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Modern Pathology : An Official Journal... Apr 2011Distinguishing adrenal cortical adenomas from carcinomas may be a difficult diagnostic problem. The criteria of Weiss are very useful because of their reliance on...
Distinguishing adrenal cortical adenomas from carcinomas may be a difficult diagnostic problem. The criteria of Weiss are very useful because of their reliance on histologic features. From a practical perspective, the most useful criteria to separate adenomas from carcinomas include tumor size, presence of necrosis and mitotic activity including atypical mitoses. Adrenal cortical neoplasms in pediatric patients are more difficult to diagnose and to separate adenomas from carcinomas. The diagnosis of pediatric adrenal cortical carcinoma requires a higher tumor weight, larger tumor size and more mitoses compared with carcinomas in adults. Pheochromocytomas are chromaffin-derived tumors that develop in the adrenal gland. Paragangliomas are tumors arising from paraganglia that are distributed along the parasympathetic nerves and sympathetic chain. Positive staining for chromogranin and synaptophysin is present in the chief cells, whereas the sustentacular cells are positive for S100 protein. Hereditary conditions associated with pheochromocytomas include multiple endocrine neoplasia 2A and 2B, Von Hippel-Lindau disease and neurofibromatosis I. Hereditary paraganglioma syndromes with mutations of SDHB, SDHC and SDHD are associated with paragangliomas and some pheochromocytomas.
Topics: Adrenal Gland Neoplasms; Adrenocortical Adenoma; Adrenocortical Carcinoma; Biomarkers, Tumor; Child; Diagnosis, Differential; Humans; Multiple Endocrine Neoplasia; Mutation; Necrosis; Neurofibromatosis 1; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Succinate Dehydrogenase; von Hippel-Lindau Disease
PubMed: 21455202
DOI: 10.1038/modpathol.2010.126 -
Iranian Journal of Otorhinolaryngology Nov 2022Generally, glomus tumors are considered tumors of the autonomic system arising from chromaffin cells of the parasympathetic paraganglia of the skull base and neck....
INTRODUCTION
Generally, glomus tumors are considered tumors of the autonomic system arising from chromaffin cells of the parasympathetic paraganglia of the skull base and neck. Glomus tympanicum is the most common primary tumor of the middle ear cavity and it arises from the paraganglia of the middle ear.
CASE REPORT
We present a case of glomus tympanicum presented in a 70-year-old woman, complicated with facial nerve palsy which at first sight was misdiagnosed as cholesteatoma. Patient presented in our clinic because of otorrhea, pulsatile tinnitus and hearing loss in the right ear. However, facial nerve function was good in the first examination (40 days before the surgery). Eventually, she treated successfully with a canal wall down mastoidectomy. Technique had been chosen because of the mass size and the involvement of external auditory canal, after a discussion with the patient.
CONCLUSIONS
Although histologically benign, glomus tympanicum is slow growing and destructs adjacent tissues potentially. The two most common complaints are hearing loss (conductive) and pulsatile tinnitus. These neoplasms are more common in women and they can be diagnosed by CT or MRI scan. It is of high importance physicians suspect a glomus tumor when patient 's clinical findings are hearing loss and pulsatile tinnitus and use an intravascular agent in imaging so that the differential diagnosis will be supported.
PubMed: 36474487
DOI: 10.22038/IJORL.2022.64737.3217 -
JCEM Case Reports Nov 2023Pheochromocytomas are intra-adrenal sympathetic neuroendocrine tumors that arise from chromaffin cells. Paragangliomas similarly arise from chromaffin cells, although at...
Pheochromocytomas are intra-adrenal sympathetic neuroendocrine tumors that arise from chromaffin cells. Paragangliomas similarly arise from chromaffin cells, although at extra-adrenal sites such as sympathetic paraganglia in the abdomen/thorax, or parasympathetic paraganglia in the head/neck. Collectively, pheochromocytomas and paragangliomas are important to diagnose and resect because they may secrete harmful levels of catecholamines, have mass effects, hemorrhage, and/or metastasize. Anatomic imaging of pheochromocytomas is usually completed with computed tomography or magnetic resonance imaging; however, functional imaging may be used to provide additional localization, staging, and/or biologic information. Accordingly, selection of the proper functional imaging modality can be critical to developing the optimal therapeutic strategy. Gallium- and Copper-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate positron emission tomography computed tomography (Ga- and Cu-DOTATATE) are widely used in evaluating pheochromocytomas and paragangliomas, although data regarding the sensitivity for diagnosing pheochromocytoma are limited. We report 2 cases of pheochromocytoma that showed nondiagnostic Ga-DOTATATE uptake but were subsequently visualized using alternative functional imaging modalities. Additionally, we provide a review of the literature to highlight the underappreciated limitations of functional adrenal imaging with somatostatin-based compounds.
PubMed: 38045868
DOI: 10.1210/jcemcr/luad149 -
Acta Otorrinolaringologica Espanola Feb 2009Paragangliomas are tumors that arise in the extraadrenal paraganglia and result from migration of neural crest cells during embryonic development. Based on their...
Paragangliomas are tumors that arise in the extraadrenal paraganglia and result from migration of neural crest cells during embryonic development. Based on their anatomical distribution, innervation and microscopic structure, these tumors can be classified into interrelated families: branchiomeric paraganglia (related to the branchial clefts and arches), intravagal, aortic-sympathetic and visceral-autonomic. Head and neck paragangliomas belong mainly to the first two of these families. The present article is divided into two parts. The first part reviews the embryological origin of these tumors. Special emphasis is placed on the process of neurulation or neural tube formation, neurosegmentation (with a summary of the mechanisms involved in the initial segmentation of the neural tube and of the hindbrain and spinal medulla), and the development of the sensory placodes and secondary inductions in the cranial region. Subsequently, the neural crest is analyzed, with special attention paid to the cranial neural crest. The embryonogenesis of paragangliomas is also described. The second part describes the topographical distribution of head and neck paragangliomas according to their localization: jugulotympanic, orbit, intercarotid, subclavian and laryngeal. The embryonogenesis and most important anatomical characteristics are described for each type.
Topics: Head and Neck Neoplasms; Humans; Paraganglioma
PubMed: 19245770
DOI: No ID Found -
Life (Basel, Switzerland) Dec 2022Diabetes mellitus (DM) is a metabolic disorder whose prevalence has continuously increased worldwide and is associated with dysfunction of the autonomic nervous system...
Diabetes mellitus (DM) is a metabolic disorder whose prevalence has continuously increased worldwide and is associated with dysfunction of the autonomic nervous system and, in particular, that of the sympathetic nervous system (SNS). The objective of this study was to analyze the interaction of DM and the SNS, building a model of sympathectomized diabetic rats to determine alterations in the content of CA (catecholamines) in different intra-abdominal organs. Sympathectomy was conducted with guanethidine (GNT). Additionally, DM was induced with STZ (Streptozotocin). Treatment with GNT decreased norepinephrine (NE) content in all analyzed tissues, with significant differences found in the paraganglia, liver, pancreas, duodenum, and heart compared to the control group. With respect to epinephrine (E), which was only found in the liver, pancreas, and heart, presenting significant differences (p < 0.05) in the heart, a decrease in its concentration was observed for all of the experimental groups with respect to the control. The decrease in dopamine (DA) content due to the GNT−STZ treatment was 30.1% in the heart with respect to the diabetic (STZ) group. The amount of CA in the adrenal medulla indicates the effect of sympathectomy on the GNT group where there was a significant reduction (p < 0.05) of DA. These findings suggest that the elimination of the sympathetic nervous system in diabetic organisms contributed to a decrease in blood glucose; likewise, an alteration in the levels of CA was observed in the different selected organs, possibly attributed to the severity, duration, and pathogenesis of the complications of acute and chronic DM.
PubMed: 36556512
DOI: 10.3390/life12122147 -
Acta Neuropathologica May 2018Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas,...
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles' heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.
Topics: Animals; Antineoplastic Agents; Cell Line; Head and Neck Neoplasms; Humans; Imatinib Mesylate; Mice, Inbred NOD; Mice, SCID; MicroRNAs; Neural Stem Cells; Organogenesis; Paraganglioma; Primary Cell Culture; Tumor Microenvironment; Xenograft Model Antitumor Assays
PubMed: 29305721
DOI: 10.1007/s00401-017-1799-2 -
Current Oncology (Toronto, Ont.) Feb 2014Pheochromocytomas (pheos) and paragangliomas (pgls) are rare tumours of the autonomic nervous system, originating from paraganglia, which are dispersed neuroendocrine...
Pheochromocytomas (pheos) and paragangliomas (pgls) are rare tumours of the autonomic nervous system, originating from paraganglia, which are dispersed neuroendocrine organs characterized by catecholamine and peptide-producing cells derived from the neural crest. Medical textbooks have traditionally suggested that 10% of pheos are heritable. However, the frequency of heritable pheo has been underestimated. Three syndromic conditions-Von Hippel-Lindau (vhl), multiple endocrine neoplasia type 2 (men2), and neurofibromatosis type 1 (nf1)-and three genes-subunits of the succinate dehydrogenase (SDH) complex: SDHB, SDHC, and SDHD-are established causes of hereditary pheo-pgl. In the last few years, four new genes (SDHA, SDHAF2, MAX, and TMEM127) have been found to be associated with predisposition to these tumours. The present review, illustrated by three case reports, gives an update of the genetic basis of pheo-pgl and of the parent-of-origin effect implicated in the transmission of SDHD and SDHAF2. We discuss the referral criteria that should guide the decision to offer genetic testing to affected patients. We also specify the genes that are most likely implicated-based on particular features such as malignancy, bilateralism, or childhood-onset-to help geneticists efficiently order appropriate genetic tests. Finally, we review the screening recommendations for carriers of a pheo-pgl predisposition mutation.
PubMed: 24523625
DOI: 10.3747/co.21.1579 -
World Journal of Surgical Oncology Feb 2012Paragangliomas represent only 10% of chromaffin tissue tumors and those arising from the mesentery seem to be a rare occurrence. We report a case of a 55 year old man in... (Review)
Review
Paragangliomas represent only 10% of chromaffin tissue tumors and those arising from the mesentery seem to be a rare occurrence. We report a case of a 55 year old man in whom an abdominal mass was discovered fortuitously by ultrasonography during a routine health exam. He presented occasional heart palpitations and diaphoresis as well as a well-demarcated mass upon abdominal physical examination. CT scan revealed a solid polylobulated mass in the right lower quadrant. Exploration laparotomy revealed a voluminous multi-nodular tumoral mass, which contained hemorrhagic spots. Histopathological studies confirmed the presence of a paraganglioma. The excision of the mass as well as the surrounding intestine and mesentery also revealed two lymphatic metastases, the first among 14 documented cases to be described concerning mesenteric paragangliomas. One year follow up and CT scan revealed neither recurrence nor the presence of distant metastases.
Topics: Autonomic Nervous System; Humans; Laparotomy; Lymphatic Metastasis; Male; Mesentery; Middle Aged; Neural Crest; Paraganglia, Chromaffin; Paraganglioma
PubMed: 22360863
DOI: 10.1186/1477-7819-10-46 -
Endocrine Regulations Apr 2011The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla - an intra-adrenal paraganglioma....
The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla - an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called "attacks" or "spells". Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto-oncogene activation, tumor suppressor gene inactivation, DNA damage, and genomic instability. Since the mitochondria serves as the main source of prooxidants, any mitochondrial impairment leads to severe oxidative stress, a major outcome of which is tumor development. In terms of cancer pathogenesis, pheochromocytomas and paragangliomas represent tumors where the oxidative phosphorylation defect due to the mutation of succinate dehydrogenase is the cause, not a consequence, of tumor development. Any succinate dehydrogenase pathogenic mutation results in the shift from oxidative phosphorylation to aerobic glycolysis in the cytoplasm (also called anaerobic glycolysis if hypoxia is the main cause of such a shift). This phenomenon, also called the Warburg effect, is well demonstrated by a positive [18F]-fluorodeoxyglycose positron emission tomography scan. Microarray studies, genome-wide association studies, proteomics and protein arrays, metabolomics, transcriptomics, and bioinformatics approaches will remain powerful tools to further uncover the pathogenesis of these tumors and their unique markers, with the ultimate goal to introduce new therapeutic options for those with metastatic or malignant pheochromocytoma and paraganglioma. Soon oxidative stress will be tightly linked to a multistep cancer process in which the mutation of various genes (perhaps in a logistic way) ultimately results in uncontrolled growth, proliferation, and metastatic potential of practically any cell. Targeting the mTORC, IGF-1, HIF and other pathways, topoisomerases, protein degradation by proteosomes, balancing the activity of protein kinases and phosphatases or even synchronizing the cell cycle before any exposure to any kind of therapy will soon become a reality. Facing such a reality today will favor our chances to "beat" this disease tomorrow.
Topics: Adenosine Triphosphate; Adrenal Gland Neoplasms; Catecholamines; Humans; Metanephrine; Multiple Endocrine Neoplasia Type 2a; Mutation; Neurofibromatosis 1; Normetanephrine; Oxidative Stress; Paraganglioma; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Proto-Oncogene Mas; Receptors, Adrenergic; Succinate Dehydrogenase; von Hippel-Lindau Disease
PubMed: 21615192
DOI: 10.4149/endo_2011_02_65 -
Journal of Medical Case Reports Dec 2019Paragangliomas and pheochromocytomas are sympathetic or parasympathetic tumors derived from the paraganglia and the adrenal medulla, respectively. Paragangliomas and...
BACKGROUND
Paragangliomas and pheochromocytomas are sympathetic or parasympathetic tumors derived from the paraganglia and the adrenal medulla, respectively. Paragangliomas and pheochromocytomas can be sporadic or familial, the latter frequently being multifocal and possibly due to succinate dehydrogenase complex genes mutations. In addition, 12% of sporadic paragangliomas are related to covered succinate dehydrogenase complex mutations. The importance of identifying succinate dehydrogenase complex mutations is related to the risk for these patients of developing multiple tumors, including non-endocrine ones, showing an aggressive clinical presentation.
CASE PRESENTATION
We report the case of a 45-year-old Caucasian man with an indolent mass in his neck. Ultrasound of his neck, magnetic resonance imaging, and 1,4,7,10-tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid(D)-Phe(1)-thy(3)-octreotide (Ga-DOTATOC) positron emission tomography-computed tomography and endocrine work-up were consistent with a carotid body paraganglioma with concomitant nodal enlargement in several body regions, which turned out to be a follicular lymphoma at histology. He was found to carry a germline Succinate dehydrogenase subunit B gene (SDHB) mutation.
CONCLUSION
It is crucial to look for a second malignancy in the case of a paraganglioma demonstrating succinate dehydrogenase complex germline mutations.
Topics: Adrenal Gland Neoplasms; Germ-Line Mutation; Head and Neck Neoplasms; Humans; Lymphoma, Follicular; Magnetic Resonance Imaging; Male; Middle Aged; Paraganglioma; Succinate Dehydrogenase; Treatment Outcome; Ultrasonography
PubMed: 31856921
DOI: 10.1186/s13256-019-2323-1