Nodule-in-nodule architecture of hepatocellular carcinomas: enhancement patterns in the hepatobiliary phase and pathological features.

Abstract

This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis.