PATH-14. A CLINICAL CONUNDRUM - INFANTILE POSTERIOR FOSSA EPENDYMOMA WITH YAP1:MAML FUSION?

Abstract

Abstract BACKGROUND Ependymomas of infancy (0-18months) have been reported to comprise distinct clinical, pathological and genetic entities. Young age is typically associated with posterior fossa group A (PF-A) tumours and therefore a poor prognosis. Treatment of these infants is challenging with limited therapeutic options that have significant long-term sequelae. METHOD We report a single case of a 4-month old baby girl who presented with obstructive hydrocephalus and a presumed posterior fossa mass. RESULTS Imaging demonstrated a large fairly well-defined solid lesion with multiple T1 high and corresponding T2 intermediate signal intensity foci scattered throughout the lesion and marked mass effect on the cerebellum and fourth ventricle. The lesion was inseparable from the pineal gland, habenula and tectum and only mild diffusion restriction. Whilst initially considered to be a posterior fossa tumour, the presence of a claw sign with the tectal plate, favoured a tectal origin. Histological appearances, together with immunohistochemistry findings (GFAP positive and EMA patchy perinuclear dot expression) were consistent with classic ependymoma. Grading was difficult as mitotic activity was relatively low, although focal areas of high ki67 proliferation index were noted suggesting at least focal grade 3 areas. Retained expression of tumour cells for H3K27me3 on immunohistochemistry suggested the likely posterior fossa group B (PF-B) ependymoma. Local SNP chromosome microarray found no acquired clonal abnormality; with no detection of gain chromosome 1q; loss/LOH 6q; Loss/LOH 9p21.3 [CDKN2A, CDKN2B], chromothripsis 11q [ZFTA::RELA], Loss/LOH 17p13 [TP53] or Loss/LOH 22q [NF2]. Additional NGS sequencing identified a YAP1::MAML2 fusion (confirmed with targeted RT-PCR followed by subsequent Sanger sequencing). CONCLUSION This case highlights the challenges with overlapping clinical, pathological and radiological features in an infant with ependymoma, necessitating a molecular diagnosis. After 21months, the patient remains in complete remission following surgery alone.