• displastic nodule
• Gd-EOB-DTPA
• liver cirrhosis
• MR imaging

Purpose: the aim of this study was to evaluate the predictive findings that might suggest a rapid progression towards malignancy of pre-malignant nodules (high grade dysplastic nodules – HGDN and early hepatocellular carcinomas – early HCC) in liver cirrhosis, showing as atypical at MR dynamic vascular examination with Gd-EOB-DTPA. Furthermore, we have assessed the time to progression of such pre-malignant lesions into overt HCC.
Materials and Methods: Among all patients who did perform a scheduled Magnetic Resonance (MR) follow up study between January 2013 and June 2015 at our institution, we did select 34 cirrhotic patients (Group 1; (M:23, F:11, mean age 66 years, range 48-84) who had performed two subsequent MR examinations with Gd-EOB-DTPA (Time-0 MR and Time-1 MR; within 6 months from Time-0 MR examination), with at least one atypical nodule (showing as hypovascular on arterial phase and hypointense on late dynamic and/or on hepatobiliary phase). A total of 59 atypical nodules were selected, which progressed into HCC at Time-1 MR examination, on the basis of current dynamic criteria.
As control group (Group 2), we did retrospectively select 13 patients (M:8, F:5, mean age 62 years, range 43-64), who had undergone orthotopic liver transplantation (OLT) within 6 months from MR study with Gd-EOB-DTPA (pre-OLT MR) and in whom livers, at least one HGDN had been diagnosed at histological examination after OLT, with a total of 33 HGDN. Nodular signal intensities on different phases and final diagnosis were compared, in order to identify specific, early, clues suggesting evolution towards malignancy. Nodule sizes were recorded at hepatobiliary phase on both subsequent MR studies (Group 1) and on pre-OLT MR and at histological examination. Months to progression from atypical nodules to HCC were also calculated.
Results: Significant association among nodule signal intensities at Time-0 MR and pre-OLT MR and nodular final diagnosis were identified: at Time-0 MR, 27/59 (45%) future HCCs did show as isointense on both T1 and T2-w.i. (p=0.03); 29/59 (49%) of future HCCs did appear as isointense on arterial phase and hypointense on late dynamic phase (p=0.03), while 34/59 (57%) of future HCCs did show as isointense on arterial phase and hypointense on hepatobiliary phase (p=0.02). No specific association at pre-OLT MR was observed for suggesting HDGN.
The most significant association (p<0.0001) in suggesting nodular malignancy/pre-malignancy were the association of hypointensity both on late dynamic and on hepatobiliary phase, detected in 63/92 (68.5%) nodules (25/33 - 75% HGDNs; 38/59 - 64% future HCCs). A significant correlation was found between the sizes of nodules that progressed into HCC, evaluated at Time-0 and Time-1 MR (p= 0.0001).
Moreover, nodular progression towards malignancy did result strongly time related since, if considering only nodules in whom MR studies (Time-0 MR and pre-OLT MR) had been performed between 2 and 6 months before OLT or Time-1 MR, 36 out of 46 nodules (78%) showing as hypointense on both late dynamic and hepatobiliary phase did result to progress into HCC, with an area under the curve (AUC) of 91%.
Conclusion: in case of hypovascular nodules within cirrhotic liver on arterial phase, the detection of hypointensity on both late dynamic and hepatobiliary phase should be considered as the strongest clue for suggesting pre-malignancy of the nodule as well as rapid evolution towards neoplasia, that in the 60% of cases can happen within 6 months. Gd-EOB-DTPA enhanced MR surveillance of patients who do present several atypical nodules could become important in order to adequately monitor high-risk patients and to suggest and help in planning the best therapeutic approach.