Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis ( ‫؍‬ 0.59) than for activity ( ‫؍‬ 0.43) and poor for lobular necrosis ( ‫؍‬ 0.15). The mean agreement was better for senior (0.60 ؎ 0.24) than junior pathologists (0.52 ؎ 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 ؎ 0.18 vs. 0.58 ؎ 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: ‫؍‬ 0.48 and 0.77, activity: ‫؍‬ 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity ( ‫؍‬ 0.22-0.25) or fibrosis ( ‫؍‬ 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading. (HEPATOLOGY 2005;41:257-264.)

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This study underlines the importance of considering hepatocyte nuclear factor-1 β mutations in fetuses with congenital anomalies of the kidney and urinary tract, especially when associated with pancreatic hypoplasia. No correlation between phenotype and genotype was found, highlighting high intra-familial variability in cases with inherited mutations. © 2016 John Wiley & Sons, Ltd.

Well-differentiated liposarcomas (WDLPS) classically contain high-level amplification of 12q14-15 sequences, including the MDM2 and CDK4 genes, while lipomas are characterized by simple structural chromosome aberrations often involving HMGA2 at 12q15. Previous studies have shown that low-level gain of the 12q14-15 region, such as trisomy 12 and 12q15-24 duplication, might be sufficient for the development of minimal atypia and formation of WDLPS. Moreover, because some features, such as overexpression of HMGA2, are shared by both lipomas and WDLPS, it has been hypothesized that lipomas and WDLPS may form a genetic and morphological continuum. We report here the results of molecular cytogenetic analysis of 8 lipomas that had unusual chromosomal features resulting in gains of 12q14-15. While 3 cases had simple numerical rearrangements (trisomy 12) or structural rearrangements (unbalanced translocations with 12q gains), 5 cases were particularly intriguing because of peculiar features such as giant chromosomes, supernumerary chromosomes or neocentromeres that usually are the hallmark of WDLPS. Gain of 12q14-15 sequences including extra copies of MDM2 and CDK4 were detected by fluorescence in situ hybridization analysis in all analyzed cases but no expression of MDM2 and CDK4 was observed suggesting that these genomic imbalances had no functional consequence. We observed rearrangements of HMGA2 in 5 out 8 cases. Altogether, our results indicate that moderate gains of 12q are not always associated with a malignant phenotype, and that some intermediary forms exist between classical lipomas and classical WDLPS. Some of these intermediary forms may correspond to a genomic premalignant condition while some may have no malignant potential. ' 2007 Wiley-Liss, Inc.

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