LGG-36. DESMOPLASTIC INFANTILE GANGLIOGLIOMA (DIG) WITH A PPP1CB-ALK FUSION IN A 6-YEAR-OLD GIRL

Abstract

Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are benign glioneuronal tumors that typically occur in infants, involve the superficial cerebral cortex, and have an excellent prognosis. DIA/DIG are a distinct molecular entity based on DNA methylation profiling. BRAF600 mutations are frequently reported in DIG/DIA. A recent comprehensive genetic analysis of infantile hemispheric gliomas identified 2 unique groups: group 1 harbored alterations in the receptor tyrosine kinase (RTK) genes ALK, ROS1, NTRK, and MET and group 2 harbored alterations in the RAS/MAPK pathway. We report a case of a 6.5-year-old girl who presented with seizures and right homonymous hemianopia. MRI of her brain demonstrated a large cystic/solid left hemispheric mass with remodelling of the overlying skull, consistent with a long-standing process. She underwent a gross total resection (GTR) and pathology demonstrated a DIG with a PPP1CB-ALK gene fusion (exon 5 to exon 20) identified by RNA sequencing. She remains disease free 12 months following GTR. A literature review identified 4 reported cases of pediatric brain tumors with PPP1CB-ALK gene fusions including: a 3-month-old with a hemispheric high-grade glioma which recurred 4 years later and pathology showed mature ganglioglioma, with both tumors showing the identical PPP1CB-ALK gene fusion; a 10-month-old infant with a hemispheric low-grade glioma; an infant with a “congenital” hemispheric high-grade glioma; and a child with an astrocytoma with no further clinical data. PPP1CB-ALK gene fusion appears to be a rare oncogenic driver in gliomas of infancy, including DIG.