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Histochemistry Sep 1976According to the earlier concept, the paraganglia of man are believed to degenerate during the first postnatal years after their dominance during the fetal period....
According to the earlier concept, the paraganglia of man are believed to degenerate during the first postnatal years after their dominance during the fetal period. Clinical case reports on persisting paraganglia led us to extensive exploration of surgical material obtained from urological and gynecological surgery. The formaldehyde induced fluorescence (FIF) was used for tracing the catecholamine containing tissues. The fluorescence intensities were recorded with a Leitz MPV 2 microspectrophotometer. Solitary, small paraganglia were found in all patients studied. They were especially frequent in the walls of the urinary bladder and in the connective tissue surrounding the urogenital organs. The intensity of the fluorescence was comparable to pharmacological standard of 10(-2) M noradrenaline and at the same level as the FIF of human fetal paraganglia. All cells of the paraganglionic clusters exhibited FIF and no signs of degeneration could be observed. It is suggested that the paraganglia of man do not degenerate postnatally but persist as a remarcable catecholamine reservoir, which might be of physiological importance.
Topics: Adult; Chromaffin System; Humans; Microscopy, Fluorescence; Norepinephrine; Paraganglia, Chromaffin; Urinary Bladder; Urogenital System
PubMed: 1022722
DOI: 10.1007/BF00499247 -
Acta Oto-laryngologica 1989Sections of rat superior and recurrent laryngeal nerves (SLN and RLN) with enclosed paraganglia and ganglionic cells were incubated with antisera against five different...
Sections of rat superior and recurrent laryngeal nerves (SLN and RLN) with enclosed paraganglia and ganglionic cells were incubated with antisera against five different neuropeptides. Vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) and neuropeptide Y (NPY)-LI was detected in a large number of varicose nerve fibres in the paraganglia. A few varicosities of the paraganglia showed substance P (SP)-LI or calcitonin gene-related peptide (CGRP)-LI, whereas there were no signs of enkephalin (ENK)-LI in these varicosities. The paraganglionic cells never exhibited immunoreactivity for any of the peptides tested, whereas some of the associated ganglionic cells showed NPY-LI, VIP-LI or ENK-LI. The study shows that the paraganglia of the SLN and RLN receive a significant peptidergic innervation and suggests that the peptide-containing nerve fibres in these structures originate from cells other than the paraganglionic cells. The findings imply that in further studies defining the function of laryngeal nerve paraganglia in larynx physiology, the role of neuropeptides should be examined.
Topics: Animals; Fluorescent Antibody Technique; Immunohistochemistry; Laryngeal Nerves; Male; Neuropeptides; Paraganglia, Nonchromaffin; Rats; Rats, Inbred Strains
PubMed: 2648751
DOI: 10.3109/00016488909127511 -
Archives of Pathology & Laboratory... Aug 2008Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These... (Review)
Review
CONTEXT
Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These developments are concurrent with the publication and dissemination of the 2004 World Health Organization bluebook on pathology and genetics of endocrine tumors.
OBJECTIVE
To summarize new information required by pathologists for effective participation in patient management and research.
DATA SOURCES
Literature review and primary material from Tufts Medical Center.
CONCLUSIONS
The World Health Organization reserves the term pheochromocytoma for tumors arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often adrenergic phenotype, relatively low rate of malignancy, and predilection to occur in particular hereditary syndromes. Malignancy is defined by presence of metastases not local invasion. Occult germline mutations characteristic of familial syndromes are now found in more than 20% of patients with apparently sporadic tumors, bringing the percentage of tumors with a known genetic basis close to 30%. In addition, tumor location and risk of malignancy vary with the underlying genetic defect. The "10 percent rule" for pheochromocytoma/paraganglioma--10% familial, 10% malignant, 10% extra-adrenal--is therefore no longer tenable. Current roles of pathology are limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy.
Topics: Adrenal Gland Neoplasms; Biomedical Research; Endocrinology; Gene Expression Profiling; Humans; Paraganglioma, Extra-Adrenal; Pheochromocytoma
PubMed: 18684026
DOI: 10.5858/2008-132-1272-PAEPU -
Neuroscience Letters Apr 1985In the cat peripheral dopaminergic organs such as the carotid body, subclavian bodies, aortico-pulmonary glomera and small intensively fluorescent cell (SIF cell)...
In the cat peripheral dopaminergic organs such as the carotid body, subclavian bodies, aortico-pulmonary glomera and small intensively fluorescent cell (SIF cell) clusters of the superior cervical ganglion and the nodose ganglion were found to contain cholecystokinin (CCK)-immunoreactive paraganglionic cells. Thus, the extra-adrenal paraganglionic system may serve as a model for studying peripheral interactions of CCKergic and dopaminergic mechanisms.
Topics: Animals; Aortic Bodies; Carotid Body; Cats; Ganglia, Sympathetic; Immunoenzyme Techniques; Nodose Ganglion; Paraganglia, Nonchromaffin; Sincalide
PubMed: 3889724
DOI: 10.1016/0304-3940(85)90021-7 -
Endocrine-related Cancer Jan 2023Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis.... (Review)
Review
Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets.
Topics: Humans; DNA, Mitochondrial
PubMed: 36219865
DOI: 10.1530/ERC-22-0217 -
Journal of Anatomy Dec 1984The catecholamine-storing cells in the paraganglia of old rats showed structural characteristics common to adrenomedullary and paraganglionic cells of young animals. No...
The catecholamine-storing cells in the paraganglia of old rats showed structural characteristics common to adrenomedullary and paraganglionic cells of young animals. No sign of degeneration was found. Lipofuscin pigment was observed in most cells. The paraganglia were innervated and well supplied by fenestrated sinusoidal capillaries. Their fine structure suggests active endocrine function. An increase in the total bulk of the paraganglia in old rats suggests that they have a physiological role in senescence.
Topics: Aging; Animals; Chromaffin System; Hypertrophy; Male; Microscopy, Electron; Nerve Endings; Paraganglia, Chromaffin; Rats; Rats, Inbred F344
PubMed: 6526715
DOI: No ID Found -
Frontiers in Molecular Neuroscience 2019In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a...
In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest, which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors.
PubMed: 30740044
DOI: 10.3389/fnmol.2019.00006 -
Endocrine Regulations Jan 2018Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues. Accordingly, there is an extreme need for new diagnostic marker(s) to identify tumors with malignant prospective. Th e aim of this study was to review all suggested genetic and epigenetic alterations that are remarkably different between benign and malignant PPGLs. It seems that more than two genetic mutation clusters in PPGLs and other genetic and methylation biomarkers could be targeted for malignancy discrimination in different studies.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Epigenesis, Genetic; Humans; Paraganglioma; Pheochromocytoma
PubMed: 29453919
DOI: 10.2478/enr-2018-0006 -
Abdominal Radiology (New York) Apr 2020Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare, heterogeneous neuroendocrine neoplasms of the autonomous nervous system of chromaffin cell origin that may... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare, heterogeneous neuroendocrine neoplasms of the autonomous nervous system of chromaffin cell origin that may arise within the adrenal medulla (PCCs) or the sympathetic and parasympathetic paraganglia (PGLs). Currently referred to by the umbrella term pheochromocytomas-paragangliomas (PPGLs), these distinct tumors are characterized by specific histopathology as well as biological and clinical profiles. PPGLs may occur as part of hereditary syndromes (40% of cases) or as sporadic tumors. Currently, there are 12 different hereditary syndromes with characteristic genetic abnormalities, at least 15 well-characterized driver genes and distinct tumor metabolic pathways. Based on the Cancer Genome Atlas (TCGA) taxonomic schemata, PPGLs have been classified into three main clusters of specific genetic mutations and tumor pathways with clinical, biochemical, and prognostic implications. Imaging plays a pivotal role in the initial diagnosis, tumor characterization, evaluation of treatment response, and long-term surveillance. While MDCT and MRI help in the anatomic localization, SPECT, and PET using different radiotracers are crucial in the functional assessment of these tumors. Surgery, chemotherapy, and radiotherapy are currently available treatment options for PPGLs; antiangiogenic drugs are also being used in treating metastatic disease. Evolving knowledge regarding the different genetic abnormalities involved in the pathogenesis of PPGLs has identified potential therapeutic targets that may be utilized in the discovery of novel drugs.
Topics: Adrenal Gland Neoplasms; Diagnosis, Differential; Humans; Paraganglioma; Pheochromocytoma; Syndrome
PubMed: 31069476
DOI: 10.1007/s00261-019-02044-w -
Annals of the New York Academy of... Aug 2006Paragangliomas are rare tumors that arise from extra-adrenal paraganglia. The effective diagnosis and management of the paraganglioma patient involves the close... (Review)
Review
Paragangliomas are rare tumors that arise from extra-adrenal paraganglia. The effective diagnosis and management of the paraganglioma patient involves the close collaboration of endocrinologists, endocrine surgeons, anesthesiologists, geneticists, laboratory specialists, radiologists, oncologists, and pathologists. Paragangliomas are diagnosed in the following clinical settings: signs and symptoms related to catecholamine hypersecretion, mass effect symptoms (e.g., with head and neck paragangliomas), incidental finding on imaging, or family screening for hereditary paraganglioma. Paragangliomas that hypersecrete catecholamines may cause signs and symptoms identical to those in patients with hyperfunctioning adrenal pheochromocytoma. When a catecholamine-secreting tumor is suspected in a patient because of paroxysmal symptoms, biochemical documentation of catecholamine and fractionated metanephrine hypersecretion should precede any form of imaging study. Catecholamine-secreting paragangliomas are found where chromaffin tissue is located (e.g., along the para-aortic sympathetic chain, or within the organs of Zuckerkandl at the origin of the inferior mesenteric artery, the wall of the urinary bladder, and the sympathetic chain in the neck or mediastinum). As many as 50% of paragangliomas are hereditary and may be associated with familial paraganglioma, neurofibromatosis Type 1, von Hippel-Lindau disease, the Carney triad, and, rarely, with multiple endocrine neoplasia Type 2. Genetic testing should be considered in all patients with paraganglioma. The treatment of choice for paraganglioma is surgical resection; most tumors are benign and can be excised totally. Following surgical cure, annual biochemical testing assesses for metastatic disease, tumor recurrence or delayed appearance of multiple primary tumors.
Topics: Adult; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Paraganglioma
PubMed: 17102068
DOI: 10.1196/annals.1353.002