Macroregenerative nodules in a series of adult cirrhotic liver explants: Issues of classification and nomenclature

Abstract

Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series. Deleting this feature from the criteria for cytological atypia resulted in a stronger association of both types

Clonal analysis of macronodules in cirrhosis

“…28,29 Indeed, recent studies have accumulated evidence suggesting that LLCC in cirrhotic liver is merely a diffuse and degenerative change to prolonged cholestasis, rather than a neoplastic feature. 4,6,30,31,32 The question arises as to whether there exists several subsets of LLCC, with a benign form of scattered LLCC associated with prolonged cholestasis and a neoplastic subset consisting of clusters of large liver cells in cirrhotic macronodules. In our study, none of the cases with LLCC showed any association with bile or cholate stasis (Table 3).…”

“…1,2 These macronodules are common findings in cirrhosis and are often related to viral infection (hepatitis C and B virus), with a prevalence ranging from 10% to 42% in cirrhotic explanted livers. [2][3][4][5][6] Interestingly, recent advances in imaging modalities have led to the detection of these large nodular lesions in follow-up of cirrhotic patients. 7 Different types of macronodules can be distinguished according to their imaging and pathological characteristics, and several classifications have already been established.…”

The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: Implications for diagnosis and classification

“…1 Although HGDNs are characterized by a number of cytoarchitectural abnormalities, [1][2][3][4][5][6] there are still difficulties in making the morphological distinction between LRNs (which are thought to be a simple hyperplastic growth) and LGDNs (which are thought to be a putative premalignant growth). Indeed, the former are lesions cytoarchitecturally similar to the adjacent cirrhotic parenchyma whereas LGDNs are characterized by mild atypias usually, but not necessarily, under the form of large cell changes.…”

“…LRNs typically take place in a cirrhotic setting and outnumber the so-called dysplastic nodules as detected in vivo by ultrasound 8 or after anatomic dissection. [2][3][4][5][6] Thus, the assessment of the arterial and capillary profile of LRNs can provide diagnostic information and clues as well as validate them as hyperplastic rather than dysplastic growths. 7,9-11 Indeed, most nonneoplastic-sizable nodules arising in cirrhosis are notoriously quite similar by image analysis, 8,[12][13][14] macroscopically, and, to some extent, also microscopically.…”

Histological features of early hepatocellular carcinomas and their developmental process: for daily practical clinical application

“…Any of these can make biopsy diagnosis difficult. Other than true dysplastic nodules [19,20], very well differentiated HCCs, large regenerative nodules [19][20][21][22][23] with high cellularity, mixture of HCC cells and benign cells, well-differentiated HCCs with marked fatty change, benign large regenerative nodules with marked fatty change, thick sliced specimens with high cellularity and strong stainability of cytoplasm, and FNH with high cellularity and microacinar formation can be arbitrarily diagnosed as dysplastic nodules despite not being true dysplastic nodules. Or the result can be a false-negative or a false-positive diagnosis.…”