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Item does not contain fulltext OBJECTIVE: Pheochromocytomas and paragangliomas (PPGL) are relatively rare and mostly benign tumours. Approximately 10% of PPGL are malignant, as defined by the presence of metastases, i.e chromaffin tissue at a location that usually does not contain chromaffin cells. However, up to 35% of tumours in patients carrying an SDHB mutation appears to be malignant. Nowadays, no reliable marker allows to predict whether a PPGL is, or will become malignant. In addition, there are no curative treatments if metastases occur. The aim of the present study was to dentify genetic markers allowing to distinguish benign from malignant tumours. DESIGN AND METHOD: An mRNA expression array was performed on benign and malignant PPGL. The genes showing a different expression between the benign and malignant tumours were selected to be confirmed and validated by qRT-PCR. Finally, the remaining genes were stained by immunohistochemistry on Tissue MicroArray including a large series of PPGL. RESULTS: Forty benign and 12 malignant PPGL were investigated for differences in mRNA expression with Affymetrix arrays. Expression data were normalized according to Affymetrix recommendations. Then, using Pomelo II (http://pomelo2.bioinfo.cnio.es/), a Limma t-test was performed, to assess which genes were differentially expressed between benign and malignant PPGL. First, a non-clustered analysis was performed and 10 genes with a False Discovery Rate (FDR) below 0.05 and a relative overexpression ratio of at least 4 were found, including Interleukin 13 Receptor alpha 2 (IL13RA2) and Monooxygenase DBH-like 1 (MOXD1). Secondly, a supervised cluster analysis was performed (based on HIF target genes), resulting in 2 groups, which were both investigated for differences in mRNA expression between benign and malignant tumours. Five genes showed an FDR below 0.01 and were overexpressed in malignant tumours with a ratio higher than 4, including Contactin 4 (CNTN4), Iroquois Homeobox 3 (IRX3), and Sulfatase 2 (SULF2). These genes were further investigated using qRT-PCR, and immunohistochemistry on Tissue Micro Array including 91 benign and 12 malignant PPGL. CONCLUSIONS: Significant overexpression of Contactin 4 was shown in malignant compared to benign tumours, and may therefore contribute to distinguish malignant from benign PPGL.

72-year-old woman with a history of primary hyperparathyroidism, for which she underwent surgery years previously, went to see her general practitioner because of a swelling in her neck that had been present for a few months and was growing in size. Other than this she had no symptoms. During the physical examination a solid elastic, non-fixed swelling with a diameter of about 3 cm was palpable on the right of the neck, medially to the sternocleidomastoid muscle. The swelling did not move when she swallowed. Laboratory tests and an MRI scan were suggestive of parathyroid carcinoma. An examination of the neck showed a large, irregular, lobed soft tumour and several small deposits with a yellowish brown appearance. Histology showed no characteristics of malignancy, but showed a picture consistent with the diagnosis of 'parathyromatosis', a rare disorder characterized by hormonally active ectopic parathyroid tissue. Treatment is primarily surgical, aimed at radical resection. Medicinal therapy using a calcimimetic agent may have a role as an adjuvant treatment

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.

A 17-year-old boy presented with an atypical manifestation of acute appendicitis. The clinical aspect, radiological investigations and peroperative aspect of the appendix were not conclusive but nevertheless a neuroendocrine tumour (carcinoid tumour) of the appendix was suspected. After ileocaecal resection and resection of pathological lymph nodes, histopathological evaluation revealed the diagnosis: a periappendicular mass without any sign of malignancy. In retrospect, ileocaecal resection was performed for a benign disease. This case illustrates that an unusual presentation of a common disease occurs more frequently than a typical presentation of a rare disease

A 49-year-old woman presented at the emergency ward in shock with upper gastrointestinal bleeding. Extensive ulceration confirmed by gastroduodenoscopy was suggestive of Zollinger-Ellison syndrome. Further evaluation by fasting gastrin assessment, CT, endosonography with cytological biopsy and somatostatin-receptor scintigraphy confirmed the diagnosis ofgastrinoma. Three enlarged lymph nodes near the pancreatic head were surgically removed; each was found to contain neuroendocrine tumour cells. The patient recovered rapidly after surgery and the gastrin level normalised. Zollinger-Ellison syndrome is uncommon but should be considered as a possible cause of upper gastrointestinal bleeding. Shock is very rarely the first sign ofZollinger-Ellison syndrome. In this case, the use of a proton-pump inhibitor may have masked the disease for years