Histological and immunohistochemical revision of hepatocellular adenomas: a learning experience.

Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1 α -inactivated HCA (H-HCA), inflammatory HCA (IHCA), and ß -catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and ß -catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of ß -catenin-activated/HNF1 α -inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of ß -catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

Characterization of ß-cell plasticity mechanisms induced in mice by a transient source of exogenous insulin.

ß-Cell plasticity governs the adjustment of ß-cell mass and function to ensure normoglycemia. The study of how ß-cell mass is controlled and the identification of alternative sources of ß-cells are active fields of research. ß-Cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major ß-cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of ß-cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 wk. Five days after IPR, enhanced ß-cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. ß-Cell mass was fully restored after an additional 2 days. For the 10-day IPI group, ß-cell and endocrine mass were no longer significantly different from those of the control group at 2 wk post-IPR. Furthermore, real-time quantitative PCR analysis of endocrine structures isolated by laser capture microdissection indicated sequentially enhanced expression of the pancreatic transcription factors ß(2)/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of ß-cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.