Sclerosing paraganglioma of the carotid body: a potential pitfall of malignancy.

Paragangliomas (PGs) of the head and neck region are typically benign, slow-growing neuroendocrine tumours. At times, they may exhibit unusual histological features, such as prominent stromal sclerosis (sclerosing PG), which may raise concerns of malignancy. We describe a case of sclerosing PG of the carotid body, emphasizing the value of immunohistochemical stains for differential diagnosis. A 43-year-old woman presented with a painless lump on the neck. A magnetic resonance imaging scan demonstrated a hypervascular lesion of the carotid body, which was surgically excised. Grossly, the lesion measured 1.8 cm at maximum diameter. On microscopic examination, irregular nests and tiny bundles of neoplastic cells were found between thick bands of fibrous tissue. Focal nuclear cytomegaly and marked pleomorphism were noted. Neoplastic cells proved to be immunoreactive for chromogranin, synaptophysin and neuron specific enolase, but negative for cytokeratins, smooth muscle actin and CD34. Ultrastructurally, numerous mitochondria, rough endoplasmic reticulum structures and endocrine granules were seen in the cytoplasm of the tumour cells. On consideration of the above-mentioned clinico-pathological and ultrastructural findings a diagnosis of sclerosing PG was established. Sclerosing PG is a rare entity which may mimic a malignant neoplasm. The recognition of this unusual morphological variant of PG, together with appropriate immunostains, leads to the correct diagnosis.

Resection of Carotid Body Tumors reduces arterial blood pressure. An underestimated neuroendocrine syndrome.

INTRODUCTION: Carotid Body Tumors (CBTs) are Paragangliomas (PGLs) located in the head and neck region which usually do not cause overt neuroendocrine symptoms and hypertension. Matrix Metalloproteinases (MMPs) have shown a strong correlation between CBTs and their clinical behavior. Aim of this study is to analyze the relationship between changes in arterial blood pressure and metalloproteinases levels after surgical resection of CBTs. METHODS: We performed a multicenter clinical study on 17 patients with benign and malignant CBTs (5 males; 12 females). Tumors were completely resected and biopsies, obtained at the time of surgery, were lysed for Western blot analysis to determine MMPs levels in tissues. An enzyme-linked immune sorbent assay (ELISA) kit was used to determine the concentration of MMPs in plasma fluid. Blood pressure values were measured at admission and at 10 days after surgery. RESULTS: At the time of the admission, blood pressure values were higher in patients with CBTs respect to control patients; moreover in patients with malignant CBTs blood pressure values were higher (P < 0.01) respect to patients with benign CBTs. 10 days after the surgery, we documented a significant decrease (P < 0.01) in blood pressure values and in MMPs levels in all patients with CBTs. CONCLUSION: These results suggest that, despite the CTBs are considered non-functional tumors, an "underestimated" neuroendocrine activity on arterial blood pressure may be detected.

The presence of SDHB mutations should modify surgical indications for carotid body paragangliomas.

OBJECTIVE: The aim of this study was to determine whether the genetic background of the disease should be incorporated into treatment decision making. BACKGROUND: Carotid body paragangliomas are rare tumors that often affect patients with genetic mutations of the succinate dehydrogenase complex (SDHx). Despite growing evidence that germ line genetic mutations alter the aggressiveness of paragangliomas, treatment decisions are currently based only on clinical symptoms and tumor size in patients with carotid body paragangliomas. METHODS: Retrospective analysis of 34 patients with carotid body paragangliomas who underwent genetic testing and surgical treatment. Recurrence was defined by the return of locoregional disease and/or development of distant metastases. Clinical characteristics and genetic testing results were analyzed as predictors of patient outcomes. RESULTS: Thirty-four patients underwent 41 primary carotid body paraganglioma resections (median follow-up time of 42 months, range: 1-293). Overall survival was 91.2%. Twelve patients had germ line mutations in SDHB, 17 in SDHD, and 5 carried no known mutation. Surgical resection of larger tumors was associated with higher operative complications (odds ratio: 5.4, P = 0.05). Tumor size at resection was significantly smaller in patients with SDHB mutations than in patients with non-SDHB mutations (2.1 vs 3.3 cm, P = 0.02). Patients with a mutation in the SDHB gene also had significantly worse disease-free survival compared with patients without an SDHB gene mutation (P = 0.03). CONCLUSIONS: Mutations in the SDHB gene are associated with worse disease-free survival after resection in patients with carotid body paragangliomas despite earlier intervention. This suggests that a more aggressive surgical approach is warranted in patients with SDHB mutations.

Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families.

Patients with germline mutations in one of the SDH genes are at substantially increased risk of developing paragangliomas, pheochromocytomas (pheos), and other tumors (all combined referred to as SDH-related tumors). However, limited data exist on screening in SDH mutation carriers and no studies have evaluated whole-body MRI as a screening tool in asymptomatic patients. This was a single-center observational study. We evaluated the results of screening in 37 SDH carriers who underwent 45 whole-body MRIs and 47 biochemical tests. Screening included annual biochemical testing (catecholamines, metanephrines and chromogranin A) and biennial or annual rapid sequence whole-body MRI from the base of the skull to the pelvis beginning at age 10 years old. Six tumors (paragangliomas of the organ of Zuckerkandl, the aortocaval/vas deferens, of the carotid body times three, and a renal cell carcinoma) were diagnosed in five patients. In total, 13.5 % of all patients screened were diagnosed with SDH-related tumors. Whole-body MRI missed one tumor, while biochemical testing was normal in five patients with SDH-related tumors. The sensitivity of whole-body MRI was 87.5 % and the specificity was 94.7 %, while the sensitivity of biochemical testing was 37.5 % and the specificity was 94.9 %. Whole-body MRI had a higher sensitivity for SDH-related tumors than biochemical testing in patients undergoing screening due to their SDHB or SDHC mutation status. Whole-body MRI reduces radiation exposure compared to computed tomography scan and time compared to dedicated MRI of the head/neck, thorax, and abdomen/pelvis.

[Clinical and pathological characteristics and surgical treatment of carotid body tumor with endocrine activity].

OBJECTIVE: To investigate the clinical and pathological characteristics and surgical treatment of carotid body tumor with endocrine activity (CBT). METHODS: Records of seven CBT patients with endocrine activity (Jan, 1991-Aug, 2011) who underwent surgical excision of tumor were retrospectively reviewed. The operations were performed with the careful peroperative preparation on the control of blood pressure, serum potassium and catecholamine. All the tumors were studied with the methods of HE staining, immunohistochemistry of chromogranin A (CgA) and S-100. RESULTS: All the operations were successfully accomplished and the patients recovered quickly. It was confirmed with pathological examination that all the tumors were CBT, coming from paraganglioma. Tumor cells and sertoli cells were found in HE staining, and all were positive of CgA and S-100. All patients were followed up for 12-60 months and no recurrence was found during the follow up. CONCLUSION: CBT with endocrine activity presents with identifiable clinical and pathological characteristics. The recommended treatment is surgical resection, careful perioperative preparation and care is important to avoid the severe complication due to the endocrine activity of tumor.

Dopamine-secreting carotid body paragangliomas-biochemical control with radiotherapy.

Head and neck paragangliomas that are exclusively or predominantly dopamine-secreting are rare. Surgery and/or radiotherapy are modalities for locoregional tumoral control. Little is known about the efficacy of radiotherapy for biochemical control in such tumors. We report a 62-year-old Chinese man with bilateral carotid body tumors which were exclusively dopamine secreting. The left-sided tumor invaded the skull base and encased the left carotid artery. Surgery was not performed due to high risk of morbidity and mortality. The patient received external beam radiotherapy to bilateral neck regions. Progressive decline and eventual normalization of urinary dopamine excretion was seen together with a slight reduction in tumor size. This is the first report demonstrating the efficacy of radiotherapy for both biochemical and locoregional control of functioning carotid body paragangliomas.

A comparison between the treatments of functional and nonfunctional carotid body tumors.

BACKGROUND: It is well known that carotid body tumors (CBTs) are rare and almost nonfunctional, and that functional CBTs are even less frequently seen, with or without catecholamine-induced symptoms. Objective of this study is to make comparison between the treatment effects on functional and nonfunctional CBTs. METHODS: The medical records of 46 patients (16 men and 30 women) of our unit who underwent surgical intervention for CBTs were retrospectively reviewed from January 2005 to July 2010. Patients were divided into two groups by function: group A (n = 5, functional CBTs) and group B (n = 41, nonfunctional CBTs). Perioperative and postoperative details were compared accordingly. RESULTS: All the patients successfully underwent tumor resection. Although symptoms were nonspecific, intraoperative hypertension (5/5, 100%) and persistent postoperative hypotension (3/5, 60%) were found in group A. No statistical difference was found in perioperative details and complications between two groups. No recurrence occurred in two groups during the follow-up period for a mean of 35.3 months (with a range of 12-60 months). CONCLUSION: Surgical resection is safe and effective even if the CBT is functional. Besides routine preparation, preoperative measurement of serum catecholamine, treatment with α- and ß-adrenergic blockade and gentle manipulation during operation are necessary.

Familial cervical paragangliomas with lymph node metastasis expressing somatostatin receptor type 2A.

We report a case of familial, bilateral cervical paragangliomas (PGs) with lymph node metastasis. Patient I-1 is a 56-year-old man with a right carotid body tumor and a left vagal PG. Patient II-1 is a 29-year-old woman and the daughter of Patient I-1; she had a left carotid body tumor with regional lymph node metastasis. Histology of all the tumors showed the typical pattern of PGs, i.e., a zellballen pattern composed of chief cells positive for chromogranin A, and sustentacular cells positive for S100 protein. The Ki-67 labeling index was 1% to 3% in these PGs in both the primary and the metastatic tumors. Immunohistochemical analysis showed expression of somatostatin receptor (sstr) type 2A, but was negative for sstr type 5. Genomic mutation in succinate dehydrogenase type D was confirmed in both patients. Here, we present a case of familial PGs, and discuss the cases with special reference to pathologic diagnosis, genetics, and treatment.

Plasticity of central chemoreceptors: effect of bilateral carotid body resection on central CO2 sensitivity.

BACKGROUND: Human breathing is regulated by feedback and feed-forward control mechanisms, allowing a strict matching between metabolic needs and the uptake of oxygen in the lungs. The most important control mechanism, the metabolic ventilatory control system, is fine-tuned by two sets of chemoreceptors, the peripheral chemoreceptors in the carotid bodies (located in the bifurcation of the common carotid arteries) and the central CO2 chemoreceptors in the ventral medulla. Animal data indicate that resection of the carotid bodies results, apart from the loss of the peripheral chemoreceptors, in reduced activity of the central CO2 sensors. We assessed the acute and chronic effect of carotid body resection in three humans who underwent bilateral carotid body resection (bCBR) after developing carotid body tumors. METHODS AND FINDINGS: The three patients (two men, one woman) were suffering from a hereditary form of carotid body tumors. They were studied prior to surgery and at regular intervals for 2-4 y following bCBR. We obtained inspired minute ventilation (Vi) responses to hypoxia and CO2. The Vi-CO2 responses were separated into a peripheral (fast) response and a central (slow) response with a two-compartment model of the ventilatory control system. Following surgery the ventilatory CO2 sensitivity of the peripheral chemoreceptors and the hypoxic responses were not different from zero or below 10% of preoperative values. The ventilatory CO2 sensitivity of the central chemoreceptors decreased by about 75% after surgery, with peak reduction occurring between 3 and 6 mo postoperatively. This was followed by a slow return to values close to preoperative values within 2 y. During this slow return, the Vi-CO2 response shifted slowly to the right by about 8 mm Hg. CONCLUSIONS: The reduction in central Vi-CO2 sensitivity after the loss of the carotid bodies suggests that the carotid bodies exert a tonic drive or tonic facilitation on the output of the central chemoreceptors that is lost upon their resection. The observed return of the central CO2 sensitivity is clear evidence for central plasticity within the ventilatory control system. Our data, although of limited sample size, indicate that the response mechanisms of the ventilatory control system are not static but depend on afferent input and exhibit a large degree of restoration or plasticity. In addition, the permanent absence of the breathing response to hypoxia after bCBR may aggravate the pathological consequences of sleep-disordered breathing.

Sclerosing paraganglioma: report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm.

Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor cells separated by broad bands of fibrous tissue. The tumor cells ranged from round to polygonal with abundant cytoplasm to elongated spindle cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a sustentacular cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.

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 mitochondrial SDHD gene is required for early embryogenesis, and its partial deficiency results in persistent carotid body glomus cell activation with full responsiveness to hypoxia.

The SDHD gene encodes one of the two membrane-anchoring proteins of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. This gene has recently been proposed to be involved in oxygen sensing because mutations that cause loss of its function produce hereditary familiar paraganglioma, a tumor of the carotid body (CB), the main arterial chemoreceptor that senses oxygen levels in the blood. Here, we report the generation of a SDHD knockout mouse, which to our knowledge is the first mammalian model lacking a protein of the electron transport chain. Homozygous SDHD(-/-) animals die at early embryonic stages. Heterozygous SDHD(+/-) mice show a general, noncompensated deficiency of succinate dehydrogenase activity without alterations in body weight or major physiological dysfunction. The responsiveness to hypoxia of CBs from SDHD(+/-) mice remains intact, although the loss of an SDHD allele results in abnormal enhancement of resting CB activity due to a decrease of K(+) conductance and persistent Ca(2+) influx into glomus cells. This CB overactivity is linked to a subtle glomus cell hypertrophy and hyperplasia. These observations indicate that constitutive activation of SDHD(+/-) glomus cells precedes CB tumor transformation. They also suggest that, contrary to previous beliefs, mitochondrial complex II is not directly involved in CB oxygen sensing.

[Intubation using an illuminating stylet in a patient with a catecholamine-secreting paraganglioma]. / Intubación con estilete iluminado en una paciente con paraganglioma secretor de catecolaminas.

Laryngoscopy and tracheal intubation produce intense noxious stimuli and are associated with an adrenergic response that can be deleterious in patients with concomitant diseases. Illuminating stylets effectively aid blind intubation by lighting the trachea, and using such devices has been associated with lower incidences of sore throat, dysphonia, and adverse hemodynamic events in comparison with rigid laryngoscopy. We report the case of a female patient with a catecholamine-secreting vagal paraganglioma. She developed multiple hypertensive episodes that were difficult to control during surgical resection of the tumor. It was decided to perform orotracheal intubation with a Light Wand (Vital Signs, Inc., Totowa, NJ, USA) to avoid oropharyngeal stimulation and to attenuate the hypertension and arrhythmias associated with laryngoscopy in such patients. The procedure was carried out without difficulty on the first attempt, in spite of tracheal displacement. The maximum increases in blood pressure and heart rate were observed 1 minute after intubation and were less than 30% of basal levels. We believe that using this light wand while intubating this patient helped keep the expected hemodynamic response to a minimum during laryngoscopy.

Hypotension in a woman with a metastatic dopamine-secreting carotid body tumor.

OBJECTIVE: To describe a woman with metastatic carotid body tumor in whom hypotension occurred in the setting of exceedingly high plasma dopamine levels. METHODS: We present a case report and review the literature on the topic of dopamine-secreting paraganglioma or pheochromocytoma. RESULTS: A previously healthy 40-year-old Asian woman noted difficulty with swallowing and hoarseness. No neck mass was visible, and she had no symptoms of catecholamine excess and no family history of endocrine disorders or malignant disease. Indirect laryngoscopy revealed a paralyzed left vocal cord and a nonulcerating mass in the left parapharyngeal space. An initial needle biopsy was interpreted as undifferentiated carcinoma. After a second biopsy, this mass was diagnosed as a neuroendocrine tumor, consistent with paraganglioma. The patient underwent surgical resection and radiation therapy (total dose, 40 Gy), after which she remained asymptomatic for 11 years. Then loss of weight, fatigue, nausea, and hypotensive episodes (blood pressures as low as 70/35 mm Hg) prompted whole-body imaging with bone scans, computed tomography, and magnetic resonance imaging, which disclosed several lesions in the liver, lungs, and spine, suggestive of metastatic disease. The adrenal glands were unremarkable. A metaiodobenzylguanidine scan with use of (131)I was negative. Liver biopsy of a hypodense lesion revealed a neuroendocrine tumor by histologic and immunohistochemical studies. Because of the patient's history, malignant paraganglioma was diagnosed. The tumor secreted predominantly dopamine at extraordinary levels (plasma concentration 27,942 pg/mL; normal, <30). The patient died before further treatment could be initiated. CONCLUSION: Carotid body tumors usually do not secrete catecholamines but frequently metastasize. During progression, these neuroendocrine tumors may become able to produce and secrete selected catecholamines such as dopamine. Dopamine can lower the blood pressure rather than causing hypertension, even though hypertension is one of the main symptoms of a pheochromocytoma.

Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC.

Mutations in SDHC cause autosomal dominant paraganglioma, type 3 (PGL3), and have to date been demonstrated in only one family. Here, we report on a novel mutation in a patient with a malignant, catecholamine-producing paraganglioma at the carotid bifurcation. The mutation is a G-->T transversion at position +1 of intron 5 of the SDHC gene, leading to the deletion of exon 5 and a shift in the reading frame.

Growth factors and cytokines in paragangliomas and pheochromocytomas, with special reference to sustentacular cells.

The aim of this study was to localize various growth factors and cytokines in paragangliomas and pheochromocytomas in order to understand their possible autocrine or paracrine functions, and to compare sustentacular cells of the adrenal medulla with pituitary stellate cells. Thirteen resected tumors, 11 paragangliomas and 2 pheochromocytomas of the adrenal medulla, were studied. In addition, five surgically removed nontumorous adrenals and five nontumorous pituitaries were studied. Varying numbers of sustentacular cells were immunopositive for S-100 protein and in most instances for glial fibrillary acidic protein. Insulin-like growth factor-1 (IGF-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were localized to both cell types in all cases, whereas epidermal growth factor (EGF) immunopositivity was noted in only three. In all tumors, leukemia inhibitory factor (LIF) was restricted to chief cells and EGF receptor to sustentacular cells. Nontumorous chief cells and sustentacular cells of adrenal medulla exhibited immunoreactivities similar to those of paragangliomas and pheochromocytomas. Secretory adenohypophysial cells displayed various immunoreactivities for all growth factors, receptors, and cytokines studied. Pituitary stellate cells were immunopositive for EGF, EGF receptor, IGF-1, LIF, and TNF-alpha. In conclusion, paragangliomas and pheochromocytomas are immunoreactive for a wide spectrum of growth factors and cytokines. Immunocytochemistry demonstrated similarities between sustentacular cells and stellate cells of the pituitary in addition to their similar morphology. The significance of these observations regarding paracrine activities of chief and sustentacular cells remains to be determined.

Prediction of malignant behavior of pheochromocytomas and paragangliomas using immunohistochemical techniques.

Pheochromocytomas and paragangliomas arise from the adrenal glands and extraadrenal paraganglia, respectively. Malignant behavior of these tumors is uncommon and is, in part, dependent on their sites of origin, such as extraadrenal location. Morphologic criteria for malignancy of pheochromocytoma and paragangliomas have not been clearly defined. In this study, to clarify the histologic features that distinguish the benign from malignant pheochromocytomas and paragangliomas, we examined metastatic and nonmetastatic tumors using immunohistochemical techniques. A total of eight cases, five pheochromocytomas from the adrenal glands (four benign and one malignant tumor) and three paragangliomas with invasion or metastasis, were studied. The markers used in this study were chromogranin A, synaptophysin, NCAM (CD56), SNAP25, neuron-specific enolase, S-100 protein, and MIB-1. Our results suggest that MIB-1 immunostaining is a useful adjunct marker to predict malignant behavior in these tumors.

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.

Catecholamine-secreting carotid body tumor and intracranial aneurysm: coincidence?

BACKGROUND: An extremely rare case of intracranial aneurysm associated with catecholamine-secreting carotid body tumor is presented. CASE DESCRIPTION: A 64-year-old woman suffering from hypertensive attacks was admitted first to the Otolaryngology Department with a neck swelling. Right common carotid angiography revealed a hypervascular mass at the carotid bifurcation. On the same angiogram a middle cerebral artery aneurysm was discovered incidentally and the patient was referred to the Neurosurgical Department. Because of her history the tumor was considered to be endocrinologically active and the patient underwent alpha- and beta-blockade to protect intraoperative cardiovascular instability. Despite all precautions, during the operation hypertensive crises developed and the aneurysm was clipped with difficulty. CONCLUSION: Perioperative management designed to avoid complications in treating this rare association is discussed. Although this is the first reported case of an intracranial aneurysm associated with a functional carotid body tumor, a possible etiopathogenesis of the relationship between the aneurysm and hypertensive attacks due to an acute catecholamine-discharging tumor is presented.

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the PGL1 gene, described here, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.