Hepatic Precancerous Lesions and Small Hepatocellular Carcinoma
Section snippets
Cytologic Changes in Hepatocarcinogenesis
According to the IWP nomenclature [1], dysplastic foci are defined as clusters of hepatocytes with atypia, measuring less than 1 mm in diameter. Although the size criterion is arbitrary, it is related to the fact that dysplastic foci nearly always are contained within a single hepatic lobule (or cirrhotic nodule, because these lesions usually are detected in the setting of cirrhosis). Of course, these small lesions cannot be recognized grossly or radiologically, but they represent incidental
Dysplastic Nodules
Dysplastic nodules (DNs) are nodular lesions that differ from the surrounding parenchyma with regard to size, color, texture, or the degree to which they bulge from the cut surface of resected specimens (Fig. 2). DNs are usually, but not always, detected in cirrhotic livers [1]. Several comprehensive reviews of the histologic features of these lesions have been published in the previous 5 years [14], [29], [30], [31], [32], [33]. Low-grade DNs have features suggestive of a clonal cell
Small Hepatocellular Carcinoma
According to the consensus nomenclature [1], small HCC is defined arbitrarily as carcinomas that measure less than 2.0 cm in diameter. Studies from Japan [48], [56], [57] have shown that there are two types of small HCC:
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Vaguely nodular HCC (also known as early HCC, or HCC with indistinct margins), which is well-differentiated, lacks a fibrous capsule, and often contains portal tracts (ie, grows around preexisting portal tracts) (Fig. 4)
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Distinctly nodular HCC, which is well- or moderately
Molecular Pathogenesis of Hepatocellular Carcinoma
The molecular changes that lead to dysplasia are initiated in chronically diseased livers, before cirrhosis is established. At that stage, alterations in gene expression are mostly quantitative, occurring by epigenetic mechanisms [62]. Alterations include increased expression of growth factors, such as transforming growth factor-α (TGF-α) and insulin-like growth factor-2 (IGF-2), which leads to accelerated hepatocyte proliferation. Promoter hypermethylation, resulting in gene inactivation, is
Stem Cells and Hepatocarcinogenesis
There are two distinct roles that stem cells play in HCC development. The first is that of an HCC initiator, such as a facultative, non-neoplastic, liver stem cell that undergoes malignant transformation. The second is that of an HCC-repopulating stem cell, such as a malignant cell that has all the functional features of a facultative stem cell (eg, self-renewal, slow cycling, production of a rapidly proliferative transit-amplifying progeny that generates the bulk of tumor cells, and resistance
Radiologic Imaging of Nodular Lesions in Cirrhotic Livers
Radiologic detection, and characterization, of nodular lesions in cirrhosis remains challenging. Although ultrasound is used widely for detection of HCC in noncirrhotic livers, it is less useful in patients with cirrhosis unless intravenous contrast agents are used. Furthermore, distinction between benign and malignant nodules is also challenging. The overall detection of DNs in explant studies is poor [100]. CT requires iodinated contrast agents and uses ionizing radiation, but it is widely
Summary
Large nodules detected in cirrhotic livers by imaging include large regenerative nodules, dysplastic nodules (low- or high grade), and small HCCs. The differential diagnosis of these lesions by ultrasound, CT, or MRI may be difficult or impossible. Even biopsies may be difficult to interpret. Nevertheless, histologic evidence of a dysplastic nodule, or cytologic change suggestive of dysplasia (dysplastic focus) indicates an increased risk for carcinoma development and warrants increased
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Cited by (0)
This study was supported in part by a grant from the National R&D Program for Cancer Control of the Ministry of Health and Welfare of the Republic of Korea (no. 0,620,210) to Dr. Young Nyun Park.