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The Journal of Clinical Endocrinology... Apr 2021Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas... (Review)
Review
CONTEXT
Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behavior.
EVIDENCE ACQUISITION
Extensive searches in the PubMed database with various combinations of the key words pheochromocytoma, paraganglioma, metastatic, malignant, diagnosis, pathology, genetic, and treatment were the basis for the present review.
DATA SYNTHESIS
To pinpoint metastatic potential in PPGLs is difficult, but nevertheless crucial for the individual patient to receive tailor-made follow-up and adjuvant treatment following primary surgery. A combination of histological workup and molecular predictive markers can possibly aid the clinicians in this aspect. Most patients with PPGLs have localized disease and may be cured by surgery. Plasma metanephrines are the main biochemical tests. Genetic testing is important, both for counseling and prognostic estimation. Apart from computed tomography and magnetic resonance imaging, molecular imaging using 68Ga-DOTATOC/DOTATATE should be performed. 123I-MIBG scintigraphy may be performed to determine whether 131I-MIBG therapy is a possible option. As first-line treatment in patients with metastatic disease, 177Lu-DOTATATE or 131I-MIBG is recommended, depending on which shows best expression. In patients with very low proliferative activity, watch-and-wait or primary treatment with long-acting somatostatin analogues may be considered. As second-line treatment, or first-line in patients with high proliferative rate, chemotherapy with temozolomide or cyclophosphamide + vincristine + dacarbazine is the therapy of choice. Other therapies, including sunitinib, cabozantinib, everolimus, and PD-1/PDL-1 inhibitors, have shown modest effect.
CONCLUSIONS
Metastatic PPGLs need individualized management and should always be discussed in specialized and interdisciplinary tumor boards. Further studies and newer treatment modalities are urgently needed.
Topics: Abdominal Neoplasms; Adrenal Gland Neoplasms; Animals; Humans; Paraganglioma; Pheochromocytoma
PubMed: 33462603
DOI: 10.1210/clinem/dgaa982 -
Journal of Oral Pathology & Medicine :... Nov 2022Paragangliomas are rare neuroendocrine tumors that can be found from the skull base to the pelvis. Head and neck paragangliomas have been historically treated with... (Review)
Review
Paragangliomas are rare neuroendocrine tumors that can be found from the skull base to the pelvis. Head and neck paragangliomas have been historically treated with surgery. However, surgical resection adds risk of injury to vascular structures and cranial nerves that can lead to morbidity such as hoarseness, dysarthria, dysphagia, or aspiration. Recently, improved understanding of the behavior of these tumors and increasing experience in non-surgical treatments, such as observation and radiation therapy, have changed the paradigms of management of this entity. Multiple series now show a trend toward a more conservative management, with a higher percentage of patients being observed or treated with radiotherapy. Several factors should be taken into consideration when deciding the most appropriate treatment for head and neck paragangliomas, starting by differentiating carotid body tumors from non-carotid body tumors. In general, surgical resection is normally recommended for carotid body tumors as the complications from treatment are usually minimal. In contrast, for non-carotid body tumors, surgery is often associated with significant functional impairment due to cranial nerve paralysis. As such, non-surgical treatment is now usually recommended for this subset of head and neck paragangliomas. In young patients with no comorbidities and a small to medium carotid body tumors, surgery should be considered. Moreover, surgery should be offered for secreting tumors, malignant tumors, tumors with rapid growth or increase in symptomatology, and when radiotherapy cannot be performed. Conversely, conservative management with active surveillance or radiotherapy can be offered in the remaining cases in order to avoid unnecessary morbidity while still providing acceptable tumor control.
Topics: Humans; Head and Neck Neoplasms; Paraganglioma; Carotid Body Tumor; Paraganglioma, Extra-Adrenal; Neck; Retrospective Studies
PubMed: 35178777
DOI: 10.1111/jop.13286 -
Nature Reviews. Cancer Feb 2014The neuroendocrine tumours pheochromocytomas and paragangliomas carry the highest degree of heritability in human neoplasms, enabling genetic alterations to be traced to... (Review)
Review
The neuroendocrine tumours pheochromocytomas and paragangliomas carry the highest degree of heritability in human neoplasms, enabling genetic alterations to be traced to clinical phenotypes through their transmission in families. Mutations in more than a dozen distinct susceptibility genes have implicated multiple pathways in these tumours, offering insights into kinase downstream signalling interactions and hypoxia regulation, and uncovering links between metabolism, epigenetic remodelling and cell growth. These advances extend to co-occurring tumours, including renal, thyroid and gastrointestinal malignancies. Hereditary pheochromocytomas and paragangliomas are powerful models for recognizing cancer driver events, which can be harnessed for diagnostic purposes and for guiding the future development of targeted therapies.
Topics: Genetic Heterogeneity; Humans; Mutation; Paraganglioma; Pheochromocytoma
PubMed: 24442145
DOI: 10.1038/nrc3648 -
The Journal of Clinical Endocrinology... Aug 2015Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother... (Review)
Review
CONTEXT
Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother and fetus need to be considered, and management can be challenging. The optimal management of women with a pheochromocytoma or paraganglioma in pregnancy is not well established.
OBJECTIVE
The objective of the study was to assess whether there is a difference in fetal or maternal mortality between pheochromocytomas and paragangliomas in pregnancy.
DESIGN
We present an experience of eight pregnancies in four SDHB germline mutation-positive women with sympathetic paragangliomas, followed by a systematic review of the literature to compare the outcome of paragangliomas with that of pheochromocytomas occurring in pregnancy.
RESULTS
In our case series, favorable fetal and maternal outcomes were seen in all eight pregnancies. From the systematic review, maternal and fetal mortality were lower in women with paragangliomas, at 3.6% and 12% respectively, compared with 9.8% and 16% in women with pheochromocytomas.
CONCLUSION
Pregnant women with paragangliomas may be at a lower risk of adverse outcome than those with pheochromocytomas, but both maternal and fetal mortality rates are still higher than that of the general obstetric population.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Female; Humans; Paraganglioma; Pedigree; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Siblings; Young Adult
PubMed: 26083822
DOI: 10.1210/jc.2015-2122 -
Cell and Tissue Research May 2018Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the... (Review)
Review
Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.
Topics: Adrenal Gland Neoplasms; Humans; Molecular Imaging; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Theranostic Nanomedicine
PubMed: 29450723
DOI: 10.1007/s00441-018-2791-4 -
JPMA. the Journal of the Pakistan... May 2022Paragangliomas are rare tumours derived from the neural crest cells. Most common site for these tumours is the adrenal medulla, where they are called as...
Paragangliomas are rare tumours derived from the neural crest cells. Most common site for these tumours is the adrenal medulla, where they are called as pheochromocytomas. Biliary system is an extremely uncommon site for extra-adrenal paraganglioma. We report the case of a 55 year old female who presented with one-month history of jaundice and right upper quadrant discomfort. Imaging showed a well-defined rounded mass at porta hepatis with arterial enhancement causing compression over the proximal common bile duct, resulting in moderate intrahepatic biliary dilatation. The patient underwent radical excision of common bile duct and roux-en-y hepaticojejunostomy. Final histopathology confirmed paraganglioma. Approximately 10% of patients may present with extra-adrenal disease, but biliary paraganglioma are extremely rare. Only few cases have been reported in literature and the management usually involves the surgical excision. Being a rare disease, a high index of suspicion is important for diagnosis of paraganglioma at such an uncommon location.
Topics: Biliary Tract Surgical Procedures; Common Bile Duct; Female; Humans; Liver; Middle Aged; Paraganglioma
PubMed: 35713072
DOI: 10.47391/JPMA.4286 -
Clinical Endocrinology Feb 2017Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine secreting neuroendocrine tumours that predispose to haemodynamic instability. Currently, surgery is the... (Review)
Review
Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine secreting neuroendocrine tumours that predispose to haemodynamic instability. Currently, surgery is the only available curative treatment, but carries potential risks including hypertensive and hypotensive crises, cardiac arrhythmias, myocardial infarction and stroke, due to tumoral release of catecholamines during anaesthetic induction and tumour manipulation. The mortality associated with surgical resection of PPGL has significantly improved from 20-45% in the early 20th century (Apgar & Papper, AMA Archives of Surgery, 1951, 62, 634) to 0-2·9% in the early 21st century (Kinney et al. Journal of Cardiothoracic and Vascular Anesthesia, 2002, 16, 359), largely due to availability of effective pharmacological agents and advances in surgical and anaesthetic practice. However, surgical resection of PPGL still poses significant clinical management challenges. Preoperatively, alpha-adrenoceptor blockade is the mainstay of management, although various pharmacological strategies have been proposed, based largely on reports derived from retrospective data sets. To date, no consensus has been reached regarding the 'ideal' preoperative strategy due, in part, to a paucity of data from high-quality evidence-based studies comparing different treatment regimens. Here, based on the available literature, we address the Clinical Question: Is there an optimal preoperative management strategy for PPGL?
Topics: Adrenergic alpha-Antagonists; Humans; Paraganglioma; Pheochromocytoma; Postoperative Complications; Preoperative Care
PubMed: 27696513
DOI: 10.1111/cen.13252 -
Current Opinion in Oncology Jan 2004Pheochromocytomas and paragangliomas are rare tumors of chromaffin cell origin. Their identification is likely increasing owing to the increased use of radiographic... (Review)
Review
PURPOSE
Pheochromocytomas and paragangliomas are rare tumors of chromaffin cell origin. Their identification is likely increasing owing to the increased use of radiographic images detecting incidental adrenal masses.
RECENT FINDINGS
The pathophysiology of hypertension induced by the release of catecholamines and newly discovered peptides has been shown to be more complex than the concept of episodic catecholamine release.
SUMMARY
This review looks at the most recent advances in the physiology and molecular basis of these tumors.
Topics: Adrenal Gland Neoplasms; Diagnosis, Differential; Humans; Hypertension; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals
PubMed: 14685086
DOI: 10.1097/00001622-200401000-00003 -
Medicina (Kaunas, Lithuania) Jan 2024: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal...
: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal paragangliomas are the rarest subtype of these tumors, with only 1.41% of all paragangliomas, arising from the supraglottic or subglottic paraganglia of the larynx. The vast majority of them are benign, but there are some cases in which they turn out to be malignant, and the only way to know with certainty the difference between them is when we identify distant metastases. The aim of this article is to share our experience with a rare case of laryngeal paraganglioma and review the clinical characteristics, methods of diagnostic, necessary investigation prior to the operation, and surgical management of this type of tumor. : We present the case of a 68-year-old female patient, a non-smoker, who accused dysphagia, dysphonia, foreign body sensation, chronic cough, and hoarseness for six months. We performed a tracheostomy prior to biopsy to secure the airways in case of bleeding and then took a few biopsy samples. The histopathological exam revealed the presence of a laryngeal paraganglioma. An enhanced CT scan was performed in order to describe the localization, size, and invasion of the tumor. We also measured the vanillylmandelic acid from the urine to determine if the tumor produced catecholamines alongside a full cardiology and endocrinology examinations. In order to prevent massive bleeding during the operation, chemoembolization was attempted before surgery, but it was unsuccessful due to an anatomical variation of the left superior thyroid artery. She underwent surgery, first through transoral endoscopic microsurgery; however, we decided to undertake an external approach because of poor bleeding control, even though we had ligated both the superior thyroid artery and the external carotid artery, with a thyrotomy and laryngofissure achieving the complete resection of the tumor. : The patient was discharged 10 postoperative days later, with the recommendation of introducing food step-by-step from liquids to solids. She was decannulated after 30 days, with no complications regarding breathing, phonation, or deglutition. Twelve months after the surgery, we did not identify any local relapses of distant metastases. : Laryngeal paragangliomas are rare neuroendocrine tumors that arise from the laryngeal paraganglia. Surgery is the best treatment option available, and it can be done by either an external approach or by transoral endoscopy. Enhanced CT or MRI, as well as full cardiological and endocrinological evaluation are mandatory prior to the operation. Measuring the catecholamines levels show the if the tumor is secretory. Controlling the bleeding poses the biggest challenge in performing the resection of the tumor, especially when a transoral endoscopic approach is chosen. Further standardized follow-up guidelines are required in the future.
Topics: Female; Humans; Aged; Neoplasm Recurrence, Local; Paraganglioma; Laryngeal Neoplasms; Neuroendocrine Tumors; Catecholamines
PubMed: 38399485
DOI: 10.3390/medicina60020198 -
Urology Feb 2023Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this...
Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this report, we detail an unusual case in which a teenager presenting with hypertension was found to have multifocal primary paragangliomas. We illustrate important considerations in management which include appropriate preoperative labs and imaging, collaboration with endocrinology for preoperative alpha-blockade, surgical management with close perioperative hemodynamic control, and genetic evaluation for all patients with paragangliomas.
Topics: Humans; Adolescent; Child; Paraganglioma; Diagnostic Imaging; Hypertension; Adrenal Gland Neoplasms
PubMed: 36283505
DOI: 10.1016/j.urology.2022.10.006