Abstract

Clear cell hepatocellular carcinoma (HCC) is a less common HCC cytologic variant associated with improved outcomes in studies prior to the advent of locoregional therapy (LRT). This study was undertaken to determine whether clear cell HCC predicts better outcomes after LRT. We retrospectively identified 124 consecutive patients (92 men, 32 women; median age 59 y) with 132 HCC (mean diameter 4.8 ± 3.9 cm) diagnosed by percutaneous biopsy between 2008-2017 prior to transarterial chemoembolization (TACE) (n = 51, 41%), yttrium-90 radioembolization (n = 17, 13%), percutaneous thermal ablation (n = 41, 33%), and combination TACE/ablation (n = 15, 12%). Baseline Barcelona Clinic Liver Cancer (BCLC) stage was 0/A (n = 48, 38%), B (n = 33, 26%), C (n = 27, 22%), and D (n = 16, 13%). Cytological subtype was determined from percutaneous core needle biopsy as 100% clear cells, focal clear cells, or no clear cells. Baseline clinical and imaging features, and radiologic response by mRECIST were correlated with cytological subtype using multinomial regression analysis. Time to progression (TTP) and transplant free survival (TFS) were analyzed by Cox proportional hazard models. Percutaneous core biopsies comprised entirely of clear cell subtype were associated with non-viral etiologies of HCC (OR 5.3 95% CI 1.64-17.16; p = 0.005), solid histological arrangement (OR 4.32 95% CI 1.14-16.37; p = 0.031), and hypo-enhancement on arterial phase CT or MRI images (OR 3.08 95% CI 1.02-9.3; p = 0.046). The clear cell subtype was not associated with improved objective response by mRECIST (OR 0.93 95% CI 0.37-2.33; p = 0.87), delayed TTP (HR 1.17 95% CI 0.86-1.6; p = 0.32), or better TFS (HR 1.01 95% CI 0.69-1.47; p = 0.96) in comparison to specimens with focal or no clear cells. There remained no significant association between the clear cell subtype and TTP or TFS after stratifying by LRT modalities. Clear cell HCC is more common in non-viral etiologies of cirrhosis and is associated with atypical enhancement on radiologic images. It does not, however, impart independent prognostic information prior to LRT.

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