraductal mucin-producing papillary cholangiocarcinoma than to hepatobiliary mucinous cystadenoma. Intraductal papillary neoplasms of the extrapancreatic biliary tree are rare tumours, and there are only a few reports of the oncocytic variant.14e16 Martin et al.15 described three cases of IOPN of the liver, predominantly found in men who
Figure 2 An intraductal oncocytic neoplasm in the left lobe of the liver in a 51-year-old man who presented with an incidentally detected cystic mass. (a) Contrast-enhanced CT image shows a 17 12 cm, well-circumscribed, lowattenuating mass with several enhancing, ill-defined, mural nodules (arrows) and a thin capsule. (b) US showed a huge unilocular cystic mass with several mural nodules (arrow). (c) A photograph of the surgical specimen showed an outgrowing unilocular cystic mass nearly replacing the left lobe of the liver (arrowheads). (d) Microscopically, the papillary epithelial cells revealed oncocytic cytoplasm (asterisks; H&E, 200). The histologic diagnosis was intraductal oncocytic papillary neoplasm, low-grade malignancy with marked cystic change.
844
presented with large (5 cm) mucinous, cystic lesions of the bile duct. A predominantly non-invasive pattern was seen and long-term survival was achieved with complete resection. Spector et al.16 reported a case of IOPN of the extrahepatic biliary tree with complex papillae, several layers of oncocytic cells, and mucin production. In the report of four cases of biliary IOPN by Rouzbahman et al.,14 the age range of the patients was 52e81 years, and symptoms were abdominal fullness/pain, chest pain, or transient jaundice, and dark urine. Two cases showed cystic mass lesions, and two cases showed the lesion confined to the intraluminal bile duct.14 In the present cases, the masses were detected incidentally without specific symptoms. However, one patient diagnosed with carcinoma complained of chronic fatigue and mild right upper quadrant pain, which was caused by unilocular cystic masses with mural nodules showing contrast enhancement. There were neither internal septa, nor calcifications, and no significant bile duct dilatation was evident. The initial radiological diagnosis was biliary cystic neoplasm. However, the pathology results indicated biliary IOPNs. According to Lim and colleagues,17 biliary cystic IPMN can be differentiated from biliary cystadenoma/carcinoma on CT images based on the presence of mural nodules and dilatation of the bile ducts distal to the cystic tumour. Based on their study, the present cases can be classified as biliary cystic IPMN morphologically because of the presence of mural nodules; however, significant bile duct dilatation was not present. To the best of the authors’ knowledge, there have been no reports of the clinical and radiological findings of biliary IOPN. The present study provides clinical and radiological findings of two cases of biliary IOPN presenting as incidentally-detected unilocular cystic masses with mural nodules.
References 1. Lee JW, Han JK, Kim TK, et al. CT features of intraductal intrahepatic cholangiocarcinoma. AJR Am J Roentgenol 2000;175:721e5.
S. Lee et al.
2. Yoon KH, Ha HK, Kim CG, et al. Malignant papillary neoplasms of the intrahepatic bile ducts: CT and histopathologic features. AJR Am J Roentgenol 2000;175:1135e9. 3. Kim HJ, Kim MH, Lee SK, et al. Mucin-hypersecreting bile duct tumor characterized by a striking homology with an intraductal papillary mucinous tumor (IPMT) of the pancreas. Endoscopy 2000;32:389e93. 4. Lim JH, Yoon KH, Kim SH, et al. Intraductal papillary mucinous tumor of the bile ducts. RadioGraphics 2004;24:53e66 [discussion -7]. 5. Adsay NV, Adair CF, Heffess CS, et al. Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol 1996;20:980e94. 6. Sessa F, Solcia E, Capella C, et al. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch 1994;425:357e67. 7. Furukawa T, Kloppel G, Volkan Adsay N, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch 2005;447: 794e9. 8. Lim JH, Yi CA, Lim HK, et al. Radiological spectrum of intraductal papillary tumors of the bile ducts. Korean J Radiol 2002;3:57e63. 9. Abraham SC, Lee JH, Hruban RH, et al. Molecular and immunohistochemical analysis of intraductal papillary neoplasms of the biliary tract. Hum Pathol 2003;34:902e10. 10. Shibahara H, Tamada S, Goto M, et al. Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms. Am J Surg Pathol 2004;28: 327e38. 11. Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors. Pathol Annu 1992;27(Pt 1):263e304. 12. Sudo Y, Harada K, Tsuneyama K, et al. Oncocytic biliary cystadenocarcinoma is a form of intraductal oncocytic papillary neoplasm of the liver. Mod Pathol 2001;14:1304e9. 13. Wolf HK, Garcia JA, Bossen EH. Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma. Mod Pathol 1992; 5:665e8. 14. Rouzbahman M, Serra S, Adsay NV, et al. Oncocytic papillary neoplasms of the biliary tract: a clinicopathological, mucin core and Wnt pathway protein analysis of four cases. Pathology 2007;39:413e8. 15. Martin RC, Klimstra DS, Schwartz L, et al. Hepatic intraductal oncocytic papillary carcinoma. Cancer 2002;95:2180e7. 16. Spector SA, Bejarano PA, Amortegui JD, et al. Intraductal oncocytic papillary neoplasm of the extrahepatic biliary tree: first report. Am Surg 2004;70:55e8. 17. Lim JH, Jang KT, Rhim H, et al. Biliary cystic intraductal papillary mucinous tumor and cystadenoma/cystadenocarcinoma: differentiation by CT. Abdom Imaging 2007;32: 644e51.