Case description
A 2-year old male with a 1.5-year history of slight developmental delay and progressive visual disturbance associated nystagmus was referred for MRI by his ophthalmologist. Family history was potentially contributory due to consanguineous marriage. The child was showing marked nystagmus, and poor vision. No stigmata of neurofibromatosis type I (NF1) were present. MRI revealed a suprasellar mass, measuring 4.9cm x 5.6cm x 3.8cm extending to the hypothalamus, basal ganglia, thalami, posterior limb of internal capsules, optic tract and lateral geniculate nuclei, as well as the cerebral peduncles (Fig 1). The patient underwent a biopsy and histological examination was consistent with the diagnosis of PLGG with piloid features. Immunostains showed positivity for GFAP and BRAFV600 mutation. Tumor cells were immunopositive for MLH1, MSH2, MSH6 and PMS2. The MIB-1 proliferation index was up to 2%. Further testing revealed the presence of a FGFR1 N546K mutation.
Postoperatively, the patient started weekly vinblastine for 70 weeks. He showed a mixed response to this treatment, with regression of the chiasmatic component, while the temporal component experienced mild progression. Due to the significant size of the tumor and poor vision, the child was then placed on dabrafenib. His tumor remained stable, although the vision continued to deteriorate. In this context, tramatenib was added 15 months later. No clear benefit of this addition was observed clinically and radiologically, and vision continued to progressively deteriorate to complete blindness. After two years of dual treatment, the patient presented with dysphagia, ataxia, dizziness, right-sided weakness and slurred speech and the decision was made switch to a trial of immune checkpoint inhibitor, as the tumor tested positive for PD-L1. One week after termination of the combination therapy, the patient experienced acute deterioration, with poor responsiveness, unsteady gait and worsening speech. His MRI showed substantial increase in tumor size. Re-introduction of dabrafenib did not improve his symptoms, and the GSC of the child was fluctuating between 7 and 11, despite high-doses of dexamethasone (4 mg//m2 QID). Parents declined the option of whole brain radiotherapy and it was decided to initiate TPCV. His condition remained severely compromised for 2 months. Due to severe side effects of high-dose dexamethasone, bevacizumab was initiated at 10mg/kg via IV biweekly for 4 cycles. His clinical condition started to improve after two cycles of TPCV, and after 4 cycles, the MRI scan show marked improvement (Fig 1). TPCV was continued for 6 cycles, after which it was discontinued due to thrombocytopenia. During treatment, he was offered intensive rehabilitation and was able to resume school 4 months following initiation of treatment. Two years after completion of TPCV, the patient is clinically well, with a Lansky score of 100% and stable MRI scan.