Síndrome de vasoconstricción cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas / Reversible cerebral vasoconstriction syndrome secondary to secreting jugular paraganglioma

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Biochemical and clinical responses after treatment of a catecholamine-secreting glomus jugulare tumor with gamma knife radiosurgery.

BACKGROUND: Functional glomus jugulare tumors (GJTs) are commonly managed with resection. Although primary radiation therapy of functional GJT can provide durable control of tumor growth, little is known of its ability to ablate functional capacity. METHODS AND RESULTS: We describe a case of a 47-year-old man with a symptomatic norepinephrine-hypersecreting GJT treated with definitive single-fraction gamma knife radiosurgery and pharmacologic catecholamine blockade. At a 32-month follow-up, he has experienced significant symptomatic improvement, excellent control of local tumor growth, minimal treatment-related morbidity, and near normalization of catecholamine levels. CONCLUSION: Radiosurgery was safe and effective in significantly reducing the functional capacity of a paraganglioma. Care must be taken to avoid inducing a hypertensive crisis during and following treatment, and longer follow-up will help determine whether and when pharmacologic blockade can be discontinued.

VEGF mRNA expression in jugulotympanic paraganglioma.

The vascular endothelial growth factor (VEGF) family are essential regulators of angiogenesis and vascular permeability. VEGF protein was found in the jugulotympanic paraganglioma, but it wasn't confirmed on mRNA level. Our aim of this study is the mRNA expression of VEGF in jugulotympanic paraganglioma. We chose six cases of primary jugulotympanic paraganglioma wax specimen by hybridisation in situ. It suggested that VEGF mRNA had significant expression in the tumour cytoplasm of jugulotympanic paraganglioma. The correlation is not yet clear. It could be suggested the higher degree of malignancy, the stronger expression of VEGF mRNA in cytoplasm, but not found in the cellular nucleus.

Secreting jugulotympanic paraganglioma with venous involvement into the thorax.

Paragangliomas are highly vascular tumors that arise from chief cells in extra-adrenal paraganglia of the autonomic nervous system. Jugulotympanic paragangliomas involve the middle ear and jugular fossa. Secreting jugulotympanic paragangliomas with thoracic extension are rare. We report a case with unexpected involvement of the internal jugular vein. Otolaryngologists should be aware that the jugulotympanic paragangliomas traverse variable anatomic pathways. Multiple imaging options, including magnetic resonance venography, are useful and should include the neck for definitive characterization of tumor anatomy. Patients with refractory hypertension and masses suspicious for paraganglioma should be examined for functional tumors.

Magnesium in the management of catecholamine-secreting glomus tumours with intracranial extension.

PURPOSE: Catecholamine-secreting glomus jugulare tumours are uncommon and their anesthetic management can be challenging. The authors present the first description of the use of magnesium sulfate in the management of two patients with catecholamine-secreting glomus jugulare tumours where there was significant intracranial extension. CLINICAL FEATURES: Patient 1 underwent a transmastoid transoccipital excision of a catecholamine-secreting glomus tumour. He exhibited marked hemodynamic instability after handling of the tumour began, which was not controlled by sodium nitroprusside. Improved hemodynamic stability was seen after the patient received magnesium sulfate. Patient 2 also underwent a transmastoid transoccipital excision of a catecholamine-secreting glomus tumour. Magnesium sulfate was commenced prior to tumour handling and continued until the tumour was removed. The patient remained hemodynamically stable. Sodium nitroprusside was not required. CONCLUSION: Magnesium sulfate may be useful in preventing or minimizing the blood pressure changes associated with handling during excision of catecholamine-secreting glomus jugulare tumours. It may be of particular benefit in patients where there is significant intracranial extension.

Vascular endothelial growth factor expression, vascularization and proliferation in paragangliomas.

OBJECTIVE/HYPOTHESIS: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth. STUDY DESIGN: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases. METHODS: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells. RESULTS: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group. CONCLUSIONS: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies.

The basic science of glomus jugulare tumors.

Glomus tumors are a fascinating group of lesions. It is a challenge for neurosurgeons and otolaryngologists to resect them completely with minimal morbidity. Laboratory researchers have discovered extremely interesting genetic and molecular biology factors involved in the development and growth of glomus tumors. In this article the author reviews the genetics, protein mutations, angiogenesis and apoptosis associated with tumor formation, and the secretion of vasoactive substances is discussed as well. It is hoped that with further research less invasive measures may be developed to treat these tumors.

Glomus jugulare tumors with intracranial extension.

Glomus tumors provide unique surgical challenges for both tumor resection and defect reconstruction. Tumors with intracranial extension compound these challenges. Surgical techniques have evolved, and now, with a multidisciplinary team, single-stage surgeries are the standard. In this paper the authors will report the results of the Otology Group protocol for surgical management of glomus tumors with intracranial extension. Particular attention will be paid to prevention of cerebrospinal fluid leaks with the use of vascularized tissue for defect reconstruction.

New parameter of hemoglobin status as an indicator of efficacy of preoperative angioembolization in extracranial hypervascular tumours.

BACKGROUND: Routinely, the standard for measuring the success of preoperative embolization procedure as an adjunct in the management of head and neck vascular tumours has been to evaluate the amount of blood loss, duration of surgery, and intraoperative neurovascular injuries. OBJECTIVE: We hypothesized that the rate of change in the preoperative hemoglobin status would more accurately and objectively reflect the effectiveness of the embolization technique. MATERIALS AND METHODS: Twenty-six patients with extracranial vascular tumours were divided into two groups (A and B) of 13. Group A patients had preoperative embolization and group B patients directly underwent surgery. The difference between the preoperative and postoperative hemoglobin levels and the percentage rate of change of hemoglobin status were calculated. RESULTS: The percentage rate of change of preoperative to postoperative hemoglobin is less in group A (9.43%) when compared with group B (18.27%). The ratio of preoperative to postoperative hemoglobin in the two groups is also statistically significant (1:1.9). CONCLUSIONS: The percentage rate of change of preoperative to postoperative hemoglobin and the ratio of preoperative to postoperative hemoglobin are more accurate and objective parameters for assessment of success of preoperative embolizations rather than other variables such as intraoperative blood loss or duration of surgery.

Immunohistochemical features of paragangliomas.

Immunohistochemistry is part of the routine diagnosis of the neuroendocrine tumors. In our study, we included 52 paragangliomas with various localizations by routine histology and immunohistochemistry. In order to increase the diagnostic specificity, a complex immunohistochemistry panel has been performed consisting of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP), somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced antigen retrieval, the immunostaining was performed by StreptABC using DAB as a chromogen. We were the first to demonstrate the presence of Bax and PACAP in paragangliomas. Some of the used markers are of prognostic value. The relationship between Bcl-2 and Bax is decisive in generating the final response to the input apoptotic signals. The Ki-67 antigen staining has gained wide acceptance in prognostic evaluation of other tumor types. We noted a small number of Ki-67 positive cases, which signifies a low mitotic activity of these tumors and a relatively high number of Bax positivities (32.9%) and the much lower number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of paragangliomas.

Expression of angiogenic growth factors in paragangliomas.

OBJECTIVE/HYPOTHESIS: To determine if angiogenic growth factors including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are expressed in human paragangliomas. STUDY DESIGN: A histopathologic and molecular examination of paraganglioma specimens obtained from surgical cases or retrieved from the Pathology Department of the Massachusetts Eye and Ear Infirmary. METHODS: Fresh tumor or archival, paraffin-embedded paraganglioma specimens were analyzed by immunohistochemistry, Western blotting, and ELISA. RESULTS: Positive immunohistochemical staining for VEGF was observed in five of nine surgical specimens and in six of eight archival specimens (11/17, or 65%). PD-ECGF immunoreactivity was detected in four of five surgical specimens and six of eight archival specimens (10/13, or 77%). The presence of PD-ECGF was confirmed by Western blot assay and ELISA confirmed the presence of VEGF in tumor extract. CONCLUSIONS: Both VEGF and PD-ECGF are expressed in paragangliomas and may contribute to the extreme vascularity of these tumors. Key Words. Vascular endothelial growth factor, platelet-derived, endothelial cell growth factor, hypoxia, tumor vasculature.

[Octreotide and a serotonin-secreting glomus tumor]. / Octreótido y tumor glómico secretor de serotonina.

Glomus tumors arise in the chemical receptors of vessels in the tympanic and jugular regions. Clinical signs depend on location, the structures invaded and a tumor's ability to secrete active amines and peptides. A 44-year-old woman was scheduled for excision of a serotonin-secreting tympanic glomus tumor. Urinary excretion of 5-hydroxyindolacetic acid (5-HIA) in urine over the previous 24 hours was 80 mg (normal < 10 mg). The patient received oral diazepam, ranitidine, intravenous diphenhydramine and subcutaneous octreotide (150 micrograms). Anesthesia was induced with propofol, alfentanil and vecuronium. The tumor produced an episode of bronchospasm and cutaneous rubor during surgical manipulation of the tumor. Airway pressure increased to 42 cmH2O and SpO2 decreased to 89%. Hypotension and bradycardia appeared. Once it was suspected that the symptoms stemmed from tumoral secretion of active substances, 20 micrograms of intravenous octreotide was administered. The bronchospasm decreased and hemodynamic changes were resolved in three minutes, with no recurrence of symptoms. The patient received 100 micrograms of octreotide subcutaneously every 8 hours throughout the 72 postoperative hours. Urinary excretion of 5-HIA was 12 mg on the fifth day and the patient was released without having experienced complications. Appropriate preoperative preparation is important in patients with such tumors, as are early detection of respiratory and hemodynamic changes that may occur during surgery and correct perioperative treatment. Octreotide, a longer-lasting somatostatin analogue, has facilitated the handling of such cases.

Intracranial pheochromocytoma--a case of noradrenaline-secreting glomus jugulare tumor.

A 43-year-old female was admitted for a labile hypertension and depression. High levels of plasma and urinary noradrenaline strongly suggested a pheochromocytoma. However, clinical investigations revealed a normal adrenal gland and thoraco-abdominal region. Venous samples from multiple sites indicated and increase in noradrenaline in the left jugular vein. Using computed tomography and Gadolinium DTPA (diethylene triamine pentaacetic acid)-enhanced dynamic MR (magnetic resonance) imaging, a tumor was discovered in the cerebello-pontine angle. Carotid angiography showed the feeder arteries clearly. Therefore, the tumor was classified as a noradrenaline-secreting glomus jugulare tumor fed by the carotid artery. After embolization and subsequent medical therapy, blood pressure was well controlled. Twenty cases of intracranial pheochromocytoma have been reported to date. This is the second such case in Japan.

Long-term effects of radiation therapy for a catecholamine-producing glomus jugulare tumor. Case report.

A 42-year-old woman presented with otorrhea 22 years after extracranial resection of a norepinephrine-secreting glomus jugulare tumor with intravascular embolization and radiation therapy to the intracranial portion of the tumor. Tumor growth was arrested and was associated with a decrease in blood and urine norepinephrine levels. Extensive evaluation of the otorrhea, including computerized tomography-cisternography, gadolinium-enhanced magnetic resonance imaging, and arteriography showed marked diffuse necrosis of the temporal bone and skull base with limited tumor vascularity. Cerebrospinal fluid (CSF) collected from the right ear showed norepinephrine levels of 2975 pg/ml; plasma norepinephrine levels were normal. The precise site of CSF leakage could not be delineated. Exploration of the posterior fossa revealed a large dural defect at the anteromedial aspect of the petrous bone through which CSF flowed over the surface of the residual extradural glomus tumor. The defect was successfully sealed with a fascial patch. Postoperatively, CSF norepinephrine levels were normal and no further leakage was observed.

Hypertension and a tumor of the glomus jugulare region. Evidence for epinephrine biosynthesis.

Glomus jugulare tumors have been reported to secrete norepinephrine and cause severe hypertension with features similar to pheochromocytoma. In contrast, epinephrine secretion has not been observed in these neoplasms. This has been attributed to the absence of the norepinephrine-methylating enzyme, phenylethanolamine-N-methyltransferase (PNMT), required for epinephrine synthesis. We report a patient with severe hypertension caused by a glomus tumor that secreted norepinephrine and epinephrine. Following selective venous sampling, catecholamines were quantified by radioenzymatic assay. Marked elevations in norepinephrine and epinephrine release were localized to the glomus tumor. The enzymes involved in catecholamine biosynthesis, including PNMT and tyrosine hydroxylase, were identified immunocytochemically in the tumor. The glomus tumor had staining patterns identical to those observed within normal rat glomus cell. Hypertension resolved with resection of the functioning tumor. This is the first report of PNMT in a functioning paraganglioma of the glomus jugulare region. The factors that determine why functional activity is expressed only rarely by paraganglioma remain undefined.