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Synchronous Presentation of Rare Brain Tumors in Von Hippel–Lindau Syndrome

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Synchronous Presentation of Rare Brain Tumors in Von Hippel–Lindau Syndrome diagnostics Case Report Synchronous Presentation of Rare Brain Tumors in Von Hippel–Lindau Syndrome Mariachiara Lodi 1, Antonio Marrazzo 2, Antonella Cacchione 1, Marina Macchiaiolo 3, Antonino Romanzo 4, Luciano Mastronardi 5, Francesca Diomedi-Camassei 6 , Alessia Carboni 2, Andrea Carai 7 , Carlo Gandolfo 2, Lidia Monti 8, Angela Mastronuzzi 1 and Giovanna Stefania Colafati 2,* 1 Department of Paediatric Haematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] (M.L.); [email protected] (A.C.); [email protected] (A.M.) 2 Neuroradiology Unit, Department of Imaging, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] (A.M.); [email protected] (A.C.); [email protected] (C.G.) 3 Rare Diseases and Medical Genetics Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] 4 Ophtalmology Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] 5 Department of Surgical Specialities, Division of Neurosurgery, San Filippo Neri Hospital/ASL, 1, 00135 Roma, Italy; [email protected] 6 Department of Laboratories, Pathology Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] 7 Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] 8 Citation: Lodi, M.; Marrazzo, A.; Department of Radiology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; [email protected] Cacchione, A.; Macchiaiolo, M.; * Correspondence: [email protected]; Tel.: +39-06-6859-4727 Romanzo, A.; Mastronardi, L.; Diomedi-Camassei, F.; Carboni, A.; Carai, A.; Gandolfo, C.; et al. Abstract: Von Hippel–Lindau (VHL) disease is a heritable cancer syndrome in which benign and Synchronous Presentation of Rare malignant tumors and/or cysts develop throughout the central nervous system (CNS) and vis- Brain Tumors in Von Hippel–Lindau ceral organs. The disease results from mutations in the VHL tumor suppressor gene located on Syndrome. Diagnostics 2021, 11, 1005. chromosome 3 (3p25-26). A majority of individuals (60–80%) with VHL disease will develop CNS https://doi.org/10.3390/diagnostics hemangioblastomas (HMG). Endolymphatic sac tumor (ELST) is an uncommon, locally aggressive 11061005 tumor located in the medial and posterior petrosal bone region. Its diagnosis is based on clinical, radiological, and pathological correlation, and it can occur in the setting of VHL in up to 10–15% of Academic Editor: Sung-Hye Park individuals. We describe a 17-year-old male who presented with a chief complaint of hearing loss. Brain and spine Magnetic Resonance Imaging documented the presence of an expansive lesion in Received: 31 March 2021 the left cerebellar hemisphere, compatible with HMG in association with a second cerebellopontine Accepted: 24 May 2021 lesion compatible with ELST. The peculiarity of the reported case is due to the simultaneous presence Published: 31 May 2021 of two typical characteristics of VHL, which led to performing comprehensive genetic testing, thus allowing for the diagnosis of VHL. Furthermore, ELST is rare before the fourth decade of life. Early Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in detection of these tumors plays a key role in the optimal management of this condition. published maps and institutional affil- iations. Keywords: hemangioblastomas; endolymphatic sac tumor; MRI; Von Hippel–Lindau syndrome 1. Introduction Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Von Hippel–Lindau syndrome (VHLs) is a rare, inherited disease with autosomal This article is an open access article dominant inheritance, caused by the mutation of the VHL gene, and in about 20% of distributed under the terms and cases the mutation occurs de novo. The incidence of VHLs is about 1/36,000 in the conditions of the Creative Commons general population and typically manifests in the second decade of life. In the CNS, Attribution (CC BY) license (https:// characteristic HMGs are seen in the retina, brain, and spine with additional ELST. Outside creativecommons.org/licenses/by/ of the CNS, VHL disease presents with tumors of the pacreas, kidneys, adrenals, and 4.0/). Diagnostics 2021, 11, 1005. https://doi.org/10.3390/diagnostics11061005 https://www.mdpi.com/journal/diagnostics Diagnostics 2021, 11, x FOR PEER REVIEW 2 of 8 VHL disease presents with tumors of the pacreas, kidneys, adrenals, and reproductive organs. Therefore, it is essential that radiologists be familiar with their imaging appear- Diagnostics 2021, 11, 1005 ance [1–3]. 2 of 8 2. Case Report A 17-year-old male was referred to our hospital with history of left hearing loss as- reproductive organs. Therefore, it is essential that radiologists be familiar with their imaging sociated with visual loss and worsening headache for about a year. Clinical evaluation appearance [1–3]. showed severe left hearing loss and diplopia occurring with the gaze toward the lower quadrants.2. Case Report No additional neurological deficits were detected. No significant familial pathologicalA 17-year-old history malewas reported. was referred Audiomet to ourry hospital confirmed with a history severe ofleft left sensorineural hearing loss hypacusia.associated with visual loss and worsening headache for about a year. Clinical evaluation showedBrain severe and spine left hearingMagnetic loss Resonance and diplopia Imaging occurring (MRI) withdocumented the gaze the toward presence the lower of a left,quadrants. solid cystic No cerebellar additional mass neurological with inhomogeneous deficits were signal detected. intensity No significantand vivid contrast familial enhancementpathological of history the solid was component reported. (Figure Audiometry 1a–d). confirmed a severe left sensorineural hypacusia.Moreover, an additional left cerebellopontine angle (CPA) tumor was detected, ex- tendingBrain into and the spineinternal Magnetic auditory Resonance canal and Imaging incorporating (MRI) documentedthe ipsilateral the facial presence acoustic of a nervesleft, solid (Figure cystic 1a–d). cerebellar A brain mass CT with scan inhomogeneouswas also performed signal to intensityallow for and a more vivid in-depth contrast pre-operativeenhancement stud of they (Figure solid component 1e,f). (Figure1a–d). Figure 1. Papillary cystadenoma of the endolymphatic sac and cerebellar hemangioblastoma (HMG) in VHL. (a,b): Axial Figure 1. Papillary cystadenoma of the endolymphatic sac and cerebellar hemangioblastoma (HMG) in VHL. (a,b): Axial T2-WI and FLAIR images; (c,d): axial and coronal post-contrast T1-WI images. A cystic mass (without signal suppression T2-WI and FLAIR images; (c,d): axial and coronal post-contrast T1-WI images. A cystic mass (without signal suppression on on FLAIR sequence) grows through the mastoid and temporal bones, disrupting bone structures (1, ELST). After Gado- liniumFLAIR injection, sequence) the grows mass through becomes the relatively mastoid more and temporal homogene bones,ous with disrupting blunt peripheral bone structures rim enhancement. (1, ELST). After HMG Gadolinium appears asinjection, cystic mass the (2) mass in the becomes cerebellar relatively hemisphere, more homogeneous showing isolated with and blunt peripheral peripheral enha rimncing enhancement. mural nodule HMG (3). ( appearse,f): Axial as andcystic coronal mass computerized (2) in the cerebellar tomography hemisphere, (CT) scans showing show isolated bone destruction and peripheral of the enhancing temporal pyramid, mural nodule more (3).evident (e,f): while Axial comparingand coronal healthy computerized contralateral. tomography Normal-appearing, (CT) scans show right-side boned destruction inner ear (star) of the and temporal endolymphatic pyramid, duct more (circle) evident are while no longercomparing recognizable healthy contralaterally contralateral. Normal-appearing,(respectively, arrowhead right-sided and thin inner arrow). ear (star) and endolymphatic duct (circle) are no longer recognizable contralaterally (respectively, arrowhead and thin arrow). Ophthalmologic evaluation showed the presence of retinal hemangioblastomas (Fig- ure 2d–f)Moreover, confirmed an additionalwith TC and left MRI cerebellopontine studies (Figure angle 2a–c). (CPA) tumor was detected, ex- tending into the internal auditory canal and incorporating the ipsilateral facial acoustic nerves (Figure1a–d). A brain CT scan was also performed to allow for a more in-depth pre-operative study (Figure1e,f). Ophthalmologic evaluation showed the presence of retinal hemangioblastomas (Figure2d–f) confirmed with TC and MRI studies (Figure2a–c). Diagnostics 2021,, 11,, 1005x FOR PEER REVIEW 3 of 8 Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 8 Figure 2. HMG of the retina. (a–c): Axial CT scan, T2-WI (volumetric sequence) and axial post- FigureFigure 2. 2. HMG HMG of of the the retina. retina. ( a(a––c):c): Axial Axial CT CT scan, scan, T2-WI T2-WI (volumetric (volumetric sequence) sequence) and and axial axial post- post- contrastcontrast T1-WI T1-WIT1-WI images. images.images. A A Afocal focal focal hyperdense hyperdense hyperdense and and and isointense isointense isointense (compared (compared (compared to to surrounding tosurrounding surrounding vitreous) vitreous) vitreous) peripheralperipheral nodule nodulenodule is is depicted depicted on on on the the the lateral
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