Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

Abstract

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge.

Aim: To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.

Methods: Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ ² test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.

Results: A total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively (P = 0.03). Peripheral rim-like arterial phase hyperenhancement (APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs (P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs (P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs (P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) had significant correlations with ICC (r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the ROC curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%.

Conclusion: Rim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

Keywords: Contrast enhanced ultrasound; Diagnosis; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Liver imaging reporting and data system.