HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial

Abstract

Objectives Hepatocellular carcinoma (HCC) upon contrast-enhanced ultrasound (CEUS) typically shows arterial phase hyperenhancement (APHE), followed by late (> 60 seconds) and mild contrast washout (WO). Although APHE is considered as the hallmark of HCC, it can be absent in some HCCs. Thus, we explored which sonomorphological and histopathological features of HCC are associated with a lack of APHE upon CEUS.

Methods Focal liver lesions in high-risk patients for HCC were assessed with CEUS following a standardized protocol in a prospective multi-center real-life setting. CEUS patterns in HCC were assessed, and tumour and patient characteristics were compared for HCCs with and without APHE.

Results 316 patients with HCC were recruited (cirrhosis, 76.9%). APHE occurred in 271/316 HCCs (85.8%). A lack of APHE was associated with portal vein thrombosis, tumour infiltration of the liver vessels (p<0.001), larger size, multilocularity, and higher depth location upon ultrasound (p<0.01). Histological grading did not differ between HCCs with and without APHE (p=0.39). Histopathological features of HCCs without APHE included cirrhotic stromal reaction, marked tumour cell steatosis and absence of the typical surrounding dilated sinusoidal vascular channels.

Conclusion Correlation with histopathological findings support the fact that HCCs with a lack of APHE in CEUS are a heterogeneous group. The examiner has to be aware that particularly HCCs with portal vein thrombosis or macro-invasion of the liver vessels may lack APHE.

Zusammenfassung

Ziele Hepatozelluläre Karzinome (HCCs) zeigen in der Kontrastmittelsonografie (CEUS) typischerweise ein arterielles Hyperenhancement (APHE) mit nachfolgend spätem (> 60 Sekunden), mildem Auswaschen (WO). Obwohl APHE das Hauptkriterium in der HCC-Diagnostik darstellt, fehlt dieses Merkmal bei einigen HCCs. Die vorliegende Arbeit sollte untersuchen, welche sonomorphologischen und histopathologischen Eigenschaften mit fehlendem APHE assoziiert sind.

Methoden Fokale Leberläsionen bei HCC-Hochrisikopatienten wurden nach einem standardisierten CEUS-Protokoll in einem prospektiven multizentrischen Ansatz untersucht. Die CEUS-Muster der HCCs wurden analysiert und Tumor- und Patientencharakteristika für HCCs mit und ohne APHE verglichen.

Ergebnisse 316 HCC-Patienten wurden eingeschlossen (76,9% Zirrhose). APHE fand sich bei 271/316 HCCs (85,8%). Fehlendes APHE war assoziiert mit Pfortaderthrombose, Tumorinfiltration in die Lebergefäße (p<0,001), größerem Tumordurchmesser, Multilokularität und größerer Tiefenlokalisation (p<0,01). Der histologische Differenzierungsgrad unterschied sich nicht zwischen HCCs mit und ohne APHE (p=0,39). Histologisch zeigten HCCs ohne APHE zirrhotische Stromareaktionen, ausgeprägte Tumorzellverfettung und ein Fehlen der typischen umgebenden erweiterten Sinusoide.

Schlussfolgerungen Die Korrelation mit histopathologischen Merkmalen belegt, dass HCCs mit fehlendem APHE im CEUS eine heterogene Gruppe darstellen. Der Untersucher sollte sich bewusst machen, dass APHE insbesondere bei HCCs mit Pfortaderthrombose oder Makrogefäßinvasion fehlen kann.

Keywords

Hepatocellular carcinoma (HCC) - Contrast-enhanced ultrasound (CEUS) - Arterial phase hyperenhancement (APHE) - Histology - Prospective multicenter study

Publication History

Received: 03 June 2022

Accepted after revision: 13 February 2023

Accepted Manuscript online:
13 February 2023

Article published online:
24 March 2023

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