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From the Archives of the AFIP

Benign Tumors and Tumorlike Lesions of the Gallbladder and Extrahepatic Bile Ducts: Radiologic-Pathologic Correlation¹

¹ From the Departments of Radiologic Pathology (A.D.L.) and Hepatic and Gastrointestinal Pathology (L.A.M.), Armed Forces Institute of Pathology, Room M-121, Alaska and Fern Sts, NW, Washington, DC 20306-6000; Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (A.D.L., R.M.A); Department of Radiology, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Tex (R.M.A.); and Department of Radiology, University of Washington, Seattle (C.A.R.). Received August 15, 2001; revision requested September 24 and received October 17; accepted October 19. Address correspondence to A.D.L. (e-mail: levya@afip.osd.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
A diverse spectrum of benign tumors and tumorlike lesions arises from the gallbladder and bile ducts, and despite their diversity, these lesions share common embryologic origins and histologic characteristics. Although these lesions are relatively uncommon, their importance lies in their ability to mimic malignant lesions in these locations. Benign neoplasms are derived from the epithelial and nonepithelial structures that compose the normal gallbladder and bile ducts. The epithelium gives rise to adenomas, cystadenomas, and the unusual condition of biliary papillomatosis. Granular cell tumors, neurofibromas, ganglioneuromas, paragangliomas, and leiomyomas are examples of benign tumors that may originate from nonepithelial structures. Tumorlike lesions are more commonly found in the gallbladder and include xanthogranulomatous cholecystitis, adenomyomatous hyperplasia, cholesterol polyps, and heterotopias. In the clinical setting of a patient with nonspecific abdominal complaints or symptoms of biliary obstruction, the discovery of a gallbladder or bile duct polyp or mass, gallbladder wall thickening, or biliary stricture is most often indicative of malignancy. However, the differential diagnosis should include benign tumors and tumorlike lesions. The preoperative determination of a benign lesion may significantly alter therapy and patient prognosis.

Index Terms: Bile ducts, neoplasms, 768.31 • Gallbladder, neoplasms, 768.31

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Identify the radiologic and pathologic features of benign tumors of the gallbladder and bile ducts.
  
• Describe the radiologic spectrum of tumorlike lesions of the gallbladder.
  
• Discuss the differential diagnosis of polypoid and infiltrating masses of the gallbladder and bile ducts.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
There is a diverse histologic spectrum of neoplasms that arise in the gallbladder and extrahepatic bile ducts. The gallbladder and extrahepatic bile ducts share this histologic diversity, since they have common embryologic origins. However, many of these neoplasms have remarkably different epidemiology and clinical manifestations. Although benign tumors of the gallbladder and bile ducts are uncommon, they are a challenge to the radiologist and surgeon because of the complex anatomic relationships that these structures share with adjacent vital organs. In addition, there are a number of nonneoplastic tumorlike lesions that should be considered in the differential diagnosis of a gallbladder or bile duct mass, polyp, focal wall thickening, or stricture.

Knowledge of the characteristics of benign tumors and tumorlike lesions of the gallbladder and bile ducts is important because they frequently mimic the more ominous malignant neoplasms that develop in these locations. This article reviews the clinical, pathologic, and radiologic features of benign tumors and tumorlike lesions of the gallbladder and bile ducts.

	Embryologic Development

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
The gallbladder, bile ducts, and liver begin to develop during the 4th week of embryogenesis as a ventral bud from the most caudal aspect of the foregut (the future duodenum). This bud is called the hepatic diverticulum, and it grows between the layers of the ventral mesentery (Fig 1). The hepatic diverticulum has two distinct components: pars hepatica and pars cystica (1). The pars hepatica, the most cranial component, gives rise to the liver, common hepatic duct, and intrahepatic bile ducts. The pars cystica, the most caudal component, gives rise to the cystic diverticulum. The cystic diverticulum is the anlage of the gallbladder and the cystic duct. The original hepatic diverticulum elongates to form the common bile duct. These structures begin as solid cords, but by the 8th week of gestation, a lumen has been established throughout the biliary tract.

View larger version (60K): [in this window] [in a new window] [Download PPT slide]   Figure 1.  Drawing of the normal embryologic development of the gallbladder and bile ducts illustrates the foregut (A), the cranial end of the hepatic diverticulum, which represents pars hepatica (B) and the cystic diverticulum (C). The ventral (D) and dorsal (E) pancreas are also demonstrated.

View larger version (160K): [in this window] [in a new window] [Download PPT slide]   Figure 2.  Normal histologic characteristics of the gallbladder. Photomicrograph (original magnification, x2; hematoxylin-eosin [H-E] stain) shows the mucosa as a single layer of columnar epithelium (solid arrow) with an underlying lamina propria, irregular muscle layer (open arrow), and loose perimuscular connective tissue (*). Note the absence of a serosa in this section of the gallbladder, which was taken from the hepatic margin.

View larger version (171K): [in this window] [in a new window] [Download PPT slide]   Figure 3.  Normal histologic characteristics of the extrahepatic bile duct. Photomicrograph (original magnification, x4; H-E stain) shows the epithelium as a single layer of columnar cells (arrow) with an underlying dense connective tissue wall.

	Tumor Classification

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

	Benign Epithelial Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

Gallbladder adenomas occur primarily in women, with a reported female-to-male ratio of 2.4:1 (6). Adenomas are usually asymptomatic and discovered incidentally during a radiologic evaluation for abdominal pain. Chronic or intermittent right upper quadrant pain may occur in patients with large adenomas or with adenomas that obstruct the cystic duct. A small proportion of gallbladder adenomas progress to carcinoma.

Gallbladder adenomas can be classified histologically as tubular, papillary, or tubulopapillary. The tubular adenoma is the most common variant (Fig 4a). It is covered by biliary epithelium and is composed of pyloric- or intestinal-type glands. In the former, cuboidal or columnar cells containing vesicular or hyperchromatic nuclei line the pyloric-type glands. In the latter, pseudostratified columnar epithelium lines the tubular intestinal-type glands. Papillary adenomas are composed of papillary structures lined by cuboidal or columnar cells (Fig 4b). The term tubulopapillary is used when both tubular glands and papillary structures each contribute to more than 20% of the tumor (6).

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  (a) Tubular adenoma of the gallbladder. Photomicrograph (original magnification, x4; H-E stain) shows a fibrovascular core lined by pyloric-type glands. (b) Papillary adenoma of the gallbladder. Photomicrograph (original magnification, x2; H-E stain) shows fingerlike processes lined by intestinal-type epithelium.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  (a) Tubular adenoma of the gallbladder. Photomicrograph (original magnification, x4; H-E stain) shows a fibrovascular core lined by pyloric-type glands. (b) Papillary adenoma of the gallbladder. Photomicrograph (original magnification, x2; H-E stain) shows fingerlike processes lined by intestinal-type epithelium.

View larger version (82K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Tubular adenoma of the gallbladder in a 67-year-old man with chronic right upper quadrant pain. (a) Photograph of the opened resected specimen shows a multilobulated, sessile, tan polyp attached to the gallbladder wall (straight arrow). Multiple gallstones are also present (curved arrow). (b) Longitudinal ultrasonographic (US) image shows an echogenic, lobulated, sessile polyp attached to the anterior wall of the gallbladder. The stones in the gross specimen were not identified in this imaging plane.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Tubular adenoma of the gallbladder in a 67-year-old man with chronic right upper quadrant pain. (a) Photograph of the opened resected specimen shows a multilobulated, sessile, tan polyp attached to the gallbladder wall (straight arrow). Multiple gallstones are also present (curved arrow). (b) Longitudinal ultrasonographic (US) image shows an echogenic, lobulated, sessile polyp attached to the anterior wall of the gallbladder. The stones in the gross specimen were not identified in this imaging plane.

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 6.  Papillary adenoma of the gallbladder in a 67-year-old man with right upper quadrant pain and a history of gallstones. Longitudinal US image of the gallbladder shows a medium echotexture mass (*) arising from the anterior wall of the gallbladder.

Extrahepatic Bile Duct Adenomas
Clinical and Pathologic Features.— Although the frequency of extrahepatic bile duct adenomas is not known, it is believed to be much lower than that of gallbladder adenomas. Because these lesions are rare, our current knowledge is based primarily on case reports. Patients with extrahepatic bile duct adenomas may present early with signs and symptoms of biliary obstruction, or the tumors may be found incidentally at surgery or during a radiologic evaluation of a patient with suspected gallbladder disease. The most common locations of biliary adenomas in descending order of frequency are the common bile duct, common hepatic duct, cystic duct, and intrahepatic bile ducts (7).

The majority of extrahepatic bile duct adenomas are tubular adenomas. They commonly are composed of intestinal-type glands (compared with the pyloric- and intestinal-type glands found in gallbladder adenomas) and are lined by pseudostratified columnar epithelium. Goblet cells, endocrine cells, and Paneth cells are frequently present within the epithelium. Papillary adenomas of the extrahepatic bile ducts also show intestinal differentiation and are commonly lined by mucin-containing columnar cells (7).

Radiologic Features.— On US images, extrahepatic bile duct adenomas appear as intraluminal, nonshadowing masses that are isoechoic relative to liver parenchyma (Fig 7) (11,12). Proximal intra- and extrahepatic biliary dilatation may also be present. Tumefactive sludge may have a sonographic appearance similar to that of these tumors; therefore, altering the patient position during the US examination may be helpful in distinguishing an intraluminal polypoid mass from sludge. If the adenoma is located in the distal common bile duct, it may simulate a pancreatic or ampullary mass at US and CT.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 7.  Tubular adenoma of the extrahepatic bile duct in a 46-year-old man with jaundice. Longitudinal US image of the common hepatic duct shows duct dilatation and a lobulated, mixed echotexture, intraluminal polypoid mass (arrow).

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Mucin-secreting extrahepatic bile duct adenoma in a 58-year-old woman with obstructive jaundice. (a) Endoscopic retrograde cholangiopancreatogram (ERCP) shows a castlike filling defect from mucin accumulation in the extrahepatic bile duct. (b) ERCP image obtained after balloon extraction of the mucus cast shows a lobulated sessile adenoma in the common hepatic duct (arrow).

View larger version (139K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Mucin-secreting extrahepatic bile duct adenoma in a 58-year-old woman with obstructive jaundice. (a) Endoscopic retrograde cholangiopancreatogram (ERCP) shows a castlike filling defect from mucin accumulation in the extrahepatic bile duct. (b) ERCP image obtained after balloon extraction of the mucus cast shows a lobulated sessile adenoma in the common hepatic duct (arrow).

Biliary Papillomatosis
Clinical and Pathologic Features.— Biliary papillomatosis is a rare disorder that was first described by Caroli and colleagues in 1959 (13). It is characterized by multiple and recurrent papillary adenomas in the biliary tract. The extrahepatic bile ducts are involved in the majority of cases. The intrahepatic bile ducts, cystic duct, gallbladder, and pancreatic duct may also be affected. Occasionally, the process involves only the intrahepatic ducts (14).

The majority of patients present for medical attention between the ages of 50 and 60 years, and men and women are equally affected (7). Patients present with signs and symptoms of biliary obstruction that is often complicated by cholangitis (15). Complete surgical excision of biliary papillomatosis is difficult and local recurrence is common. Some authors regard this lesion as a form of low-grade intraductal carcinoma (7). Papillomatosis has a greater potential for malignant transformation than a solitary adenoma.

Biliary papillomatosis is histologically characterized by biliary duct dilatation and multiple papillary adenomas. The epithelium of the papillary adenomas is composed of mucin-secreting columnar or cuboidal cells with basal nuclei. A fibrovascular core supports the epithelium (Fig 9a). Complex glandular structures (representing in situ carcinoma) and occasionally papillary carcinoma may be present.

View larger version (160K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Biliary papillomatosis in a 65-year-old man who presented with jaundice and sepsis. (a) Photomicrograph (original magnification, x2; H-E stain) shows multiple papillary projections lining the bile duct wall. (b) Photograph of the cut surface of the autopsy liver specimen shows multiple, tan, cauliflowerlike polyps within dilated intrahepatic bile ducts (arrows). There is fibrosis and thickening of the bile duct walls.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Biliary papillomatosis in a 65-year-old man who presented with jaundice and sepsis. (a) Photomicrograph (original magnification, x2; H-E stain) shows multiple papillary projections lining the bile duct wall. (b) Photograph of the cut surface of the autopsy liver specimen shows multiple, tan, cauliflowerlike polyps within dilated intrahepatic bile ducts (arrows). There is fibrosis and thickening of the bile duct walls.

Radiologic Features.— The most common sonographic feature of biliary papillomatosis is intra- and extrahepatic biliary dilatation. Single or multiple, nonshadowing, medium echotexture, intraluminal masses may be visualized (16–18). Low-level echoes within the lumen of the bile ducts may represent mucin, sludge, or debris. Occasionally, sloughed tumor fragments may be seen as mobile masses within the bile ducts.

CT images of biliary papillomatosis in the liver and biliary tree also demonstrate intra- and extrahepatic duct dilatation. Hypoattenuating intraductal soft-tissue masses may be seen before and after intravenous administration of contrast material.

To our knowledge, the magnetic resonance (MR) imaging findings of biliary papillomatosis have been described in only two case reports in the literature (18,19). The lesions of biliary papillomatosis are low signal intensity on T1-weighted images and slightly hyperintense on T2-weighted images. The lesions do not significantly enhance following administration of gadolinium and remain hypointense relative to the adjacent liver parenchyma.

At direct cholangiography, biliary papillomatosis classically appears as multiple, irregularly marginated, polypoid filling defects within dilated intra- and extrahepatic bile ducts (Fig 10) (17,18).Irregular, granular, or shaggy margins of the bile duct walls may represent small adenomas or inflammatory changes from secondary cholangitis (Fig 10b). Lack of mobility during irrigation may help distinguish the papillary adenomas from intraductal stones or mucous plugs. Focal areas of biliary obstruction may be present.

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Cholangiographic features of biliary papillomatosis. (a) Intraoperative cholangiogram of a 65-year-old man with jaundice shows multiple, polypoid filling defects in dilated intra- and extrahepatic bile ducts (straight arrows). The filling defect in the left hepatic duct (curved arrow) prevents contrast material filling of the left intrahepatic ducts. (b) ERCP image of a 75-year-old man with recurrent biliary papillomatosis shows multiple filling defects in a dilated common bile duct (solid arrows). There is irregularity and granularity of the distal common duct walls (open arrow).

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Cholangiographic features of biliary papillomatosis. (a) Intraoperative cholangiogram of a 65-year-old man with jaundice shows multiple, polypoid filling defects in dilated intra- and extrahepatic bile ducts (straight arrows). The filling defect in the left hepatic duct (curved arrow) prevents contrast material filling of the left intrahepatic ducts. (b) ERCP image of a 75-year-old man with recurrent biliary papillomatosis shows multiple filling defects in a dilated common bile duct (solid arrows). There is irregularity and granularity of the distal common duct walls (open arrow).

Cystadenomas occur less commonly in the extrahepatic biliary system and gallbladder than in the liver. In the series reported by Devaney et al (22), 83% of cases were located within the liver, 13% were in the extrahepatic bile ducts (common bile duct, common hepatic duct, and cystic duct), and only one case (0.02%) was in the gallbladder.

At histologic analysis, cystadenomas have multiple loculations lined by cuboidal or columnar epithelium that resembles biliary epithelium. Only in rare cases are they unilocular. Underlying the epithelium, there is a highly cellular, mesenchymal, "ovarianlike" stroma and an outer layer of hyalinized fibrous tissue (Fig 11) (7). Goblet cells, Paneth cells, and scattered argyrophilic endocrine cells may be present in the epithelium. Ten percent to 15% of cystadenomas lack ovarian stroma. Approximately 13% of cystadenomas demonstrate dysplastic changes, findings that suggest that some may progress to carcinoma (22).

View larger version (187K): [in this window] [in a new window] [Download PPT slide]   Figure 11.  Biliary cystadenoma. Photomicrograph (original magnification, x50; H-E stain) shows the cyst wall lined by benign cuboidal epithelium (arrow) with a subepithelial mesenchymal "ovarianlike" stroma.

Radiologic Features.— Biliary cystadenomas range in size from 3 to 40 cm (23). Large cystadenomas may demonstrate mass effect on adjacent organs or may be associated with hepatomegaly, which will be apparent on abdominal radiographs (Fig 12). Abdominal radiographs may also demonstrate curvilinear calcification that may be present in the septa or cyst wall.

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 12.  Biliary cystadenoma in a 45-year-old woman who presented with complaints of abdominal fullness. Abdominal radiograph shows a soft-tissue opacity in the upper to mid abdomen that displaces the stomach and transverse colon.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  US features of biliary cystadenoma. (a) Transverse US image of the liver in a 43-year-old woman with a biliary cystadenoma shows a well-defined anechoic cyst with enhanced through transmission. There are multiple echogenic tumor excrescences extending into the cyst lumen (arrows). (b) Transverse US image of the left hepatic lobe in a 52-year-old woman shows a complex anechoic cyst containing echogenic septa (straight arrow) and tumor nodules (curved arrow). (c) Transverse US image of the liver in a 55-year-old woman shows a biliary cystadenoma composed of complex fluid containing diffuse low-level internal echoes. Echogenic septa course through the complex fluid. A portion of the cystadenoma (*) contains simple anechoic fluid.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  US features of biliary cystadenoma. (a) Transverse US image of the liver in a 43-year-old woman with a biliary cystadenoma shows a well-defined anechoic cyst with enhanced through transmission. There are multiple echogenic tumor excrescences extending into the cyst lumen (arrows). (b) Transverse US image of the left hepatic lobe in a 52-year-old woman shows a complex anechoic cyst containing echogenic septa (straight arrow) and tumor nodules (curved arrow). (c) Transverse US image of the liver in a 55-year-old woman shows a biliary cystadenoma composed of complex fluid containing diffuse low-level internal echoes. Echogenic septa course through the complex fluid. A portion of the cystadenoma (*) contains simple anechoic fluid.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 13c.  US features of biliary cystadenoma. (a) Transverse US image of the liver in a 43-year-old woman with a biliary cystadenoma shows a well-defined anechoic cyst with enhanced through transmission. There are multiple echogenic tumor excrescences extending into the cyst lumen (arrows). (b) Transverse US image of the left hepatic lobe in a 52-year-old woman shows a complex anechoic cyst containing echogenic septa (straight arrow) and tumor nodules (curved arrow). (c) Transverse US image of the liver in a 55-year-old woman shows a biliary cystadenoma composed of complex fluid containing diffuse low-level internal echoes. Echogenic septa course through the complex fluid. A portion of the cystadenoma (*) contains simple anechoic fluid.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  Biliary cystadenoma in a 55-year-old woman with abdominal pain and jaundice. (a, b) Contrast-enhanced CT scans (a at a more cephalic level than b) show a multilocular cyst with septations and mural calcifications (straight arrow) in the left hepatic lobe. There is biliary duct dilatation and extension of the cyst into the left hepatic and common bile ducts (curved arrow). (c) Photograph of the bisected specimen shows the smooth inner surface of the cyst with multiple loculi and septations.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  Biliary cystadenoma in a 55-year-old woman with abdominal pain and jaundice. (a, b) Contrast-enhanced CT scans (a at a more cephalic level than b) show a multilocular cyst with septations and mural calcifications (straight arrow) in the left hepatic lobe. There is biliary duct dilatation and extension of the cyst into the left hepatic and common bile ducts (curved arrow). (c) Photograph of the bisected specimen shows the smooth inner surface of the cyst with multiple loculi and septations.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 14c.  Biliary cystadenoma in a 55-year-old woman with abdominal pain and jaundice. (a, b) Contrast-enhanced CT scans (a at a more cephalic level than b) show a multilocular cyst with septations and mural calcifications (straight arrow) in the left hepatic lobe. There is biliary duct dilatation and extension of the cyst into the left hepatic and common bile ducts (curved arrow). (c) Photograph of the bisected specimen shows the smooth inner surface of the cyst with multiple loculi and septations.

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Biliary cystadenoma in a 40-year-old woman with right upper quadrant pain. (a) Contrast-enhanced CT scan shows a well-defined water-attenuation cyst with enhancing loculi (arrow) in the left hepatic lobe. (b) Photograph of the cut resected left lobe shows the fibrous wall of the cystadenoma, multiple tumor nodules (curved arrow), and loculi. The mass arises from the compressed bile duct (straight arrow).

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Biliary cystadenoma in a 40-year-old woman with right upper quadrant pain. (a) Contrast-enhanced CT scan shows a well-defined water-attenuation cyst with enhancing loculi (arrow) in the left hepatic lobe. (b) Photograph of the cut resected left lobe shows the fibrous wall of the cystadenoma, multiple tumor nodules (curved arrow), and loculi. The mass arises from the compressed bile duct (straight arrow).

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.  Biliary cystadenoma in a 50-year-old woman who presented with increasing abdominal girth and jaundice. (a) Contrast-enhanced CT scan shows a large multilocular cyst that contains fluid of high (*) and low attenuation, mural calcifications, and septa. Biliary dilatation is present. (b) T1-weighted MR image shows high-signal-intensity mucoid fluid in the large loculus (*) and low-signal-intensity serous fluid in the smaller loculi. Intermediate-signal-intensity fluid is also present. (c) T2-weighted MR image shows the mucoid fluid as low signal intensity (*) and the remainder of the loculi containing high-signal-intensity fluid. The septations within the cystadenoma are more prominent on the T2-weighted image.

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 16b.  Biliary cystadenoma in a 50-year-old woman who presented with increasing abdominal girth and jaundice. (a) Contrast-enhanced CT scan shows a large multilocular cyst that contains fluid of high (*) and low attenuation, mural calcifications, and septa. Biliary dilatation is present. (b) T1-weighted MR image shows high-signal-intensity mucoid fluid in the large loculus (*) and low-signal-intensity serous fluid in the smaller loculi. Intermediate-signal-intensity fluid is also present. (c) T2-weighted MR image shows the mucoid fluid as low signal intensity (*) and the remainder of the loculi containing high-signal-intensity fluid. The septations within the cystadenoma are more prominent on the T2-weighted image.

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 16c.  Biliary cystadenoma in a 50-year-old woman who presented with increasing abdominal girth and jaundice. (a) Contrast-enhanced CT scan shows a large multilocular cyst that contains fluid of high (*) and low attenuation, mural calcifications, and septa. Biliary dilatation is present. (b) T1-weighted MR image shows high-signal-intensity mucoid fluid in the large loculus (*) and low-signal-intensity serous fluid in the smaller loculi. Intermediate-signal-intensity fluid is also present. (c) T2-weighted MR image shows the mucoid fluid as low signal intensity (*) and the remainder of the loculi containing high-signal-intensity fluid. The septations within the cystadenoma are more prominent on the T2-weighted image.

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 17.  Biliary cystadenoma in a 56-year-old woman who had no hepatobiliary symptoms. Lateral radiograph of the abdomen obtained after ERCP shows communication of the cystadenoma (arrow) with the biliary system. The gallbladder has an anterior location.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 18a.  Biliary cystadenoma in a 39-year-old woman with an elevated bilirubin level. (a) Contrast-enhanced CT scan shows a small cyst in the region of the falciform ligament. There is dilatation of the left hepatic ducts (arrow). (b) ERCP image shows dilatation of the left hepatic and common ducts. There is a filling defect (arrow) in the common duct from intraductal extension of the cystadenoma. (c) Photograph of the resected surgical specimen shows the opened biliary cystadenoma (*) with a polypoid component (straight arrow) extending into the opened common hepatic duct.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 18b.  Biliary cystadenoma in a 39-year-old woman with an elevated bilirubin level. (a) Contrast-enhanced CT scan shows a small cyst in the region of the falciform ligament. There is dilatation of the left hepatic ducts (arrow). (b) ERCP image shows dilatation of the left hepatic and common ducts. There is a filling defect (arrow) in the common duct from intraductal extension of the cystadenoma. (c) Photograph of the resected surgical specimen shows the opened biliary cystadenoma (*) with a polypoid component (straight arrow) extending into the opened common hepatic duct.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 18c.  Biliary cystadenoma in a 39-year-old woman with an elevated bilirubin level. (a) Contrast-enhanced CT scan shows a small cyst in the region of the falciform ligament. There is dilatation of the left hepatic ducts (arrow). (b) ERCP image shows dilatation of the left hepatic and common ducts. There is a filling defect (arrow) in the common duct from intraductal extension of the cystadenoma. (c) Photograph of the resected surgical specimen shows the opened biliary cystadenoma (*) with a polypoid component (straight arrow) extending into the opened common hepatic duct.

	Nonepithelial Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
Granular Cell Tumors
Clinical and Pathologic Features.— Granular cell tumors have been found in virtually every location in the body. The tongue is the single most common site of occurrence, but these tumors have been identified in the oropharynx, gastrointestinal tract, respiratory tract, breast, skin, and subcutaneous tissues. One percent of these tumors occur in the biliary tract.

Granular cell tumors account for 10% of benign biliary tumors. The most frequent location of these tumors in the biliary tree is the common bile duct (50% of cases), followed by the cystic duct (37%), common hepatic duct (11%), gallbladder (4%), and intrahepatic ducts (4%) (27). Ninety percent of patients are women, 76% of whom are African-American. The mean age at presentation is 34 years (27).

The clinical manifestation of these tumors is based on their location within the biliary system. When located in the common duct, these tumors typically manifest with painless jaundice caused by biliary obstruction. As a result, these tumors often initially mimic cholangiocarcinoma or focal sclerosing cholangitis (28). Patients with gallbladder or cystic duct granular cell tumor may present with biliary colic or acute cholecystitis. Although uncommon, this entity should be considered in the differential diagnosis of biliary tract disease in young patients, particularly African-American women (29).

There has been considerable debate about the histologic origin of granular cell tumor. First described in 1926 as granular cell myoblastoma, these tumors were thought to arise from striated muscle cells. It is now thought that granular cell tumor is of Schwann cell origin, since the tumor cells react with antibodies to the S-100 protein, which is normally found in the central nervous system and peripherally in Schwann cells.

Granular cell tumors are composed of large polygonal cells with eosinophilic granular cytoplasm and centrally located, small, dark and uniform nuclei (Fig 19). The cytoplasm reacts positively to the periodic acid-Schiff stain, and recently, immunoreactivity to inhibin has been demonstrated in granular cell tumor of the extrahepatic bile ducts (30). Use of frozen sections may not be reliable for establishing the diagnosis unless there is a high degree of suspicion for the diagnosis of granular cell tumor preoperatively (28,31).

View larger version (209K): [in this window] [in a new window] [Download PPT slide]   Figure 19.  Granular cell tumor of the common bile duct. Photomicrograph (original magnification, x20; H-E stain) shows large polygonal cells with eosinophilic granular cytoplasm (arrow) below the biliary epithelium in the wall of the common bile duct.

Radiologic Features.— Because granular cell tumors are so small, it may be difficult to depict them with US or CT. On US images, granular cell tumor is a heterogeneous, mildly hyperechoic, poorly defined mass that may have faint posterior acoustic shadowing (32). On CT scans, granular cell tumor is a nonspecific soft-tissue mass. Calcification is not typically seen with either US or CT; however, biliary duct dilatation is usually evident with both US and CT.

At direct cholangiography (ERCP or percutaneous cholangiography), granular cell tumor manifests as a short (1–3-cm) segment annular stricture (Fig 20) or abrupt obstruction of the extrahepatic bile ducts. Narrowing of the extrahepatic ducts, which maybe symmetric or eccentric, typically results from the intramural growth of the tumor. These stenotic areas are morphologically characterized by a smooth mucosa without irregularity, nodularity, or ulceration. Completely obstructing lesions are characterized by abrupt obstruction without areas of irregularity or ulceration (Fig 21). Although biliary granular cell tumor usually occurs as a solitary tumor, multifocal tumors have been reported (33,34). MR cholangiography, although not previously reported in conjunction with the diagnosis of granular cell tumor, has the added benefit of demonstrating both the intraluminal and extraluminal extent of disease in patients who present with biliary obstruction.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 20a.  Granular cell tumor in a 27-year-old woman who presented with jaundice. (a) ERCP image shows a focal stricture in the distal common hepatic duct (arrow). (b) Photograph of the resected specimen shows marked mural thickening of the distal common hepatic duct (arrows). The gallbladder is reflected upward.

View larger version (101K): [in this window] [in a new window] [Download PPT slide]   Figure 20b.  Granular cell tumor in a 27-year-old woman who presented with jaundice. (a) ERCP image shows a focal stricture in the distal common hepatic duct (arrow). (b) Photograph of the resected specimen shows marked mural thickening of the distal common hepatic duct (arrows). The gallbladder is reflected upward.

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 21a.  Granular cell tumor in a 30-year-old woman who presented with pruritis and jaundice. (a) Percutaneous transhepatic cholangiogram shows extrahepatic biliary dilatation with high-grade obstruction of the distal common bile duct (arrow). There is contrast material in the duodenum. (b) Photograph of the resected distal common bile duct and duodenum shows tumor infiltration (arrows) of the ductal wall with luminal narrowing. The probe indicates the papilla of Vater.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 21b.  Granular cell tumor in a 30-year-old woman who presented with pruritis and jaundice. (a) Percutaneous transhepatic cholangiogram shows extrahepatic biliary dilatation with high-grade obstruction of the distal common bile duct (arrow). There is contrast material in the duodenum. (b) Photograph of the resected distal common bile duct and duodenum shows tumor infiltration (arrows) of the ductal wall with luminal narrowing. The probe indicates the papilla of Vater.

Involvement of the gallbladder and biliary tract in type 1 neurofibromatosis is an uncommon gastrointestinal manifestation. Gastrointestinal involvement occurs in 25% of patients with neurofibromatosis. Gastrointestinal dysmotility with hyperplasia of the intestinal myenteric and submucosal plexuses, mucosal ganglioneuromatosis, and gastrointestinal stromal tumors are the more common manifestations (38). Biliary involvement is usually secondary to obstructing duodenal and periampullary neuroendocrine tumors (39).

Neurofibromas of the gallbladder have been described as intraluminal polypoid masses or intramural nodules (7). The histologic characteristics of neurofibromas of the gallbladder and bile ducts do not differ from those in other anatomic sites. The tumors are composed of spindle-shaped cells with wavy nuclei (Fig 22). The spindle-shaped cells are organized into fascicles and stain focally positive for S-100 protein. There are areas within the tumor that have loose stromal tissue with a mucin-rich matrix.

View larger version (224K): [in this window] [in a new window] [Download PPT slide]   Figure 22.  Neurofibroma. Photomicrograph (original magnification, x50; H-E stain) shows spindle-shaped cells (arrow) in a moderately cellular area adjacent to an area with loose mucin-rich matrix.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 23a.  Plexiform bile duct neurofibroma in a 44-year-old man with neurofibromatosis type 1 who presented with uncontrolled hypertension. Contrast-enhanced CT scans (a at a more cephalic level than b) show a low-attenuation mass paralleling the intra- and extrahepatic bile ducts (solid arrow). The patient also has a pheochromocytoma of the right adrenal gland (open arrow in b).

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 23b.  Plexiform bile duct neurofibroma in a 44-year-old man with neurofibromatosis type 1 who presented with uncontrolled hypertension. Contrast-enhanced CT scans (a at a more cephalic level than b) show a low-attenuation mass paralleling the intra- and extrahepatic bile ducts (solid arrow). The patient also has a pheochromocytoma of the right adrenal gland (open arrow in b).

	Tumorlike Lesions

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Symptoms typically develop in cases of gastric and pancreatic heterotopia. In gastric heterotopia, hemorrhage and inflammation may occur because of peptic ulceration, and in pancreatic heterotopia, pancreatitis may occur. Patients present with symptoms of epigastric distress (pain, nausea, and vomiting) or biliary obstruction and jaundice (7).

At histologic examination, gastric heterotopia may have pyloric-, antral-, or fundic-type epithelium with parietal or chief cells in the mucosa (Fig 24). Pancreatic heterotopia is characterized by the presence of normal pancreatic structures (Fig 25), including acini, small ducts, and islets (7).

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 24a.  (a) Gallbladder gastric heterotopia. Photomicrograph (original magnification, x20; H-E stain) shows a polypoid mass (*) containing gastric fundic-type mucosa. The polyp extends into the gallbladder lumen. Gastric pyloric-type glands line the lower wall of the gallbladder (arrow), along with adjacent intramural (peribiliary) glands. (b) Higher power photomicrograph (original magnification, x50; H-E stain) shows fundic-type mucosa (solid arrow) with parietal and chief cells. The surface mucosa shows gastric foveolar-type glands (open arrow).

View larger version (195K): [in this window] [in a new window] [Download PPT slide]   Figure 24b.  (a) Gallbladder gastric heterotopia. Photomicrograph (original magnification, x20; H-E stain) shows a polypoid mass (*) containing gastric fundic-type mucosa. The polyp extends into the gallbladder lumen. Gastric pyloric-type glands line the lower wall of the gallbladder (arrow), along with adjacent intramural (peribiliary) glands. (b) Higher power photomicrograph (original magnification, x50; H-E stain) shows fundic-type mucosa (solid arrow) with parietal and chief cells. The surface mucosa shows gastric foveolar-type glands (open arrow).

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 25a.  Heterotopic pancreas of the distal common bile duct in a 12-year-old boy who presented with a 3-week history of jaundice, abdominal pain, and diarrhea. (a) ERCP image shows a 1.5-cm stricture of the distal common bile duct (arrow). (b) Photomicrograph (original magnification, x50; H-E stain) shows pancreatic acinar cells (arrow) in the wall of the common bile duct.

View larger version (202K): [in this window] [in a new window] [Download PPT slide]   Figure 25b.  Heterotopic pancreas of the distal common bile duct in a 12-year-old boy who presented with a 3-week history of jaundice, abdominal pain, and diarrhea. (a) ERCP image shows a 1.5-cm stricture of the distal common bile duct (arrow). (b) Photomicrograph (original magnification, x50; H-E stain) shows pancreatic acinar cells (arrow) in the wall of the common bile duct.

Radiologic Features.— Heterotopic gastric and pancreatic tissue in the gallbladder appears sonographically as an echogenic, polypoid mass projecting into the lumen of the gallbladder (43,46). If the mass occurs near the neck of the gallbladder or near the cystic duct, there may be obstructive findings such as gallbladder hydrops or cholecystitis. The CT features of gastric heterotopia are a solitary, polypoid soft-tissue mass in the gallbladder that enhances slightly after intravenous administration of contrast material (47).

Heterotopic mucosa in the bile duct may manifest as an intraluminal polyp (45) or a focal stricture (Fig 25) that causes biliary obstruction (48). The polyp usually has medium echotexture on US images and can be demonstrated as an immobile intraluminal mass on cholangiograms.

Cholesterol Polyps
Clinical and Pathologic Features.— Cholesterol polyps of the gallbladder represent approximately one-half of all polypoid lesions in the gallbladder and have no malignant potential (49,50). The majority of patients are women between 40 and 50 years of age. The female-to-male ratio is 2.9:1 (49). Cholesterol polyps are typically found in patients who are being evaluated for epigastric distress and right upper quadrant pain. Only a small number of cases are associated with cholelithiasis and cholesterolosis (8).

At histologic examination, cholesterol polyps are composed of lipid-laden macrophages that are positive for oil red O stain. Normal gallbladder epithelium covers the polyp (Fig 26a), and its infoldings may form glandlike structures (6).

View larger version (165K): [in this window] [in a new window] [Download PPT slide]   Figure 26a.  Cholesterol polyp. (a) Photomicrograph (original magnification, x100; H-E stain) shows normal gallbladder epithelium overlying sheets of lipid-laden macrophages, forming the head of the polyp. (b) Photograph of an opened resected gallbladder shows multiple, yellow, lobulated polyps attached to the gallbladder mucosa.

View larger version (169K): [in this window] [in a new window] [Download PPT slide]   Figure 26b.  Cholesterol polyp. (a) Photomicrograph (original magnification, x100; H-E stain) shows normal gallbladder epithelium overlying sheets of lipid-laden macrophages, forming the head of the polyp. (b) Photograph of an opened resected gallbladder shows multiple, yellow, lobulated polyps attached to the gallbladder mucosa.

Radiologic Features.— On US images, small cholesterol polyps appear as brightly echogenic masses or nodules attached to the gallbladder wall (Fig 27a). They are typically round or slightly lobulated and do not produce posterior acoustic shadowing. It is often difficult to distinguish a nonshadowing adherent stone from a cholesterol polyp, as they have similar US characteristics. Large cholesterol polyps are generally less echogenic than smaller polyps (Fig 27b) and may contain a characteristic aggregation of echogenic foci. The finding of echogenic aggregates with transabdominal or endoscopic US may be useful in differentiating large cholesterol polyps from adenomas or adenocarcinomas (9).

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 27a.  Sonographic appearance of cholesterol polyps. (a) Longitudinal US image of the gallbladder in a 35-year-old woman with epigastric distress shows multiple small hyperechoic polyps (arrow) in the gallbladder. (b) Longitudinal US image of the gallbladder in a 40-year-old man with right upper quadrant pain shows two 5-mm hypoechoic cholesterol polyps (arrows) in the gallbladder fundus.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 27b.  Sonographic appearance of cholesterol polyps. (a) Longitudinal US image of the gallbladder in a 35-year-old woman with epigastric distress shows multiple small hyperechoic polyps (arrow) in the gallbladder. (b) Longitudinal US image of the gallbladder in a 40-year-old man with right upper quadrant pain shows two 5-mm hypoechoic cholesterol polyps (arrows) in the gallbladder fundus.

Xanthogranulomatous Cholecystitis
Clinical and Pathologic Features.— Xanthogranulomatous cholecystitis is an unusual form of chronic cholecystitis that may simulate malignancy radiologically and pathologically (51). It is predominantly seen in women between the ages of 60 and 70 years (52). Patients present with signs and symptoms of cholecystitis: right upper quadrant pain, vomiting, leukocytosis, and a positive Murphy sign. Slightly less than one-half of patients have a tender, palpable, right upper quadrant mass at physical examination (53). Complications are present in 32% of cases (54) and include perforation, abscess formation, fistulous tracts to the duodenum or skin, and extension of the inflammatory process to the liver, colon, or surrounding soft tissues.

Although the mechanism leading to the formation of xanthogranulomatous cholecystitis has not been firmly established, extravasation of bile into the gallbladder wall is believed to have a role in the development of the inflammatory process. It has been postulated that bile enters the gallbladder wall through mucosal ulceration or rupture of Rokitansky-Aschoff sinuses when there is gallbladder or cystic duct obstruction that results in increased intraluminal pressure.

The histologic components of xanthogranulomatous cholecystitis include foamy histiocytes, lymphocytes, plasma cells, polymorphonuclear leukocytes, fibroblasts, and foreign body giant cells. The foamy histiocytes predominate and may contain bile or ceroid pigment (Fig 28) (7). Bands of collagen and cholesterol clefts may be present. Xanthogranulomatous cholecystitis can coexist with malignancy (55,56).

View larger version (207K): [in this window] [in a new window] [Download PPT slide]   Figure 28.  Xanthogranulomatous cholecystitis. Photomicrograph (original magnification, x2; H-E stain) shows a thickened, fibrotic gallbladder wall with a centrally located xanthogranulomatous cholecystitis lesion (arrows) containing chronic inflammatory cells, bile pigment, and foamy pigment-laden macrophages.

Radiologic Features.— Gallbladder wall thickening is the hallmark of xanthogranulomatous cholecystitis on cross-sectional images. Wall thickening may be focal or diffuse and has been reported to range from 3 to 25 mm thick (55,56). The gallbladder wall may be well defined, or it may have an indistinct margin with the liver. When the inflammatory process extends to involve the adjacent liver, there is often loss of a well-defined fat plane between the gallbladder and liver (Fig 29).

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 29a.  Xanthogranulomatous cholecystitis in a 67-year-old woman who presented with fever, sweats, and painless jaundice. (a) Longitudinal US image of the right upper quadrant shows disruption of the mucosal line of the gallbladder (arrow). The gallbladder contains echogenic material. There is pericholecystic fluid, focal hypoattenuation in the adjacent liver, and loss of the normal plane between the gallbladder and liver. (b) Unenhanced CT scan shows a stone impacted in the gallbladder neck, pericholecystic fluid, and extension of the inflammatory process to the adjacent liver (black arrow) and fat (white arrow). (c) Photograph of the cut surface of the resected gallbladder shows diffuse wall thickening and disruption of the gallbladder wall (arrows) with extension of inflammation into the liver bed.

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 29b.  Xanthogranulomatous cholecystitis in a 67-year-old woman who presented with fever, sweats, and painless jaundice. (a) Longitudinal US image of the right upper quadrant shows disruption of the mucosal line of the gallbladder (arrow). The gallbladder contains echogenic material. There is pericholecystic fluid, focal hypoattenuation in the adjacent liver, and loss of the normal plane between the gallbladder and liver. (b) Unenhanced CT scan shows a stone impacted in the gallbladder neck, pericholecystic fluid, and extension of the inflammatory process to the adjacent liver (black arrow) and fat (white arrow). (c) Photograph of the cut surface of the resected gallbladder shows diffuse wall thickening and disruption of the gallbladder wall (arrows) with extension of inflammation into the liver bed.

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 29c.  Xanthogranulomatous cholecystitis in a 67-year-old woman who presented with fever, sweats, and painless jaundice. (a) Longitudinal US image of the right upper quadrant shows disruption of the mucosal line of the gallbladder (arrow). The gallbladder contains echogenic material. There is pericholecystic fluid, focal hypoattenuation in the adjacent liver, and loss of the normal plane between the gallbladder and liver. (b) Unenhanced CT scan shows a stone impacted in the gallbladder neck, pericholecystic fluid, and extension of the inflammatory process to the adjacent liver (black arrow) and fat (white arrow). (c) Photograph of the cut surface of the resected gallbladder shows diffuse wall thickening and disruption of the gallbladder wall (arrows) with extension of inflammation into the liver bed.

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 30a.  Xanthogranulomatous cholecystitis in a 55-year-old man who presented with right upper quadrant pain, fever, and leukocytosis. (a) Longitudinal US image of the gallbladder shows marked gallbladder wall thickening and prominent hypoechoic nodules (solid arrows) in the gallbladder wall. The gallbladder mucosa is echogenic (open arrows) and the lumen of the gallbladder compressed. (b) Contrast-enhanced CT scan shows large hypoattenuating nodular areas in the thickening gallbladder wall (solid arrows). There is hypoattenuation in the adjacent liver (open arrow).

View larger version (142K): [in this window] [in a new window] [Download PPT slide]   Figure 30b.  Xanthogranulomatous cholecystitis in a 55-year-old man who presented with right upper quadrant pain, fever, and leukocytosis. (a) Longitudinal US image of the gallbladder shows marked gallbladder wall thickening and prominent hypoechoic nodules (solid arrows) in the gallbladder wall. The gallbladder mucosa is echogenic (open arrows) and the lumen of the gallbladder compressed. (b) Contrast-enhanced CT scan shows large hypoattenuating nodular areas in the thickening gallbladder wall (solid arrows). There is hypoattenuation in the adjacent liver (open arrow).

View larger version (176K): [in this window] [in a new window] [Download PPT slide]   Figure 31.  Xanthogranulomatous cholecystitis in a 78-year-old man with intermittent fever and right upper quadrant pain. Contrast-enhanced CT scan shows marked gallbladder wall thickening with enhancement and a hypoattenuating wall. There are inflammatory changes in the fat medial to the gallbladder and an indistinct margin between the gallbladder and liver.

Adenomyomatous Hyperplasia
Clinical and Pathologic Features.— Adenomyomatous hyperplasia is now recognized as a common condition of the gallbladder wall, occurring in up to 8.7% of cholecystectomy specimens (60). Throughout the literature, a variety of names have been applied to this lesion, including adenomyomatosis, adenomyoma, diverticular disease, intramural diverticulosis, cholecystitis cystica, and cholecystitis glandularis proliferans. Adenomyomatous hyperplasia is more common in women than men (7). The majority of patients present with complaints of chronic right upper quadrant pain, and 90% have coexistent gallstones.

There are three variants of adenomyomatous hyperplasia: localized (or fundal), segmental, and diffuse. The localized variant is the most common and is also known as an adenomyoma. At gross examination, it is characterized by a well-formed mass in the gallbladder fundus. The mass may have a semilunar or crescent shape (8). Cut sections of the mass have a honeycombed appearance that is created by multiple, small cystic spaces (7). The cystic spaces represent prominent epithelial invaginations (Rokitansky-Aschoff sinuses or intramural diverticula). The segmental variant is characterized by focal circumferential thickening in the gallbladder wall. The segmental variant is typically located in the body of the gallbladder, giving it an hourglass configuration at gross inspection. Diffuse adenomyomatous hyperplasia is characterized by diffuse gallbladder wall thickening with intramural diverticula that appear as cystic spaces within the wall.

Adenomyomatous hyperplasia is histologically characterized by epithelial and smooth muscle proliferation (Fig 32). Normal gallbladder epithelium lines the epithelial structures that may extend down into the subserosa and reach the serosa. Hyperplastic smooth muscle cells accompany the epithelial invaginations that contain inspissated bile, mucus, or stones. Inflammatory and fibrotic changes may be present as well as metaplastic changes (intestinal metaplasia, pyloric gland metaplasia). Dysplastic changes and in situ and invasive carcinomas may arise from the epithelium of adenomyomatous hyperplasia. However, most authors believe that the development of carcinoma is related to the presence of stones, chronic inflammation, and metaplastic changes rather than adenomyomatous hyperplasia. Thus, adenomyomatous hyperplasia is not considered a premalignant lesion (7).

View larger version (179K): [in this window] [in a new window] [Download PPT slide]   Figure 32.  Adenomyomatous hyperplasia. Photomicrograph (original magnification, x4; H-E stain) shows papillary hyperplasia of the surface mucosa (*) and deeply penetrating dilated glands (solid arrows) surrounded by hyperplastic smooth muscle cells (open arrow).

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 33.  Adenomyomatous hyperplasia in a 65-year-old woman with chronic right upper quadrant pain. Abdominal radiograph shows multiple, punctate, calcific opacities in the right upper quadrant.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 34a.  Diffuse adenomyomatous hyperplasia in a 48-year-old woman with postprandial pain. (a) Longitudinal US image of the gallbladder shows diffuse gallbladder wall thickening with areas of polypoid nodularity. (b) Photograph of the opened resected gallbladder shows hemorrhagic gallbladder mucosa with multiple, small, cystic spaces in the wall (arrows). Some of the cystic spaces contained pigmented calculi.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 34b.  Diffuse adenomyomatous hyperplasia in a 48-year-old woman with postprandial pain. (a) Longitudinal US image of the gallbladder shows diffuse gallbladder wall thickening with areas of polypoid nodularity. (b) Photograph of the opened resected gallbladder shows hemorrhagic gallbladder mucosa with multiple, small, cystic spaces in the wall (arrows). Some of the cystic spaces contained pigmented calculi.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 35a.  Segmental adenomyomatous hyperplasia in a 38-year-old woman with fatty food intolerance. (a) Longitudinal US image of the gallbladder shows segmental wall thickening of the gallbladder body and fundus. There are multiple reverberation artifacts emanating from the thickened gallbladder wall. The lumen of the gallbladder is narrowed in the involved segment. (b) Transverse US image shows V-shaped reverberation artifact from the anterior wall of the gallbladder (arrow).

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 35b.  Segmental adenomyomatous hyperplasia in a 38-year-old woman with fatty food intolerance. (a) Longitudinal US image of the gallbladder shows segmental wall thickening of the gallbladder body and fundus. There are multiple reverberation artifacts emanating from the thickened gallbladder wall. The lumen of the gallbladder is narrowed in the involved segment. (b) Transverse US image shows V-shaped reverberation artifact from the anterior wall of the gallbladder (arrow).

The localized or focal variant of adenomyomatous hyperplasia appears as a mass in the gallbladder fundus (Fig 36). It may be impossible to distinguish this form of adenomyomatous hyperplasia from neoplasia (Fig 37). However, the identification of a comet-tail artifact emanating from the mass is a helpful discriminator.

View larger version (155K): [in this window] [in a new window] [Download PPT slide]   Figure 36a.  Focal adenomyomatous hyperplasia (adenomyoma) in a 35-year-old man who was evaluated for intermittent abdominal pain. (a) Longitudinal US image of the gallbladder fundus shows an ill-defined mass. There is edge shadowing and reverberation artifact emanating from the mass. (b) Photograph of the opened resected gallbladder shows the bivalved fundal mass (arrows), which contains multiple cystic spaces, and a hemorrhagic mucosa.

View larger version (101K): [in this window] [in a new window] [Download PPT slide]   Figure 36b.  Focal adenomyomatous hyperplasia (adenomyoma) in a 35-year-old man who was evaluated for intermittent abdominal pain. (a) Longitudinal US image of the gallbladder fundus shows an ill-defined mass. There is edge shadowing and reverberation artifact emanating from the mass. (b) Photograph of the opened resected gallbladder shows the bivalved fundal mass (arrows), which contains multiple cystic spaces, and a hemorrhagic mucosa.

View larger version (170K): [in this window] [in a new window] [Download PPT slide]   Figure 37a.  Focal adenomyomatous hyperplasia (adenomyoma) in a 40-year-old woman with right upper quadrant pain. (a) Longitudinal US image of the gallbladder shows an ill-defined mass and wall thickening in the gallbladder fundus (arrows). (b) Photograph of the opened resected gallbladder shows wall thickening in the fundus (black arrows) with a narrow opening (white arrow) into the fundic adenomyoma.

View larger version (100K): [in this window] [in a new window] [Download PPT slide]   Figure 37b.  Focal adenomyomatous hyperplasia (adenomyoma) in a 40-year-old woman with right upper quadrant pain. (a) Longitudinal US image of the gallbladder shows an ill-defined mass and wall thickening in the gallbladder fundus (arrows). (b) Photograph of the opened resected gallbladder shows wall thickening in the fundus (black arrows) with a narrow opening (white arrow) into the fundic adenomyoma.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 38a.  Diffuse adenomyomatous hyperplasia in a 72-year-old patient who was being evaluated for gastric carcinoma. (a) Contrast-enhanced CT scan shows diffuse gallbladder wall thickening with focal hypoattenuating nodularity (arrow). There is also a gastric mass present. (b) Photograph of an axial cross-section of the resected gallbladder shows diffuse thickening of the gallbladder wall with pigmented stones and debris embedded into cystically dilated glands of the adenomyomatous hyperplasia.

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 38b.  Diffuse adenomyomatous hyperplasia in a 72-year-old patient who was being evaluated for gastric carcinoma. (a) Contrast-enhanced CT scan shows diffuse gallbladder wall thickening with focal hypoattenuating nodularity (arrow). There is also a gastric mass present. (b) Photograph of an axial cross-section of the resected gallbladder shows diffuse thickening of the gallbladder wall with pigmented stones and debris embedded into cystically dilated glands of the adenomyomatous hyperplasia.

	Radiologic Patterns and Differential Diagnosis

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

Polypoid gallbladder masses are commonly demonstrated with US and are often incidentally identified in the imaging evaluation of the abdomen. Polypoid lesions are estimated to be present in approximately 3% of gallbladders (65). The differential diagnosis for a polypoid mass in the gallbladder includes benign and malignant entities. Cholesterol polyps, adenomas, adenomyomatous hyperplasia, inflammatory polyps, heterotopia, neurofibromas, carcinomas, carcinoid tumors, lymphoma, and metastasis may all manifest as polypoid masses. However, the majority of gallbladder polyps are benign. In a recent study of 100 cases of gallbladder polyps, 74% were benign, and cholesterol polyps were found to be the most common type, representing 53% of benign polyps (49).

The management of gallbladder polyps is based on the risk of malignancy, which increases for polyps greater than 10 mm in size and in patients over 60 years of age. The prevalence of malignancy in polyps greater than 10 mm ranges from 37% to 88% (50,65). Therefore, it has been recommended that patients undergo cholecystectomy for symptomatic polypoid lesions and polyps greater than 10 mm. Polypoid lesions less than 10 mm should be followed up periodically with US. At sonography, careful search should be made for other features associated with malignancy, such as thickening or nodularity of the gallbladder wall; evidence of hepatic invasion, such as an indistinct margin between the liver and gallbladder; biliary duct dilatation; and peripancreatic hepatoduodenal ligament adenopathy (66).

Xanthogranulomatous cholecystitis and adenomyomatous hyperplasia manifest as gallbladder wall thickening. The differential diagnosis for focal and diffuse gallbladder wall thickening also includes heart failure, hepatitis, hypoalbuminemia, cirrhosis, renal failure, cholecystitis, and primary or secondary malignancies. Complications from cholecystitis or xanthogranulomatous cholecystitis may mimic malignancy and often cannot be differentiated from malignancy preoperatively. Nevertheless, the sonographic features of hypoechoic nodules or bands in the thickened gallbladder wall may suggest a diagnosis of xanthogranulomatous cholecystitis. The sonographic finding of reverberation artifact in a thickened gallbladder wall or the demonstration of Rokitansky-Aschoff sinuses on MR images is helpful in the differentiation of adenomyomatous hyperplasia from other causes of gallbladder wall thickening.

Polypoid bile duct masses are less commonly encountered than gallbladder polyps. Adenomas, inflammatory polyps, neurofibromas, metastasis, and adenocarcinomas should be considered in the differential diagnosis. In rare cases, multiple polypoid lesions are present within the bile ducts, in which case biliary papillomatosis, inflammatory polyps, and metastasis should be considered in the differential diagnosis.

The majority of bile duct lesions have an intramural growth pattern and manifest as biliary strictures. Granular cell tumor; heterotopia; neuroendocrine tumors such as carcinoid, metastasis, and adenocarcinoma; and inflammatory conditions such as primary sclerosing cholangitis commonly manifest as focal strictures or abrupt obstruction of the bile duct. All of these lesions are managed invasively because they cause biliary obstruction. However, a good differential diagnosis and knowledge of histologic characteristics are helpful in planning for surgery or endoscopy.

	Conclusions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 
Benign tumors and tumorlike lesions of the gallbladder and bile ducts are an uncommon group of lesions. This diverse group appears on radiologic images with four distinct patterns: gallbladder polyps, gallbladder wall thickening, bile duct polyps, and bile duct strictures. Distinction of benign entities from the malignancies that occur in these structures is important clinically since gallbladder and biliary malignancies have grave prognoses.

	Footnotes

 
Abbreviations: ERCP = endoscopic retrograde cholangiopancreatography, H-E = hematoxylin-eosin

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Army, Air Force, Navy, or Defense.

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Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Embryologic Development Tumor Classification Benign Epithelial Tumors Nonepithelial Tumors Tumorlike Lesions Radiologic Patterns and... Conclusions References

 

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