MR imaging features of benign retroperitoneal extra-adrenal paragangliomas

The goal of this study was to retrospectively review the magnetic resonance imaging (MRI) features of retroperitoneal extra-adrenal paragangliomas and to evaluate the diagnostic capabilities of MRI. Twenty-four patients with confirmed benign retroperitoneal extra-adrenal paragangliomas who underwent preoperative MRI and surgical resection were enrolled. The patients’ clinical characteristics and MRI features were reviewed by two radiologists. There were no significant differences in the qualitative and quantitative MRI features were determined by the reviewers. High signal intensity in T2- weighted imaging (T2WI) and diffusion-weighted imaging (DWI) was observed in all tumors. In contrast T1-weighted imaging (T1WI) in the arterial phase, 83.33% of the tumors were clearly enhanced. In 87.5% of cases, a persistent enhancement pattern was observed in the venous and delayed phases, and 12.5% of tumors showed a “washout” pattern. The tumor capsule, intratumoral septum and degenerations were visualized in the tumors and may be helpful in the qualitative diagnosis of extraadrenal paragangliomas in MRI. MRI was useful in locating the position, determining the tumor ranges and visualizing the relationship between the tumors and adjacent structures. The presence of typical clinical symptoms and positivity of biochemical tests are also important factors in making an accurate preoperative diagnosis

Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases

BACKGROUND: The family of proprotein convertases has been recently implicated in tumorigenesis and metastasis in animal models. However, these studies have not yet been completely corroborated in human tumors. METHODS: Using RT PCR, immunoblot and immunohistochemistry we assessed the presence and the processing patterns of the convertases PC1 and PC2 as well as the PC2 specific chaperone 7B2 in human liver metastases originating from colorectal cancer and compared them to unaffected and normal liver. Furthermore, we assessed the presence and processing profiles of PC1, PC2 and 7B2 in primary colon cancers. RESULTS: mRNA, protein expression, and protein cleavage profiles of proprotein convertases 1 and 2 are altered in liver colorectal metastasis, compared to unaffected and normal liver. Active PC1 protein is overexpressed in tumor, correlating with its mRNA profile. Moreover, the enhanced PC2 processing pattern in tumor correlates with the overexpression of its specific binding protein 7B2. These results were corroborated by immunohistochemistry. The specific and uniform convertase pattern observed in the metastases was present only in a fraction of primary colon cancers. CONCLUSION: The uniformly altered proprotein convertase profile in liver metastases is observed only in a fraction of primary colon cancers, suggesting possible selection processes involving PCs during metastasis as well as an active role of PCs in liver metastasis. In addition, the exclusive presence of 7B2 in metastatic tumors may represent a new target for early diagnosis, prognosis and/or treatment

POMC: The Physiological Power of Hormone Processing.

Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon

Association of RET codon 691 polymorphism in radiation-induced human thyroid tumours with C-cell hyperplasia in peritumoural tissue

The RET proto-oncogene encodes a protein structurally related to transmembrane receptors with an intracellular tyrosine kinase domain. In human thyroid gland, the RET proto-oncogene is normally expressed in parafollicular C-cells. Thyroid C-cell hyperplasia is associated with inherited medullary thyroid carcinomas and is considered as a pre-neoplastic stage of C-cells disease. It has also been observed in thyroid tissues adjacent to follicular and papillary carcinomas. In order to study the relationship between a misfunctioning of the RET proto-oncogene and the presence of C-cell hyperplasia, we compared a series of thyroid glands presenting sporadic or radiation-associated tumours, as well as samples of unrelated normal thyroid tissues, for alteration in exons 10 and 11 of the gene and for the presence or absence of C-cell hyperplasia. Here we report a significantly higher frequency of C-cell hyperplasia present in peritumoural thyroid tissues of radiation-induced epithelial thyroid tumours, than in peritumoural of sporadic thyroid tumours or in control normal thyroid tissues (P=0.001). A G691S RET polymorphism was present with a higher frequency in radiation-induced epithelial thyroid tumours (55%) than in sporadic tumours (20%) and in control normal thyroid tissues (15%). Interestingly, this polymorphism was associated in the majority (88%) of radiation-induced tumours with a C-cell hyperplasia in the peritumoural tissues. Several explanations for this association are discussed

Prognostic impact of thyroid lymphocytic infiltration in patients with medullary thyroid carcinoma

A retrospective search for lymphocytic infiltration of the thyroid was performed on archival paraffin specimens from 95 cases of thyroid medullary carcinoma observed at a single institution during a 30-year period. A mild lymphocytic infiltration of the nonneoplastic thyroid tissue, mainly concentrated at the edge of the tumor mass, was observed in 33 cases, while in a further 24 cases a moderate to marked lymphocytic infiltration, resembling that seen in chronic lymphocytic thyroiditis, was homogeneously distributed all over the gland, with no apparent relationship to the site of the primary tumor. Virtually no lymphocytic infiltration was detected inside of any of the tumors. The presence of chronic lymphocytic thyroiditis seemed to be a characteristic of the host rather than a tumor-induced event. Statistical univariate analysis of relapse-free survival and overall survival showed that lack of chronic lymphocytic thyroiditis marked those patients with an increased risk of disease recurrence and death. However, the observed risk for survival was statistically nonsignificant, whereas that for disease recurrence was significant and remained in a multivariate model of statistical analysis

Differentiation in paediatric peripheral primitive neuroectodermal tumours of bone. A critical contribution to its assessment

Differentiation was studied in 73 paediatric peripheral primitive neurorectodermal tumours (pPNETs) of bone observed during 1974 through 1992. The presence of rosettes, pseudorosettes, and/or a rosette-like arrangement of tumour cells (the morphological neural marker, MNM) occurred in 29% of these cases. NSE and N-CAM were expressed by nearly all tumours; synaptophysin was present in 30% of cases, not significantly associated with the MNM status. Neuroendocrine (NE) markers were present in 25% (chromogranin B, secretogranin II) to 40% (chromogranin A, 7B2 protein) of cases. Focal expression of cytokeratins, S100 protein and/or desmin was also noted in a minority of cases. In univariate statistical analysis, only the presence of MNM conferred a significantly higher (about twofold) risk of death than its absence. This study demonstrates the occurrence of at least one immunocytochemical N and/or NE differentiation marker in all pPNETs of bone and a focal expression of cytokeratins, S100 protein and/or desmin in a minority of cases. Synaptophysin and MNM were present each in less than 1/3 of the cases, and no association was noted between them. Statistical analyses highlighted the prognostic role of MNM per se and discourage the sole use of immunocytochemistry in the assessment of neuroectodermal differentiation for prognostic purposes in paediatric pPNETs of bone