Birke Bausch1, Ulrich Wellner2, Mathieu Peyre3,4, Carsten C Boedeker5,6, Frederik J Hes7, Mariagiulia Anglani8, Jose M de Campos9, Hiroshi Kanno10, Eamonn R Maher11, Tobias Krauss12, Gabriela Sansó13, Marta Barontini13, Claudio Letizia14, Claudia Hader15,16, Francesca Schiavi17, Elisabetta Zanoletti18, Carlos Suárez19, Christian Offergeld5, Angelica Malinoc20, Stefan Zschiedrich20, Sven Glasker21, Serge Bobin22, Olivier Sterkers23,24, Patrice Tran Ba Huy25, Sophie Giraud3,26, Thera Links27, Charis Eng28, Giuseppe Opocher17, Stephane Richard3,4, Hartmut P H Neumann20. 1. Second Department of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. 2. Department of Surgery, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. 3. Center Expert National Cancers Rares PREDIR, AP-HP INCa, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. 4. Génétique Oncologique EPHE, INSERM U 753, Faculté de Médecine Paris Sud and Institut de Cancérologie Gustave Roussy, Villejuif, France and Service de Neurochirurgie, AP-HP, Hôpital Beaujon, Clichy, France. 5. Department of Otorhinolaryngology, University Medical Center, Albert-Ludwigs-University, Freiburg. 6. HELIOS Hanseklinikum Stralsund, Stralsund, Germany. 7. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. 8. Department of Neuroradiology, University of Padova, Padova, Italy. 9. Department of Neurosurgery, IIS - Fundación Jiménez Díaz. UAM, Madrid, Spain. 10. Department of Neurosurgery, Yokohama City University, Yokohama, Japan. 11. Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Center, Cambridge, United Kingdom. 12. Department of Radiology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. 13. Centro de Investigaciones Endocrinológicas (CONICET), Hospital de Niños "R. Gutiérrez,", Buenos Aires, Argentina. 14. Department of Internal Medicine and Medical Specialities, University of Rome "Sapienza,", Rome, Italy. 15. Department of Neuroradiology, Albert-Ludwigs-University, Freiburg, Germany. 16. Department of Radiology and Nuclear Medicine, Kantonsspital St., Gallen, Switzerland. 17. Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology IRCCS, Padova, Italy. 18. Otolaryngology, Department of Otosurgery - Neurosciences, University Hospital of Padova, Padova, Italy. 19. Department of Otolaryngology, Hospital Universitario Central de Asturias and IUOPA, Universidad de Oviedo, Spain. 20. Department of Nephrology and Hypertension, Albert-Ludwigs-University, Freiburg, Germany. 21. Department of Neurosurgery, Albert-Ludwigs-University, Freiburg, Germany. 22. Service d'ORL, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. 23. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Unité Otologie, Implants auditifs et Chirurgie de la base du crâne, Paris, France. 24. Université Paris, Pierre et Marie Curie, France. 25. Service d'ORL, AP-HP, Hôpital Lariboisière, Paris, France. 26. Laboratoire de Génétique, Hôpital Edouard Herriot, Lyon, France. 27. Department of Endocrinology, Groningen University Medical Center, Groningen, The Netherlands. 28. Genomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Abstract
BACKGROUND: Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. METHODS: Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients. RESULTS: Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST. CONCLUSION: Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST.
BACKGROUND:Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. METHODS: Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients. RESULTS: Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST. CONCLUSION: Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST.
Authors: Gautam U Mehta; H Jeffery Kim; Paul W Gidley; Anthony B Daniels; Mia E Miller; Gregory P Lekovic; John A Butman; Russell R Lonser Journal: J Neurol Surg B Skull Base Date: 2021-04-08