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OBJECTIVE--Maturity onset diabetes of the young type 3 (MODY3) is a consequence of heterozygous germline mutation in HNF1A. A subtype of hepatocellular adenoma (HCA) is also caused by biallelic somatic HNF1A mutations (H-HCA), and rare HCA may be related to MODY3. To better understand a relationship between the development of MODY3 and HCA, we compared both germline and somatic spectra of HNF1A mutations. RESEARCH DESIGN AND METHODS--We compared 151 somatic HNF1A mutations in HCA with 364 germline mutations described in MODY3. We searched for genotoxic and oxidative stress features in HCA and surrounding liver tissue. RESULTS--A spectrum of HNF1A somatic mutations significantly differed from the germline changes in MODY3. In HCA, we identified a specific hot spot at codon 206, nonsense and frame-shift mutations mainly in the N[H.sub.2]-terminal part, and almost all amino acid substitutions were restricted to the POU-H domain. The high frequency of G-to-T tranversions, predominantly found on the nontranscribed DNA strand, suggested a genotoxic mechanism. However, no features of oxidative stress were observed in the nontumor liver tissue. Finally, in a few MODY3 patients with HNF1A germline mutation leading to amino acid substitutions outside the POU-H domain, we identified a different subtype of HCA either with a gpl30 and/or CTNNB1 activating mutation. CONCLUSIONS--Germline HNF1A mutations could be associated with different molecular subtypes of HCA. H-HCA showed mutations profoundly inactivating hepatocyte nuclear factor-lα function; they are associated with a genotoxic signature suggesting a specific toxicant exposure that could be associated with genetic predisposition. Diabetes 59:1836-1844, 2010, Hepatocellular adenoma (HCA) is a rare, benign, liver tumor frequently associated with oral contraception (1,2). HCA usually manifests as a single tumor, but in some cases, several adenomas are detected [...]

La classification OMS des tumeurs du système nerveux central distingue les hémangiopéricytomes (HPC) des tumeurs fibreuses solitaires (TFS) des méninges. Celle des tissus mous les a réunis depuis la découverte en 2013 d’une oncogenèse commune, avec fusion des gènes NAB2et STAT6. Un gradinghistopronostique commun dit « de Marseille » a récemment été proposé, basé sur la densité cellulaire, le compte mitotique et la présence ou non de nécrose. Nous avons évalué l’immunophénotype et l’histopronostic d’une série rétrospective de 17 HPC et TFS.

Introduction: Les gliomes hémisphériques infantiles font partie des gliomes diffus de haut grade de type pédiatrique selon l’OMS 2021 des tumeurs du système nerveux central. Ces gliomes sont caractérisés par des réarrangements de gènes codant pour des récepteurs à activité tyrosine kinase (NTRK1/2/3, ALK, ROS, MET). Nous rapportons ici les caractéristiques cliniques, histopathologiques et moléculaires de quatre cas et présentons une revue de la littérature.

L’encéphalocèle est une pathologie malformative congénitale due à une anomalie de fermeture du tube neural pendant l’embryogenèse. Nous rapportons un cas d’encéphalocèle postérieure chez une enfant de 7 mois, présentant une tuméfaction occipitale connue depuis la naissance. L’examen anatomopathologique de la lésion montrait différents tissus matures issus du système nerveux central et de ses enveloppes : du tissu neuroglial, des structures canalaires épendymaires et des amas de cellules méningothéliales. Le diagnostic d’encéphalocèle a donc été retenu. Cette observation nous permet de revoir les principales anomalies de fermeture du tube neural, notamment les formes « larvées » (tuméfaction non spécifique ou angiome de la ligne médiane) auxquelles un pathologiste général peut être confronté en pratique courante.

Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1-inactivated HCA, inflammatory HCA, -catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53 of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7 as compared with 100 on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6 as compared with 94.3 on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3 certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each “certain diagnosis” paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P<0.001). No significant difference was observed between groups A and B for FNH (P=0.714) or for HCA subtypes (P=0.750). Compared with surgical specimens, immunohistochemical analysis performed on biopsies allowed the discrimination of FNH from HCA and the identification of HCA subtypes with good performance.

Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a distinct entity that is increasingly being recognized, with 96 cases now reported. This tumor shares morphologic features with both ependymomas and choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern in which the vessels are covered by layers of tumor cells forming perivascular pseudorosettes. These tumors exhibit various combinations of papillary and solid architecture, making the differential diagnosis of PTPR difficult to establish. We report the detailed description of the histopathologic features of a large series of PTPRs from 20 different centers and distinguish 2 subgroups of tumors with either a striking papillary growth pattern or a papillary and solid growth pattern. We highlight the findings that PTPRs have unusual vessels with multiple lumina and frequently show detachment of the border of the tumoral cells from the vascular wall. The 2 PTPR subgroups present similar clinical characteristics and immunophenotypes. We confirmed and extended the results of previous ultrastructural studies on the presence of intercellular junctions at the apical part of tumoral cells. The expression of the tight junction proteins claudin-1, claudin-2, and claudin-3 was investigated by immunohistochemistry. Claudin-1 and claudin-3, but not claudin-2, were expressed in PTPRs and in the fetal subcommissural organ, potentially the origin of this tumor. In contrast, all 3 claudins were expressed in choroid plexus papillomas. Claudin expression may help in the diagnosis of PTPRs and can be used in combination with other markers, such as CK18, NCAM, E-cadherin, MAP-2, and Kir 7.1.