Multistep human hepatocarcinogenesis: correlation of imaging with pathology

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The majority of HCCs develop in cirrhotic livers, and the early detection and characterization of this entity is very important. Pathologically, human HCC develops in a multistep fashion in the following sequence: from low-grade dysplastic nodule (LGDN), to high-grade dysplastic nodule (HGDN), early HCC, well-differentiated HCC, nodule-in-nodule HCC, and, finally, to moderately differentiated HCC. Differentiation between early HCC and DN is the most important issue in the clinical setting. CT during hepatic angiography (CTHA) and CT during arterial portography (CTAP) are the most sensitive tools in the differentiation of premalignant/borderline lesions (LGDN and HGDN) and early HCC. Recent progress in imaging modality, especially Sonazoidenhanced US and Gd-EOB-DTPA MRI, is starting to play a very important role in the imaging of multistep hepatocarcinogenesis, resulting in changing the therapeutic strategy of these nodular lesions associated with liver cirrhosis.

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

“…Occasionally cancerous foci of very well differentiated HCC are encountered within dysplastic nodules, which are called nodule-in-nodule lesions or dysplastic nodules with a focus of HCC [62] . Differentiation between HCC and these nodules is always a major concern in cirrhotic liver, as the appearance in BUS may be similar but their prognosis is substantially different from each other: regenerative nodules are considered as benign lesions; dysplastic nodules are considered as precancerous lesions; while nodule-in-nodule lesions are considered malignant [62] . As definite differentiation among …”

“…CEUS with Sonazoid provides the additional post-vascular or Kupffer phase, such that it allows an assumption of the degree of malignancy based on Kupffer function. When uptake of contrast agent is reduced in the Kupffer phase of CEUS with Sonazoid in nodules not depicted as hypervascular lesions by CT or MRI, these lesions should basically be treated as malignant and a biopsy is not indispensable [62] . However, only a part of the liver can be evaluated in the short arterial phase of 20 to 30 s after administration of the contrast agent.…”

Natural Course of Hypovascular Nodules Detected on Gadoxetic Acid-enhanced MR Imaging: Presence of Fat is a Risk Factor for Hypervascularization

“…[13][14][15] Therefore, this technique may more readily detect early-stage lesions than CT arterial portography, 16 which was believed to have the highest sensitivity for this purpose. 9 The increased use of gadoxetic acid for routine examination may lead to the more frequent detection of hypovascular nodules that are hypointense on hepatocyte-phase (15 to 20 min after administration of gadoxetic acid) images of gadoxetic acidenhanced MR imaging. However, the management of these nodules is a contentious issue.…”

“…7,8 The limitations of these modalities are mainly because of the di‹culty in detecting hypovascular and isovascular lesions that occur during the early stages of multistep hepatocarcinogenesis. 9 Gadoxetic acid is a recently developed MR contrast agent that is speciˆcally taken up by hepatocytes and provides a better lesion-liver contrast, which is not achievable with extracellular gadolinium-based agents. [10][11][12] Gadoxetic acid-enhanced MR imaging is known to have a higher sensitivity than dynamic CT for detecting HCC, especially le-D. Joishi et al…”

Time to update radiological criteria for non-invasive diagnosis of hepatocellular carcinoma

“…Today, computed tomography (CT) scanning and magnetic resonance (MR) imaging are commonly employed for detecting and characterizing nodules in cirrhotic livers [6]. Due to heterogeneity in tumor biology, for lesions 1 cm and larger, strict CT and MR criteria are used for noninvasive diagnosis of HCC allowing patient prioritization for transplantation [7,8].…”