Incidental prostatic paraganglia in radical prostatectomy specimens: a diagnostic pitfall.

Paraganglia are an uncommon but previously reported finding in the genitourinary system. Recognition of this entity in the prostate is important in distinguishing it from prostatic adenocarcinoma. In this series, 1230 radical prostectomy specimens were examined for the presence of paraganglia, and a total of 57 cases (4.5%) were found to contain paraganglia. The majority of paraganglia were extraprostatic and could easily mimic extension of prostatic adenocarcinoma into extraprostatic tissue. It is important to recognize paraganglia, particularly when they are extraprostatic and could confer a falsely higher tumor stage to the patient. The paraganglia demonstrated characteristic histology, and immunohistochemistry was supportive when enough tissue was available. No association between patient age and frequency of paraganglia was found.

Paraganglia mimicking metastatic seminomatous tumor.

Two cases are presented in which microscopic groups of retroperitoneal paraganglionic cells simulated metastatic seminomatous tumor. Both patients had histories of mixed testicular germ cell tumor with abdominal metastases and had been treated with chemotherapy. Persistent retroperitoneal disease was favored on follow-up imaging studies. Subsequent retroperitoneal lymph node dissection disclosed multifocal epithelioid cell groups with clear/vacuolated cytoplasm in the fibroconnective and adipose tissue, ranging from 1.0 to 3.0 mm in size. These cell groups were initially interpreted as recurrent metastatic seminoma, but were later reinterpreted as paraganglionic cells, which were confirmed by immunohistochemical analysis. The pathologic features for distinguishing paraganglionic cells from metastatic seminoma are discussed. Awareness of the presence of paraganglia and their distinction from metastatic disease is of practical importance in avoiding an overdiagnosis of malignancy and assuring proper patient management.

Mechanisms of low-glucose sensitivity in carotid body glomus cells.

OBJECTIVE: Glucose sensing is essential for the adaptive counterregulatory responses to hypoglycemia. We investigated the mechanisms underlying carotid body (CB) glomus cells activation by low glucose. RESEARCH DESIGN/METHODS AND RESULTS: Removal of extracellular glucose elicited a cell secretory response, abolished by blockade of plasma membrane Ca(2+) channels, and a reversible increase in cytosolic Ca(2+) concentration. These data indicated that glucopenia induces transmembrane Ca(2+) influx and transmitter secretion. In patch-clamped glomus cells, exposure to low glucose resulted in inhibition of macroscopic outward K(+) currents and in the generation of a depolarizing receptor potential (DRP). The DRP was abolished upon removal of extracellular Na(+). The membrane-permeable 1-oleoyl-2-acetyl-sn-glycerol induced inward currents of similar characteristics as the current triggered by glucose deficiency. The functional and pharmacological analyses suggest that low glucose activates background cationic Na(+)-permeant channels, possibly of the transient receptor potential C subtype. Rotenone, a drug that occludes glomus cell sensitivity to hypoxia, did not abolish responsiveness to low glucose. The association of Glut2 and glucokinase, characteristic of some high glucose-sensing cells, did not seem to be needed for low glucose detection. CONCLUSIONS: Altogether, these data support the view that the CB is a multimodal chemoreceptor with a physiological role in glucose homeostasis.

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Aporte de las imágenes en el diagnóstico de los paragangliiomas de cabeza y cuello / Radiologic support for the diagnosis of paragangliomas of the head and neck

Los paragangliomas de cabeza y cuello son tumores que derivan de las células neuroendócrinas de los paraganglios extrasuprarrenales y se extienden desde la base de cráneo hasta el cayado aórtico. El pronóstico es en general favorable, excepto los que se ubican en el hueso temporal. En el presente trabajo se describen las características en imágenes de las diferentes localizaciones y subtipos de este tumor, en conjunto con una revisión de la literatura hasta la actualidad. Los métodos por imágenes son muy útiles para poder arribar al diagnóstico. El diagnóstico diferencial es de vital importancia a la hora de evitar procedimientos invasivos riesgosos y contraindicados en estos pacientes, como la biopsia

Aporte de las imágenes en el diagnóstico de los paragangliiomas de cabeza y cuello / Radiologic support for the diagnosis of paragangliomas of the head and neck

Los paragangliomas de cabeza y cuello son tumores que derivan de las células neuroendócrinas de los paraganglios extrasuprarrenales y se extienden desde la base de cráneo hasta el cayado aórtico. El pronóstico es en general favorable, excepto los que se ubican en el hueso temporal. En el presente trabajo se describen las características en imágenes de las diferentes localizaciones y subtipos de este tumor, en conjunto con una revisión de la literatura hasta la actualidad. Los métodos por imágenes son muy útiles para poder arribar al diagnóstico. El diagnóstico diferencial es de vital importancia a la hora de evitar procedimientos invasivos riesgosos y contraindicados en estos pacientes, como la biopsia

HIF-2alpha expression in human fetal paraganglia and neuroblastoma: relation to sympathetic differentiation, glucose deficiency, and hypoxia.

Solid tumors are frequently necrotic and hypoxic due to poor vascularization. Tumor cells adapt to hypoxia by modulating their phenotype. Key players in this process are the hypoxia-inducible factors (HIF-1alpha to 3alpha). HIFs are also expressed during normal development; for example, HIF-2alpha is specifically expressed and appears to be involved in the development of the murine sympathetic nervous system (SNS). Here, we demonstrate that HIF-2alpha protein is selectively present in human fetal week 8.5 SNS paraganglia. Neuroblastoma is derived from SNS precursors. In a subset of neuroblastomas, a spontaneous neuronal to neuroendocrine differentiation occurs in areas adjacent to necrotic zones. As HIF-2alpha activity has been associated not only with hypoxic but also with hypoglycemic conditions, we have investigated putative effects of hypoxia, glucose depletion, and HIF-2alpha on the neuroblastoma phenotype. HIF-2alpha was detected in hypoxic and in well-oxygenized neuroblastoma cells and tissue, presumably reflecting their embryonic features. With regard to differentiation, hypoxic cells lost their neuronal/neuroendocrine features and gained marker gene expression associated with an immature, neural crest-like phenotype. Low glucose potentiated the effect of hypoxia. These findings suggest that poorly vascularized neuroblastomas become immature and maintain a more aggressive phenotype, which possibly could involve a sustained stabilization and activation of HIF-2alpha.

Epistaxis as a rare presenting feature of glomus tympanicum.

Glomus tumours are the most common primary neoplasms of the middle ear, typically benign and slowly progressive. Pulsatile tinnitus and ipsilateral hearing loss are the most common symptoms at presentation by far; otalgia, aural fullness and otorrhoea being less frequent. A case of primary glomus tympanicum presenting with recurrent epistaxis, previously unreported in the literature, is described and associated imaging presented.

Glomus tympanicum tumour: an alternative surgical technique.

Glomus tympanicum tumour is one of the commonest neoplasms of the middle ear. It is more common in females. The most common presenting symptom is pulsatile tinnitus. A retrotympanic mass is found in the middle ear in all the cases. Computed tomography (CT) scan is the investigation of choice, however in difficult cases magnetic resonance imaging (MRI) can be helpful. Surgery is regarded as the gold standard of treatment in spite of the fact that radiation therapy has also been advocated in the literature. In this series 17 cases of glomus tympanicum treated at Gruppo Otologico Piacenza - Rome (Italy) were analysed retrospectively. A simple and safe technique has been described. All the cases were female and treated by surgery. The tumour was removed completely in all the cases and the ossicular chain kept intact. Recurrence was encountered in only one case after nine years. Surgical removal of the tumour is recommended as the treatment of choice with the following advantages: complete removal, a low complication rate, a low recurrence rate, acceptable hearing level and minimum morbidity.

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.

Hereditary paraganglioma targets diverse paraganglia.

Paragangliomas are highly vascularised and often heritable tumours derived from paraganglia, a diffuse neuroendocrine system dispersed from skull base to the pelvic floor. The carotid body, a small oxygen sensing organ located at the bifurcation of the carotid artery in the head and neck and the adrenal medulla in the abdomen, are the most common tumour sites. It now appears that mutations in SDHB, SDHC, and SDHD, which encode subunits of mitochondrial complex II (succinate dehydrogenase; succinate-ubiquinone oxidoreductase), are responsible for the majority of familial paragangliomas and also for a significant fraction of non-familial tumours. Germline mutations in complex II genes are associated with the development of paragangliomas in diverse anatomical locations, including phaeochromocytomas, a finding that has important implications for the clinical management of patients and genetic counselling of families. Consequently, patients with a paraganglioma tumour, including phaeochromocytoma, and a complex II germline mutation should be diagnosed with hereditary paraganglioma, regardless of family history, anatomical location, or multiplicity of tumours. This short review attempts to bring together relevant genetic data on paragangliomas with a particular emphasis on head and neck paragangliomas and phaeochromocytomas.

Sonographic findings in glomus tympanicum tumor.

A glomus tympanicum tumor that is associated with a visible retrotympanic mass is the most frequent cause of pulsatile tinnitus. The preoperative diagnostic approach to this lesion includes a meticulous physical examination as well as high-resolution CT, magnetic resonance angiography, and digital angiography, which can also be used for preoperative embolization. We report the use of color transcranial Doppler sonography in the evaluation of glomus tympanicum tumor in a 67-year-old woman with a 3-year history of left tinnitus. An otoscopic examination revealed a reddish pulsatile mass behind an intact tympanic membrane. No lesions were visualized on gray-scale sonography. Contrast-enhanced color transcranial Doppler sonography showed a vascular ovoid mass that measured 2 x 1 x 1 cm; spectral analysis of the lesion revealed arterial flow with a low resistance index. Color transcranial Doppler sonography helped define the dimensions and vascular characteristics of the lesion.

The distribution of presumptive thoracic paraganglionic tissue in the common marmoset (Callithrix jacchus).

The aortic-pulmonary regions (APR) of seven adult marmosets (Callithrix jacchus) and the region of the right subclavian artery of a further three marmosets were diffusion-fixed with 10% buffered formol-saline solution. In both regions serial 5 microm sections were cut and stained by the Martius yellow, brilliant crystal scarlet and soluble blue method. Presumptive thoracic paraganglionic (PTP) tissue was only observed in the APR. PTP tissue was composed of small groups of cells that varied in size and number. The distribution of the groups of cells was extremely variable, so much so that it would be misleading to attempt to classify their position; they were not circumscribed by a connective tissue capsule, but were always related to the thoracic branches of the left vagus nerve. The cells lay in loose areolar tissue characteristic of this part of the mediastinum and received their blood supply from small adjacent connective tissue arterioles. Unlike the paraganglionic tissue found in the carotid body the cells in the thorax did not appear to have a profuse capillary blood supply. There was, however, a close cellular-neural relationship. The cells, 10-15 microm in diameter, were oval or rounded in appearance and possessed a central nucleus and clear cytoplasm. No evidence was found that these cells possessed a 'companion' cell reminiscent of the arrangement of type 1 and type 2 cells in the carotid body. In conclusion, we found evidence of presumed paraganglionic tissue in the APR of the marmoset which, however, did not show the characteristic histological features of the aortic body chemoreceptors that have been described in some non-primate mammals. A survey of the mediastina of other non-human primates is required to establish whether this finding is atypical for these animals.

The distribution of presumptive thoracic paraganglionic tissue in the common marmoset (Callithrix jacchus)

The aortic-pulmonary regions (APR) of seven adult marmosets (Callithrix jacchus) and the region of the right subclavian artery of a further three marmosets were diffusion-fixed with 10 percent buffered formol-saline solution. In both regions serial 5-æm sections were cut and stained by the Martius yellow, brilliant crystal scarlet and soluble blue method. Presumptive thoracic paraganglionic (PTP) tissue was only observed in the APR. PTP tissue was composed of small groups of cells that varied in size and number. The distribution of the groups of cells was extremely variable, so much so that it would be misleading to attempt to classify their position; they were not circumscribed by a connective tissue capsule, but were always related to the thoracic branches of the left vagus nerve. The cells lay in loose areolar tissue characteristic of this part of the mediastinum and received their blood supply from small adjacent connective tissue arterioles. Unlike the paraganglionic tissue found in the carotid body the cells in the thorax did not appear to have a profuse capillary blood supply. There was, however, a close cellular-neural relationship. The cells, 10-15 æm in diameter, were oval or rounded in appearance and possessed a central nucleus and clear cytoplasm. No evidence was found that these cells possessed a 'companion' cell reminiscent of the arrangement of type 1 and type 2 cells in the carotid body. In conclusion, we found evidence of presumed paraganglionic tissue in the APR of the marmoset which, however, did not show the characteristic histological features of the aortic body chemoreceptors that have been described in some non-primate mammals. A survey of the mediastina of other non-human primates is required to establish whether this finding is atypical for these animals

Computed tomography and magnetic resonance imaging of pathologic conditions of the middle ear.

Computed tomography (CT) is an excellent technique for demonstrating even small abnormalities of the thin and complex bony structures of the middle ear. For this reason, it is the modality of choice in the study of conductive hearing loss (CHL). However, not every patient complaining of CHL requires a CT study. In fact, established indications encompass complex conditions, such as the complications of acute and chronic otomastoiditis, the postoperative ear in chronic otomastoiditis or in the localization of prosthetic devices, and the assessment of congenital or vascular anomalies. Particularly, the precise extent of bone erosion associated with cholesteatoma is correctly demonstrated by high resolution CT. Conversely, although fistulization through the tegmen tympani or the posterior wall of temporal bone is usually detectable by CT, the actual involvement of meninges and veins are better assessed by magnetic resonance (MR). MR is also indicated when complicated inflammatory lesions are suspected to extend into the inner ear or towards the sigmoid sinus or jugular vein. Neoplasms arising from or extending into the middle ear require the use of both techniques as their combined data provide essential information. Most important data for surgical planning concern the destruction of thin bony structures and the relationships of the lesion with the dura and surrounding vessels. DSA and interventional vascular techniques maintain an essential role in the presurgical work-up and embolization of paragangliomas extended into the middle ear.

Immunohistochemical localization of WE-14 in the developing porcine sympathoadrenal cell lineage.

Immunohistochemical investigation of the post-translational processing of chromogranin A (CgA) to generate WE-14 in the sympathoadrenal cell lineage of the developing porcine fetus (F) detected intense CgA and weak WE-14 immunoreactivity in migrating neuroblast cells of the diffuse sympathetic ganglia adjacent to the dorsal aorta and projecting toward the cortical mass at F24-27. F37-42; WE-14 immunoreactivity was detected in chromaffinoblasts at the periphery of the developing cortex and at F54-56 days gestation WE-14 immunoreactivity was detected in a large population of central medullary cells. From F74 to F76 days and thereafter the number of cells exhibiting intense WE-14 immunostaining decreased, and the majority of chromaffin cells exhibited uniform weak WE-14 immunostaining. At postnatal day 1 (P1) intense WE-14 immunoreactivity was primarily confined to clusters of chromaffin cells with weak immunostaining in the general population. The transitory neuroblasts, chromaffinoblasts, and maturing chromaffin cell population exhibited uniform intense CgA immunostaining through gestation and after birth. Additional observations detected intense CgA and WE-14 immunostaining in extrachromaffin tissue at P1 and in neuronal-like cells in vessels of the aortic arch at F37. This study has demonstrated that CgA is post-translationally processed to generate WE-14 during early fetal development in the migrating progenitor cells of the porcine sympathoadrenal lineage.

Long-term control of surgically treated glomus tympanicum tumors.

OBJECTIVE: The glomus tumor is an enigmatic middle ear neoplasm commonly delayed in diagnosis. Frequently grouped with its skull base counterpart, surgery and radiation are often recommended as therapy. The objective of this report is to highlight the diagnosis and surgical treatment of this neoplasm in a large series. Tumor control in the long term is defined. STUDY DESIGN: Retrospective case review. SETTING: Private practice-tertiary referral center. PATIENTS: All patients surgically treated for glomus tympanicum tumors from May 25, 1972 to July 3, 1998 (N = 80). INTERVENTIONS: Surgical excision of glomus tympanicum tumors. MAIN OUTCOME MEASURE: Total tumor control in the long term. RESULTS: Surgical treatment resulted in long-term tumor control for the vast majority of the patients studied. CONCLUSIONS: Surgery provides excellent control of glomus tympanicum tumors. It is safe and well tolerated, with minimal morbidity.