Disorders of the Intra- and Extrahepatic Bile Ducts
Case 11 -
Biliary Cystadenocarcinoma Arising in Benign Cystadenoma
Kay Washington, M.D., Ph.D.
Pathology, C-3321 MCN
Vanderbilt University Medical Center
Nashville, TN 37232-2561
This 62 year old woman presented to the emergency room with crushing chest pain, diagnosed
as angina, and was found to have an enlarged liver. Abdominal CT scan showed two cystic masses in the
liver and bilateral adrenal hyperplasia but no adenopathy. Positron emission scan showed two
metabolically active areas within one of the cystic masses. At surgery a small amount of mucoid ascites
was found. The cystic hepatic lesions were resected; this section is from the larger mass, which
measured 8.6 cm in greatest dimension.
In the more cystic areas, the tumor is composed of cysts of varying sizes,
lined by a single layer of cuboidal to columnar epithelium with apical mucin. Occasional goblet cells
are identified. The stroma is cellular and resembles ovarian stroma, with focal hyalinization and
inflammation. In the more solid portion, the tumor forms complex papillary structures lined by multiple
layers of large atypical cells. Loss of nuclear polarity is seen in these areas, and there are numerous
mitoses, some atypical. The cells have large pleomorphic nuclei and a high nuclear to cytoplasmic ratio.
Focally frank invasion of the stroma by small clusters of atypical cells and single cells is identified.
Borderline areas with nuclear crowding and intermediate cellular atypia and without papillary formations
are also present.
Click on each slide thumbnail image for an enlarged view:
Adenocarcinoma Arising in Biliary Cystadenoma
Cytologically malignant cells forming cribriform and papillary structures infiltrate the cyst wall.
Biliary Cystadenoma with Mesenchymal Stroma
The cysts of biliary cystadenoma are lined by simple columnar to cuboidal epithelium; goblet cells are occasionally seen. The underlying mesenchymal stroma may be densely packed and resemble ovarian stroma, a feature found exclusively in female patients.
Diagnosis: Biliary Cystadenocarcinoma Arising in Benign Cystadenoma
The benign biliary epithelial tumors are the bile duct adenoma and the biliary cystadenoma. Bile
duct adenomas are generally incidental findings at surgery or autopsy. They appear as discrete firm
white masses usually 1 centimeter or less in diameter and are often subcapsular. Microscopically they
are composed of a compact uniform proliferation of ductular structures in a desmoplastic stroma. The
lack of cytologic atypia and lack of infiltration are features serving to distinguish the biliary adenoma
from cholangiocarcinoma or metastatic carcinoma. Distinction from a biliary microhamartoma or von
Meyenburg complex is occasionally difficult, but the biliary microhamartoma is made up of dilated bile
duct-like structures, occasionally containing bile, located adjacent to a portal tract.
The biliary cystadenoma is an uncommon hepatic neoplasm occurring predominantly in women. These
lesions are large multiloculated cysts histologically similar to mucinous cystic tumors arising in the
pancreas. The cysts are lined by mucin-secreting cells similar to bile duct epithelium ranging from
flattened cuboidal to tall columnar; occasional goblet cells are seen. The epithelial lining is usually
simple, although areas of nuclear pseudostratification and crowding may be seen. In tumors from men, the
supporting stroma is composed of dense fibrous tissue; in women, the stroma may be densely cellular and
resemble ovarian stroma. The biliary cystadenoma should be distinguished from the simple biliary cyst,
which is unilocular and lacks a distinctive supporting stroma.
Biliary cystadenocarcinoma is a rare tumor, generally arising in a pre-existing biliary cystadenoma.
These tumors arise in adults, and although benign biliary cystadenomas are more common in women, for
cystadenocarcinomas the sex ratio is approximately 1:1 .46 The most common presenting symptoms are
abdominal pain or an abdominal mass. The etiology remains unknown, although there are reports of
cystadenocarcinomas arising in the setting of polycystic liver disease, such as Caroli's disease .47
Most biliary cystadenocarcinomas are multilocular, although rare unilocular cases
have been reported .47 Cystadenocarcinomas in one series ranged in size from 3 to 30 cm, essentially
no different in size from benign biliary cystadenomas .46 The cyst fluid may be clear mucinous,
bile-stained, or blood tinged. The cyst lining may contain papillary projections into the cyst lumen.
Areas of solid thickening and large papillary projections are clues to malignancy.
The epithelial lining of the cysts generally consists of tall columnar cells
and should display cytologic features of malignancy. The tumor infiltrates the underlying cyst wall.
Most biliary cystadenocarcinomas are well-differentiated; the most common patterns are a tubulopapillary
or tubular adenocarcinoma. Rarely, the tumor shows adenosquamous differentiation. The stroma is
variable in biliary cystadenocarcinomas; ovarian-type stroma is often present in tumors in women; in men,
the stroma consists of dense fibrosis.
Determination of Malignancy
The prediction of behavior from morphologic features is difficult in
cystic mucinous neoplasms. Many otherwise benign biliary cystadenomas have areas of nuclear enlargement,
crowding, and stratification, considered areas of dysplastic change. Many pathologists reserve the term
"cystadenocarcinoma" for cases with frankly invasive adenocarcinoma involving the stroma or adjacent
parenchyma. Surgical resection offers the greatest opportunity for cure; long-term survival is
relatively high for women with biliary cystadenocarcinomas arising in pre-existing cystadenomas with
ovarian-type stroma. Cystadenocarcinomas in men may have a more aggressive course .46
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