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Frontiers in Endocrinology 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term "silent" PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, "clinically silent" is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term "silent" and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Catecholamines
PubMed: 36325453
DOI: 10.3389/fendo.2022.1021420 -
Cancer Control : Journal of the Moffitt... Jul 2016Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra-adrenal paraganglia of... (Review)
Review
BACKGROUND
Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra-adrenal paraganglia of the neural crest. Frequently, these tumors are associated with the vagus or tympanic plexus nerve or the carotid artery, or jugular bulb. Their clinical presentation can vary across a wide spectrum of signs and symptoms.
METHODS
We reviewed and compared standard treatment approaches for paragangliomas of the head and neck.
RESULTS
In general, surgery is the first-line choice of therapy for carotid body tumors, whereas radiotherapy is the first-line option for jugular and vagal paragangliomas.
CONCLUSIONS
Because of the complexity of clinical scenarios and treatment options for paragangliomas, a multidisciplinary algorithmic approach should be used for treating paragangliomas. The approach should emphasize single-modality treatment that yields excellent rates of tumor control, low rates of severe, iatrogenic morbidity, and the preservation of long-term function in this patient population.
Topics: Female; Head and Neck Neoplasms; Humans; Male; Paraganglioma
PubMed: 27556663
DOI: 10.1177/107327481602300306 -
Hormone and Metabolic Research =... May 2012After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging... (Review)
Review
After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using 123I-metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no 'gold-standard' imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.
Topics: Adrenal Gland Neoplasms; Animals; Diagnostic Imaging; Humans; Paraganglioma; Pheochromocytoma; Radionuclide Imaging
PubMed: 22399235
DOI: 10.1055/s-0031-1299712 -
European Annals of Otorhinolaryngology,... Sep 2017To review the optimal techniques for localization and characterization of neck paragangliomas (PGL). (Review)
Review
OBJECTIVE
To review the optimal techniques for localization and characterization of neck paragangliomas (PGL).
MATERIAL AND METHODS
Systematic review of the literature from the PubMed/Medline database.
RESULTS
Neck PGL are hypervascular tumours essentially arising from paraganglionic tissue situated at the carotid bifurcation (carotid body) and along the vagus nerve. Morphological and functional imaging are indicated to confirm the diagnosis, identify multifocal disease and for local and regional staging. MR angiography is the noninvasive technique of choice. CT scan and especially CT angiography are excellent alternatives for diagnosis and staging. Conventional arteriography remains useful preoperatively for embolization and occlusion tests. Functional imaging allows localization and characterization of PGLs. Somatostatin receptor scintigraphy (SRS) was the reference imaging technique for staging of sporadic PGLs. The indications for PET imaging have been extended over recent years in parallel with the development of new tracers such as [F]-FDOPA PET or Gallium-labelled DOTA peptides. Gallium-labelled DOTA peptides has become the first-line imaging modality in the evaluation of cervical PGLs, regardless of the genetic background.
CONCLUSION
Morphological and functional imaging is essential for the staging of neck PGL.
Topics: Computed Tomography Angiography; Head and Neck Neoplasms; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Neoplasm Staging; Paraganglioma; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 27887852
DOI: 10.1016/j.anorl.2016.10.003 -
Archives of Pathology & Laboratory... Feb 2015von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by heterozygous mutations in the VHL tumor suppressor gene that is characterized by the... (Review)
Review
von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by heterozygous mutations in the VHL tumor suppressor gene that is characterized by the occurrence of multiple endocrine and nonendocrine lesions. This review focuses on the endocrine manifestations of VHL disease. Pancreatic neuroendocrine proliferations (ductuloinsular complexes, islet dysplasia, endocrine microadenoma, and neuroendocrine tumors), pheochromocytomas, and extra-adrenal paragangliomas are important endocrine manifestations of VHL disease. They frequently display characteristic clinical, biochemical, and histopathologic features that, although not pathognomonic, can be helpful in suggesting VHL disease as the underlying etiology and distinguishing these tumors from sporadic cases. Recent improvements in treatment and outcomes of renal cell carcinomas have allowed pancreatic neuroendocrine tumors to emerge as a significant source of metastatic disease, making the accurate recognition and classification of these neoplasms by the pathologist of utmost importance to determine prognosis, treatment, and follow-up strategies for affected patients.
Topics: Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Cell Proliferation; Diagnosis, Differential; Humans; Kidney Neoplasms; Mutation; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Paraganglioma; Pheochromocytoma; Von Hippel-Lindau Tumor Suppressor Protein; von Hippel-Lindau Disease
PubMed: 25611110
DOI: 10.5858/arpa.2013-0520-RS -
Cancer Genetics 2012Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors... (Review)
Review
Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors that are associated with high morbidity and mortality due to mass effect and high circulating catecholamines. Although most PCCs and PGLs are thought to be sporadic, over one third are associated with 10 known susceptibility genes. Mutations in three genes causing well characterized tumor syndromes are associated with an increased risk of developing PCCs and PGLs, including VHL (von Hippel-Lindau disease), NF1 (Neurofibromatosis Type 1), and RET (Multiple Endocrine Neoplasia Type 2). Mutations in any of the succinate dehydrogenase (SDH) complex subunit genes (SDHA, SDHB, SDHC, SDHD) can lead to PCCs and PGLs with variable penetrance, as can mutations in the subunit cofactor, SDHAF2. Recently, two additional genes have been identified, TMEM127 and MAX. Although these tumors are rare in the general population, occurring in two to eight per million people, they are more commonly associated with an inherited mutation than any other cancer type. This review summarizes the known germline and somatic mutations leading to the development of PCC and PGL, as well as biochemical profiling for PCCs/PGLs and screening of mutation carriers.
Topics: Adrenal Gland Neoplasms; Animals; Comprehension; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Multiple Endocrine Neoplasia; Paraganglioma; Pheochromocytoma; Syndrome; von Hippel-Lindau Disease
PubMed: 22429592
DOI: 10.1016/j.cancergen.2012.01.009 -
Oncology Research 2022Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various... (Review)
Review
Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various malignancies. During transcription, the expression and functionality of coding gene products are altered following the histone acetylation and deacetylation. These processes are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. HDAC inhibitors (HDACis) have been developed as promising therapeutic agents, to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some specific malignant diseases with limited options. Mechanistically, these agents affect many intracellular pathways, including cell cycle arrest, apoptosis and differentiation, and their mechanism of action mainly depends on the type of cancer. Currently, five HDACis have been approved for the treatment of several hematological malignancies (e.g., T-cell lymphoma subtypes and multiple myeloma); while, many of them are tested for further therapeutic indications in solid tumors (e.g., colorectal, thyroid, breast, lung and pancreatic cancer). Herein, we review the literature and gather all available evidence, from and data to clinical trial results, that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas; and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.
Topics: Humans; Pheochromocytoma; Histone Deacetylase Inhibitors; Paraganglioma; Pancreatic Neoplasms; Adrenal Gland Neoplasms
PubMed: 37305348
DOI: 10.32604/or.2022.026913 -
Turkish Neurosurgery 2017Paragangliomas of the spine are rare tumors. Clinical presentations and courses of spinal paragangliomas are varied, and there are no standard principles of treatment to...
AIM
Paragangliomas of the spine are rare tumors. Clinical presentations and courses of spinal paragangliomas are varied, and there are no standard principles of treatment to date. The purpose of this study was to explore the diagnosis, treatment and prognosis of spinal paragangliomas.
MATERIAL AND METHODS
The clinical data of 7 consecutive cases, with complete medical records and follow-up results that were treated in our institutions from October 2000 to October 2011, was retrospectively reviewed.
RESULTS
There were 6 males and 1 female with a mean age of 40 years (range, 16?61). The follow-up period ranged from 40 to 98 months (mean, 72 months). Of the 6 primary spinal paragangliomas, one lesion was in the cervical intradural extramedullary space, one in the thoracic epidural space and four in the lumbar intradural extramedullary space. All tumors were totally resected and no recurrence was detected during the follow-up period. Of the metastatic case, the lesion of the spine was located in the first lumbar epidural space and vertebra. The patients underwent surgical resection two times with radiotherapy, but the tumor recurred and the patient suffered from the paraplegia of lower limbs and urine and stool incontinence during the follow-up period. No patient died.
CONCLUSION
Spinal paragangliomas are rare lesions and seldom considered in the presurgical differential diagnosis due to its rarity and non-specific clinical symptoms and imaging features. Clinical follow-up was necessary to determine the outcome. Complete resection is necessary to prevent recurrence. The role of radiotherapy in the management of these lesions needs further assessment.
Topics: Adolescent; Adult; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Paraganglioma; Retrospective Studies; Spinal Neoplasms
PubMed: 27593782
DOI: 10.5137/1019-5149.JTN.16276-15.1 -
Medecine Sciences : M/S Mar 2022Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes...
Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, and more rarely, to gastrointestinal stromal tumors or renal cell carcinomas. A decrease in SDH activity, not explained by genetics, has also been observed in more common cancers. One of the consequences of the inactivation of SDH is the excessive production of its substrate, succinate, which acts as an oncometabolite by promoting a pseudohypoxic status and an extensive epigenetic rearrangement. Understanding SDH-related oncogenesis now makes it possible to develop innovative diagnostic methods and to consider targeted therapies for the management of affected patients.
Topics: Adrenal Gland Neoplasms; Gastrointestinal Stromal Tumors; Humans; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 35333162
DOI: 10.1051/medsci/2022024 -
European Annals of Otorhinolaryngology,... Dec 2012Over the last decade, it has been clearly established that one-third of all paragangliomas are genetically determined. Genetic testing, guided by the family history and... (Review)
Review
Over the last decade, it has been clearly established that one-third of all paragangliomas are genetically determined. Genetic testing, guided by the family history and clinical findings, must now be proposed to all subjects undergoing surgery for head and neck paraganglioma. When a mutation is identified on one of the susceptibility genes (SDHD, SDHB, SDHC, SDHAF2, VHL), at-risk subjects should be investigated for the presence of other supra- and infradiaphragmatic paragangliomas and functional catecholamine-secreting paragangliomas and/or phaeochromocytomas. Identification of a germline mutation on the SDHB gene is a high-risk factor for malignancy and poor prognosis and requires close surveillance of subjects carrying this mutation. The diagnosis of hereditary paraganglioma also allows predictive genetic screening in first-degree relatives of the index subject. Genetic testing for paraganglioma is therefore now an important component of the diagnostic and therapeutic management of these patients.
Topics: Head and Neck Neoplasms; Humans; Paraganglioma
PubMed: 23078982
DOI: 10.1016/j.anorl.2012.04.007