Discussion

Diagnosis

Intrahepatic Cholangiocarcinoma​

Discussion

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy and accounts for approximately 15% of primary liver cancers. For unclear reasons, the incidence of CCA has been increasing. Currently, in the United States the incidence is 0.85/100,000 per year. CCA occurs more frequently in white males, and the average age of presentation is 55-65-years-old. The overall prognosis is very poor, with 1 and 5-year survival rates of 27% and <5%, respectively. The only curative treatment is surgery, as chemotherapy and radiation are relatively ineffective; however, less than half of cases are deemed to be resectable at the time of presentation. Eighty-five percent of patients present with abdominal pain or biliary obstructive symptoms. While carcinoembryonic antigen (CEA) and CA19-9 levels may be elevated, alpha fetoprotein (AFP) is usually normal.

Conditions that have been clearly associated with CCA include liver fluke infections, primary sclerosing cholangitis, fibrocystic liver diseases (Caroli disease, and congenital hepatic fibrosis), and exposure to toxic agents (alcohol, thorotrast, and dioxin). Recent associations described include hepatolithiasis, hepatitis B and C viral infections, and obesity. Most cases arise in non-cirrhotic livers, in contrast to hepatocellular carcinoma.

Grossly, CCA is often large, tan-white, and nodular. Calcifications may be present, as can satellite nodules. Microscopically, CCA is an adenocarcinoma forming tubules or acini almost invariably within a dense desmoplastic stroma. Perineural invasion is common. Cytologically, the cells may be columnar or cuboidal with clear or eosinophilic cytoplasm. The nuclei are round to oval without prominent nucleoli. Ninety percent are adenocarcinoma with some other less common variants including mucinous, adenosquamous, clear cell, spindle cell, and mucoepidermoid carcinomas.

The key challenge for diagnosing CCA is differentiating it from metastatic adenocarcinoma and from hepatocellular carcinoma (HCC). There is no immunohistochemical marker that is specific for CCA, and it is essentially a diagnosis of exclusion. Cytokeratin 7/Cytokeratin 20 staining is useful for differentiating metastatic colon cancer (CK7-/CK20+) from CCA (CK7+/CK20+/-). Other more organ specific immunohistochemical markers may be utilized to exclude metastatic adenocarcinomas from other sites. HCC most commonly occurs in a background of cirrhosis and HepPar-1 and arginase-1 are negative in CCA and usually, but not always, positive in HCC. Positive mucin staining can favor CCA over HCC; however, mucin can be negative in CCA, as seen in this case.

References

Ghouri, Yezaz Ahmed, Idrees Mian, and Boris Blechacz. "Cancer review: cholangiocarcinoma." Journal of carcinogenesis 14.1 (2015): 1.

Kwon, Youngmee, et al. "Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules." Modern Pathology 15.10 (2002): 1096-1101.

Mills, S. E., & Sternberg, S. S. (2015). Sternbergs diagnostic surgical pathology. Philadelphia, PA: Lippincott Williams et Wilkins.

Rullier, Anne, et al. "Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis." The American journal of surgical pathology 24.6 (2000): 870-876.

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