Title

BILIARY CYSTADENOCARCINOMA WITH MESENCHYMAL STROMA: A CASE REPORT

Background

Hepatobiliary cystadenocarcinomas with mesenchymal stroma is a rare cystic lesion. This tumor needs to be distinguished from the benign biliary cystadenoma, which in most cases is antecedent. The treatment of choice is radical excision of the mass.
Purpose - Patients and Methods

We describe here the diagnostic evaluation, surgical management, pathological characteristics, treatment and follow up of one patient with hepatobiliary cystadenocarcinoma with ovarian stroma.
Conclusions

Diagnosis of biliary cystadenocarcinomas if often difficult preoperatively, because its clinical manifestation are similar to those of other hepatic cystic lesions. MRI is suitable for accurate characterization of cystic biliary lesion but the distinction between cystadenoma and cystadenocarcinoma remains difficult on the basis of imaging findings. Complete surgical excision gives a relatively good chance of long-term survival due to the slow growth rate of these tumors.
Key words: hepatic cystic tumors; biliary cystadenocarcinoma; liver

neoplasms.

Introduction

Cystadenoma and cystadenocarcinoma are rare cystic tumors constituting fewer than 5% of all intrahepatic cysts of biliary origin [1]. These lesions are mainly seen in middle-aged females and they arise from the intrahepatic and rarely from the extrahepatic bile ducts. Most of these patients are asymptomatic. If there are presenting symptoms, these are right upper quadrant pain, abdominal mass or an abdominal distension. Obstructive jaundice only rarely occurs. [1-2] It was associated with raised serum CA 19-9 and Ca125 levels. [7] The preoperative diagnosis is difficult. Surgical resection yields excellent results [1]. We reported the case of one patient with cystadenocarcinoma with presence of ovarian stroma, and discussed the characteristic clinical, radiologic, and histologic features of this disease.

Case report A 43-year-old woman with a surgery of papillary thyroid tumor, treated with total thyroidectomy nine years prior to presentation and positive for hepatitis B surface antigen as previous medical history; was admitted for painful epigastric mass. She complained of tree months history of intermittent epigastric colicky pain, radiating to right upper quadrant and aggravated by deep breathing, without nausea and weight loss. Physical examination showed an increase in abdominal girth and a presence of a palpable epigastric mass. Routine liver function tests revealed elevated plasma levels of alkaline phospatase (AP) of 257 U/L (normal range, 40-120 U/L) and gammaglutamyltransferase (GGT) of 71 U/L (normal, < 40 U/L). Serum bilirubin and alanine transaminase levels were normal. Serological markers for hydatid disease were negative. Serum levels of two tumor markers (CEA and alpha-fetoprotein) were normal. The level of the tumor marker CA 19-9 was raised at 1534 U/ml (normal, < 25 U/ml) and CA 12-5 was raised at 305. Ultrasonography revealed a multilocular cystic mass on the surface of the right lobe involving segment VI and VII of the liver (diameter 20 x13x 25 cm), with partial obstruction of the right hepatic duct, resulting in dilatation of the proximal biliary tree. Computed tomography (CT) demonstrated a cyst of the same diameter and dilation of the intrahepatic bile ducts of the right lobe. Percutaneous transhepatic aspiration needle biopsy was performed but it could not made the diagnosis. The patient underwent an hemihepatectomy. On laparotomy, the cystic mass was found to be projecting through the visceral surface of the liver. The tumour was seen protruding inside the pelvis. The mass was resected en bloc with a margin of normal liver tissue. Cut sections revealed a multicystic lesion encapsulated by a thick fibrous capsule arising from the hepatic duct. The cystic lesion was surrounded by stroma containing spindle-shaped cells, resembling ovarian stroma. The diagnosis of hepatobiliary cystadenocarcinoma with mesenchymal stroma was made. The postoperative course was uneventful and the complaints resolved after operation. We decided adjunctive treatment with six cycles of taxane and platinum based system chemotherapy. The patient had no show signs of local or distant recurrence during a follow-up of 2 years. Laboratory tests were normal.

Discussion Hepatobiliary cystadenocarcinomas are rare neoplasms that may occur in the liver or in extrahepatic biliary system, accounting for less than 5% of all cystic liver lesions. [2]. They represent a subtype of hepatic cystic disease estimated to be 1000 times less prevalent than simple cysts. Biliary cystadenoma (BCA) and its malignant counterpart biliary cystadenocarcinoma (BCAC) are cystic tumors that arise from the hepatobiliary epithelium. They are mucinous cystic tumors very similar to those occurring in pancreas and ovary. [4]. Approximately 85% of previously reported tumors have been intrahepatic, whereas the others usually arise from the extrahepatic biliary ducts or, rarely, the gallbladder. [8]. The etiology of the tumors is largely unknown. One of the proposed theories is the development from ectopic remnants of primitive foregut sequestered within the liver. [1]. The primordial germ cells normally migrate from the posterior wall of the yolk sac along the wall of the hindgut through the yolk stalk, a structure that is intimately related with the gut (from which the primordia of the major digestive glands arise, to include the pancreas and hepatobiliary system). This helps reconcile the ovarian-like stroma seen so frequently in these hepatobiliary tumors. [8]. These tumors are known to occur more frequently in middle-aged females. Clinical presentation is usually mild and atypical. They are found incidentally during abdominal imaging. Only a minority of patients with BCAC develop symptoms, because they usually grow slowly; the most commonly reported symptoms are right abdominal pain, increase in abdominal girth, anorexia, a palpable mass, or nausea. Rarely, patients present with colicky pain or jaundice caused by obstruction of the biliary system. The duration of symptoms ranges from days to years. Late symptoms, due to recurrence or metastatic disease, include ascites, jaundice, weigh loss, or bone pain. Reported complications include hemorrhage, rupture, and inflammation. [1-2]. Biliary cystic tumors are histologically heterogeneous with regard to tumor cell types (mucinous or non-mucinous) and tumor stroma (presence or absence of ovarian- like stroma). [5]

Recently, biliary cystadenocarcinoma was further subdivided into two groups because most pathologists believe that all biliary cystadenomas are premalignant, the presence of ovarian stroma in biliary cystadenoma and biliary cystadenocarcinoma may be considered a favourable prognostic sign those with ovarian stroma and those without ovarian stroma bad prognosis group biliary cystic tumors with ovarian-like stroma occurred only in younger females. [4-5] If imaging features could aid prediction of the presence or absence of ovarian stroma, the good prognosis group could be differentiated from the bad prognosis group. We reviewed on the literature, the role of imaging in the distinction of biliary cystadenoma from biliary cystadenocarcinoma and of those neoplasms with ovarian stroma from those without. [4] Ultrasound and computed tomography are the initial imaging modalities used in the preoperative characterization and localization of biliary cystadenomas and cystadenocarcinomas. Magnetic resonance imaging (MRI) improves tissue characterization, it allows detection of mucin and blood in a cystic lesion. On imaging studies, distinction between BCA or BCAC and simple cysts can be made by the presence of internal nodularity and septation, wall hemorrhage, or hemorrhagic internal fluid are all suggestive of biliary cystadenocarcinoma; septation without nodulanity and simple internal fluid are seen in biliary cystadenoma In the study of Mat Lewin supports that gadolinium enhanced MRI in combination with cholangio-pancreatography (MRCP) is a helpful technic to determine the diagnosis and the extension of hepatobiliary cystic tumors, however, the morphologic features of biliary cystadenoma and biliary cystadenocarcinoma cannot distinguish those with ovarian stroma from those without ovarian stroma. [4- 9] The use of percutaneous biopsy for preoperative diagnosis has no additional value considering the fact that it rarely produces a definitive diagnosis. There is also the additional risk of peritoneal dissemination in case of malignancy. However, this discrimination is of a little practical importance because the treatment for both benign and malignant forms is complete surgical excision. Histopathological examination is required for definitive diagnosis. [2] The treatment of choice is radical excision of the mass, either with a wide margin of normal liver or by means of a typical lobectomy, depending on the size and the location of the lesion. In the past, different treatment strategies such as partial resection, application of sclerosant agents inside the lesions or percutaneous aspiration have been applied with a high recurrence rates when compared to those who have undergone radical partial liver resection. [1-2]. Some authors have suggested that serum carcinoembryonic antigen (CEA) a CA-19-9 levels can be used for diagnosis or as a parameter of tumor

activity during follow-up after resection. Many markers are not specific. [7] However, an elevated serum CEA, CA 199 and Ca 125 level was found in our patient with BCAC. CA-19-9, a serum marker normally synthesized by normal pancreatic and biliary ductal epithelium, is elevated both in benign biliary lesions and in malignant pancreatic carcinomas we did not confirm with immunohistochemical analysis the presence of any markers in the epithelial component of the tumor. The differential diagnosis of BCAC without symptoms includes simple cysts, choledochal cysts, hepatobiliary cystadenocarcinoma, primary or metastatic necrotic neoplasms, Carolis disease or haematoma. A metastatic cystadenocarcinoma to the liver from a pancreatic or ovarian primary must be excluded with certainty. [1]. Both pyogenic and amebic abscesses may have a septated and multiloculated appearance on CT scans. The combination of clinical and laboratory findings should, however, point to an infectious cause in these cases. Hydatid cysts, in addition, usually have a thicker wall and round or oval daughter cysts; serologic tests may offer additional help in making the distinction. Other neoplasms that may have a multiloculated cystic appearance include a mesenchymal hamartoma and undifferentiated (embryonal) sarcoma. These occur, almost exclusively in children and young adults and do not have a female predilection. Rarely, metastatic disease or cystic primary hepatocellular carcinoma may simulate biliary cystadenoma or biliary cystadenocarcinoma [4]. The treatment is surgical the BCAC are excised to prevent metastases, and the BCA are also excised because of their propensity for malignant degeneration. [7] Preoperative or postoperative chemotherapy does not significantly improve survival. [3]. We decided adjuvant systemic therapy with a combination regimen of taxane and platinum like an ovarian cancer sustented in the histology and in her medical previous history with a another tumor. Conclusions Radical surgical treatment of cystic hepatobiliary tumors is necessary to obtain histopathological examination which is essential for a correct evaluation of the malignant potential of the lesion and for prolonged survival.

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