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Biliary Intraductal Papillary-Mucinous Neoplasm Manifesting Only as Dilatation of the Hepatic Lobar or Segmental Bile Ducts: Imaging Features in Six Patients

¹ Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul, Korea.
² Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Received February 19, 2007; accepted after revision April 13, 2008.

 
Address correspondence to J. H. Lim.

Abstract

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OBJECTIVE. The purpose of this study was to evaluate the imaging features of intrahepatic biliary intraductal papillary-mucinous neoplasm manifesting only as dilatation of the lobar or segmental bile ducts without a visible mass to determine whether this type of cholangiocarcinoma can be recognized on the basis of distinct imaging features.

CONCLUSION. Intrahepatic biliary intraductal papillary-mucinous neoplasm can spread along the mucosa without forming a mass and can produce a large amount of mucin. Severe dilatation of the lobar or segmental intrahepatic bile ducts with crowding and severe atrophy of the hepatic parenchyma are helpful imaging findings.

Keywords: bile duct dilatation • bile duct tumor • CT • MRI • mucin-producing tumor

Introduction

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Tumors of intrahepatic bile ducts arise from stem cells of the bile ductules, lining biliary epithelium, or epithelium of peribiliary glands [1]. Although most intrahepatic bile duct tumors cause luminal obliteration or stenosis due to tumor nodule formation or periductal infiltration, some exhibit intraductal papillary growth and mucosal spread along the bile duct lumen [2]. Growing or spreading intraductal biliary tumors have been found in association with chronic biliary disease, such as hepatolithiasis and clonorchiasis [1, 3], but they also occur without preexisting biliary disease. Biliary papillomatosis and intraductal mucin-producing papillary neoplasms seem to be in this category [4–8]. Mucin hypersecretion is a frequent manifestation of biliary intraductal papillary neoplasia [6]. Biliary mucosal dysplasia and in situ and microinvasive carcinoma with a papillary configuration also can be included [1]. Because of mucin hypersecretion, affected bile ducts exhibit marked dilatation, and tumors are confined within the dilated part of the bile ducts [8–10]. Parts of the biliary tree not affected by neoplasia also sometimes are dilated.

Although most intrahepatic bile duct tumors, mostly cholangiocarcinomas, manifest as gross large or small intrahepatic tumors [4], in some cases the tumor is not visible on images or even in gross specimens, and severe dilatation of the hepatic lobar or segmental bile ducts is the only finding. We have found biliary intraductal papillary-mucinous neoplasms (IPMNs) diagnosed only after hepatic resection for the management of intrahepatic bile duct dilatation of unknown causation. The purpose of this study was to discern the imaging features of intrahepatic biliary IPMNs manifesting only as lobar or segmental bile duct dilatation in six patients to determine whether this type of cholangiocarcinoma can be recognized on the basis of its imaging features.

Materials and Methods

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Patients
From January 2003 to January 2007, the cases of 128 patients with pathologically proven intrahepatic biliary neoplasms were identified in a search of the pathology database at our hospital. Twenty-nine of the patients had biliary intraductal papillary neoplasms. After thorough review of radiology and pathology reports in conjunction with informal review of personal logs, we identified the cases of six patients with biliary IPMN with only dilatation of the lobar or segmental bile ducts without a gross visible mass or thickening of the bile duct wall (four women, two men; mean age, 60 years; range, 51–73 years). Twenty-three patients had measurable tumors in the bile ducts. Hospital records, photographs of resected specimens, and histopathologic slides were available in all cases. CT was performed on all six patients, MRI on four, sonography on two, and cholangiography on three.

Imaging Methods
CT—CT scans of five patients were obtained on a single-detector or an MDCT scanner (LightSpeed QX/i, LightSpeed Ultra, or LightSpeed 16, GE Healthcare; Brilliance, Philips Healthcare; Aquilion, Toshiba) before and after IV administration of contrast material. With bolus-triggered technique, scanning was started 45 and 70 seconds for the arterial and portal venous phases after the start of injection of 120 mL of nonionic contrast material (iopamidol, Iopamiro 300, Bracco) at 4 mL/s through an antecubital vein. Images were obtained with 2.5- to 5.0-mm slice thickness and 2.5- to 5.0-mm intervals. For one patient, the scanner manufacturer and scanning technique were unknown because CT was performed at a hospital other than ours.

MR cholangiography—Three patients underwent MR cholangiopancreatography with a 3.0-T superconducting MRI unit (Intera Achieva, Philips Healthcare) with a phased-array multicoil system. Coronal T2- and heavily T2-weighted single-shot fast spin-echo images were obtained with the following parameters: TR/effective TE, shortest/80–150; field of view, 34 x 34 cm; slice thickness, 5 mm; no interslice gap; reconstruction matrix size, 512 x 512; fat saturation; number of signals acquired, 2; acquisition time, approximately 1 minute 10 seconds; reduction factor, 2. Coronal single-projection images and 3D heavily T2-weighted images were obtained with singleshot fast spin-echo sequence with the following para meters: TR/effective TE, shortest/740; acquisition time, 2 seconds in a single projection; slab thickness, 5 cm; no sensitivity encoding. The other parameters were the same as for the fast spin-echo technique. With coronal multislab fast spin-echo and single-shot fast spin-echo se quences, source images were processed on a con sole with maximum-intensity-projection re con struction, including target-volume maximum intensity projection. The MRI technique for a fourth patient was unknown because imaging was performed at a hospital other than ours.

Correlation of Image Features and Pathologic Findings
Two gastrointestinal radiologists reviewed CT scans, cholangiograms, and MR cholangiograms in one interpretation session. Decisions regarding imaging features were determined by consensus. The radiologists evaluated the images in terms of presence of a mass, bile duct dilatation, hepatic lobar or segmental atrophy, and mucin in the bile ducts on cholangiograms. A pathologist sub-specialized in examinations of the pancreatobiliary system reviewed photographs of resected specimens and histopathologic slides. Special attention was paid to the presence of any visible mass in the bile ducts, histopathologic diagnosis, and growth pattern of tumor spread. Imaging findings were correlated with photographic findings of resected gross specimens by the two interpreting radiologists and the pathologist. The small number of cases precluded meaningful statistical analysis.

Results

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CT, MRI, and sonography depicted dilatation of lobar and segmental bile ducts in all six patients (Figs. 1A, 1B, 1C, 1D, 1E, 1F, 1G and 2A, 2B, 2C, 2D, 2E). In three patients, only affected lobar or segmental bile ducts were dilated, probably owing to partial or complete obstruction, but in another three patients, affected and unaffected bile ducts and extrahepatic bile ducts were dilated without evidence of obstruction. All patients had severe parenchymal atrophy of the affected hepatic lobe or segment. In five patients, hepatic parenchymal atrophy was so severe that there was almost no hepatic parenchyma in the affected liver (Figs. 1A, 1B, 1C, 1D, 1E, 1F, 1G and 2A, 2B, 2C, 2D, 2E). In one patient, parenchymal atrophy was moderate. In all patients, gross and microscopic examination of the dilated bile ducts of the involved hepatic lobes or segments revealed mucin. In two patients, mucin was present in the affected bile ducts and in the distal bile ducts (Fig. 2A, 2B, 2C, 2D, 2E).

View larger version (143K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Unenhanced CT images show severe dilatation of bile ducts of left hepatic lobe containing several small calcified stones (arrows).

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Unenhanced CT images show severe dilatation of bile ducts of left hepatic lobe containing several small calcified stones (arrows).

View larger version (148K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Contrast-enhanced CT images show severe dilatation of bile ducts of left hepatic lobe with no visible hepatic parenchyma because of severe parenchymal atrophy. Dilated intrahepatic ducts are filled with fluid and small stones (arrows).

View larger version (168K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Contrast-enhanced CT images show severe dilatation of bile ducts of left hepatic lobe with no visible hepatic parenchyma because of severe parenchymal atrophy. Dilated intrahepatic ducts are filled with fluid and small stones (arrows).

View larger version (153K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Endoscopic retrograde cholangiogram shows marked dilatation of intrahepatic and extrahepatic ducts. Large and small filling defects (arrows) due to stones and mucin are evident.

View larger version (72K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1F —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Photograph of resected specimen of left hepatic lobe shows severe dilatation of bile ducts with fibrous thickening (arrows). Hepatic parenchyma is almost absent. No tumor is visible in dilated bile ducts. Bile ducts were filled with mucopurulent fluid.

View larger version (113K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1G —73-year-old man with intraductal papillary-mucinous adenoma spreading along entire length of intrahepatic bile ducts of left hepatic lobe. Photomicrograph shows intraductal proliferation of papillary-mucinous epithelium of adenoma. (H and E, x40)

View larger version (164K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —66-year-old woman with epithelial hyperplasia and moderate to severe dysplasia of entirety of right hepatic bile ducts. Contrast-enhanced CT images show markedly dilated bile ducts in right and left hepatic lobes and extrahepatic ducts (arrow, C). Severe parenchymal atrophy of right hepatic lobe is evident. GB = gallbladder.

View larger version (167K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —66-year-old woman with epithelial hyperplasia and moderate to severe dysplasia of entirety of right hepatic bile ducts. Contrast-enhanced CT images show markedly dilated bile ducts in right and left hepatic lobes and extrahepatic ducts (arrow, C). Severe parenchymal atrophy of right hepatic lobe is evident. GB = gallbladder.

View larger version (164K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —66-year-old woman with epithelial hyperplasia and moderate to severe dysplasia of entirety of right hepatic bile ducts. Contrast-enhanced CT images show markedly dilated bile ducts in right and left hepatic lobes and extrahepatic ducts (arrow, C). Severe parenchymal atrophy of right hepatic lobe is evident. GB = gallbladder.

View larger version (135K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —66-year-old woman with epithelial hyperplasia and moderate to severe dysplasia of entirety of right hepatic bile ducts. Cholangiogram through drainage catheter shows severe dilatation of extrahepatic duct containing multiple elongated filling defects (arrows) caused by mucin.

View larger version (130K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E —66-year-old woman with epithelial hyperplasia and moderate to severe dysplasia of entirety of right hepatic bile ducts. Photomicrograph of pathologic specimen shows intraductal proliferation of papillary-mucinous epithelium of high-grade dysplasia and dysplastic cells diffusely lining bile ducts. (H and E, x40)

Discussion

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Most cases of intrahepatic bile duct tumor, including cholangiocarcinoma, manifest as a sizable mass with or without bile duct dilatation proximal to the tumor [4]. A mass that originates in a small peripheral bile duct can grow to appreciable size. Because only small bile ducts may be obstructed, patients usually have no symptoms. When a mass grows large enough to produce pressure on the liver capsule, symptoms appear. On the other hand, when a number of bile ducts are obstructed by a large mass, the patient may experience jaundice. In patients with periductal-infiltrating or intraductal-growing cholangiocarcinoma, a mass may be evident on images and in pathologic specimens.

In our series of six cases of surgically and pathologically confirmed biliary tumors, the bile ducts were dilated and lined by papillarymucinous epithelial cells with varying degrees of dysplasia without a gross mass. The clinical features were nonspecific or nonexistent. Preoperative interpretations of imaging studies also were nonspecific or misleading: lobar or segmental biliary duct dilatation with severe hepatic parenchymal atrophy.

The gross and microscopic appearance of biliary IPMNs depends on the interplay of two factors: epithelial proliferation and mucin secretion. When the former predominates, the result is intraductal formation of a papillary mass; when the latter predominates, the result is gross dilatation of ducts, which are filled with mucin rather than a mass [10]. Thus we suspect that our cases of intrahepatic biliary IPMN represent mucin secretion rather than epithelial proliferation in pathogenesis and thus did not manifest as a visible mass at either imaging or pathologic examination. When the papillary-mucinous epithelial cells of biliary IPMN spread superficially along the mucosa of the bile duct without formation of a mass and bile ducts are partially occluded, at imaging it is difficult or impossible to recognize a tumor within bile ducts. Bile ducts with mucosal epithelial hyperplasia or dysplasia fall into this category. Bile ducts are dilated by excessive mucin produced by papillary-mucinous epithelial cells with varying degrees of dysplasia.

A small intraductal papillary mass in patients with biliary IPMN can be friable and easily detached from the mucosal surface of the bile duct and therefore not be detected [1, 5, 6]. Papillary tumors of the bile ducts are intraluminal with innumerable minute frond-like projections. Because the papillary projections are long and slender, the tumors are friable and slough spontaneously. The sloughed tumor fragments can float within the bile duct, resulting in intermittent partial biliary obstruction, which mimics bile duct stones clinically and radiologically [5]. In patients with this type of tumor, when the intraductal portion sloughs, there is no tumor in the bile ducts. Dilation of the bile ducts is caused by chronic incomplete biliary obstruction.

Biliary papillary neoplasms can produce large amounts of mucin [1, 6]. This type of neoplasm tends to contain foci of a mucinous carcinoma element, and this element can predominate and excrete mucin [1]. The viscous mucin does not drain easily, and the bile ducts become dilated owing to retention of a large amount of mucin. Therefore, tumor-harboring bile ducts and other bile ducts, frequently entire biliary trees, become dilated [6].

In all of the cases in our study, there was profound atrophy of the hepatic parenchyma of affected hepatic lobes or segments. Severe hepatic parenchymal atrophy of involved hepatic lobes or segments can be explained by long-standing increased ductal pressure on adjacent hepatic parenchyma caused by partial obstruction and the presence of excessive mucin. In severe cases, hepatic parenchyma is almost absent. These features result in compensatory hypertrophy in the hepatic lobe that does not contain a neoplasm. Intrahepatic peripheral or hilar cholangiocarcinoma can cause lobar or segmental hepatic parenchymal atrophy due to tumor invasion in corresponding portal vein branches [11]. When cholangiocarcinoma arises on the back ground of recurrent pyogenic cholangitis, the hepatic segment harboring the tumor exhibits severe parenchymal atrophy, and the portal venous branch is markedly narrowed or obliterated [12]. Differentiation is possible: In these patients, a sizable hepatic mass is evident and may be associated with bile duct stones; the bile ducts are not markedly dilated.

Biliary IPMN has been described [13–16] as a counterpart of pancreatic IPMN in terms of its histopathologic and pathophysiologic features, production of a large amount of mucin, and clinical behavior. Cases of papillary-mucinous tumors simultaneously involving bile ducts and pancreatic ducts have been reported [17, 18]. Because of the embryologically common origins of the biliary and pancreatic systems, homology of the pancreatic condition theoretically exists between the two systems. In the pancreas, mucin-producing tumors often spread diffusely along the pancreatic ducts without gross mass formation. Depending on the location of the tumors, the main pancreatic duct is dilated diffusely (main duct type) or branch ducts are dilated cystically (branch duct type). Similarly in the biliary system, biliary IPMN can manifest as localized bile duct dilatation without a sizable gross mass. Like pancreatic IPMN, biliary IPMN is more likely a benign biliary mucin-producing lesion, such as biliary papillary hyperplasia, dysplasia, or adenoma (Table 1).

The clinical implications of our findings are important. When they recognize lobar or segmental bile duct dilatation without a visible mass and with severe hepatic parenchymal atrophy of the affected liver, radiologists should keep in mind the possibility of biliary IPMN manifesting only as bile duct dilatation without a visible mass. If early surgery eradicates the tumor, such patients can be expected to survive a long time [1]. The imaging findings among patients with recurrent pyogenic cholangitis with resultant stricture of a bile duct may be similar, but atrophy of the hepatic parenchyma is mild.

References

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1. Nakanuma Y, Sasaki M, Ishikawa A, Tsui W, Chen TC, Huang SF. Biliary papillary neoplasm of the liver. Histol Histopathol 2002; 17:851 –861[Medline]
2. Colombari R, Tsui WM. Biliary tumors of the liver. Semin Liver Dis 1995; 15:402 –413[Medline]
3. Kim YI, Yu ES, Kim ST. Intraductal variant of peripheral cholangiocarcinoma of the liver with Clonorchis sinensis infection. Cancer 1989; 63:1562 –1566[CrossRef][Medline]
4. Lim JH. Cholangiocarcinoma: morphologic classification according to growth pattern and imaging findings. AJR2003; 181:819 –827[Free Full Text]
5. Lim JH, Kim MH, Kim TK, et al. Papillary neoplasms of the bile duct that mimic biliary stone disease. RadioGraphics2003; 23:447 –455[Abstract/Free Full Text]
6. Lim JH, Yoon KH, Kim SH, et al. Intraductal papillary mucinous tumor of the bile duct. RadioGraphics2004; 24:53 –66[Abstract/Free Full Text]
7. Okulski EG, Dolin BJ, Kandawalla NM. Intrahepatic biliary papillomatosis. Arch Pathol 1997;103 : 647–649
8. Terada T, Mitsui T, Nakanuma Y, Miura S, Toya D. Intrahepatic biliary papillomatosis arising in nonobstructive intrahepatic biliary dilatation confined to the hepatic lobe. Am J Gastroenterol 1991; 86:1523 –1526[Medline]
9. Ohashi K, Nakajima Y, Kanehiro H, et al. Ki-rad mutations and p53 protein expression in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology 1995;109 :1612 –1617[CrossRef][Medline]
10. Rosai T. Ackerman's surgical pathology, 9th ed. St. Louis, MO: Mosby, 2004:1078 –1080
11. Takayasu K, Muramatsu Y, Shima Y, Moriyama N, Yamada T, Makuuchi M. Hepatic lobar atrophy following obstruction of the ipsilateral portal vein from cholangiocarcinoma. Radiology 1986;160 : 389–393[Abstract/Free Full Text]
12. Kim JH, Kim TK, Eun HW, et al. CT findings of cholangiocarcinoma associated with recurrent pyogenic cholangitis. AJR2006; 187:1571 –1577[Abstract/Free Full Text]
13. Kloppel G, Kosmahl M. Is the intraductal papillary mucinous neoplasia of biliary tract a counterpart of the pancreatic papillary mucinous neoplasm? J Hepatol 2006;44 : 249–250[CrossRef][Medline]
14. Zen Y, Sasaki M, Fujii T, et al. Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct: an immunohistochemical study of 110 cases of hepatolithiasis. J Hepatol 2006;4 : 350–358
15. 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. Endoscopy2000; 32:389 –393[CrossRef][Medline]
16. Oshikiri T, Kashimura N, Katanuma A, et al. Mucin-secreting bile duct adenoma: clinicopathological resemblance to intraductal papillary mucinous tumor of the pancreas. Dig Surg2002; 19:324 –327[CrossRef][Medline]
17. Hubens G, Delvaux G, Williams G, et al. Papillomatosis of the intra- and extrahepatic bile ducts with involvement of the pancreatic duct. Hepatogastroenterology 1991;38 : 413–418[Medline]
18. Joo YH, Kim MH, Lee SK, et al. A case of mucin-hypersecreting intrahepatic bile duct tumor associated with pancreatic intraductal papillary mucinous tumor. Gastrointest Endosc 2000;52 : 409–412[CrossRef][Medline]

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This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lim, J. H. Articles by Choi, D. Search for Related Content PubMed PubMed Citation Articles by Lim, J. H. Articles by Choi, D. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?