Simultaneous Contralateral Vestibular Schwannoma and Middle Ear Paraganglioma Tumor

To the best of our knowledge, only 2 cases of a simultaneous contralateral vestibular schwannoma (VS) and middle ear paraganglioma (MEP) have previously been reported in literature. We report the third case observed in a 43-year-old male, who presented with an 11-year history of right-sided hearing loss and a 1-year history of left-sided pulsatile tinnitus. A magnetic resonance imaging (MRI) showed a VS on the right side and computer tomography (CT) identified a Fisch type A1 paraganglioma on the left side. The VS was treated using a translabyrinthine approach and the MEP was kept under radiological observation for 1 year. Due to the growth of the MEP (Fisch type A2), it was treated with excision via a retroauricular approach. Our case was very challenging because there was a different and important pathology on each side, both carrying a risk of deafness as a consequence of the disease and/or the treatments

Treatment responses to antiangiogenetic therapy and chemotherapy in nonsecreting paraganglioma (PGL4) of urinary bladder with SDHB mutation: a case report

Paraganglioma (PGL) is a rare neuroendocrine tumor. Currently, the malignancy is defined as the presence of metastatic spread at presentation or during follow-up. Several gene mutations are listed in the pathogenesis of PGL, among which succinate dehydrogenase (SDHX), particularly the SDHB isoform, is the main gene involved in malignancy. A 55-year-old male without evidence of catecholamine secretion had surgery for PGL of the urinary bladder. After 1 year, he showed a relapse of disease and demonstrated malignant PGL without evidence of catecholamine secretion with a germline heterozygous mutation of succinate dehydrogenase B (SDHB). After failure of a second surgery for relapse, he started medical treatment with sunitinib daily but discontinued due to serious side effects. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapeutic regimen stopped the disease progression for 7 months. Conclusion: Malignant PGL is a very rare tumor, and SDHB mutations must be always considered in molecular diagnosis because they represent a critical event in the progression of the oncological disease. Currently, there are few therapeutic protocols, and it is often difficult, as this case demonstrates, to decide on a treatment option according to a reasoned set of choices. Abbreviations: CVD = cyclophosphamide, vincristine and dacarbazine, HIF-1a = hypoxia inducible factor 1 alpha, PGL = paraganglioma, SDH = succinate dehydrogenase, VEGF = vasoendothelial growth factor

Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMPheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitorsThis work was supported by the Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofounded by FEDER, [grant number PI14/00240, PI17/01796 to M.R., PI15/00783 to A.C], the Paradifference Foundation [no grant number applicable to M.R.], the ANR [ANR-2011-JCJC-00701 MODEOMAPP to AP.G-R], the European Union [FP7/2007-2013 n° 259735, Horizon 2020 n° 633983 to AP.G-R], Epigénétique et Cancer [EPIG201303 METABEPIC to AP.G-R], the the Ligue Nationale contre le Cancer ["Cartes d'Identité des Tumeurs (CIT) program" to AP.G-R], the Institut National du Cancer, the Direction Générale de l’Offre de Soins [PRT-K 2014, COMETE-TACTIC, INCa-DGOS_8663 to AP.G-R], the Deutsche Forschungsgemeinschaft (DFG) [CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease“ to F.B, M.F and G.E], the Rafael del Pino Foundation [Becas de Excelencia Rafael del Pino 2017 to B.C], the Severo Ochoa Excellence Programme [project SEV-2011-0191 to M.C-F], La Caixa Foundation [B004235 to JM.R-R], the Spanish Ministry of Education, Culture and Sport [grant number FPU16/05527 to M.S.], the Site de Recherche Intégré sur le Cancer-SIRIC [CARPEM Project to N.B.] and the AECC Foundation [grant number AIO15152858 to C.M-C

Hypoglossal schwannoma masquerading as a carotid body tumor.

Study Objective. To describe the clinical presentation, evaluation, and treatment of a hypoglossal schwannoma. Methods. We report an unusual case of a hypoglossal schwannoma presenting as a pulsatile level II neck mass at the bifurcation of the external and internal carotid arteries, mimicking a carotid body tumor. Radiologic findings are reviewed in detail. Results. A 59-year-old female presented to a tertiary care medical center with complaints of a pulsatile right-sided neck mass. An MRA of the neck was obtained demonstrating a 5 cm mass located at the carotid artery bifurcation and causing splaying of the internal and external carotids. Based on clinical presentation and imaging, a diagnosis of a carotid body tumor was conferred and the patient scheduled for excision. Intraoperatively, the mass was noted to arise from the hypoglossal nerve, remaining independent of the carotid artery. On histopathologic analysis, the mass was determined to be consistent with hypoglossal schwannoma. Conclusion. Though rare, the hypoglossal schwannoma should remain a consideration in the evaluation of a parapharyngeal space mass. As this report demonstrates, the clinical and radiologic presentation of a hypoglossal schwannoma may closely mimic that of the more common carotid body tumor

Pheochromocytoma – clinical manifestations, diagnosis and current perioperative management

Pheochromocytoma is a neuroendocrine tumor characterized by the excessive production of catecholamines (epinephrine, norepinephrine, and dopamine). The diagnosis is suspected due to hypertensive paroxysms, associated with vegetative phenomena, due to the catecholaminergic hypersecretion. Diagnosis involves biochemical tests that reveal elevated levels of catecholamine metabolites (metanephrine and normetanephrine). Functional imaging, such as 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG), has increased specificity in identifying the catecholamine-producing tumor and its metastases. The gold-standard treatment for patients with pheochromocytoma is represented by the surgical removal of the tumor. Before surgical resection, it is important to optimize blood pressure and intravascular volume in order to avoid negative hemodynamic events

Analysis of short-term blood pressure variability in pheochromocytoma/paraganglioma patients

Data on short-term blood pressure variability (BPV), which is a well-established cardiovascular prognostic tool, in pheochromocytoma and paraganglioma (PPGL) patients is still lack and conflicting. We retrospectively evaluated 23 PPGL patients referred to our unit from 2010 to 2019 to analyze 24 h ambulatory blood pressure monitoring (24-h ABPM)-derived markers of short-term BPV, before and after surgical treatment. PPGL diagnosis was assessed according to guidelines and confirmed by histologic examination. The 24-h ABPM-derived markers of short-term BPV included: circadian pressure rhythm; standard deviation (SD) and weighted SD (wSD) of 24-h, daytime, and night-time systolic and diastolic blood pressure (BP); average real variability (ARV) of 24-h, daytime, and night-time systolic and diastolic BP. 7 males and 16 females of 53 ± 18 years old were evaluated. After surgical resection of PPGL we found a significant decrease in 24-h systolic BP ARV (8.8 ± 1.6 vs. 7.6 ± 1.3 mmHg, p < 0.001), in 24-h diastolic BP ARV (7.5 ± 1.6 vs. 6.9 ± 1.4 mmHg, p = 0.031), and in wSD of 24-h diastolic BP (9.7 ± 2.0 vs 8.8 ± 2.1 mmHg, p = 0.050) comparing to baseline measurements. Moreover, baseline 24-h urinary metanephrines significantly correlated with wSD of both 24-h systolic and diastolic BP. Our study highlights as PPGL patients, after proper treatment, show a significant decrease in some short-term BPV markers, which might represent a further cardiovascular risk factor

Magnetic resonance and computed tomography imaging of a carotid body tumor in a dog

A 5-year-old castrated male Labrador Retriever was presented to a referring veterinarian for a swelling in the neck region. Based on the results of histopathology, a carotid body tumor, was diagnosed. The dog was referred to a medical imaging unit for further staging and follow up. This report describes the magnetic resonance (MR) and computed tomographic (CT) appearance of a carotid body tumor

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early