*Purpose: Combined hepatocholangiocarcinomas (HCC-CCA) are rare tumors with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) differentiations. They are usually associated with a worse prognosis after liver transplantation (LT) than pure HCC tumors, however they are almost always diagnosed postoperatively. No clear radiological features or guidelines are currently available to differentiate HCC-CCA from HCC on preoperative imaging. We sought to assess the diagnostic accuracy of preoperative imaging and identify imaging characteristics associated with HCC-CCA.

*Methods: A total of 21 patients (out of 645) who underwent LT for HCC at a single center from January 1998 to January 2019 were found to have HCC-CCA on explant pathology. Fourteen of these patients had available diagnostic MRIs, they were consequently matched 2:1 with patients with pure HCC (n=28) on explant based on tumor size, MELD and highest pre-LT AFP. All images were reviewed by 2 radiologists who were blinded to the final pathological diagnosis, MRI features were systematically reported for each lesion. Features were grouped into “typical HCC” or “atypical HCC features” (Table 1), LIRADS scores were also reported.

*Results: Despite some overlap in “typical features” between HCC and HCC-CCA, “atypical features” were significantly more common in combined HCC-CCA vs HCC tumors (50, 40 and 40% vs 31, 23 and 1% for heterogeneous, atypical and delayed enhancement respectively). Moreover, whereas 21, 7, 46 and 7% of HCC lesions were respectively LIRADS 3, 4, 5 and M, all HCC-CCA were either LIRADS 5 or M. Based on this observation, the combination of LIRADS M or 5 and at least 1 “atypical feature” would allow for the correct diagnosis of 80% of HCC-CCA (sensitivity=0.8), while 22% of HCCs would be misdiagnosed as HCC-CCA (specificity=0.78) (Table 2). Clinically, patients with combined HCC-CCA tumors had a significantly lower 5-year survival rate of 39 vs 75% (p<0.001) as well as a lower 5-year recurrence-free survival rate of 42 vs 87% (p<0.001).

*Conclusions: Preoperative diagnosis of combined HCC-CCA tumors on the basis of imaging is possible if atypical features, beyond the LIRADS HCC features, are systematically assessed and incorporated in the diagnosis. Considering the dismal outcomes of HCC-CCA following LT, biopsy should be considered for all suspicious lesions in order to preoperatively confirm the diagnosis and potentially guide management.

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