Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis

Abstract

Liver cell dysplasia is the term originally applied by AnLarge cell change (LCC), characterized by cellular enthony et al. 1 in 1973 to cytologically atypical hepatocytes largement, nuclear pleomorphism and hyperchromasia, showing cellular enlargement, nuclear pleomorphism with and multinucleation of hepatocytes, is a common lesion hyperchromasia, and multinucleation. In their study, this in cirrhotic livers, but its nature, significance, and pathoalteration was uncommon in normal livers and occasionally genesis remain uncertain. Therefore, we assessed the noted in cirrhotic livers, particularly with chronic hepatitis prognostic value of LCC as a marker of subsequent hepato-B infection, but was most prevalent in cirrhotic livers bearing cellular carcinoma (HCC) through a case-control study hepatocellular carcinoma (HCC). Because of this relationthat compared pretransplant liver biopsy specimens from ship, liver cell dysplasia, later termed large cell dysplasia, 37 cirrhotic liver transplant recipients with HCC to speciwas proposed to represent a premalignant change.1 mens from a control group of recipients without HCC, Over the succeeding 25 years, however, this proposal has matched for sex, age ({5 years), and cause of cirrhosis.been contested, and other workers have concluded that large LCC was identified in 16 (43%) of the study and 7 (19%) cell dysplasia instead represents a regenerative or degeneraof the control group biopsy specimens. By matched-pair tive phenomenon. Evidence has been marshalled to support analysis, LCC conveyed a moderately increased risk of both sides of this controversy, but much of the data are later HCC with an estimated odds ratio of 3.3 (95% CI, conflicting or circumstantial in nature, and no consensus has 1.2-15; P Å .038). However, a pathology review of 45 been reached as to the nature or significance of the alteration. HCCs showed adjoining LCC in only 12 (27%) and didBecause of this lingering uncertainty, the pathogenetically not suggest a morphological transition or a histogenetic noncommittal term large cell change (LCC) is now recomassociation between the two lesions. LCC hepatocytes dismended as an alternative designation.2 played a low proliferative rate by Ki-67 or proliferating The controversy over LCC poses a practical conundrum: cell nuclear antigen immunostaining (labeling indices of Should it receive special notice as a potential precursor of 0.27 and 0.73) but showed a greater degree of apoptosis malignancy, or should it be dismissed as an inconsequential than normal hepatocytes (labeling indices of 1.9 and 0.23; marker of chronic liver injury? To address this issue, we P Å .03) To reconcile these findings, we propose that LCC evaluated three different aspects of LCC. First, we performed derives from derangements in the hepatocyte's normal a case-control study to evaluate whether the presence of LCC process of polyploidization. Such derangements, possibly presaged any increased risk for the subsequent presence of caused by chronic inflammation-induced DNA damage, HCC...

Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion

“…The LI of cyclin A was much higher in HCC than in other groups. In addition, no significant expression of ss DNA was seen in LCC, suggesting little apoptosis among hepatocytes with LCC, consistent with previous studies using the TUNEL assay [5]. These observations indicate that areas of LCC show no proliferative or apoptotic activity.…”

“…In addition to chronic viral hepatitis (CVH) B, LCC is also reported in other chronic liver diseases such as chronic cholestatic diseases [3,4]. Although LCC is associated with hepatocellular carcinoma (HCC) and a risk factor for its development, hepatocytes with LCC reportedly demonstrate little proliferative activity [5].…”

“…LCC was morphologically defined as a focus of hepatocytes showing cellular enlargement, nuclear pleomorphism, and hyperchromasia [1,2]. The extent of LCC was semiquantitatively assessed as 0 (absent), 1+ (few scattered), 2+ (occasional foci), and 3+ (multiple or widespread foci) according to Lee et al [5]. In this study, the cases of LCC with 2+ and 3+ were histochemically and immunohistochemically examined as LCC.…”

Large liver cell dysplasia: A controversial entity

“…1C and D). Indeed, in a recent study specifically targeted on this issue, Lee et al reported that in none of the cases they studied was there a recognizable transition from focal to diffuse LCC to HCC [14]. Clearly, there is a consistent paucity of information addressing the spatial relationship between LCC and HCC.…”

Pathology for the HPB Surgeon

“…Without tests of monoclonality, and other molecular markers, many so-called large cell dysplasias actually represent regenerating nodules [3]. Therefore, the incidence of large cell dysplasia showing progression to hepatocellular cancer (HCC) is low and clinically insignificant [4]. In contrast, small cell dysplasia represents fast multiplying cells, more uniform nuclear shape, greater chance of being clonal and is, therefore, much more frequently associated with progression to HCC [5].…”