RB1 Loss as a Diagnostic Clue in a High-Grade Glioma With Pleomorphic and Pseudopapillary Features (HPAP): The First Reported Case With Spinal Metastasis and a Review of the Literature.

High-grade glioma with pleomorphic and pseudopapillary features (HPAP) is a recently described entity defined by a distinct DNA methylation signature, recurrent monosomy 13, and mutations in TP53, RB1, and NF1. Most cases are supratentorial with a relatively favorable prognosis. We report a 45-year-old woman who presented with a right cerebellar mass exhibiting striking histopathological heterogeneity comprising low-grade and high-grade components. The high-grade component demonstrated a p53 null immunophenotype and complete loss of RB1 expression, contrasting with wild-type staining in the low-grade areas. Molecular analysis confirmed pathogenic variants in TP53 (p.Pro27LeufsTer17), NF1, and NF2, with losses of chromosomes 13 and 17. Despite gross total resection and adjuvant chemoradiotherapy, the patient developed spinal intradural metastasis 26 months postoperatively. The metastatic lesion mirrored the high-grade primary component immunohistochemically and harbored a newly acquired TERT promoter mutation. DNA methylation profiling of the spinal metastasis classified the tumor as HPAP. This case represents the first documented spinal metastasis and the first p53 null phenotype in HPAP, suggesting a potential role for combined RB1 and p53 immunohistochemistry in the diagnostic workup and highlighting the capacity for neuraxis dissemination in this emerging entity.