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September 2024

MRI imaging features for predicting macrotrabecularmassive subtype hepatocellular carcinoma: a systematic review and metaanalysis
Journal Watch by Dr. Antonino Andrea Blandino and Dr. Roberto Cannella

MRI imaging features for predicting macrotrabecularmassive subtype hepatocellular carcinoma: a systematic review and metaanalysis

Authors:TaeHyung Kim, Sungmin Woo, Dong Ho Lee, Richard K. Do and Victoria Chernyak

Journal: European Radiology. 2024. DOI: 10.1007/s00330-024-10671-1

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth leading cause of cancer-related deaths worldwide. It displays significant genomic, molecular, and histological diversity, with various histopathological subtypes on the latest WHO classification linked to different prognostic features [1, 2]. The macrotrabecular-massive (MTM) subtype, accounting for around 10% of all HCCs [3], is an aggressive form associated with increased angiogenesis and a poor prognosis following curative treatment. It is associated with high serum α-fetoprotein levels and histologic features of aggressiveness, including micro- and macro-vascular invasion and satellite nodules. Emerging evidence suggests that MTM-HCC may benefit from immunotherapy, making early detection through imaging crucial for better treatment planning. However, since diagnosis of HCC before treatment rarely involves histopathologic analysis, accurately identifying this aggressive subtype remains challenging [1, 4, 5].

Several studies have highlighted imaging features on contrast-enhanced MRI, such as necrosis and intratumoral arteries, to non-invasively differentiate MTM-HCC from non-MTM-HCC (NMTM-HCC), although the results have been variable and occasionally contradictory [6, 7]. Moreover, Liver Imaging Reporting and Data System (LI-RADS) [8] algorithm is essential for guiding clinical decisions, with the LR-M category requiring histopathological diagnosis and the LR-5 category allowing for definitive HCC diagnosis without such confirmation. However, the impact of HCC subtypes on LI-RADS categorization is not well understood, as few studies have examined this in small patient populations [6, 9].

Kim and colleagues [6] conducted a systematic review and meta-analysis with two objectives: first, to identify significant MRI features that differentiate MTM-HCC from NMTM-HCC; second, to assess the distribution of LI-RADS category assignments between these subtypes.

A comprehensive search was conducted in PubMed and Embase up to March 28, 2023, focusing on studies evaluating the diagnostic performance of MRI for MTM-HCC. Ten studies involving 1978 patients and 2031 HCCs (426 MTM and 1605 NMTM) were included in the analysis.  Only seven of these studies reported the distribution of LI-RADS categories and were analyzed for the secondary objective. The MRI features associated with MTM-HCC were evaluated, and the distribution of LI-RADS categories between MTM and NMTM-HCCs was compared. A random-effects model was applied to calculate diagnostic odds ratios (DORs) and confidence intervals for each MRI feature while the proportions of LI-RADS categories (LR-3, LR-4, LR-5, LR-M, LR-TIV) in MTM and NMTM-HCCs were compared using z-test.

This meta-analysis identified six MRI features significantly associated with MTM-HCC: tumor in vein (TIV) (DOR = 2.35), rim arterial phase hyperenhancement (APHE) (DOR = 2.63), necrosis (DOR = 4.2), corona enhancement (DOR = 2.55), intratumoral arteries (DOR = 2.58) and peritumoral hypointensity on hepatobiliary phase (HBP) (DOR = 2.21). In terms of LI-RADS category distribution, MTM-HCC cases had a significantly (p < 0.01) lower proportion of LR-5 (63% vs 77% of NMTM-HCCs) and significantly higher proportions of LR-M (12% vs 5% of NMTM-HCCs) and LR-TIV (13% vs 6% of NMTM-HCCs).

Although these imaging characteristics show high specificity for diagnosing MTM-HCC (71%-92%), their sensitivity varies from low to moderate (16%-58%), suggesting not all cases will exhibit these features. Thus, investigating combinations of multiple imaging features in future studies could enhance the diagnostic accuracy for MTM-HCC [6]. Kim et al. [6] also explain that while some of these features associated with MTM-HCC are included in the LI-RADSv2018 algorithm and lexicon, its coverage is incomplete. Among the six imaging features associated with this subtype, only two - rim APHE and tumor in vein - consistently influence categorization, potentially contributing to the distinction of MTM-HCC from other types and explaining the higher occurrence of LR-M and LR-TIV categories in MTM-HCC compared to NMTM-HCC. Tumoral necrosis can lead to a LR-M designation if the observation doesn’t meet LR-5 or LR-TIV criteria, while corona enhancement - an ancillary feature of malignancy - can upgrade observations (up to LR-4), but its use is optional. Additionally, intratumoral arteries and peritumoral hypointensity on HBP are not part of the LI-RADS lexicon and do not impact categorization. As a result, LR-5 observations exhibiting necrosis, intratumoral arteries, corona, or peritumoral hypointensity on HBP would still be classified as LR-5, potentially overlooking MTM-HCC. Therefore, since MTM-HCC can be reliably diagnosed through biopsy, identifying and describing these features in reports along with LI-RADS categories could help recognizing HCCs with a greater likelihood of aggressive behavior and select patients who may benefit from biopsy confirmation.

This study has some limitations. It only includes studies on surgically resected HCCs, limiting applicability to advanced cases like unresectable HCCs. Most NMTM-HCCs were conventional or unspecified, with a few including favorable or aggressive subtypes. Variations in MRI feature definitions across studies highlight the need for cautious interpretation of the results due to inconsistent terminology. Finally, caution is necessary regarding the specificity of some MRI features linked to MTM-HCC, such as rim APHE, since they may also appear in other primary liver tumors, complicating differential diagnosis.

In conclusion, this review identifies key MRI features linked to the macrotrabecular-massive HCC subtype and emphasizes the need to expand LI-RADS criteria for better risk stratification and personalized treatment.

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6.          Kim T-H, Woo S, Lee DH, Do RK, Chernyak V (2024) MRI imaging features for predicting macrotrabecular-massive subtype hepatocellular carcinoma: a systematic review and meta-analysis. Eur Radiol 34:6896–6907. doi.org/10.1007/s00330-024-10671-1

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Comments may be sent to antoninoandrea.blandino(at)gmail.com

Dr. Antonino Andrea Blandino is a second-year radiology resident at the University of Palermo in Italy. He graduated at the University of Palermo in March 2022. His main interest is abdominal and gastrointestinal radiology, with particular attention to hepatobiliary disease. He is currently engaged in multidisciplinary oncology group and serves as consulting editor for the American Journal of Roentgenology (AJR) podcast series. Dr. Blandino has developed a strong interest in scientific research, actively participating in various research projects, some of which have already been published in peer-reviewed journals.