Malignant hereditary paraganglioma: problems raised by non-functional forms management

Non-functional paraganglioma have not clinical or biological characteristics, so that the diagnostic is most of the time delayed and made on the occasion of advanced abdominal tumor or symptomatic metastasis management. Hereditary forms, notably those with SDHB mutation, seem to have a poor prognosis. On the other hand, and on the oposite to sporadic forms, they are the only ones to benefit from genetic testing which make possible, if positive, an earlier diagnostic, before apparition of symptoms, recurrence or metastasis. We report a case of non-functional malignant hereditary paraganglioma diagnosed belatedly and we will consider management problems raised by non-functional forms.     

Pheochromocytoma: rare lethal challenging diagnosis that may be encountered by gynecologists and obstetricians

Pheochromocytomas are rare but potentially lethal tumors responsible for malignant hypertension. They may be encountered by gynecologists and obstetricians. The diagnosis is difficult because it can be mistaken for diseases more frequent like preeclampsia or other pelvic tumors. We report two cases highlighting clinical clues such as labile hypertension, headache, sweating, palpitations and failure to respond to conventional treatment should prompt physicians to screen patients for pheochromocytoma by measuring the 24-hour urinary catecholamines. The surgery must be performed after using an appropriate preoperative treatment, in order not to trigger lethal outcome. During pregnancy, C-section is recommended.     

Paragangliomas: clinical and secretory profile. Result of 39 cases

THIS RETROSPECTIVE STUDY AIMS: To define a clinical and secretory profile of paragangliomas extra-adrenal chromaffin tumors. METHODS: From 1971 throughout 2002, 39 paragangliomas have been observed in 38 patients (22 male, 16 female, average age 41,2 years). RESULTS: Four were located above the diaphragm, 35 were sub-phrenic (6 of the organ of Zuckerkandl), 32 secreted catecholamines, 23 were hypertensive (with only one without hypersecretion of catecholamines). Among 29 (131)I-metaiodobenzylguanidine scans (MIBG) reviewed, 20 tumors took up the radiopharmaceutical. The treatment was surgical in 35 cases with addition of external radiotherapy and MIBG in one case each; two patients died before any treatment. Two patients with persistent disease after surgery were successfully treated by surgery or MIBG. Histologically, 20 were malignant and 17 were seemingly benign. All exclusive dopamine secreting paragangliomas were malignant. Six patients relapsed two of which for a tumor initially classified as benign. The treatment of recurrences was surgical, by MIBG or by external radiotherapy. Nine patients had a family history of chromaffin tumor(s). The genetic survey made in five of these nine patients was positive in all cases.     

Surgical management of a preaortic paraganglioma: Report of one case

Paragangliomas (PG) are rare and often diagnosed in the young adult. One case of retroperitoneal preaortic paraganglioma localised between the celiac trunk and the superior mesenteric artery is reported. The management of paraganglioma involves endocrinologists, geneticists and surgeons but the only potentially curative treatment remains surgical resection. Pathology reports can not always discriminate between benign or malignant tumors. Hereditary in paraganglioma occurs in approximately 25% of cases. Genetic investigation is therefore mandatory in all patients with PG. Since the type of genetic mutation is correlated with tumoral aggressiveness, genetic investigation results should be taken into account when a surgical procedure is planned.     

Genetics of pheochromocytoma and paraganglioma: New developments

Since 2000, several new susceptibility genes for hereditary pheochromocytoma or paraganglioma have been discovered. The aim of this review is to highlight how these discoveries have improved our knowledge on the mode of inheritance of these tumors and also on their molecular pathogenesis. Concerning this specific point, we will show that the different key players of tumorigenesis can converge on two pathways, the first being the hypoxia/angiogenesis pathway and the second being the control of neural crest cell development pathway. Finally, practical issues are considered; for us, it would be preferable to apply easy-to-identify clinical predictors to preselect patients eligible for molecular testing in order to improve the efficiency of these high-cost tests.     

Emerging molecular markers of metastatic pheochromocytomas and paragangliomas

Metastatic pheochromocytoma/paraganglioma (PPGL) represents a major clinical challenge due to limitations in accurate diagnostic tools and effective treatments. Currently, patients classified at high-risk by means of clinical, biochemical and genetic criteria, require a lifelong monitoring, while it remains difficult to determine the metastatic potential of PPGL only on the basis of histopathological features. Thus, tumor molecular markers that improve the risk stratification of these patients are needed. In the past few years, we have witnessed an unprecedented molecular characterization of PPGL, which led to the emergence of promising candidate biomarkers predictive of metastatic behavior. Here, we briefly discuss these breakthroughs and provide some insights for the prospective implementation of molecular markers of metastatic PPGL in the clinical setting in years to come.     

Paragangliome der Kopf-Hals-Region

Paragangliomas of the head and neck region are usually benign tumors that develop from chemoreceptors of paraganglionic origin in the majority of patients. These receptors play an important role in sensing and regulation of the blood CO(2) level. Genetic alterations in the mitochondrial enzyme complex II (SDH), which is involved in respiratory chain and citric acid cycle reactions, have been shown to lead to sporadic as well as familial cases of these tumors. The gene encoding the subunit SDHD shows mutations in up to 50% of these cases. In addition, loss of heterozygosity (LOH) was demonstrated in these tumor samples and has been shown to be connected with oncogenesis of paragangliomas. Thus, SDHD is the first known tumor suppressor gene encoding a mitochondrial protein. In this article we summarize the current state of knowledge concerning the development of paragangliomas.