Journal of Surgical Oncology 51:207-210 (1992)
Mucinous Biliary Cystadenoma: A Case Report and Review of the literature D. SCOTT LIND, MD, VINCENT ADOLPH, MD, AND GEORGE A. PARKER, MU from the Division of Surgical Oncology, Department of Surgery, Massey Cancer Center, Medical College of Virginia, Richmond, Virginia
Mucinous biliary cystadenomas are rare neoplasms with protean manifestations. In most cases the mucinous material is retained within the cyst itself. We describe an asymptomatic case of a mucin secreting biliary cystadenoma in which the mucin presented as an amorphous intraluminal filling defect in the common hepatic duct on endoscopic retrograde cholangiopancreatography (ERCP). The neoplasm itself was confined to the posterior segment of the right hepatic lobe and was treated by formal right hepatic lobectomy. This case prompted a review of mucinous biliary cystadenomas. 0 1992 Wiiey-Liss, Inc. KEYWORDS:benign bile duct neoplasm, mucin, hepatic lobectomy
INTRODUCTION Cystadenomas of the bile ducts are uncommon lesions and the correct diagnosis rarely is made preoperatively . The majority arise from an intrahepatic bile duct and become symptomatic by producing obstruction of the bile duct either directly by the tumor itself or, infrequently, by the secretion of mucin. When discovered incidentally in the asymptomatic patient, such a lesion may be difficult to distinguish from a bile duct carcinoma. Because there is a possibility of malignant degeneration complete excision remains the treatment of choice.
CASE REPORT In December 1990, during routine preoperative evaluation prior to a corneal transplant, a 68-year-old Caucasian male was noted to have an asymptomatic elevation of his serum alkaline phosphatase to 142 IU/dl (normal 38126 IU/dl). This was repeated in January 1991 and had risen to 205 IU/dl and at this time the gamma glutamyl transferase was 613 IU/dl (normal 8-78 IU/dl) while his serum bilirubin was normal. His past medical history was notable only for gout treated with allopurinol. He did not smoke or drink. The remainder of his serum chemistries, complete blood count, and coagulation profile were all normal. His physical exam was entirely unremarkable. Radiologic evaluation included an abdominal ultrasound which revealed a solitary 2.5 cm gallstone with intra and extrahepatic biliary ductal dilatation. An abdominal computerized axial tomography (CAT) scan also demon0 1992 Wiley-Liss, Inc.
strated the gallstone but suggested regional ductal dilatation confined to the posterior segment of the right lobe of the liver with no associated masses (Fig. 1). The patient underwent an endoscopic retrograde cholangiopancreatography (ERCP) that revealed a somewhat irregular intraluminal filling defect in the common hepatic duct and a normal pancreatic duct (Fig. 2). Although the patient was asymptomatic, the appearance of this filling defect was suggestive of neoplasm and the patient underwent exploratory celiotomy in March of 1991. At operation palpation of the liver and extrahepatic bile ducts was normal. A cholecystectomy and common bile duct exploration were performed. Choledochoscopy failed to disclose the filling defect in the common hepatic duct seen on ERCP, however mucinous material was noted to be coming from the right intrahepatic duct. Closer inspection demonstrated an irregularity of the duct originating from the posterior segment of the right lobe. Frozen section done on material retrieved through the choledochoscope returned “mucinous neoplasm, carcinoma not excluded,” In view of this the patient underwent a formal right hepatic lobectomy that was complicated intraoperatively by a transfusion reaction precipitating coagulopathy. In addition, despite stress ulcer prophylaxis postop-
Accepted for publication February 28, 1992 Address reprint requests to George A . Parker, MD, Division of Surgical Oncology, Department of Surgery, Medical College of Virginia, Box 1 1 , MCV Station, Richmond, VA 23298.
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Fig. 1. Abdominal CAT scan showing a cystic mass (CM) within the liver (A) associated with regional dilatation (RD) of the intrahepatic bile ducts (B).
eratively, he developed a bleeding duodenal ulcer requiring endoscopic electrocautery. The patient eventually recovered and was discharged on the 20th postoperative day. The gross pathology revealed a hemorrhagic,
mucoid, sessile mass measuring 0.8 X 0.6 X 0.5 cm located just proximal to the transected right hepatic duct. Histologically this lesion was a mucinous biliary cystadenoma and the margins of resection were clear (Fig. 3 ) .
Mucinous Biliary Cystadenoma
Fig. 2 . Endoscopic retrograde cholangiogram showing a large gallstone as well as an intraluminal filling defect (FD) in the common hepatic duct.
Fig. 3. Photomicrograph showing mesenchymal stroma with mucinous pools (MP).
DISCUSSION Biliary cystadenomas are uncommon tumors accounting for fewer than 5% of neoplasms of bile duct origin [ 11. The first reported case of resection of a biliary cystadenoma was by Keen in 1982 [2]. Up until 1988, only 71 cases had been reported in the literature [ 3 ] .The origin of these tumors is uncertain, with some proposing a congenital origin from aberrant bile duct rests, while others favor an acquired etiology such as a reactive process to some focal injury [4].The majority arise from the intrahepatic biliary ducts and most are located in the posterior seg-
209
ment of the right lobe. The preponderance for this location probably lies in the fact that the bulk of liver tissue is located in the right lobe. Contrary to the case presented here, these tumors tend to present in middle aged women [ 5 ] . The size of these neoplasms varies from 2-25 cm accounting for the symptoms of jaundice, right upper quadrant pain, and/or an abdominal mass [6]. In spite of sophisticated hepatobiliary imaging studies, the diagnosis is rarely made preoperatively . Asymptomatic lesions may be discovered incidentally during radiologic or surgical procedures for unrelated conditions. Radiologic studies, such as sonograghy and CAT scan, may reveal an intrahepatic cyst but it is often difficult to distinguish between simple liver cyst and cystadenoma. The latter occasionally shows internal septations or papillary infoldings within the cyst itself. A significant solid component to the cyst may suggest malignancy, but radiologic diagnosis of cystadenocarcinoma is not possible. Even percutaneous fine needle aspiration biopsy may miss microscopic foci of carcinoma in a cystadenoma 171. Dilatation of the bile ducts seen on sonography or CAT scan may lead to percutaneous transhepatic cholangiography (PTC) or ERCP. Contrast injected into the biliary tree may show an intraluminal filling defect which may be the primary tumor or, as in the case presented, may represent intraluminal mucin that cleared the bile duct prior to surgical exploration. Mucin as apposed to tumor, stones, air bubbles, or blood clots is described as being amorphous although this may be a subtle distinction. An infrequent but dramatic experience is the endoscopic visualization of mucin being extruded through the ampulla of Vater [8]. Pathologically these neoplasms bear strong resemblance to mucinous cystadenomas of the pancreas and the two may coexist, suggesting a common etiology [9]. They may be predominantly cystic or polypoid, with the cystic variety containing mucin within the cyst. Mucin secreting variants, with much filling the biliary tree, are extremely rare. The mucin can produce ductal dilatation distal to the tumor. Just as the pancreatic tumors can produce hyperamylasemia and abdominal pain secondary to mucin obstructing the pancreatic duct, similarly, the biliary neoplasms can manifest hyperbilirubinemia and biliary colic as a result of mucin obstructing the biliary tree [ 101. In addition to the symptoms that these benign neoplasms may produce by virtue of size or production of mucin, like their pancreatic counterparts, they are felt to be prone to malignant transformation. The evolution from cystadenoma to cystadenocarcinoma has been documented [ 1 11. Therefore, this real malignant potential, combined with a natural history of progressive enlargement, mandates therapeutic intervention. In spite of the difficult perioperative course endured by this patient, the literature supports resection as the treatment of choice for biliary cystadenomas. In a recent
210
Lind et al.
report, 15 patients underwent resection with no recurrences noted with a median follow-up of 20 months [ 3 ] . Typically the size of the symptomatic neoplasms and deep location of the incidentally discovered asymptomatic lesions demands formal hepatic resection. Therefore, the propensity for recurrence and the potential for malignant change make any therapy short of complete excision inadequate.
REFERENCES Cahill CJ, Bailey ME, Smith MGM: Mucinous cystadenoma of the liver. Clin Oncol 8:171-177, 1982 Henson SW, Gray HK, Dockerty MB: Benign tumors of the 1iver:VI. Multilocular cystadenoma. Surg Gynecol Obstet 46:551-5S4.12, 1957. Lewis WD, Jenkins RL, Rossi RL, et al: Surgical treatment of biliary cystadenoma. Arch Surg 123563-568, 1988. Ishak KG, Willis GW, Cummins SD, Bullock AA: Biliary cysta-
5. 6. 7. 8.
9. 10. 1I .
denoma and cystadenocarcinoma: report of 14 cases and review of the literature. Cancer 38:322-338, 1977. Short WF, Nedwich A, Levy HA, Howard JM: Biliary cystadenoma: report of a case and review of the literature. Arch Surg l02:78-80, 1971. Wheeler DA, Edmondson HA: Cystadenoma with niesenchymal stroma (cms) in the liver and bile ducts. Cancer 56:143&1445, 1985. lemoto Y , Kondo Y, Nakano T, et al: Biliary cystadenocarcinoma diagnosed by liver biopsy performed under ultrasonographic guidance. Gastroenterology 8 4 3 9 9 4 0 3 , 1983. KokuboT, Itai Y , Ohtomo K, et al: Mucin-hypersecreting intrahepatic biliary neoplasms. Radiology 168:609-614, 1988. Keech MK: Cystadenoma of the pancreas and intrahepatic bile ducts. Gastroenterology 19:568-574, 195 1 . Itai Y , Kokubo T, Atomi Y , et al: Mucin-hypersecreting carcinoma of the pancreas. Radiology 1655 1-55, 1987. Woods G: Biliary cystadenoma: case report of hepatic malignancy originating in a benign cystadenoma. Cancer 47:2936-2940, 1981.
Mucinous Biliary Cystadenoma: A Case Report and Review of the literature D. SCOTT LIND, MD, VINCENT ADOLPH, MD, AND GEORGE A. PARKER, MU from the Division of Surgical Oncology, Department of Surgery, Massey Cancer Center, Medical College of Virginia, Richmond, Virginia
Mucinous biliary cystadenomas are rare neoplasms with protean manifestations. In most cases the mucinous material is retained within the cyst itself. We describe an asymptomatic case of a mucin secreting biliary cystadenoma in which the mucin presented as an amorphous intraluminal filling defect in the common hepatic duct on endoscopic retrograde cholangiopancreatography (ERCP). The neoplasm itself was confined to the posterior segment of the right hepatic lobe and was treated by formal right hepatic lobectomy. This case prompted a review of mucinous biliary cystadenomas. 0 1992 Wiiey-Liss, Inc. KEYWORDS:benign bile duct neoplasm, mucin, hepatic lobectomy
INTRODUCTION Cystadenomas of the bile ducts are uncommon lesions and the correct diagnosis rarely is made preoperatively . The majority arise from an intrahepatic bile duct and become symptomatic by producing obstruction of the bile duct either directly by the tumor itself or, infrequently, by the secretion of mucin. When discovered incidentally in the asymptomatic patient, such a lesion may be difficult to distinguish from a bile duct carcinoma. Because there is a possibility of malignant degeneration complete excision remains the treatment of choice.
CASE REPORT In December 1990, during routine preoperative evaluation prior to a corneal transplant, a 68-year-old Caucasian male was noted to have an asymptomatic elevation of his serum alkaline phosphatase to 142 IU/dl (normal 38126 IU/dl). This was repeated in January 1991 and had risen to 205 IU/dl and at this time the gamma glutamyl transferase was 613 IU/dl (normal 8-78 IU/dl) while his serum bilirubin was normal. His past medical history was notable only for gout treated with allopurinol. He did not smoke or drink. The remainder of his serum chemistries, complete blood count, and coagulation profile were all normal. His physical exam was entirely unremarkable. Radiologic evaluation included an abdominal ultrasound which revealed a solitary 2.5 cm gallstone with intra and extrahepatic biliary ductal dilatation. An abdominal computerized axial tomography (CAT) scan also demon0 1992 Wiley-Liss, Inc.
strated the gallstone but suggested regional ductal dilatation confined to the posterior segment of the right lobe of the liver with no associated masses (Fig. 1). The patient underwent an endoscopic retrograde cholangiopancreatography (ERCP) that revealed a somewhat irregular intraluminal filling defect in the common hepatic duct and a normal pancreatic duct (Fig. 2). Although the patient was asymptomatic, the appearance of this filling defect was suggestive of neoplasm and the patient underwent exploratory celiotomy in March of 1991. At operation palpation of the liver and extrahepatic bile ducts was normal. A cholecystectomy and common bile duct exploration were performed. Choledochoscopy failed to disclose the filling defect in the common hepatic duct seen on ERCP, however mucinous material was noted to be coming from the right intrahepatic duct. Closer inspection demonstrated an irregularity of the duct originating from the posterior segment of the right lobe. Frozen section done on material retrieved through the choledochoscope returned “mucinous neoplasm, carcinoma not excluded,” In view of this the patient underwent a formal right hepatic lobectomy that was complicated intraoperatively by a transfusion reaction precipitating coagulopathy. In addition, despite stress ulcer prophylaxis postop-
Accepted for publication February 28, 1992 Address reprint requests to George A . Parker, MD, Division of Surgical Oncology, Department of Surgery, Medical College of Virginia, Box 1 1 , MCV Station, Richmond, VA 23298.
208
Lind et al.
Fig. 1. Abdominal CAT scan showing a cystic mass (CM) within the liver (A) associated with regional dilatation (RD) of the intrahepatic bile ducts (B).
eratively, he developed a bleeding duodenal ulcer requiring endoscopic electrocautery. The patient eventually recovered and was discharged on the 20th postoperative day. The gross pathology revealed a hemorrhagic,
mucoid, sessile mass measuring 0.8 X 0.6 X 0.5 cm located just proximal to the transected right hepatic duct. Histologically this lesion was a mucinous biliary cystadenoma and the margins of resection were clear (Fig. 3 ) .
Mucinous Biliary Cystadenoma
Fig. 2 . Endoscopic retrograde cholangiogram showing a large gallstone as well as an intraluminal filling defect (FD) in the common hepatic duct.
Fig. 3. Photomicrograph showing mesenchymal stroma with mucinous pools (MP).
DISCUSSION Biliary cystadenomas are uncommon tumors accounting for fewer than 5% of neoplasms of bile duct origin [ 11. The first reported case of resection of a biliary cystadenoma was by Keen in 1982 [2]. Up until 1988, only 71 cases had been reported in the literature [ 3 ] .The origin of these tumors is uncertain, with some proposing a congenital origin from aberrant bile duct rests, while others favor an acquired etiology such as a reactive process to some focal injury [4].The majority arise from the intrahepatic biliary ducts and most are located in the posterior seg-
209
ment of the right lobe. The preponderance for this location probably lies in the fact that the bulk of liver tissue is located in the right lobe. Contrary to the case presented here, these tumors tend to present in middle aged women [ 5 ] . The size of these neoplasms varies from 2-25 cm accounting for the symptoms of jaundice, right upper quadrant pain, and/or an abdominal mass [6]. In spite of sophisticated hepatobiliary imaging studies, the diagnosis is rarely made preoperatively . Asymptomatic lesions may be discovered incidentally during radiologic or surgical procedures for unrelated conditions. Radiologic studies, such as sonograghy and CAT scan, may reveal an intrahepatic cyst but it is often difficult to distinguish between simple liver cyst and cystadenoma. The latter occasionally shows internal septations or papillary infoldings within the cyst itself. A significant solid component to the cyst may suggest malignancy, but radiologic diagnosis of cystadenocarcinoma is not possible. Even percutaneous fine needle aspiration biopsy may miss microscopic foci of carcinoma in a cystadenoma 171. Dilatation of the bile ducts seen on sonography or CAT scan may lead to percutaneous transhepatic cholangiography (PTC) or ERCP. Contrast injected into the biliary tree may show an intraluminal filling defect which may be the primary tumor or, as in the case presented, may represent intraluminal mucin that cleared the bile duct prior to surgical exploration. Mucin as apposed to tumor, stones, air bubbles, or blood clots is described as being amorphous although this may be a subtle distinction. An infrequent but dramatic experience is the endoscopic visualization of mucin being extruded through the ampulla of Vater [8]. Pathologically these neoplasms bear strong resemblance to mucinous cystadenomas of the pancreas and the two may coexist, suggesting a common etiology [9]. They may be predominantly cystic or polypoid, with the cystic variety containing mucin within the cyst. Mucin secreting variants, with much filling the biliary tree, are extremely rare. The mucin can produce ductal dilatation distal to the tumor. Just as the pancreatic tumors can produce hyperamylasemia and abdominal pain secondary to mucin obstructing the pancreatic duct, similarly, the biliary neoplasms can manifest hyperbilirubinemia and biliary colic as a result of mucin obstructing the biliary tree [ 101. In addition to the symptoms that these benign neoplasms may produce by virtue of size or production of mucin, like their pancreatic counterparts, they are felt to be prone to malignant transformation. The evolution from cystadenoma to cystadenocarcinoma has been documented [ 1 11. Therefore, this real malignant potential, combined with a natural history of progressive enlargement, mandates therapeutic intervention. In spite of the difficult perioperative course endured by this patient, the literature supports resection as the treatment of choice for biliary cystadenomas. In a recent
210
Lind et al.
report, 15 patients underwent resection with no recurrences noted with a median follow-up of 20 months [ 3 ] . Typically the size of the symptomatic neoplasms and deep location of the incidentally discovered asymptomatic lesions demands formal hepatic resection. Therefore, the propensity for recurrence and the potential for malignant change make any therapy short of complete excision inadequate.
REFERENCES Cahill CJ, Bailey ME, Smith MGM: Mucinous cystadenoma of the liver. Clin Oncol 8:171-177, 1982 Henson SW, Gray HK, Dockerty MB: Benign tumors of the 1iver:VI. Multilocular cystadenoma. Surg Gynecol Obstet 46:551-5S4.12, 1957. Lewis WD, Jenkins RL, Rossi RL, et al: Surgical treatment of biliary cystadenoma. Arch Surg 123563-568, 1988. Ishak KG, Willis GW, Cummins SD, Bullock AA: Biliary cysta-
5. 6. 7. 8.
9. 10. 1I .
denoma and cystadenocarcinoma: report of 14 cases and review of the literature. Cancer 38:322-338, 1977. Short WF, Nedwich A, Levy HA, Howard JM: Biliary cystadenoma: report of a case and review of the literature. Arch Surg l02:78-80, 1971. Wheeler DA, Edmondson HA: Cystadenoma with niesenchymal stroma (cms) in the liver and bile ducts. Cancer 56:143&1445, 1985. lemoto Y , Kondo Y, Nakano T, et al: Biliary cystadenocarcinoma diagnosed by liver biopsy performed under ultrasonographic guidance. Gastroenterology 8 4 3 9 9 4 0 3 , 1983. KokuboT, Itai Y , Ohtomo K, et al: Mucin-hypersecreting intrahepatic biliary neoplasms. Radiology 168:609-614, 1988. Keech MK: Cystadenoma of the pancreas and intrahepatic bile ducts. Gastroenterology 19:568-574, 195 1 . Itai Y , Kokubo T, Atomi Y , et al: Mucin-hypersecreting carcinoma of the pancreas. Radiology 1655 1-55, 1987. Woods G: Biliary cystadenoma: case report of hepatic malignancy originating in a benign cystadenoma. Cancer 47:2936-2940, 1981.
