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Hepatocellular carcinoma (HCC) is a unique malignancy that can be diagnosed and treated based on non-invasive imaging criteria without histological confirmation in cirrhotic patients, which opens the possibility, although rare, of false-positive diagnosis of the tumor. This brief review illustrates benign and non-HCC malignant lesions arising in cirrhotic liver that could have been erroneously diagnosed as HCC based on imaging criteria: focal nodular hyperplasia-like nodules, serum amyloid A-positive nodules, dysplastic nodules, spontaneously regressing lesions, combined hepatocellular-cholangiocarcinoma, cholangiocarcinoma, sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, hepatoblastoma, and metastatic adenocarcinoma. To determine the potential differences in clinical courses and post-treatment outcome of HCC diagnosed by imaging alone and those histologically, we suggest the terms HCCi and HCCp to distinguish between lesions that are diagnosed as HCC based on imaging alone from those diagnosed based on pathological examination, respectively.Key Points • Benign lesions, such as focal nodular hyperplasia-like nodules, serum amyloid A-positive nodules, dysplastic nodules, and spontaneously regressing lesions, may show imaging findings that mislead to the diagnosis of HCC. • Non-hepatocellular malignant lesions, such as sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, hepatoblastoma, and metastatic adenocarcinomas, can be erroneously diagnosed as HCC based on imaging findings alone, even in cirrhotic liver.

Objective: We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. Methods: The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. Results: Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61–70%) and 91% (95% CI, 89–93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70–82%]) than CT (66% [95% CI, 58–73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60–70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61–82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80–93%) for CT, 92% (95% CI, 86–95%) for ECA-MRI, 93% (95% CI, 91–95%) for Gx-MRI, and 91% (95% CI, 84–95%) for gadobenate-MRI without significant differences (p = 0.084–0.803). Conclusions: LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. Clinical relevance statement: Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. Key Points: • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88–93%) for HCC diagnosis regardless of modality or contrast material type. [ABSTRACT FROM AUTHOR]

Objectives: The current LR-5 criteria of Liver Imaging Reporting and Data System (LI-RADS) determined by only major features provide high specificity, but unsatisfactorily low sensitivity for the noninvasive diagnosis of hepatocellular carcinoma (HCC). This study aimed to identify significant ancillary features (AFs) in LI-RADS version 2018 and develop the upgraded LR-5 criteria to improve diagnostic performance on gadoxetic acid–enhanced magnetic resonance imaging (MRI). Methods: This retrospective study included 280 patients (366 observations including 281 HCCs) at high-risk for HCC who underwent gadoxetic acid–enhanced MRI between 2015 and 2017. Two readers evaluated major features and AFs for each observation and assigned a LI-RADS category. Independently significant AFs were identified through logistic regression analysis. Upgraded LR-5 criteria were developed by combining independently significant AFs with LR-4 assigned by major features alone. Sensitivities and specificities of the diagnostic criteria were compared using McNemar's test. Results: Two of the AFs favoring malignancy in general (mild-moderate T2 hyperintensity and hepatobiliary phase hypointensity) and two of the AFs favoring HCC in particular (nonenhancing "capsule" and mosaic architecture) were independently significant features for diagnosing HCC. By using the upgraded LR-5 criteria (LR-4 by major features alone + each aforementioned AF), sensitivities were significantly increased (69.4–76.9%) compared with the standard LR-5 (66.2%; all, p ≤ 0.004), whereas specificities (95.3–96.5%) were not significantly different (96.5%; all, p > 0.999). Conclusions: Independently significant AFs may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid–enhanced MRI. Key Points: • Independently significant AFs for HCC on gadoxetic acid–enhanced MRI were mild-moderate T2 hyperintensity, hepatobiliary phase hypointensity, nonenhancing "capsule," and mosaic architecture. • When LR-4 criteria by major features alone in combination with significant AFs were upgraded to LR-5, sensitivities were higher than the standard LR-5, without impairing specificity. • Independently significant ancillary features in Liver Imaging Reporting and Data System version 2018 may be used to upgrade from LR-4 to LR-5 to improve sensitivity without impairing specificity on gadoxetic acid–enhanced MRI. [ABSTRACT FROM AUTHOR]