Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Benign and Malignant Tumors of Bile Ducts
Abbreviations
CA
cancer antigen
CC
cholangiocarcinoma
CEA
carcinoembryonic antigen
CT
computed tomography
HCC
hepatocellular carcinoma
HCC-CC
hepatocellular-cholangiocarcinoma
ICC
intrahepatic cholangiocarcinoma
IPMN
intraductal papillary mucinous neoplasm
IPNB
intraductal papillary neoplasm of bile duct
K
a keratin
a Although the prefix CK is widely used in surgical pathology to designate human cytokeratins, consensus nomenclature recommends the replacement of “cytokeratin” with “keratin” and the prefix “CK” with “K.” (Schweizer J, Bowden PE, Coulombe PA, et al. New consensus nomenclature for mammalian keratins. J Cell Biol . 2006;174:169–174.)
MRCP
magnetic resonance cholangiopancreatography
MRI
magnetic resonance imaging
Tumors and tumor-like lesions of the bile ducts may cause symptoms and signs resulting from abdominal pain or obstruction. Recognition of these structures has increased in recent decades, partly because advances in imaging techniques have led to increasing discovery of incidental lesions. These tumors are a group of heterogeneous lesions, ranging from hamartomas to malignant neoplasms. Some are of no clinical consequence and are not known to undergo malignant transformation but are often encountered during surgical exploration where they raise suspicions of malignant or metastatic process; accurate identification during intraoperative consultation is crucial for proper management. Some lesions such as mucinous cystic neoplasm or intraductal papillary neoplasm of bile duct, on the other hand, are premalignant with known risk of malignant transformation; careful and thorough evaluation of the pathologic specimens is critical for subsequent treatment and follow up.
It is important to correlate the patient’s age, gender, geographic background, imaging and clinical history to arrive at a diagnosis of these lesions. For instance, although the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing, metastatic carcinoma is still the most common malignancy in the liver in North America. However, this may not be true in other parts of the world. Furthermore, the index of suspicion for metastatic adenocarcinoma is usually higher than that for a benign lesion when a laparotomy is performed for a Whipple procedure than when a laparotomy is performed for an appendectomy or cholecystectomy.
This chapter discusses the pathology of benign and malignant tumors and tumor-like lesions of the bile ducts, emphasizing their differential diagnosis as well as imaging and immunohistochemical features.
Benign Tumors or Tumor-like Lesions
Solitary Bile Duct Cyst
Clinical Manifestations
Solitary bile duct cysts are usually small, asymptomatic, and found incidentally. Rarely, they may cause symptoms and require surgical intervention. Unlike polycystic liver disease, malignant transformation of the solitary bile duct cyst is extremely rare.
Pathology
The cystic fluid is usually clear but may be hemorrhagic, purulent, or stained with bile if the cyst has been traumatized or infected. Bile duct cysts are unilocular and lined by a single layer of columnar or cuboidal epithelium ( Fig. 34.1 ) that are immunoreactive for these keratins (K): K8, K18, K7, and K19, reflecting their cell lineages.
Differential Diagnosis
Most solitary bile duct cysts are small and asymptomatic, in contrast to polycystic liver disease, which is often symptomatic and shows multiple cysts in the liver as well as in the kidney. In addition, polycystic livers are often associated with von Meyenburg complexes (bile duct hamartoma) because both lesions are within the spectrum of bile ductal plate malformation (see eSlide 25.2 ). At times, solitary bile duct cysts need to be distinguished from echinococcal (hydatid) cysts. The latter often have typical imaging features such as the presence of daughter cysts and a rim of calcification, and their cystic walls are often grossly thickened. Serologic tests and the presence of the hydatid elements, especially the hooklets (scoleces), are useful in diagnosing echinococcal cysts. The distinction between solitary bile duct cysts and mucinous cystic neoplasm is usually not difficult because the latter typically shows an ovarian-type stroma ( eSlide 34.4 ); however, the stroma may be scant and not readily identified. Table 34.1 lists the differential diagnosis of benign cystic lesions of the liver.
Table 34.1
Benign Cysts of the Liver
| Type of Cyst | Clinical Features | Salient Pathologic Features |
|---|---|---|
| Solitary bile duct cyst |
|
|
| Hydatid (echinococcal) cysts |
|
|
| Mucinous cystic neoplasm |
|
|
| Ciliated hepatic foregut cyst |
|
|
| Intraductal papillary neoplasm of the bile duct, cystic variant |
|
|
K , Keratin.
Ciliated Hepatic Foregut Cyst
Clinical Manifestations
Most ciliated hepatic foregut cysts are small and asymptomatic. They are so rare that their exact prevalence is not certain. A majority of cases are incidental findings during surgery or at autopsy.
Pathology
The liver, like the tracheobronchial tree and esophagus, arises from the primitive foregut during fetal development. Ciliated hepatic foregut cysts may result from a process of ciliation occurring in an anomalous detached primordium of the hepatic diverticulum or in an independent bud from the nearby enteric foregut. Ciliated hepatic foregut cysts are usually small, unilocular, and partially lined by ciliated pseudostratified columnar epithelium ( Fig. 34.2 ) ( eSlide 34.1 ), although they may also be partially lined by cuboidal or squamous epithelium. Bundles of smooth muscle are usually present surrounding the cysts.
Differential Diagnosis
Differential diagnosis of ciliated hepatic foregut cysts includes solitary bile duct cysts, mucinous cystic neoplasm, and echinococcal cysts. The lining epithelia of all these other cystic lesions are not ciliated, a distinctive feature found in ciliated foregut cysts. In addition, mucinous cystic neoplasms typically have a distinctive ovarian-type stroma, whereas daughter cysts and scoleces are distinctive findings in echinococcal cysts.
Bile Duct Hamartoma
These lesions are also known as von Meyenburg complexes or biliary microhamartomas . They are usually small (up to several millimeters in diameter), multiple, and located adjacent to a portal region. They are thought to arise as a developmental anomaly caused by ductal plate malformation and are often associated with polycystic liver or kidney disease.
Clinical Manifestations
These lesions are almost always incidental findings found at abdominal surgery. They are multiple, firm, and white, appearing as metastatic seedlings on the surface of the liver and are thus sampled for intraoperative consultation, underlining the importance of intraoperative frozen section for liver lesions of unknown origin. Bile duct hamartomas are also common incidental findings at autopsy. In a series of almost 3000 consecutive autopsies, bile duct hamartomas were found in 5.6% of adults and in 0.9% of children, reflecting the fact that they are fairly common. In this series, macroscopic hepatic cysts were found in 16% of livers that also had bile duct hamartomas; of livers with hepatic cysts, 73% also had bile duct hamartomas, suggesting an association of bile duct hamartomas with polycystic liver.
Radiologic Features
On computed tomography (CT) or magnetic resonance imaging (MRI), bile duct hamartomas usually present as multiple or numerous tiny intrahepatic cystoid lesions with irregular contours, scattered throughout the liver and in the subcapsular regions. They are detected in much greater number by enhanced CT or T2-weighted MRI scans than by unenhanced CT or T1-weighted images. They usually show no remarkable change on long-term follow-up imaging.
Pathology
Gross Pathology
On gross examination, bile duct hamartomas are small, ranging from 2 to 5 mm in diameter. They are usually multiple, gray to white, and irregular in shape.
Microscopic Pathology
Microscopically, bile duct hamartomas are composed of a variable number of ductal structures embedded in a hyalinized stroma. The ductal structures are variably dilated and may have microcystic dilatation with or without bile in the ductal lumens ( Fig. 34.3 ) ( eSlide 34.2, eSlide 25.1 ). The ductal lumens are lined by a flattened or cuboidal epithelium and are immunoreactive for K7, K8, K18, and K19, reflecting a lineage of biliary cell origin.
Differential Diagnosis
Adenocarcinoma
Bile duct hamartomas need to be distinguished from malignant neoplasms in the liver such as metastatic adenocarcinoma or cholangiocarcinoma (CC), especially during frozen section consultation. They are often multiple and draw the surgeon’s attention during laparotomy that prompts the intraoperative consultation. The typical luminal dilatation with bile is a helpful feature that distinguishes bile duct hamartomas from metastatic adenocarcinoma. In addition, the epithelial cells of bile duct hamartoma are typically bland and lack the malignant features seen in adenocarcinoma, including pleomorphism, hyperchromasia, and mitoses.
Peribiliary Gland Hamartoma
Benign lesions that can be confused with bile duct hamartomas are peribiliary gland hamartomas (see later discussion). Peribiliary gland hamartomas are usually single, do not show dilatation of the ductal structures, and have ductal lumina that do not contain bile ( eSlide 34.2, eSlide 34.3 ).
Prognosis
Although bile duct hamartomas are generally considered benign without malignant potential, they have been associated with neoplastic transformation in a few reported cases.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here