Prolonged Response Induced by Single Agent Vemurafenib in a BRAF V600E Spinal Ganglioglioma: A Case Report and Review of the Literature

Abstract

Spinal ganglioglioma is a rare low-grade, slow-growing tumor of the central nervous system affecting mostly children and young adults. After surgery, some patients show tumor recurrence and/or malignant transformation. Gangliogliomas harbor molecular deficiencies such as mutations in the B-rapidly accelerated fibrosarcoma (BRAF) gene, resulting in activation of a downstream signaling pathway and cancer development. Vemurafenib is a BRAF inhibitor used to treat patients with BRAF V600E-mutated cancer. Although a few studies have reported the clinical responses in gangliogliomas, the sequence and duration of treatment have not been established. We describe a case of an adult with a progressive BRAF V600E mutant spinal cord ganglioglioma 9 years after surgery who was treated with vemurafenib. This treatment resulted in a partial response within 2 months, which was sustained for more than a year. The patient then decided to stop treatment because of side effects. Despite this decision, the tumor showed no sign of progression 21 months after treatment discontinuation. This is the first reported case of a response to vemurafenib in an adult with progressive spinal cord BRAF V600E-mutated ganglioglioma which was sustained after treatment discontinuation.

Keywords: BRAF; central nervous system tumor; ganglioglioma; safety; spinal cord; tumor regression; vemurafenib.

Figure 1

Axial T1-weighted images between C3 and C4 of T1-weighted cervical spine magnetic resonance imaging (MRI) after gadolinium injection administration show dominant, patchy intense enhancing left-sided lesion within the spinal cord (arrows) 1 month after surgery, in pre-treatment with vemurafenib, 8 weeks after the beginning of vemurafenib, 2 months after vemurafenib discontinuation, and last follow-up (A). Sagittal post contrast T1-weighted images revealed lesions between C3 and C4 as well as C4 and C5 (arrows) 1 month after surgery, in pre-treatment, 8 weeks after beginning treatment, 2 months after discontinuation, and last follow-up (B). Sagittal T2-weighted images showing syringomyelia (arrowheads) rostral and caudal to the intramedullary tumor 1 month after surgery, at pre-treatment, 8 weeks after beginning treatment, 2 months after discontinuation, and last follow-up. Note the T2 hyperintensity in the spinal cord above and below the syringomyelia without associated enhancement (C).

Figure 2

Astrocytic glial cell population with grouped ganglion cells, marked in hematoxylin-Eosin-Saffron staining (original magnification X18) (A), neuronal components characterized by larger numbers of binucleated or multinucleated cells (arrowheads) with a cellular glial background evaluated by hematoxylin-Eosin-Saffron staining (original magnification X28) (B).

Figure 3

Dermatological toxicities after 13 months of vemurafenib, representing a grade II maculopapular rash (A), microcysts (B), and hyperkeratosis as part of palmar-plantar erythrodysesthesia syndrome (C).