Cerebellar Hemangioblastoma with Leptomeningeal Spread and a Fatal Outcome: A Rare Case Report with MDM2 and EGFR Alterations

Abstract

Luis Miguel Chinchilla-Tábora,1 Javier Ortiz Rodríguez-Parets,1 Álvaro Otero-Rodríguez,2 Laura Ruiz Martín,2 Juan Carlos Paniagua Escudero,3 Luis Miguel Navarro Martín,4 Belén Cigarral García,4 Adelaida Nieto Palacios,5 Idalia González Morais,1 José María Sayagués,1 María Dolores Ludeña de la Cruz1 1Department of Pathology, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, Spain; 2Department of Neurosurgery, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, Spain; 3Department of Radiology, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, Spain; 4Department of Clinical Oncology, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, Spain; 5Department of Radiation Oncology, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Salamanca, SpainCorrespondence: Luis Miguel Chinchilla-Tábora, Department of Pathology, University Hospital of Salamanca and Institute for Biomedical Research of Salamanca, Paseo de San Vicente, 58-182, Salamanca, PC. 37007, Spain, Tel +34 923291100. Extension: 56738, Email [email protected]: Hemangioblastoma (HB) is a Central Nervous System (CNS) tumor with a generally favorable behavior and prognosis, classified as WHO grade 1. Sporadic HB is not related to any inherited disease, and it usually appears in a single location. Sporadic or VHL-related HBs show variable patterns of growth velocity. Cases of growing HB can cause mild symptoms such as headache, but some cases develop serious complications such as accumulation of cerebrospinal fluid in the brain with secondary neurological damage sometimes being irreversible when early treatment is not started. Our case showed some clinical characteristics more frequently observed in VHL-related HB rather than sporadic HB, and the presence of alterations in MDM2 and EGFR that could be related to the oncogenesis of these tumors. Even when the treatment of choice for HB is surgery, the presence of these genetic alterations could open a new window for research aimed at assessing the possibility of new therapies with TKIs-EGFR and anti-MDM2 inhibitors in those HB cases with multifocal recurrences or cases with an adverse clinical behavior.Keywords: haemangioblastoma, mouse double minute 2, epidermal growth factor receptor, hydrocephalus, immunohistochemistry, fluorescence in situ hybridizatio