Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors

Tumors with combined hepatocellular and cholangiocellular features are well known histopathologically but their clinical behavior is poorly understood. The objectives of the current study were to define the demographic profile of the patients in whom these uncommon tumors occur and to evaluate treatment outcome in comparison with that in patients with either hepatocellular carcinoma (HCC) or peripheral cholangiocarcinoma (CC) alone.

Twenty-seven patients with combined tumors were identified from a prospective database. Pathologic specimens were analyzed to confirm the diagnosis. Demographics, clinical data, and survival were analyzed. Outcome after resection was compared with that of patients with CC and with a matched group of patients with HCC.

The gender distribution of the combined tumors (52% men and 48% women) was intermediate between HCC (67% men and 33% women) and CC (30% men and 70% women) (P = 0.03). The incidence of positive hepatitis B or C serology and cirrhosis was similar in patients with combined tumors and those with CC (15% and 0% vs. 13% and 4%, respectively); similarly, patients of Asian heritage constituted 7% and 9%, respectively, of the patients with these tumors. By contrast, cirrhosis (41%) and positive hepatitis serology (56%) were far more common in patients with HCC, and 19% of these patients were of Asian heritage. Twenty-one of 27 patients with combined tumors (78%) underwent resection. All 6 patients with combined tumors that were not amenable to resection died of disease within 18 months. After resection, the 5-year survival was lowest in patients with combined tumors (24%) but was not significantly different from that in patients with CC (33%) or HCC (37%). The liver was the most common site of recurrence in all three groups.

The demographic and clinical features of patients with combined tumors were most similar to those of patients with CC. Most important, combined tumors were not found to be associated with chronic liver disease; consequently, the resectability rate was higher for these tumors than typically is reported for HCC. Resection was associated with long-term survival in some patients, but recurrent hepatic disease was common. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance.