Hepatic cyst arising from the left hepatic duct. (Pathologic Quiz Case).
Abdominal ultrasound studies showed a lobulated cystic mass in the left lobe of the liver and a filling defect in the left hepatic duct, extending 4 cm along the common bile duct. Computed tomographic scan demonstrated a large cystic mass involving the left lobe of the liver, measuring 14 x 9 cm; the tumor was homogeneous and had a few septa (Figure 1). There was compression of the porta hepatis with dilatation of the intrahepatic bile ducts.
[FIGURE 1 OMITTED]
Surgical treatment was undertaken and consisted of a left hepatic lobectomy with resection of the common hepatic duct and common bile duct, followed by anastomosis to the right hepatic duct. Cholecystectomy was also performed. The filling defect in the extrahepatic ducts was found to be a polypoid tumor measuring 5.5 cm with a gelatinous appearance.
On gross examination, the left hepatectomy specimen included a globular, 15-cm, cystic tumor arising from the left hepatic duct. The cut surface demonstrated multiple loculi ranging in size from 2 to 10 cm, a smooth white internal lining, and mucinous content (Figure 2).
[FIGURE 2 OMITTED]
Microscopically, the cysts were lined by a single layer of cuboidal or flattened mucinous epithelial cells with round regular nuclei that were basally located (Figure 3). There were occasional small papillary structures and cystic invaginations, but there was no evidence of malignancy or dysplasia. The underlying stroma was cellular and was composed of compact spindle-shaped cells with uniform ovoid nuclei and small blood vessels (Figure 4). Focal collections of foamy macrophages and cholesterol clefts associated with foreign-body giant cells were present beneath areas denuded of lining cells. The separate pedunculated lesion resected from the extrahepatic ducts had an identical microscopic appearance.
[FIGURE 3 & 4 OMITTED]
The postoperative recovery was uneventful, and after 2 years of follow-up the patient was well without any clinical or computed tomographic scan evidence of recurrence.
What is your diagnosis?
Pathologic Diagnosis: Hepatobiliary Cystadenoma With Mesenchymal Stroma
Hepatobiliary cystadenoma is a rare intrahepatic neoplasm representing approximately 5% of intrahepatic cystic lesions. (1) It was defined by Edmondson in 1958 as a multilocular lesion lined by columnar epithelium with an accompanying densely cellular "ovarian-like" stroma. (2) In recent years, reports of this tumor have appeared more frequently in the radiological and surgical literature, largely due to wider use of and improved diagnostic imaging techniques, (3) but cases arising in the extrahepatic biliary tree remain rare. (4)
This tumor occurs more frequently in middle-aged women. It may be associated with preexisting lesions, such as polycystic disease of the liver, and abnormalities in hepatobiliary anatomy. (4) The most frequent symptoms and signs are pain, nausea, fullness, and palpable mass, and less frequently jaundice, rupture, or infection are present.(5)
In most instances, hematologic and biochemical tests are normal, but elevated levels of alkaline phosphatase, [gamma]-glutamyl transpeptidase, and bilirubin can be found when intrahepatic or extrahepatic biliary duct compression is present. (3) Elevated serum CA 19-9 levels have been demonstrated in a few cases. (6) Ultrasonography, computed tomographic scan, and magnetic resonance imaging are the most discriminating noninvasive diagnostic techniques, but a definite diagnosis is rarely made with imaging alone. Frequent complications include intracystic hemorrhage, bacterial infection, or rupture, which may complicate the diagnosis. (3)
Grossly, hepatobiliary cystadenoma is usually a multiloculated tumor, which may present as a cyst within the liver, as a pedunculated lesion arising from its surface, or as a polyp within a large bile duct. (5) The size ranges from 15 to 25 cm for all types noted, and it has a globular shape and a smooth external surface. The cut surface shows locules of various size containing yellow, brown, or hemorrhagic mucinous fluid. (5, 7)
Microscopically, the cysts are lined by a single layer of cuboidal, columnar, or flattened mucinous epithelial cells. The nuclei are basally located and regular. Occasional small papillary structures or cystic invaginations may be seen. Focal intestinal and Paneth cell metaplasia have been described, as well as oncocytic differentiation. (4)
A basement membrane separates the epithelium from the underlying ovarian-like stroma. This stroma is composed of spindle cells with round to elongated nuclei and a small amount of pink cytoplasm. (7) The septa between cysts often show secondary changes, such as foamy or pigmented macrophages, cholesterol clefts, multinucleated giant cells, fibrosis, scarring, and calcification. (4, 5, 7)
On immunohistochemistry, the epithelial component stains positive for cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. Scattered lysozyme positivity with apical accentuation may be seen, as well as chromogranin, serotonin, gastrin, and somatostatin positivity in the endocrine component. (4, 8) Stromal cells are strongly immunoreactive for vimentin and smooth muscle actin; they show focal positivity with desmin, lysozyme, type IV collagen, progesterone, and estrogen receptors. (4)
The histogenesis of this tumor is still unknown. The positivity of epithelial lining for cytokeratin and carcinoembryonic antigen (4) and the appearance of the stroma, similar to mesenchymal tissue in the fetal gallbladder, support the hypothesis that remnants of primitive hepatobiliary cells constitute the progenitor of the hepatic cystadenoma. (3, 9) Meanwhile, the positivity of the stroma for hormone receptors and its apparent restriction to tumors arising in female patients suggest a sex-specific (perhaps hormonal) factor. (1, 4)
The only curative therapy is complete surgical resection. (5, 10) Partial excision and drainage procedures have usually been unsuccessful. (7, 10) Undetected synchronous malignancy corresponding to biliary cystadenocarcinoma occurs in 2% to 4% of cases, (10) Benign and malignant areas may coexist. Foci of cellular atypia, multilayering, or solid epithelial masses indicate borderline changes; capsular invasion signifies malignancy. (4, 7)
In summary, hepatobiliary cystadenoma with mesenchymal stroma is a rare multilocular tumor that arises in women and has potential for malignant transformation. Benign and malignant areas may coexist, emphasizing the need for thorough pathologic sampling. The only curative therapy is total excision, even if the lesion presents as a benign tumor.
The authors thank S. Caplin, FRCS, for reviewing the English text.
(1.) Pedram-Canihac M, Le Bail B, Rivel J, Blanc JF, Saric J, Bioulac-Sage P. Cystadenome hepatobiliaire a stroma mesenchymateux: une tumeur hormonodependante? A propos de cinq cas avec etude immunohistochimique des recepteurs hormonaux. Ann Pathol. 2000;20:14-18.
(2.) Edmondson HA. Tumors of the Liver and Intrahepatic Bile Ducts. Washington, DC: Armed Forces Institute of Pathology; 1958: 24-28. Atlas of Tumor Pathology; 2nd series, fascicle 26.
(3.) Gadzijev EM, Pleskovic A, Stanisavljevic D, Ferlan-Marolt V, Trotovsek B. Hepatobiliary cystadenoma can protrude and grow into the bile ducts. Hepatogastroenterology. 1998;45:1446-1451.
(4.) Daveny K, Goodman ZD, Ishak KG. Hepatobiliary cystadenoma and cystadenocarcinoma: a light microscopic and immunohistochemical study of 70 patients. Am J Surg Pathol. 1994;18:1078-1091.
(5.) Paradinas FJ. Liver tumors and tumor-like conditions. In: Wight DG, ed. Liver, Biliary Tract and Exocrine Pancreas. New York, NY: Churchill Livingstone; 1994:469-541. Systemic Pathology; 3rd ed.
(6.) Thomas JA, Scriven MW, Puntis MCA, Jasani B, Williams GT. Elevated serum CA 19-9 levels in hepatobiliary cystadenoma with mesenchymal stroma: two case reports with immunohistochemical confirmation. Cancer. 1992;70:1841-1846.
(7.) Wheeler DA, Edmondson HA. Cystadenoma with mesenchymal stroma (CMS) in the liver and bile ducts: a clinicopathological study of 17 cases, 4 with malignant change. Cancer. 1985;56:1434-1445.
(8.) Gourley WK, Kumar D, Bouton MS, Fish JC, Nealon W. Cystadenoma and cystadenocarcinoma with mesenchymal stroma of the liver: immunohistochemical analysis. Arch Pathol Lab Med. 1992;116:1047-1050.
(9.) Subramony C, Herrera GA, Turbat-Herrera EA. Hepatobiliary cystadenoma: a study of five cases with reference to histogenesis. Arch Pathol Lab Med. 1993; 117:1036-1042.
(10.) Knott AW, Ampudia RJ, Evankovich CH, et al. Biliary cystadenoma: rare variant of intrahepatic cystic disease. South Med J. 2000;93:698-702.
Accepted for publication March 15, 2001.
From the Departments of Pathology (Dr Mourra) and Radiology (Dr Arrive), Hopital St-Antoine Paris, France; and the Department of Surgery (Dr Hannoun), Hopital Pitie-Salpetriere, Paris, France.
Reprints not available from the authors.