Table 2 Pediatric CNS-JXG cases with BRAF V600E status with clinical, imaging, and treatment findings
Case | BRAF V600E Status | Sex | Age at diagnosis (y) | Radiology/ Location | Systemic Disease | Treatment and follow-up |
|---|---|---|---|---|---|---|
Pediatric BRAF-V600E CNS-JXG patients (n = 5). | ||||||
1 | Mutated | M | 3 | Unifocal: Pituitary stalk thickening and loss of bright spot on MRI. | No; LCH staging did not reveal additional lesions, including PET and CT of chest and abdomen | Presumptive MRI diagnosis of LCH with DI, started on LCH III based Rx (Prednisone and vinblastine) with mild progression of the lesion and suprasellar extension at 12 weeks. Bx performed with Rx continued for 12 mo. Stable thickening of pituitary at 2.5 y following Rx completion. No other lesions noted with central diabetes insipidus. |
2 | Mutated | F | 4 | Multifocal: Enhancing, dominant, right frontal lobe lesion, along with T2 hypointense cerebral, cerebellar, and brain stem nodules with background of symmetric T2 white matter hyperintensity. | Yes-systemic with JXG BRAF-V600E positive cutaneous lesions; but: no imaging suggestive of classic ECD lesions | Clofarabine and dexamethasone (cycle 4, 4 months after initial biopsy), demonstrating clinical and radiographic improvement |
3* | Mutated | M | 7 | Multifocal: Enhancing intracranial, dural plaque-like thickening, sellar/suprasellar, 4th ventricle, posterior fossa, cavernous sinus | Yes –ECD confirmed on bone scan and bx with bilateral tibial sclerosing lesions | Partial resection/debulking with progression after 6 mo. 2 cycles clofarabine with progression. After dx of ECD, started on Anakinra 2 mg/kg. At 2 y f/u MRI improvement of CNS and osseous lesions. |
4 | Mutated | M | 9 | Multifocal: Enhancing Intraventricular and subependymal masses (bilateral), enlarged pituitary, Increased T2 signal pons, WM of cerebellum including dentate nuclei, post-enhanced T1 signal increase of basal ganglia (bilateral), expansion of cavernous sinuses (bilateral) (Ddx included LCH) | N – Multiple body imaging including MRI of spine, negative skeletal survey | Progressive ataxia since 4.5 yo. Imaging 4 mo after bx with extensive enhancing lesions suggestive of ‘perivascular spread’ abnormal WM signal (FLAIR): bihemispheric subcortical areas (subinsular, thalami, basal ganglia), WM of temporal/parietal/occipital lobe, and WM of cerebellar hemispheres, brain stem, mesial temporal (Comment concerning for malignant histiocytosis or demyelinating disease). 23 mo after bx: Encephalomalacia, atrophic changes of the brain, bright T2 both in WM of cerebellum, no enhancing lesions 4 y after bx: Developmental delay with ventriculomegaly and periventricular WM T2 prolongation; Persistent, stable cerebellar WM T1 and T2 prolongation without enhancing lesions 5 yr after dx: Lost to f/u in hospice care |
5 | Mutated | M | 12 | Multifocal: Large sellar mass (pituitary and optic chiasm), (enhancing) two dural based temporal masses, two lateral intraventricular masses and cerebellar ND-white changes. | No; After tissue diagnosis: no imaging s/o of ECD lesions. Subsequent MRI showed ND changes in cerebellum | DI since age 7yo, then 4th cranial nerve palsy, decreased visual acuity. MRI and Bx (originally called RDD) with subsequent resection of temporal mass; following 9 mo later with surgical decompression of optic chiasm and panhypopituitarism with cognitive decline. Started on dabrafenib (100 mg ×2/day) with dramatic clinical response. MRI 2 years on I-Rx showed no new lesions and moderate reduction tumor size. No other new lesions noted; with occasional CSF drainage through Ommaya reservoir for intermittent headache. |
Pediatric BRAF wild type CNS-JXG patients (n = 5). | ||||||
6** | Wild-type | M | 1 | Unifocal: Cerebellopontine Angle with encasement of cranial nerves V and VI; MRI heterogenous T1 iso to hypointense and T2 hypointense with contrast enhancement | No | Initial radiographic concern for malignant ependymoma. Gross total resection. Started on prednisone/vinblastine. Postoperative MRI about 1 year with no evidence of recurrent disease. Unchanged postsurgical appearance of the brain including linear/nodular enhancement along the medial aspect of the left posterior fossa resection cavity that is favored to represent postsurgical change. |
7 | Wild-type | F | 2 | Unifocal Thalamus | No | Right hemiplegia at presentation that persists. IV methylprednisolone, follow-ed by oral Prednisolone at presentation that was weaned. No subsequent treatment. Followed with q6 months and now annual MRI brain surveillance scanning with no significant change in the size of the lesion and no new lesions in brain or elsewhere at 4 y follow-up. |
8^ | Wild-type | F | 3 | Multifocal: Cranial nerve/trigeminal involvement with Meckel’s cave, cavernous sinus, orbit, dural, skull base extension | No | Subtotal resection with progression and leptomeningeal spread at 9 mo and 12 mo f/u, managed with prednisone/vinblastine and then cladribine. 18 mo after chemotherapy and 3 yr after surgery, clinically stable with marked shrinkage of multifocal tumor without adjuvant therapy |
9 | Wild-type | M | 14 | Unifocal: Intraparenchymal right temporal lobe | No | Presentation with new onset seizures, hyponatremia, F/u: NA |
10 | Wild-type | F | 18 | Unifocal: Enhancing (homogenously) dural based lesions within the right frontal region (4.4 cm) with regional mass effect and vasogenic edema without restricted diffusion | NA | No significant prior medical history presents with 2 wk. history of progressive worsening bifrontal headaches, dizziness, and intermittent left periorbital and hand paresthesia. After resection, chronic, recurrent headache. 2 year post-resection MRI head surveillance imaging no recurrent tumor |