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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 -
Clinical Endocrinology Nov 2017The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL).
DESIGN
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016.
PATIENTS
Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow-up data.
MEASUREMENTS
Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle-Ottawa tool. Random-effects meta-analysis was used to pool event rates across studies.
RESULTS
Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow-up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five-year (7 studies, n = 738) and 10-year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%-51%) and 29% (95% CI, 17%-42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85).
CONCLUSIONS
Available low-quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.
Topics: Adrenal Gland Neoplasms; Adult; Female; Humans; Male; Middle Aged; Mortality; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Treatment Outcome
PubMed: 28746746
DOI: 10.1111/cen.13434 -
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 -
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 -
Frontiers in Endocrinology 2023To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence...
PURPOSE
To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease).
METHODS
This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection.
RESULTS
A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in gene (hazard ratio [HR] 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence.
CONCLUSION
The recurrence of PPGLs occurred more frequently in patients with mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.
Topics: Humans; Pheochromocytoma; Normetanephrine; Neoplasm Recurrence, Local; Paraganglioma; Adrenal Gland Neoplasms; Brain Neoplasms; Neoplasms, Second Primary
PubMed: 38155946
DOI: 10.3389/fendo.2023.1279828 -
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 -
Critical Reviews in Oncology/hematology Apr 2016Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo... (Review)
Review
Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1Bβ, MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL. Also, GDNF, H-ras, K-ras, GNAS, CDKN2A (p16), p53, BAP1, BRCA1&2, ATRX and KMT2D mutations have roles in the development of PCC/PGLs. Overall, known genetic mutations account for the pathogenesis of approximately 60% of PCC/PGLs. Genetic mutations, pathological parameters and biochemical markers are used for better prediction of the outcome of patients with this group of tumours. Immunohistochemistry and gene sequencing can ensure a more effective detection, prediction of malignant potential and treatment of PCC/PCLs.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Germ-Line Mutation; Humans; Immunohistochemistry; Paraganglioma; Pheochromocytoma; Signal Transduction
PubMed: 26839173
DOI: 10.1016/j.critrevonc.2016.01.022 -
Hormones & Cancer Dec 2015There has been increasing evidence that pseudohypoxia--a phenomenon that we refer to as "gasping for air"--along with mitochondrial enzyme dysregulation play a crucial... (Review)
Review
There has been increasing evidence that pseudohypoxia--a phenomenon that we refer to as "gasping for air"--along with mitochondrial enzyme dysregulation play a crucial role in tumorigenesis, particularly in several hereditary pheochromocytomas (PHEOs) and paragangliomas (PGLs). Alterations in key tricarboxylic acids (TCA) cycle enzymes (SDH, FH, MDH2) have been shown to induce pseudohypoxia via activation of the hypoxia-inducible transcription factor (HIF) signaling pathway that is involved in tumorigenesis, invasiveness, and metastatic spread, including an association with resistance to various cancer therapies and worse prognosis. This review outlines the ongoing story of the pathogenesis of hereditary PHEOs/PGLs, showing the unique and most updated evidence of TCA cycle dysregulation that is tightly linked to hypoxia signaling.
Topics: Animals; Carbohydrate Metabolism; Cell Transformation, Neoplastic; Citric Acid Cycle; Humans; Hypoxia; Mitochondria; Oxygen; Paraganglioma; Pheochromocytoma; Signal Transduction
PubMed: 26138106
DOI: 10.1007/s12672-015-0231-4