Ronald R de Krijger

..We report novel VHL mutations in sporadic pheochromocytomas, which are slightly correlated with malignancy. VHL mutations may have some impact on the malignant transformation of pheochromocytomas...

..CLINICAL HISTORY AND METHODS: We describe a 45-year-old man with a non catecholamine-producing paraganglioma of the spermatic cord. We performed SDHB immunohistochemistry and performed mutation analysis of the SDHB, SDHC, and SDHD genes...

..We speculate that the expression of these GAD67 splice variants might be related to human fetal pancreas development...

..From our findings we conclude that (a) a large proportion (40%) of pediatric PCC patients is diagnosed in the context of inherited cancer syndromes, and (b) candidate gene analysis appears to be indicated to detect germline mutations...

..To our knowledge, this is only the fourth reported case of heterotopic pancreatic tissue in the lung, and the first case where this bronchopulmonary foregut anomaly is not associated with a enteric duplication...

..Also, current screening and/or treatment guidelines are included...

..In this article, recent attempts at marker detection, such as those mentioned above, as well as emerging knowledge on the molecular abnormalities in benign and malignant PCC and PGL will be presented...

..We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma-carcinoma sequence as well...

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..We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL...

..We conclude that, although there is frequent loss of the p53 locus on 17p, the p53 gene does not appear to play a major role in pheochromocytoma tumorigenesis...

..In addition, genes on 21q and 22q might play a more important role in PCC pathogenesis than had been assumed thus far...

..Analysis of SDHD can also help to distinguish synchronous primary tumors from abdominal metastases...

..We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series...

..This review presents an overview of our current understanding of the molecular pathogenesis of pheochromocytoma and paraganglioma...

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..A recent report described a patient with an abdominal paraganglioma, immunohistochemically negative for SDHA, and identified a causal germline mutation in SDHA...

..However, in parasympathetic paragangliomas occurring in VHL disease, biallelic inactivation of the VHL gene has not been demonstrated to date...

..A lower expression of VEGF mRNA in CDH patients in the alveolar stage, possibly as a result of downregulation of HIF-2? might indicate a role for these factors in the pathophysiology of CDH...

..3, and 1p34.3-1p36.33. In conclusion, these data strongly suggest that chromosome arm 1p is the site for multiple tumor suppressor genes, although the potential candidate genes CDKN2C and PTPRF/LAR are not included in these regions...

..Given the fact that hypoxia induces p53 expression and regarding the absence of p53 mutations, these results suggest that p53 inactivation does not play a major role in the tumorigenesis of hereditary and sporadic paragangliomas...

..Conclusion: IDH mutations are very rare in paragangliomas and pheochromocytomas and do not appear to play an important role in oncogenic HIF activation known to be present in these tumors...

..We used conformation-dependent gel electrophoresis and sequence determination analysis of germ-line and tumor DNA to identify SDHD mutations. We compared the clinical and molecular characteristics of sporadic and hereditary PGLs...

..No common deletions or duplications are found in our cohort, suggesting that TA is a genetically heterogeneous disorder...

..We demonstrate that malignant PCC and sPGL have more intra-tumoral molecular heterogeneity than benign tumors, which suggests that benign and malignant PCC and sPGL have a different pathogenesis...

..The mouse model should allow further studies into the pathogenesis of human malignant PCCs and into therapeutic strategies for these tumours...

..In conclusion, ALK positivity by IHC is an independent, poor prognostic factor in patients with GNBL and NBL. ALK IHC is an easy test suitable for future risk stratification in patients with NBL and GNBL...

..As such, our results form the baseline data for the evaluation and interpretation of abnormal pulmonary vascular development...

..Also, a link has been established between malignant behavior and inactivating mutations of SDHB. In this article we review the published SDHB gene mutations, as well as the location and behavior of the resulting PCCs...

..In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted...

..The differential expression of these proteins may provide a molecular basis for the histological differences observed in the lung vessels of patients with CDH...

..These findings are compatible with the hypothesis that CIS/ITGCNU arises from developmentally arrested germ cells, most likely primordial germ cells/gonocytes, at an early time point during intrauterine development...

..Our results suggest that, as far as receptors are concerned, hypoplastic lungs of fetuses and newborns with CDH are potentially as responsive to glucocorticoids, thyroid hormone, and retinoic acid as the lungs of normal children...

..However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvessel density higher than this threshold of 28.5%...

..The difficulties in reaching a causal diagnosis are illustrated here by a 23-week-old fetus with nonrhizomelic CDP characterized by extensive cartilage stippling, brachyphalangy, and nasal hypoplasia...

..007) of materno-fetal placental inflammation. C. trachomatis DNA was frequently detected in the placenta of women with early preterm delivery, and was associated with histopathological signs of placental inflammation...

..Associated anomalies were found in five cases. The classification of tracheal agenesis, associated anomalies and potential therapeutic options are discussed...

..Besides screening for abdominal tumours, analysis of plasma and/or urinary catecholamines and/or their metabolites should be considered...

..Anticancer treatment with the tyrosine kinase inhibitor sunitinib causes thyroid dysfunction...

..To our knowledge, this is the first time the co-occurrence of MFD and CI is reported in the literature...

..This would seem to indicate that the developing small intestinal epithelium matures independently of luminal components...

..We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound...

..CONCLUSION: CST may have a broader functional role than previously assumed...

..quot;Pancreatic endocrine tumors with entrapped ductules" would be the preferred nomenclature since it better reflects the nonneoplastic nature of the ductules...

..We concluded that postmortem examination has an important additional role in the detection of structural cardiac defects and malformations of the urogenital system and digestive tract in children with CDH...

..In addition, several individual neuroendocrine tumors are described, such as medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma, emphasizing specific histopathologic characteristics...

..Malignant struma ovarii is a rare malignant germ cell tumor of the ovary. Due to the rarity of this disease, treatment has not been uniform throughout the published literature...

..We examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated and wild type (WT) NBL cell lines...

..Overall, these findings provide evidence that CCAM is nonneoplastic. Although some may view CCAM as a PPB precursor, it remains biologically distinct in terms of karyotype and p53 status...

..We postulate that the upregulation of VEGF-C may be involved in PEN progression and metastases, although not via a direct proangiogenic mechanism...

..The best prediction can be achieved by combining clinical, biometric, and Doppler parameters...

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..Again the success of this will require well-designed and coordinated multi-center studies...

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..Dopamine receptor (DR) expression and dopamine agonist (DA) effectiveness have never been demonstrated in neuroendocrine tumors associated with ectopic ACTH syndrome (EAS)...