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European Annals of Otorhinolaryngology,... Jun 2014The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics,... (Comparative Study)
Comparative Study
BACKGROUND
The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics, their natural history and their treatment with those of a series of 131 benign paragangliomas.
PATIENTS AND METHODS
Retrospective analysis of 142 patients with head and neck paraganglioma managed between 2001 and 2008. Age at the time of diagnosis, gender, primary tumour site, presence of other non-head/neck paragangliomas and/or metastases diagnosed by imaging (CT, MRI, Octreoscan or (18)F-FDG PET), histology, urinary catecholamine and metanephrine levels, family history, and genetic test results were recorded.
RESULTS
This series comprised 131 benign head and neck paragangliomas, mostly observed in women with a mean age at diagnosis of 45 years and a predominance of tympanojugular sites (followed by carotid and vagal sites) with 5% of secreting tumours and 20% of multifocal tumours. Eleven patients (7.7%) with a 1:1 sex ratio presented criteria of malignancy. These patients, with a lower mean age (38 years), predominantly presented carotid lesions with a higher rate of secreting and multifocal tumours, 27% and 46% respectively. The main sites of metastases were bone and lymph nodes. No tympanic paragangliomas were observed.
CONCLUSIONS
Malignant paragangliomas are mainly observed in young patients with multifocal tumours, particularly carotid tumours, and are predominantly related to subunit SDH-B mutation. The work-up in these high-risk patients must include whole body scintigraphy and spine MRI. Malignancy is not necessarily associated with a poor short-term prognosis due to the slow course of the disease.
Topics: Adolescent; Adult; Aged; Bone Neoplasms; Diagnostic Imaging; Female; Genetic Testing; Head and Neck Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mutation; Neck Dissection; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Paraganglioma; Retrospective Studies; Sex Distribution; Succinate Dehydrogenase; Thyroid Neoplasms; Young Adult
PubMed: 24239180
DOI: 10.1016/j.anorl.2013.05.003 -
Journal of Neurosciences in Rural... Jan 2021The aim of the study is to determine the surgical candidacy and nuances of skull base paraganglioma surgery in the era of radiotherapy. This was a retrospective...
The aim of the study is to determine the surgical candidacy and nuances of skull base paraganglioma surgery in the era of radiotherapy. This was a retrospective observational study conducted in patients who presented with skull base paragangliomas between January 2017 and December 2019. Primary data, including indication for surgery, the approach used, the extent of resection, complications, and postoperative lower cranial nerve status were studied. A total of 21 cases of skull base paragangliomas were analyzed, including seven cases of tympanic paraganglioma, 10 cases of jugular foramen paraganglioma, three cases of multiple paragangliomas, and one case of vagal paraganglioma. Indications for surgery were young age, bleeding from ear, neck mass with upper aerodigestive pressure symptoms, lower cranial nerve paralysis, and patients with intracranial pressure symptoms. Total excision was done in 11 patients, near-total excision in five patients, subtotal in three patients, and surgery was not done in two patients. Facial nerve paralysis was the most common complication observed, followed by bleeding and flap necrosis. Radiotherapy was considered as adjuvant treatment wherever indicated. A thorough knowledge and understanding of the pathophysiology of the skull base paragangliomas and its management strategies can help to achieve excellent results in terms of tumor clearance and reduction in complications. A multidisciplinary team approach and meticulous skull base surgical techniques have a significant role to play in the management of paragangliomas, especially in developing countries where availability of radiosurgery is still a challenge.
PubMed: 33531769
DOI: 10.1055/s-0040-1721201 -
Endocrine-related Cancer Sep 2016The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of... (Review)
Review
The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors.
Topics: Cranial Nerve Neoplasms; Humans; Paraganglioma; Parathyroid Neoplasms; Vagus Nerve; Vagus Nerve Diseases
PubMed: 27406876
DOI: 10.1530/ERC-16-0241 -
Clinics (Sao Paulo, Brazil) 2012Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic... (Review)
Review
Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.
Topics: Carotid Body Tumor; Genes, Neoplasm; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Neoplasm Staging; Paraganglioma; Skull Base Neoplasms
PubMed: 22584701
DOI: 10.6061/clinics/2012(sup01)05 -
Translational Medicine @ UniSa 2013Between 1972 and 2012, 25 patients presenting 32 paragangliomas of the neck were observed. Tumor locations included the carotid body (CBTs) in 21 patients and the vagus...
Between 1972 and 2012, 25 patients presenting 32 paragangliomas of the neck were observed. Tumor locations included the carotid body (CBTs) in 21 patients and the vagus nerve in 4. Four patients had bilateral CBT and one a bilateral vagal tumor; a metachronous bilateral jugulare paraganglioma was diagnosed in one patient with bilateral CBT Shamblin type III. Five patients presented CBTs type II and three type III. Preoperative embolization was performed in 5 CBTs, with no significant difference in blood loss. Twenty-nine paragangliomas were resected (with three internal carotid artery resection): there were no cerebrovascular accident or perioperative death. Nine patients (36%) had cranial nerve palsy prior to surgery and a postoperative nerve dysfunction occurred in four other tumors (16%). Persistent nerve deficits occurred in 3 patients (12%). No evidence of malignancy was shown, intraoperatively or during a postoperative follow-up period (9 months to 18 years; mean: 8 years).
PubMed: 24251239
DOI: No ID Found -
Indian Journal of Otolaryngology and... Dec 2022Paragangliomas of the head and neck can arise in many locations along the carotid sheath and middle ear. A hypervascular tumor in relation to the major cervical vessels...
Paragangliomas of the head and neck can arise in many locations along the carotid sheath and middle ear. A hypervascular tumor in relation to the major cervical vessels can be either a carotid body tumor or vagal paraganglioma. Carotid bifurcation separation is a characteristic feature of carotid body tumours. We present a case of vagal paraganglioma of the neck, causing carotid bifurcation separation similar to that of a carotid body tumor. In this case report, we highlight the imaging features that can differentiate these two paragangliomas in such a confusing situation.
PubMed: 36742569
DOI: 10.1007/s12070-021-03005-w -
Frontiers in Endocrinology 2024Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of...
Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the gene. Using whole-exome sequencing, a variant, p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, , , and . The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, -mutated VPGL was characterized by a molecular phenotype different from -mutated PPGLs. In conclusion, the association of genetic changes in the gene with the development of VPGL was demonstrated. The germline variant : p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of -related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.
Topics: Adult; Female; Humans; Acid Anhydride Hydrolases; Cranial Nerve Neoplasms; Exome Sequencing; Germ-Line Mutation; Paraganglioma; Vagus Nerve Diseases
PubMed: 38721148
DOI: 10.3389/fendo.2024.1381093 -
Cancers Apr 2024Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed...
Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.
PubMed: 38672605
DOI: 10.3390/cancers16081523 -
Clinical Cancer Research : An Official... Jan 2011Hereditary head and neck paraganglioma (HNPGL) syndromes are associated with mutations in the SDHD(PGL1), SDHC(PGL3), and SDHB(PGL4) genes encoding succinate...
PURPOSE
Hereditary head and neck paraganglioma (HNPGL) syndromes are associated with mutations in the SDHD(PGL1), SDHC(PGL3), and SDHB(PGL4) genes encoding succinate dehydrogenase subunits. We recently described mutations in a previously uncharacterized human gene, now called SDHAF2, and showed that this was the long-sought "imprinted" PGL2 gene. Here, we present a new branch of the Dutch SDHAF2 (PLG2-SDH5) family.
EXPERIMENTAL DESIGN
The SDHAF2 family has been collected over a 30-year period. The family described here was linked to PGL2 and at-risk family members were invited to participate in this study. Patients were investigated and treated dependent on tumor size and localization. All family members have now been analyzed for the SDHAF2 mutation status.
RESULTS
Among the 57 family members, 23 were linkage positive including 7 risk-free carriers (maternal imprinting). Of the 16 at-risk individuals, 11 had a total of 24 tumors with primarily carotid (71%) and vagal locations (17%). Multifocality of tumors was prominent (91%). Malignancy was not detected. The average age at onset was 33 years, and many patients (42%) were asymptomatic prior to screening. SDHAF2 mutation analysis confirmed the findings of the previously performed linkage analysis without detection of discrepancies.
CONCLUSIONS
We established the SDHAF2 mutation status of PGL2 family members. Phenotypic characterization of this family confirms the currently exclusive association of SDHAF2 mutations with HNPGL. This SDHAF2 family branch shows a young age at onset and very high levels of multifocality. A high percentage of patients were asymptomatic at time of detection.
Topics: Adult; Female; Genotype; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mutation; Neoplastic Syndromes, Hereditary; Paraganglioma; Pedigree; Protein Subunits; Succinate Dehydrogenase
PubMed: 21224366
DOI: 10.1158/1078-0432.CCR-10-0420 -
Cureus Oct 2021Vagal paraganglioma is a rare finding that develops from paraganglionic tissue found around the vagus nerve; it has a prevalence of 0.012% of all tumors. It is the...
Vagal paraganglioma is a rare finding that develops from paraganglionic tissue found around the vagus nerve; it has a prevalence of 0.012% of all tumors. It is the third most common paraganglioma of the head and neck but still accounts for less than 5% of these tumors, and it has a well-established female prevalence. It is a difficult tumor to identify early based on its symptoms alone and only a thorough investigation can help solidify its diagnosis. In this report, we discuss a presentation of this phenomenon that is not only unique in its manifestation but also a very difficult diagnosis due to its deceptive presentation and multiple extensions. These masses need a good surgical regime to be removed properly and postoperative complications are very frequent in most of these cases.
PubMed: 34733595
DOI: 10.7759/cureus.18423