0000000000384297
AUTHOR
Konstantinos Papaspyrou
Hypoxia-Inducible Factor 2α Mutation-Related Paragangliomas Classify as Discrete Pseudohypoxic Subcluster
Contains fulltext : 172720.pdf (Publisher’s version ) (Open Access) Recently, activating mutations of the hypoxia-inducible factor 2alpha gene (HIF2A/EPAS1) have been recognized to predispose to multiple paragangliomas (PGLs) and duodenal somatostatinomas associated with polycythemia, and ocular abnormalities. Previously, mutations in the SDHA/B/C/D, SDHAF2, VHL, FH, PHD1, and PHD2 genes have been associated with HIF activation and the development of pseudohypoxic (cluster-1) PGLs. These tumors overlap in terms of tumor location, syndromic presentation, and noradrenergic phenotype to a certain extent. However, they also differ especially by clinical outcome and by presence of other tumors o…
Malignant and benign sinonasal paragangliomas
Objectives/Hypothesis To report on the clinical course and management of sinonasal paragangliomas (PGLs). Study Design and Methods Retrospective chart review of six patients with PGLs of the nasal cavity and paranasal sinuses. Results Three patients had tumors with malignant clinical behavior with cerebral metastases or infiltration of brain and local recurrence, despite surgery and/or radiotherapy, while three patients demonstrated a benign course. Conclusion Sinonasal paragangliomas are frequently malignant. If malignant, they are very aggressive, with rapid local spread as well as high metastatic potential despite surgical resection; and they have a poor prognosis. Malignancy cannot be d…
Head and neck paragangliomas: Report of 175 patients (1989-2010)
Attention of the otorhinolaryngologist needs to be drawn to the versatile aspects of head and neck paragangliomas (PGLs).This study is a retrospective, nonrandomized clinical study of all 175 individuals with PGLs treated in our department between 1989 and 2010. A genetic analysis was performed on 86 patients.The 175 patients presented 224 head and neck PGLs as well as 2 thyroid papillary carcinomas. Genetic analysis resulted in 1 patient positive for a von Hippel-Lindau (VHL) gene mutation and 34 for succinate dehydrogenase (SDH) gene mutations (22 SDHD, 7 SDHC, and 5 SDHB), 12 of the latter carrying a novel mutation. Thirty-three patients (18.9%) had multiple PGLs and 11 patients (6.3%) h…
Fascin upregulation in primary head and neck squamous cell carcinoma is associated with lymphatic metastasis
Fascin is an actin-bundling protein that is associated with cellular motility and cancer-cell invasion. The present study aimed to examine the expression of fascin in head and neck squamous cell carcinoma (HNSCC) and its potential use as a biomarker. In a prospective study with a median follow-up time of 48.8 months, tumor tissues, adjacent healthy tissues and cervical lymph node metastases were collected from 25 patients and analyzed by immunohistochemistry. The specimens were scored according to the intensity of fascin staining and the percentage of tumor cells stained using a semi-quantitative scoring approach; the data were analyzed and correlated with clinical follow-up observations. A…
Management of head and neck paragangliomas: review of 120 patients.
Head and neck paragangliomas (PGL) are rare, mostly benign tumors. About 10% to 15% of PGL are caused by mutations in the succinate dehydrogenase genes B, C, or D and may appear multifocally.A retrospective review of 120 patients with 146 head and neck PGL, including 46 carotid body tumors (CBT), 13 vagal tumors, 55 jugulotympanic tumors (JTT), 25 tympanic tumors (TT) and 7 tumors in other locations are included. The internal carotid artery was preserved in 97.5% of CBT resections. Preservation of hearing was achieved in 92% of JTT and 88% of TT resections.According to our experience, the treatment of PGL must be individualized, taking into account the patient's age, medical condition, tumo…
Malignant paraganglioma caused by a novel germline mutation of the succinate dehydrogenase D-gene--a case report.
Background Paragangliomas of the head and neck are rare, mostly benign tumors. Approximately 10% to 15% of paragangliomas are caused by mutations in the succinate dehydrogenase (SDH) genes B, C, or D. These are often multifocal as part of paraganglioma syndromes and hormone secreting, and malignant particularly associated with mutations in SDHB. Methods and Results A 29-year-old man was seen with recurrent paraganglioma. The patient's father reportedly suffered from bilateral carotid body tumors. Imaging studies showed metastases in both lungs and the liver. There was no increased hormone production by the tumor. Sequence analysis of the SDH genes revealed a novel C to T nonsense mutation i…
Hearing results after hypotympanotomy for glomus tympanicum tumors.
We postulate, that glomus tympanicum tumors (GTTs) may be safely removed without interference with the ossicular chain via a hypotympanotomy approach.Prospective, nonrandomized anatomic and clinical study.Tertiary referral center.All 17 patients between 1989 and 2009 with GTTs without involvement of the lumen of the jugular bulb.We used a modified hypotympanotomy approach. Our technique is a modification of the one first published by Shambaugh (1955). Pure-tone audiograms were performed in all patients. Preoperative and postoperative audiograms were modeled in a linear mixed model evaluating hearing threshold for air and bone conduction and air-bone gap at 500, 1,000, 2,000, and 3,000 Hz. I…
Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis
ObjectiveAlthough the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated.Design and methodsThree unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RC…