Carcinomatous arteriopathy as an unusual feature of pulmonary spread of cholangiocarcinoma arising in Caroli disease

Archives of Pathology & Laboratory Medicine,  Jun 2002  by Wang, Hanlin L

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* Carcinomatous arteriopathy is a rare and distinct form of pulmonary spread of solid malignant tumors characterized by fibrointimal proliferation of small pulmonary arteries and arterioles initiated by tumor emboli. Although it has been reported in many types of adenocarcinomas, no case of carcinomatous arteriopathy induced by cholangiocarcinoma has been described in the literature. We report a unique case of cholangiocarcinoma that arose in Caroli disease. Postmortem examination revealed extensive pulmonary vascular spread in the form of carcinomatous arteriopathy.

(Arch Pathol Lab Med. 2002;126:717-720)

Pulmonary carcinomatous arteriopathy, also referred to as pulmonary tumor thrombotic microangiopathy, carcinomatous endarteritis, or embolic carcinomatosis1,2 is a rare and distinct form of pulmonary spread of solid malignant tumors. It is characterized by fibrointimal prolif eration of small pulmonary arteries and arterioles initiated by tumor emboli that may be accompanied by fibrin thrombosis. Although patients with profound pulmonary vascular involvement may present clinically with progressive dyspnea, pulmonary hypertension, and even cor pulmonale, they may show clear lung fields on chest radiography.1,2 In autopsy series, carcinomatous arteriopathy is found in 3.3% of cancer patients,2 mostly associated with adenocarcinomas, including adenocarcinomas of the stomach, breast, colon, pancreas, and prostate, as well as choriocarcinoma and hepatocellular carcinomas-3 To our knowledge, no case of carcinomatous arteriopathy associated with cholangiocarcinoma has been described in the literature to date,2,3 even though pulmonary metastasis has been found in up to 15% of cases.4

Cholangiocarcinoma is a relatively uncommon tumor with an autopsy incidence ranging from 0.01% to 0.5%, which accounts for about 3% of all cancers.4,5 In most cases, the etiology is obscure. Identifiable risk factors, such as hepatolithiasis, sclerosing cholangitis, liver flukes, and exposure to Thorotrast, account for only a small proportion of the cases.5,6 Cholangiocarcinoma has been reported to occur as a complication of Caroli disease, an extremely rare congenital disease of the intrahepatic biliary tree characterized by segmental cystic dilatation of the larger intrahepatic bile ducts, recurrent bacterial cholangitis, and biliary lithiasis.5-8 More than 300 cases of Caroli disease and Caroli syndrome (Caroli disease associated with congenital hepatic fibrosis) have been reported in the world literature? and cholangiocarcinoma has been found in 7% to 14% of the cases.5,7,9

We report a case of cholangiocarcinoma that arose in Caroli disease. Postmortem examination revealed extensive pulmonary vascular spread in the form of carcinomatous arteriopathy in addition to metastasis to the regional lymph nodes.

REPORT OF A CASE

A 61-year-old African American woman with a 2-month history of jaundice was hospitalized because of abdominal pain, nausea, and vomiting. She had a 10-year history of "liver disease" and was told she had had "hepatitis" in the past, but she received no treatment. On admission, the patient was cachectic and afebrile. The liver was enlarged and slightly tender. Laboratory studies showed elevated bilirubin and liver enzyme levels and elevated white blood cell counts. Results of her hepatitis serologies were all negative. Serologic tumor marker study results were negative for a-fetoprotein but positive for CA 19-9 (37800 U/mL; normal,

PATHOLOGIC FINDINGS

At autopsy, icterus and anasarca were present. The liver (2466 g) was bile stained but noncirrhotic. Cystically dilated intrahepatic bile ducts, typical of Caroli disease, were observed in both left and right lobes. They measured up to 2 cm in diameter and were filled with pigmented calculi (Figure 1, A). The intervening liver parenchyma contained many irregular, ill-defined, gray-white, and firm areas. Microscopically, the dilated ducts were lined with a single layer of columnar epithelium and showed marked fibrosis and mild chronic inflammation (Figure 1, B). Multiple sections failed to demonstrate the presence of dysplasia in the lining epithelium. Histologic examination of the gray-white intervening areas revealed well-differentiated cholangiocarcinoma characterized by infiltrating glandular structures in a fibrotic background (Figure 1, C). The neoplastic epithelial cells were cuboidal and had round or oval nuclei and inconspicuous nucleoli. Mitotic figures were sparse. No bile production was evident. Pathologic examination of the liver also identified a 10-cm abscess in the right lobe that had extended into the subphrenic space. Choledochal cyst and cystic kidney disease, 2 abnormalities that could be associated with Caroli disease,8 were not found in this patient.

Metastases were grossly identified in the porta hepatis, pancreatic, and mesenteric lymph nodes, which were confirmed by histologic examination. No portal tumor thrombosis was present.

The lungs (left, 565 g; right, 439 g) had smooth and glisteeing pleural surfaces, and both were congested. Gross examination was unremarkable, except for several tiny thromboemboli and a few small areas of hemorrhagic infarction. No metastatic nodules were appreciated grossly. On histologic examination, however, numerous microscopic tumor emboli were found that extensively involved the arterioles and small arteries in both lungs. Tumor cells were present within the vascular lumens without invading the vascular walls. Three histologic patterns were recognized, in which tumor cells were either closely attached to the endothelium or replacing the endothelial lining without causing significant intimal proliferation or luminal obstruction (Figure 2, A), were associated with fibrin thrombi (Figure 2, B), or were embedded in obliterated lumens caused by marked fibrointimal proliferation (Figure 2, C). Careful examination of the lungs revealed no evidence of lymphangitic metastasis or involvement of the lung parenchyma. No tumor thromboemboli or overt metastasis was found in other organs.