BACKGROUND: Giant cell tumors (GCTs) are rare, benign but osteolytic neoplasms that typically arise from the epiphyses of long bones; fewer than 1% have been found to involve the skull or skull base, most of which involve the sphenoid and temporal bones, less commonly the occipital bone.1 These tumors are primarily diagnosed in young adulthood, 3,4 with very few documented cases in childhood, and only two publications to date involving infants. Further, there is a paucity of literature regarding the subset of GCTs with the HMGA::NOCR2 mutation.2 These authors discuss an extremely rare case of a neonate diagnosed with a primary skull base HMGA::NCOR2 fusion GCT treated with surgical management.
CASE PRESENTATION: An 8-day-old female, who failed her newborn hearing screen with her left ear, initially presented to an outside hospital for progressive difficulty breathing and vomiting. Medical workup was negative for structural or infectious etiologies. CT Head was performed, showing a large, left occipital enhancing extra-axial mass with associated erosion of the occipital and temporal bones, destruction of the mastoid air cells, semi-circular canals, and widening of the jugular foramen at the skull base with severe mass effect on the cerebellum. Subsequent MRI demonstrated a T1 isointense, T2 hypointense, enhancing, hypervascular extra-axial lesion with central necrotic core (Figure 1). At 16-days-old, the patient underwent lesional biopsy, with initial pathology suggestive of juvenile xanthogranuloma, however, final pathology and updated gene sequencing demonstrated a HMGA-NCOR2 mutation, consistent with giant cell neoplasm. Given the very young age of the patient, she was initially treated with chemotherapy including prednisone, vincristine and cytarabine, with no response. Rather, progression of the tumor was noted and patient underwent two subtotal surgical debulkings at ages 3 and 4 months (Figure 2). The patient was transferred to our institution for a higher level of care and additional management. After optimization of nutrition and weight, patient underwent definitive resection of the tumor at 6-months of age. Surgical treatment resulted in near total resection with residual tumor notably left on CN VII where additional tumor removal threatened cranial nerve dysfunction (Figure 3).
DISCUSSION: Skull base GCTs are a rare entity, accounting for only 1% of all GCTs, with the majority of cases described in young adults.3,4 Even rarer, is the incidence of pediatric skull base GCTs, particularly the subset of tumors harboring the HMGA2::NCOR2 fusion. Furthermore, prior literature describing the HMGA2::NCOR2 fusion subtype of GCTs in children demonstrate keratin-positivity on pathology, 4 which was not seen in this patient’s tumor histopathology. Interestingly, tumors with this translocation have also been documented to overexpress CSF1R and thus, susceptible to pexidartinib treatment; we did not identify overexpression of CSF1R in our case. While the clinical relevance of this is unclear, our case report further informs our understanding this subset of GCTs.
CONCLUSION: To our knowledge, we present the youngest documented case to date treated primarily with surgical intervention with a promising outlook. We are also the first to describe this already rare GCT subtype with these unique pathology characteristics.
