Successful surgical management of an extrahepatic biliary cystadenocarcinoma.

Extrahepatic bile duct cancer is an uncommon disease, and few cases are curable by surgery. We report a case of extrahepatic biliary cystadenocarcinoma (BCAC) associated with atrophy of the left hepatic lobe. A 54-year old male was admitted with painless obstructive jaundice and a hepatic palpable mass noticed one month before presentation. Liver functions tests were consistent with cholestatic damage and serum carbohydrate antigen 19.9 (CA 19-9) was increased before treatment. Magnetic resonance imaging (MRI) disclosed dilatation of the left hepatic bile duct with irregular wall thickening close to the hepatic confluence, and atrophy of left hepatic lobe. The patient was submitted to en bloc extended left hepatectomy with resection of caudate lobe, hilar lymphadenectomy, and suprapancreatic biliary tree resection. All surgical margins were grossly negative, and postoperative course was uneventful, except for a minor bile leak. The patient was discharged on the 15th postoperative day; he is alive without tumor recurrence one year after primary therapy. Although technically challenging, extended en bloc resection is feasible in adults with extrahepatic BCAC and can improve survival with acceptable and manageable morbidity.

Introduction

Extrahepatic bile duct cancer is an uncommon disease, and few cases are curable by surgery. Prognosis depends in part on the tumor's anatomic location, which affects its resectability with complete resection feasible in 25% to 30% of lesions from distal bile duct, a resectability rate clearly better than attained in lesions at more proximal sites.[1-3] Adenocarcinoma comprises the most common histology of bile duct cancer, and biliary cystadenocarcinoma (BCAC) is a quite rare entity.[4]

BCAC often occurs as slow growing lesion in the liver parenchyma and is difficult to distinguish from its benign counterpart, biliary cystadenoma. In addition, BCAC radiologically resembles simple hepatic cysts, mainly when unilocular, hydatid cysts, and a number of metastatic tumors that undergo cystic degeneration. Extrahepatic BCAC have unique traits with specialized treatment needs.[2,5,6]

We describe a case of extrahepatic BCAC localized closing to the hepatic duct confluence. The patient successfully underwent successfully an en bloc suprapancreatic biliary tract resection with left hepatectomy plus caudate lobectomy.

Case Report

An otherwise healthy 54-year-old Caucasian male was admitted to the surgical ward due to painless obstructive jaundice and a hepatic palpable mass which was noticed one month before presentation. Serum bilirubin (241 µmol/L), alkaline phosphatase (1067 U/L) and gamma glutamyl transferase (550 U/L) were markedly elevated; serum aspartate aminotransferase (175 U/L) and alanine aminotransferase (143 U/L) were only mildly elevated. Serum levels of carcinoembryonic antigen and alpha-fetoprotein were normal, but CA 19-9 was elevated (345 U/L). A CT scan showed a cystic lesion with irregular wall thickening near the hepatic hilum, dilatated intrahepatic bile ducts, and atrophy of the left hepatic lobe. A magnetic resonance cholangiogram showed dilatation of intrahepatic biliary tree, predominantly at the left side, absence of duct stones, and bile duct with irregular wall thickening close to the hepatic confluence (Figure 1).

Figure 1

Magnetic resonance imaging showed predominant dilatation of the left biliary tree, atrophy of left hepatic lobe particularly lateral segment, and wall thickening near hepatic duct confluence (arrow).

There were no suspicious findings of locoregional or systemic dissemination in imaging studies. Provisional diagnoses of biliary cyst adenoma, hilar cholangiocarcinoma (T3N0M0, stage IIIA) or extrahepatic bile duct cancer (T3N0M0, stage IIA) were made, and the lesion was deemed resectable. Surgery consisted of suprapancreatic biliary tree resection, including hepatic duct confluence, hilar lymphadenectomy, and en bloc extended left hepatectomy with caudate lobectomy. All surgical margins were negative. A histopathological examination showed cystadenocarcinoma arising from the left hepatic duct (Figure 2). The immunohistochemical analysis for CEA, cytokeratin 19 and CA 19-9 showed positive staining at the tumor level. Postoperative course was uneventful, except for a minor bile leak requiring no therapy. The patient was discharged on the 15th postoperative day and no postoperative adjuvant therapy was necessary. He is alive without tumor recurrence one year after the primary therapy.

Figure 2

Neoplastic epithelia with acidophilic cytoplasm cover the papillary structure of this tumor, and the stroma of these papillae are edematous and myxoid. The neoplastic epithelia are artificially desquamated. HE, ×150.

Discussion

Biliary cystoadenocarcinoma is a rare, indolent disease typically diagnosed in middle-aged people. It predominantly affects women and has a less favorable outcome among men.[4,7] At diagnosis, patients with intrahepatic BCAC often present for evaluation of an abdominal mass or regional pain, but cholestasis is a frequent and early feature in extrahepatic BCAC.[8-11] Extrahepatic BCAC can cause asymmetric bile duct dilatation and secondary segmental hepatic atrophy due to adjacent tumor compression or invasion of the left portal vein, pressure atrophy of hepatic cells, or bile salt toxicity.[12,13]

Tumor arises more frequently from the hepatic confluence or sectoral bile ducts than from the gallbladder.[7,10,14] Endoscopic retrograde cholangiopancreatography (ERCP) ERCP is no longer a decisive component in diagnostic work-up as non-invasive modalities clearly elucidate location and extent of disease. Imaging studies usually reveal multilocular cystic lesions with internal septations and nodularities, but a unilocular lesion may be observed as in this case.[5,15,16] Some authors have suggested that presence of nodules or coarse calcifications along the duct wall or septa increases the odds in favor of BCAC.[15,17]

CA19-9 and CEA serum levels can be used in conjunction with radiological methods to determine tumor resectability: normal marker levels assure resectability in half of cases, while elevated CA 19-9 (>1000 U/mL) and CEA (>14.4 ng/mL) strongly suggest unresectable disease.[18] The differential diagnosis includes biliary cystoadenoma, cholangiocarcinoma and, less commonly, benign papilloma, carcinoid tumor, villous tumor, neurofibroma, and plasmacytoma. Besides intraductal neoplasm, the differential diagnosis of regional biliary ductal obstruction includes calculus disease, sclerosing cholangitis, metastatic disease, hepatoma, and hepatic cysts.[4,9,19] In this case, radiological findings of asymmetric bile duct dilatation in the absence of identifiable calculi and segmental hepatic atrophy favor a diagnosis of an intraductal neoplasm, such as hilar cholangiocarcinoma or extrahepatic bile duct cancer.

Histology of BCAC is characterized by moderate mitotic activity seen in papillary projections of stratified cells lining the foci of dysplasia.[7,10] Tumor specimen may show areas of frank stromal invasion, oncocytic differentiation, have an endocrine cell component, and coexist with benign cystic structures.[20,21] Almost exclusively in females the underlying layer of connective tissue shows a distinctive aspect with increased stromal cellularity, closely resembling ovarian stroma.[7,17] Rarely the malignant epithelial cells exhibit a spindle-shaped pseudosarcomatous morphology.[22] Most tumor cells are positive on immunohistochemical staining for tissue polypeptide antigen, cytokeratin, CA 19-9, and CEA.[7,10,23] Devaney et al.[7] noticed a favorable prognosis for tumors with ovarian-like stroma, when compared to those predominantly seen in males having notably inconspicuous stromal features and increased propensity for locoregional dissemination.

Surgery is the mainstay of curative treatment in localized extrahepatic bile duct cancer.[1,24] The optimum surgical procedure (Table 1) will vary according to tumor location along the biliary tree, involvement of normal liver parenchyma, and the proximity of the tumor to major blood vessels in this region (Table 1). En bloc resection as performed may be necessary to attain free surgical margins and favorable outcome, as partial resection has been associated to high rates of recurrence and dismal prognosis.[1,2,6] Cytotoxic chemotherapy, targeted therapy, and radiation therapy have no proven role in the management of BCAC patients.

Table 1

Surgical management of extrahepatic biliary cystoadenocarcinoma in the literature.

Author	Cases (n)	Age/gender	Presentation	Procedure	Follow-up
Owono et al.[9]	3	62–67 y/ 2F:1M	Cholangitis	Hepatectomy	21–134 mo, two recurrences.
Tseng et al.[13]	1	68 y/ F	Cholangitis	Hepatectomy + BDR	Not informed.
Devaney et al.[7]	3	59 y/ 2F:1M	Jaundice	Hepatectomy + BDR	18–40 mo, two recurrences.
Erdogan et al.[8]	1	39 y/ F	Jaundice	Hepatectomy + BDR	59 mo, no recurrence.
Present case	1	54 y/ M	Jaundice	Hepatectomy + BDR	12 mo, no recurrence.

BDR, bile duct resection plus intra-hepatic bilioenteric bypass.

Conclusions

Although technically challenging, extensive hepatobiliary resection is feasible in adults with extrahepatic BCAC, and can offer long-term survival with acceptable and manageable morbidity. Early recognition of clinical and radiological features of rare tumors arising in bile ducts enables the early diagnosis and successful treatment.