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Page 2 of 10 Fowler et al. Hepatoma Res 2020;6:19 I http://dx.doi.org/10.20517/2394-5079.2020.21

in high-risk patients. There are substantial differences in the treatment strategy and prognosis between HCC
and non-HCC malignancies and it is critical to differentiate between the two.

The Liver Imaging Reporting and Data System (LI-RADS) is endorsed by the American College of Radiology
[3]
and the American Association for the Study of Liver Diseases . LI-RADS provides the most comprehensive
guidance for imaging in at risk patients, with imaging algorithms covering ultrasound screening/surveillance,
diagnosis on CT/MRI, diagnosis on contrast enhanced ultrasound (CEUS), and treatment response on CT/
MRI. This manuscript will provide an overview of the imaging appearances and LI-RADS approach to
diagnosing iCCA and cHCC-CCA in at risk patients, both on CT/MRI and on CEUS.

CT/MRI
Imaging appearance of iCCA and cHCC-CCA
On CT and MRI, both iCCA and HCC may show arterial phase hyperenhancement (APHE) and washout.
It is the morphology of the enhancement during the dynamic postcontrast phases that helps differentiate
between them. These differences in morphology are likely attributable to different histological composition.
Intrahepatic mass forming cholangiocarcinomas frequently show rim APHE, peripheral washout appearance
[4]
and often delayed central enhancement . It is hypothesized that this targetoid pattern on dynamic imaging
[5]
may reflect the peripheral cellularity, central necrosis and dense fibrous stroma seen in iCCA . This same
histological constitution likely also explains the targetoid appearance seen on MRI diffusion weighted and
hepatobiliary phase imaging that has been described in iCCA [6-10] . Other ancillary features reported in iCCA
include capsular retraction, peripheral biliary duct dilation, and central T2 hypointensity.

On the contrary, HCC tends to have nonrim APHE, nonperipheral washout appearance and delayed
enhancing capsule (i.e., major features). These features are likely attributable to the changes during
[5]
hepatocarcinogenesis that result in the development of unpaired arteries and loss of portal tracts . Unlike
iCCA, HCC may be encapsulated by a true fibrous capsule or compressed liver parenchyma, which may
explain the delayed enhancing “capsule” described on imaging.

Small iCCAs can have overlaps in imaging appearance with HCC [11,12] . Small iCCAs have a greater propensity
for showing nonrim APHE and nonperipheral washout appearances, potentially due to a preservation of
portal tract architecture and the lack of significant central necrosis in smaller, early stage lesions [5,13] . Atypical
appearances and overlap with HCC may be more commonly observed in patients with risk factors for HCC
[14]
such as background liver cirrhosis . The reason for this is not entirely understood but could relate to
alterations in background liver blood supply (e.g., in the setting of cirrhosis, the liver receives more arterial
supply and relatively less portal venous supply).

LI-RADS approach to diagnosis on CT/MRI
The LI-RADS CT/MRI diagnostic algorithm provides a step-wise approach for arriving at a highly specific
diagnosis of HCC. The intention of the algorithm is to achieve a greater than 95 percent positive predictive
value of the LR-5 (definite HCC) category for the diagnosis of HCC. The philosophy behind this approach
rests in the fact that liver transplantation is considered the optimal cure for patients in the United States and
Canada with cirrhosis and early stage HCC. In this context, definitive imaging diagnosis of HCC is sufficient
for assigning priority on the transplantation waitlist and as such, demands a near zero false positive rate.

The algorithm begins with assessment of imaging adequacy and assignment of LR-NC (not categorizable) if
imaging is not adequate to narrow in on a final diagnostic category. Second, the radiologist should determine
if there is advanced disease, such as tumor in vein (LR-TIV). The next step involves identifying definitely
or probably benign entities (e.g., perfusional shunts or hemangiomas) and assigning them an LR-1 or LR-2
categorization. Next, the radiologist is tasked with identifying possible or probable non-HCC malignancy