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

Abstract

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 hybridization

Abbreviations

HB, hemangioblastoma; CNS, central nervous system; VHL-gene, von Hippel-Lindau gene; VHL-syndrome, von Hippel-Lindau syndrome; pVHL, von Hippel–Lindau protein; FFPE, formalin-fixed paraffin-embedded; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; CNAs, copy number alterations; RT-PCR, reverse transcription-polymerase chain reaction; EGFR, epidermal growth factor receptor; MDM2, murine double minute 2; TKIs-EGFR, EGFR tyrosine kinase inhibitors; EGFR1, epidermal growth factor receptor 1; HER1, human epidermal growth factor receptor 1; EPAS1, Endothelial PAS Domain Protein 1; HIF2A, hypoxia-inducible factor 2-alpha; TGF-α, transforming growth factor-alpha; FGFR3, fibroblast Growth Factor Receptor 3; PDGFRA, platelet Derived Growth Factor Receptor Alpha; CD56, cluster of differentiation 56; CD31, cluster of differentiation 31; CaIX, carbonic anhydrase IX; PAX8, paired box gene 8; PAX2, paired box gene 2; VEGF, vascular endothelial growth factor; ERG, erythroblast transformation-specific [ETS]-related gene; GLUT-1, glucose transporter 1; EMA, epithelial membrane antigen; CD10, cluster of differentiation 10; HIV, human immunodeficiency virus; MRI, Magnetic Resonance Imaging; DW-MRI, diffusion-weighted magnetic resonance imaging; ADC, apparent diffusion coefficient; Brain-CT, computed tomography of the brain; PEG, percutaneous endoscopic gastrostomy; WHO, World Health Organization.

Data Sharing Statement

The data are publicly available in the following link:

https://github.com/LMCT-Repository/MDM2-and-EGFR-Alterations-in-HaemangioblastomaHemangioblastoma.git.

Ethics Approval Statement

This manuscript has been reviewed and authorized by the ethics committee of the University Hospital of Salamanca. No private personal data of the patient have been revealed in this manuscript.

Patient and Patient’s Family’s Consent Statement

The patient’s family authorized and consented to the publication. The informed consent signed by the patient’s family included in the clinical data contemplates the scientific disclosure of relevant findings if the privacy of personal data is respected.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare for this work.

Additional information

Funding

No funding was received by the authors to make this article.