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Endocrine Reviews Mar 2022Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters based on underlying genetic alterations. With... (Review)
Review
Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters based on underlying genetic alterations. With around 30% to 35% of Caucasian patients (a lower percentage in the Chinese population) showing germline mutations in susceptibility genes, pheochromocytomas/paragangliomas have the highest rate of heritability among all tumors. A further 35% to 40% of Caucasian patients (a higher percentage in the Chinese population) are affected by somatic driver mutations. Thus, around 70% of all patients with pheochromocytoma/paraganglioma can be assigned to 1 of 3 main molecular clusters with different phenotypes and clinical behavior. Krebs cycle/VHL/EPAS1-related cluster 1 tumors tend to a noradrenergic biochemical phenotype and require very close follow-up due to the risk of metastasis and recurrence. In contrast, kinase signaling-related cluster 2 tumors are characterized by an adrenergic phenotype and episodic symptoms, with generally a less aggressive course. The clinical correlates of patients with Wnt signaling-related cluster 3 tumors are currently poorly described, but aggressive behavior seems likely. In this review, we explore and explain why cluster-specific (personalized) management of pheochromocytoma/paraganglioma is essential to ascertain clinical behavior and prognosis, guide individual diagnostic procedures (biochemical interpretation, choice of the most sensitive imaging modalities), and provide personalized management and follow-up. Although cluster-specific therapy of inoperable/metastatic disease has not yet entered routine clinical practice, we suggest that informed personalized genetic-driven treatment should be implemented as a logical next step. This review amalgamates published guidelines and expert views within each cluster for a coherent individualized patient management plan.
Topics: Adrenal Gland Neoplasms; Germ-Line Mutation; Humans; Mutation; Paraganglioma; Pheochromocytoma
PubMed: 34147030
DOI: 10.1210/endrev/bnab019 -
Endocrine Practice : Official Journal... Feb 2023To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas. (Review)
Review
OBJECTIVE
To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas.
METHODS
A literature review of english language papers with focus on most current literature.
RESULTS
Paragangliomas (PGLs) are a group of neuroendocrine tumors that arise in the parasympathetic or sympathetic ganglia. Head and neck PGLs (HNPGLs) comprise 65% to 70% of all PGLs and account for 0.6% of all head and neck cancers. The majority of HNPGLs are benign, and 6% to 19% of all HNPGLs develop metastasis outside the tumor site and significantly compromise survival. PGLs can have a familial etiology with germline sequence variations in different susceptibility genes, with the gene encoding succinate dehydrogenase being the most common sequence variation, or they can arise from somatic sequence variations or fusion genes. Workup includes biochemical testing to rule out secretory components, although it is rare in HNPGLs. In addition, imaging modalities, such as computed tomography and magnetic resonance imaging, help in monitoring in surgical planning. Functional imaging with DOTATATE-positron emission tomography, 18F-fluorodeoxyglucose, or 18F-fluorohydroxyphenylalanine may be necessary to rule out sites of metastases. The management of HNPGLs is complex depending on pathology, location, and aggressiveness of the tumor. Treatment ranges from observation to resection to systemic treatment. Similarly, the prognosis ranges from a normal life expectancy to a 5-year survival of 11.8% in patients with distant metastasis.
CONCLUSION
Our review is a comprehensive summary of the incidence, mortality, pathogenesis, presentation, workup and management of HNPGLs.
Topics: Humans; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Paraganglioma; Paraganglioma, Extra-Adrenal; Succinate Dehydrogenase; Tomography, X-Ray Computed
PubMed: 36252779
DOI: 10.1016/j.eprac.2022.10.002 -
International Braz J Urol : Official... 2023Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other... (Review)
Review
Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37115176
DOI: 10.1590/S1677-5538.IBJU.2023.0038 -
Pediatric Nephrology (Berlin, Germany) Apr 2020Pheochromocytomas and paragangliomas (PPGLs) generally grouped together are rare catecholamine-secreting endocrine tumors. Symptoms of catecholamine excess are... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) generally grouped together are rare catecholamine-secreting endocrine tumors. Symptoms of catecholamine excess are non-specific and therefore a high index of suspicion in children with sustained hypertension, family history of endocrine tumors, or features of syndromes associated with PPGLs leads to a timely diagnosis and treatment. Free metanephrines in the plasma or 24-h urine are the preferred tests to establish catecholamine excess. Considerations for false-positive conditions improve diagnostic yield and accuracy. Functional imaging, targeting either specific cell membrane transporters or vesicular catecholamine transport systems, is indicated for incidental lesions suspicious for PPGLs with inconclusive biochemical testing, assessment of regional extension or multifocality, and exclusion of metastases. Surgery is the mainstay of treatment for PPGLs. Preoperatively, sequential use of alpha adrenergic receptor blockade and volume expansion followed by beta blockade is mandatory to reduce intraoperative intravascular instability and blood pressure fluctuation due to tumor manipulation. Since genetic mutations have been reported in tumor susceptibility genes in nearly 50% of patients with PPGLs, genetic counselling and testing should be considered in all patients with a confirmed tumor.
Topics: Adolescent; Adrenal Gland Neoplasms; Catecholamines; Child; Female; Genetic Testing; Germ-Line Mutation; Humans; Male; Paraganglioma; Pheochromocytoma
PubMed: 30603807
DOI: 10.1007/s00467-018-4181-2 -
Advances in Experimental Medicine and... 2017Phaeochromocytomas and paragangliomas are relatively uncommon tumours which may be manifest in many ways, specifically as sustained or paroxysmal hypertension, episodes... (Review)
Review
Phaeochromocytomas and paragangliomas are relatively uncommon tumours which may be manifest in many ways, specifically as sustained or paroxysmal hypertension, episodes of palpitations, sweating, headache and anxiety, or increasingly as an incidental finding. Recent studies have shown that an increasing number are due to germline mutations. This review concentrates on the diagnosis, biochemistry and treatment of these fascinating tumours.
Topics: Adrenal Gland Neoplasms; Blood Pressure; Catecholamines; Genetic Predisposition to Disease; Humans; Hypertension; Paraganglioma; Phenotype; Pheochromocytoma; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 27888488
DOI: 10.1007/5584_2016_76 -
Journal of Cardiac Surgery Feb 2015Cardiac paragangliomas are rare tumors arising from chromaffin cells. Two patients with cardiac paragangliomas underwent surgical resection with no evidence of... (Review)
Review
Cardiac paragangliomas are rare tumors arising from chromaffin cells. Two patients with cardiac paragangliomas underwent surgical resection with no evidence of recurrence three and 13 years following surgery. This report describes these two patients with cardiac paragangliomas and discusses their management.
Topics: Adult; Biomarkers, Tumor; Cardiac Surgical Procedures; Chromaffin Cells; Follow-Up Studies; Heart Neoplasms; Humans; Magnetic Resonance Imaging; Male; Paraganglioma; Sternotomy; Thoracotomy; Tomography, X-Ray Computed
PubMed: 25533017
DOI: 10.1111/jocs.12479 -
World Journal of Surgery May 2008Paraganglioma are rare chromaffin cell tumors that develop from the neural crest cells. Parasympathetic ganglia-derived tumors are found almost exclusively in the neck... (Review)
Review
Paraganglioma are rare chromaffin cell tumors that develop from the neural crest cells. Parasympathetic ganglia-derived tumors are found almost exclusively in the neck and skull base and typically do not secrete catecholamines. In contrast, most sympathetic ganglia-derived tumors are found in the abdomen and produce an excess of catecholamines. Those grow within the adrenal medulla and are known as pheochromocytoma. Other sympathetic paragangliomas are also known as extra-adrenal pheochromocytomas. They arise outside of the adrenal gland and can be found anywhere along the sympathetic chain from the base of the skull and neck (5% of cases) to the bladder and prostate gland (10%). We use the term paraganglioma to refer to extra-adrenal tumors and pheochromocytoma to refer to intra-adrenal tumors. The majority of sympathetic paragangliomas are familial, commonly associated with the SDHB and SDHD gene mutations. Many are malignant. Medical management of catecholamine-secreting paraganglioma is the same as for pheochromocytoma. Favorably located abdominal paragangliomas can be safely resected laparoscopically, but the operation is technically more challenging than that for adrenalectomy.
Topics: Adrenal Gland Neoplasms; Head and Neck Neoplasms; Humans; Paraganglioma
PubMed: 18224469
DOI: 10.1007/s00268-007-9360-4 -
Endocrine-related Cancer Jul 2020Metastatic pheochromocytomas and paragangliomas are rare, highly vascular tumors that spread primarily to the lymph nodes, skeletal tissue, lungs, and liver. Tumor... (Review)
Review
Metastatic pheochromocytomas and paragangliomas are rare, highly vascular tumors that spread primarily to the lymph nodes, skeletal tissue, lungs, and liver. Tumor morbidity is related to their size, location, hormonal activity, vascular nature, and rate of progression. Systemic therapies for this indication are limited. Only high-specific-activity iodine-131 metaiodobenzylguanidine is approved in the Unites States for treatment of these patients, and not all patients are candidates for this radiopharmaceutical. Antiangiogenic medications are currently being evaluated in prospective clinical trials for patients with metastatic pheochromocytomas and paragangliomas, and preliminary results have been encouraging. Antiangiogenic medications frequently offer antineoplastic effects with sometimes durable responses. However, cardiovascular toxicity and the development of tumor resistance may limit their efficacy. Experience derived from clinical trials is being used to identify mechanisms to effectively improve drug toxicity and possibly prevent the emergence of resistance. Therefore, antiangiogenic medications represent a therapeutic option for patients with metastatic pheochromocytomas and paragangliomas. Furthermore, in the world of oncology, there is strong scientific interest in the development of clinical trials that combine antiangiogenic medications with other modalities such as immunotherapy, radiopharmaceuticals, and hypoxia inhibitors since these combinations may substantially enhance clinical outcomes, including survivorship. In this review, we examine the progress made to date on antiangiogenic treatments for patients with metastatic pheochromocytomas and paragangliomas.
Topics: Adrenal Gland Neoplasms; Angiogenesis Inhibitors; Humans; Paraganglioma; Pheochromocytoma
PubMed: 32369773
DOI: 10.1530/ERC-20-0043 -
Expert Review of Endocrinology &... Sep 2019: Pheochromocytomas/paragangliomas (PPG) are rare tumors. In theory the diagnosis of PPG should be straightforward. In clinical practice, however, considerable delays... (Review)
Review
: Pheochromocytomas/paragangliomas (PPG) are rare tumors. In theory the diagnosis of PPG should be straightforward. In clinical practice, however, considerable delays are noted in establishing such a diagnosis. : We assess the characteristics of various approaches to diagnosis and localization of PPG lesions (and their relevant caveats). We also evaluate potential biases to diagnosis. : A high degree of suspicion - particularly in younger patients - is required by clinicians. The availability of diagnostic means (mainly of biochemical tools) to establish the diagnosis of PPG should be increased.
Topics: Adrenal Gland Neoplasms; Biomarkers; Delayed Diagnosis; Diagnostic Imaging; Humans; Paraganglioma; Pheochromocytoma
PubMed: 31429343
DOI: 10.1080/17446651.2019.1657007 -
The Journal of the Louisiana State... 2012Paragangliomas are tumors of the sympathetic and parasympathetic paraganglia. While most paraganglioma are of parasympathetic origin and present as benign palpable... (Review)
Review
Paragangliomas are tumors of the sympathetic and parasympathetic paraganglia. While most paraganglioma are of parasympathetic origin and present as benign palpable masses of the neck, sympathetic paraganglioma are often secretory, presenting with symptoms related to excess catecholamines. Such symptoms include hypertension, headache, palpitations, and diaphoresis. Most sympathetic paraganglioma form within the adrenal medulla, the largest sympathetic paraganglia, and are commonly known as pheochromocytomas. However, sympathetic paragangliomas may present extra-adrenally, carrying a significantly higher risk of malignancy. In this manuscript, we examine a case of a young man with an extra-adrenal sympathetic paraganglioma of the Organ of Zuckerkandl. Furthermore, we discuss appropriate diagnostic workup and treatment of pheochromocytomas and sympathetic paragangliomas.
Topics: Aorta, Abdominal; Catecholamines; Dissection; Humans; Male; Monitoring, Physiologic; Para-Aortic Bodies; Paraganglioma; Preoperative Care; Prognosis; Radiography; Treatment Outcome; Young Adult
PubMed: 22533110
DOI: No ID Found