Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review

Abstract

Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. It may arise sporadically in a solitary form, or associated with Von Hippel-Lindau (VHL) disease with multiple tumors. Surgery is the mainstay treatment, but management is challenging in case of recurrent and/or multiple tumors. VHL protein is defective in both forms of hemangioblastoma, leading to the accumulation of hypoxia-inducible factor, stimulating angiogenesis via VEGF and PDGF mainly. Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-β pathways. Despite moderate radiological changes, progressive improvement in her clinical condition persisting over 3 years was observed. Inhibiting angiogenesis is a therapeutic option that may improve the quality of life and the autonomy of VHL patients disabled with multiple hemangioblastomas.

Keywords: Von Hippel–Lindau disease; hemangioblastoma; pazopanib.

Figure 1.. Illustrative examples of the hemangioblastomas arising from 2002 to 2012.

Figure 2.. Pathology description.

Hematoxylin and Eosin (H/E) staining (A) or immunostaining (B–D) were performed on formalin-fixed and paraffin-embedded histological sections. (A) Tumor proliferation is characterized by stromal cells situated in a dense capillary network. (B) Immunostaining demonstrates strong and diffuse S100 positivity in stroma cells. (C) The presence of a dense capillary network is illustrated by the endothelial marker CD34 staining. (D) Only few proliferating cells are detected by immunostaining for Ki67. Scale bars for A–C: 100 μm, for D: 200 μm.

Figure 3.. C3-C4 target lesion evolution under therapy.

Intramedullary contrast-enhancing lesion at the level of C3–C4 (white arrow) with associated myelopathy (A), February 2012 baseline MRI (sag T1Gd), which remains stable at follow-up (9 months later (B) and 15 months later (C)). Note the presence of the other known lesion at the level of C1 (gray arrow), the postoperative changes at the level of C6 (only partially displayed), and the anterior spinal artery (blue arrow).