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Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

 Hyungjin Rhee  ;  Chansik An  ;  Hye-Young Kim  ;  Jeong Eun Yoo  ;  Young Nyun Park  ;  Myeong-Jin Kim 
 LIVER CANCER, Vol.8(1) : 24-40, 2019 
Journal Title
Issue Date
Fibrous stroma ; Hypoxia ; Macrotrabecular pattern ; Microvascular density ; Stemness
Background and Aims: The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior.

Methods: We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared.

Results: IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm2), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). p values were < 0.001 for all comparisons except for EpCAM (p = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients (p = 0.005).

Conclusions: IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myeong Jin(김명진) ORCID logo https://orcid.org/0000-0001-7949-5402
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
An, Chansik(안찬식) ORCID logo https://orcid.org/0000-0002-0484-6658
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Rhee, Hyungjin(이형진) ORCID logo https://orcid.org/0000-0001-7759-4458
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