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Archives of Pathology & Laboratory... Apr 2021The identification of paraganglia (PG) in the gallbladder (GB) is infrequent, and easily overlooked as it is not something routinely reported. Occasionally they may be...
CONTEXT.—
The identification of paraganglia (PG) in the gallbladder (GB) is infrequent, and easily overlooked as it is not something routinely reported. Occasionally they may be misinterpreted as neoplastic cells, such as low-grade carcinomas, germ cell tumors, or because of their close resemblance to neuroendocrine cells, as low-grade neuroendocrine neoplasms.
OBJECTIVE.—
To evaluate the incidence and histological features of PG of the GB in patients that underwent cholecystectomy, and discuss the potential misinterpretation of these benign structures as clusters of neoplastic cells.
DESIGN.—
A retrospective study of cholecystectomy specimens performed during a 6-month period were reviewed for identification of PG. Immunohistochemical studies for chromogranin, synaptophysin, S100, and cytokeratin AE1/AE3 were performed in selected cases.
RESULTS.—
A total of 365 GBs were reviewed and in 16 cases (4.4%) PG was identified within the subserosal connective tissue of the GB wall or cystic duct adjacent to small capillaries, nerves, and ganglia. They consisted of well-demarcated, lobular structures ranging in size from 0.2 to 0.5 cm, which were predominantly composed of chief cells, with strong expression for chromogranin and synaptophysin and negative CKAE1/AE3, and a minor component of S100-positive sustentacular cells.
CONCLUSIONS.—
PG is an uncommon finding with a prevalence of 4.4% in our study. Awareness of their location, histologic features, and immunohistochemical profile may help practicing pathologists to confirm their benign nature, avoid a misdiagnosis of malignancy, and prevent unnecessary diagnostic work-up and treatment.
Topics: Adult; Aged; Biomarkers; Cholecystectomy; Diagnosis, Differential; Female; Gallbladder; Gallbladder Neoplasms; Humans; Immunohistochemistry; Incidental Findings; Male; Middle Aged; Paraganglia, Chromaffin; Predictive Value of Tests; Retrospective Studies
PubMed: 32886744
DOI: 10.5858/arpa.2020-0041-OA -
The Anatomical Record. Part A,... Sep 2004Vagal and spinal afferent innervation of the portal hepatic area has not been studied as thoroughly as the innervation of other important organs. It is generally agreed... (Comparative Study)
Comparative Study Review
Vagal and spinal afferent innervation of the portal hepatic area has not been studied as thoroughly as the innervation of other important organs. It is generally agreed that unlike noradrenergic sympathetic efferent nerve fibers, sensory nerve fibers of either vagal or dorsal root/spinal origin do not directly innervate hepatocytes, but are restricted to the stroma surrounding triades of hepatic vasculature and bile ducts, and to extrahepatic portions of the portal vein and bile ducts. For vagal afferent innervation, retrograde and anterograde tracing studies in the rat have clearly shown that only a minor portion of the common hepatic branch innervates the liver area, while the major portion descends in the gastroduodenal branch toward duodenum, pancreas, and pylorus. Hepatic paraganglia, bile ducts, and portal vein receive the densest vagal afferent innervation. Calretinin may be a relatively specific marker for vagal afferent innervation of the portal-hepatic space. Calcitonin gene-related peptide (CGRP) is a specific marker for dorsal root afferents, and CGRP-immunoreactive fibers are mainly present near the intrahepatic vascular bundles and bile ducts, and in the same extrahepatic compartments that contain vagal afferents. Because of the specific anatomical organization of hepatic nerves, selective hepatic denervation, whether selective for the vagal or sympathetic division, or for efferents and afferents, is nearly impossible. Great caution is therefore necessary when interpreting functional outcomes of so-called specific hepatic denervation studies.
Topics: Animals; Calbindin 2; Calcitonin Gene-Related Peptide; Eating; Energy Metabolism; Ganglia, Spinal; Humans; Liver; Neurons, Afferent; Portal System; Rats; S100 Calcium Binding Protein G
PubMed: 15382018
DOI: 10.1002/ar.a.20088 -
Frontiers in Endocrinology 2023Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia....
OBJECTIVE
Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. However, there are few bibliometric studies on Pheochromocytoma. Therefore, this study was employed to summarize the global trends and current status in pheochromocytoma by bibliometric analysis.
MATERIALS AND METHODS
The Web of Science (WOS) core collection database was searched for publications relating to pheochromocytoma from 2001 to 2021. Bibliometric analysis was used to examine the data, and Microsoft Excel was utilized to create bar graphs. In addition, VOSviewer was used to carry out co-authorship analysis, co-citation analysis and co-occurrence analysis. CiteSpace was used to analyze the keywords citation bursts.
RESULTS
A total of 8,653 publications published in 1,806 journals by 38,590 authors in 6,117 organizations from 100 countries/regions were included in our study. Among them, USA was the leading countries in terms of total publications and sum of time cited, whereas Eunice Kennedy Shriver Natl Inst Child Hlth & Hum was the leading institutions. The main publications for pheochromocytoma-related articles were . Pacak karel and Eisenhofer Graeme were the main contributing authors. The studies on pheochromocytoma could be grouped into five clusters: Treatment, Mechanism, Etiology, Radiology and Hormones study. Moreover, the radiology study, etiology study and some specific keywords such germlines mutation, mesenchymal stem-cells, autophagy, neuroinflammation, neurotoxicity, and hemodynamic instability, may become the hot spots of future.
CONCLUSION
Although the number of articles on pheochromocytoma has fluctuated slightly over the past 20 years, there has been an overall upward trend. In general, precision medicine research on pheochromocytoma, especially metastatic pheochromocytoma, in terms of diagnosis, treatment, and etiology will be a hot research topic in the future. This study helps to understand the research perspectives, hot spots and trends of pheochromocytoma and provide new insight and a basis for future pheochromocytoma research quickly.
Topics: Child; Humans; Pheochromocytoma; Neuroendocrine Tumors; Adrenal Medulla; Adrenal Gland Neoplasms; Bibliometrics; Dermatitis
PubMed: 37680890
DOI: 10.3389/fendo.2023.1167796 -
Indian Journal of Endocrinology and... 2015Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL...
BACKGROUND
Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL secrete either catecholamine or their metabolites, metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and metanephrine (MN) for the diagnosis of PHEO/PGL.
MATERIALS AND METHODS
Sixty-five patients referred to endocrine/ENT clinics were enrolled. Twelve patients with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients (39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14 patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age- and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN were measured using high-performance liquid chromatography. Receivers operating characteristics was plotted and cut-off levels were established.
RESULTS
When compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in 3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL, there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-, 6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in combination with MN was high in 97% of the patients with PHEO/PGL. All three metabolites in combination were high in 83% of patients with HNPGL. In malignant PHEO/PGL, 50% subjects had increased levels of both NM and 3MT.
CONCLUSIONS
Measurement of plasma-free NM along with 3MT and MN provides a better tool for the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT can be used for the diagnosis of malignant PHEO/PGL.
PubMed: 26425473
DOI: 10.4103/2230-8210.163183 -
Medicina (Kaunas, Lithuania) Oct 2023Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that... (Review)
Review
Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. Most of the parasympathetic ganglia-derived paragangliomas are nonfunctional, and symptoms result from mass effect. Conversely, the sympathetic paragangliomas are functional and produce catecholamine. Although such patients could have symptoms similar to pheochromocytoma, mass effect symptoms, or non-specific symptoms, being benign tumors, they can also present with anemia, specifically iron-deficiency anemia. Considering that neoplastic pathology is chronically accompanied by moderate, normochromic, normocytic anemia, association between paragangliomas that are mostly benign but with a potential degree of malignancy and anemia is not as frequent as expected, with only 12 cases reported in the literature. We report a case of a 54-year-old female patient diagnosed with a paraganglioma of the carotid glomus accompanied by severe normochromic, normocytic anemia, which reached normal limits after excision of the paraganglioma.
Topics: Female; Humans; Middle Aged; Paraganglioma; Pheochromocytoma; Catecholamines; Adrenal Gland Neoplasms; Anemia
PubMed: 38003974
DOI: 10.3390/medicina59111925 -
Frontiers in Physiology 2014Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play... (Review)
Review
Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.
PubMed: 25566088
DOI: 10.3389/fphys.2014.00489 -
Cancers Oct 2019Pheochromocytomas and paragangliomas (PCC/PGLs) are rare, mostly catecholamine-producing neuroendocrine tumors of the adrenal gland (PCCs) or the extra-adrenal... (Review)
Review
Pheochromocytomas and paragangliomas (PCC/PGLs) are rare, mostly catecholamine-producing neuroendocrine tumors of the adrenal gland (PCCs) or the extra-adrenal paraganglia (PGL). They can be separated into three different molecular clusters depending on their underlying gene mutations in any of the at least 20 known susceptibility genes: The pseudohypoxia-associated cluster 1, the kinase signaling-associated cluster 2, and the Wnt signaling-associated cluster 3. In addition to tumor size, location (adrenal vs. extra-adrenal), multiplicity, age of first diagnosis, and presence of metastatic disease (including tumor burden), other decisive factors for best clinical management of PCC/PGL include the underlying germline mutation. The above factors can impact the choice of different biomarkers and imaging modalities for PCC/PGL diagnosis, as well as screening for other neoplasms, staging, follow-up, and therapy options. This review provides a guide for practicing clinicians summarizing current management of PCC/PGL according to tumor size, location, age of first diagnosis, presence of metastases, and especially underlying mutations in the era of precision medicine.
PubMed: 31597347
DOI: 10.3390/cancers11101505 -
Journal of Surgical Case Reports Apr 2018Paragangliomas and pheochromocytomas are rare catecholamine secreting neoplasms that arise in the extra-adrenal autonomic paraganglia and adrenal medulla, respectively....
Paragangliomas and pheochromocytomas are rare catecholamine secreting neoplasms that arise in the extra-adrenal autonomic paraganglia and adrenal medulla, respectively. Although typically presenting with paroxysms of headaches, palpitations, diaphoresis and hypertension, a broad spectrum of clinical manifestations may occur. Diagnosis relies on biochemical studies followed by adequate imaging investigation. Cross sectional morphological and functional imaging modalities have improved diagnostic accuracy and are crucial in the surgical planning. The authors report on a case of a 64-year-old female that presented with severe hypertension, palpitations and fatigue as the manifestations of a catecholamine secreting neoplasm. Abdominal contrast enhanced computer tomography revealed a right sided 78 mm adrenal medullary tumor suggestive of a pheochromocytoma. Standard therapeutical strategies were initially unsuccessful, and additional investigation and therapy were required to cure the patient. The challenges faced by the multidisciplinary team in the pre-operative evaluation, medical management and surgical treatment are reported.
PubMed: 29644041
DOI: 10.1093/jscr/rjy060 -
Genes Jun 2022Despite two decades of paraganglioma-pheochromocytoma research, the fundamental question of how the different succinate dehydrogenase (SDH)-related tumor phenotypes are... (Review)
Review
Despite two decades of paraganglioma-pheochromocytoma research, the fundamental question of how the different succinate dehydrogenase (SDH)-related tumor phenotypes are initiated has remained unanswered. Here, we discuss two possible scenarios by which missense (hypomorphic alleles) or truncating (null alleles) SDH gene variants determine clinical phenotype. Dysfunctional SDH is a major source of reactive oxygen species (ROS) but ROS are inhibited by rising succinate levels. In scenario 1, we propose that SDH missense variants disrupt electron flow, causing elevated ROS levels that are toxic in sympathetic PPGL precursor cells but well controlled in oxygen-sensing parasympathetic paraganglion cells. We also suggest that SDHAF2 variants, solely associated with HNPGL, may cause the reversal of succinate dehydrogenase to fumarate reductase, producing very high ROS levels. In scenario 2, we propose a modified succinate threshold model of tumor initiation. Truncating SDH variants cause high succinate accumulation and likely initiate tumorigenesis via disruption of 2-oxoglutarate-dependent enzymes in both PPGL and HNPGL precursor tissues. We propose that missense variants (including SDHAF2) cause lower succinate accumulation and thus initiate tumorigenesis only in very metabolically active tissues such as parasympathetic paraganglia, which naturally show very high levels of succinate.
Topics: Adrenal Gland Neoplasms; Cell Transformation, Neoplastic; Humans; Phenotype; Pheochromocytoma; Reactive Oxygen Species; Succinate Dehydrogenase; Succinates; Transcription Factors
PubMed: 35741787
DOI: 10.3390/genes13061025 -
Virchows Archiv : An International... Feb 2024Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular... (Review)
Review
Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia. All endocrine gland tumors enjoy a robust correlation between genotype and phenotype. High-throughput molecular analysis demonstrates that endocrine gland tumors can be grouped into molecular groups that are relevant from both pathologic and clinical point of views. In this review, genetic alterations have been discussed and tabulated with respect to their molecular pathogenetic role and clinicopathologic implications, addressing the use of molecular biomarkers for the purpose of diagnosis and prognosis and predicting response to molecular therapy. Hereditary conditions that play a key role in determining predisposition to many types of endocrine tumors are also discussed.
Topics: Humans; Pathology, Molecular; Endocrine Gland Neoplasms; Mutation; Thyroid Gland; Adrenal Gland Neoplasms
PubMed: 38108848
DOI: 10.1007/s00428-023-03713-4