The patient is a 45-year-old man who presented with a six-month history of progressive rib and spine pain. An MRI demonstrated a 6.4 cm T2 hyperintense expansile mass with patchy peripheral enhancement involving the thoracic cord from the T8-9 interspace level (Image 1). He subsequently underwent resection. Representative images of the histology and immunohistochemistry are below (Images 2-5). Next generation sequencing revealed this tumor harbored an NF1 and ATRX mutation. Chromosomal microarray analysis demonstrated a CDKN2A/CDKN2B homozygous deletion (Image 6).
The correct answer is ...
Anaplastic pilocytic astrocytoma / High-grade astrocytoma with piloid features.
High-grade astrocytoma with piloid features (HGAP) is a new tumor type in the 2021 WHO Classification of CNS Tumors.1 Epidemiologic data is limited, but non-population based case series suggest this tumor type is rare, particularly in the pediatric population, as the median age at diagnosis is 40 years (range: 4-88 years).2-5 These can occur throughout the CNS, but most commonly arise in the cerebellum.2
Histologically, these tumors can vary greatly in appearance, ranging from histologically bland to high-grade. Importantly, these may show elongated, hair-like cytoplasmic processes, at times morphologically resembling pilocytic astrocytoma. The majority of cases demonstrate abnormal vasculature, ranging from hyperplastic to glomeruloid proliferation.1
Given its morphologic heterogeneity, the diagnosis of this tumor type requires assessment of its molecular profile. Three molecular pathways have been identified as drivers for HGAP, and all three are altered simultaneously in approximately 50% of cases.2 These include MAPK pathway activating mutations; deregulation of the retinoblastoma tumor suppressor protein cell cycle pathway (by CDKN2A/ CDKN2B inactivation or CDK4 amplification); and activation of telomer maintenance by ATRX mutations.2 Currently, DNA methylation profiling is required for the definitive diagnosis of HGAP.
Kathryn Eschbacher, M.D.
Fellow, Anatomic Pathology/Neuropathology
Jorge Trejo-Lopez, M.D.
Senior Associate Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science