May 2022 – Neuropathology Case One

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).

Image 1: Sagittal T1 post-contrast
Image 2: H&E 100x
Image 3: H&E 200x
Image 4: H&E 400x
Image 5: (A) GFAP 200x; (B) ATRX 200x; (C) IDH1-R132H, H3 K27M, BRAF V600E 200x; (D) Ki-67 200x
Image 6: Chromosomal microarray analysis demonstrating CDKN2A and CDKN2B homozygous deletion (arrow)

Further characterization by whole genome methylation was performed. Which methylation class did this tumor most likely match to?

  • IDH glioma, subclass astrocytoma
  • Low-grade glioma, subclass midline pilocytic astrocytoma
  • High-grade astrocytoma with piloid features
  • Glioblastoma, IDH wildtype, subclass midline

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.


  1. WHO Classification of Tumours Editorial Board. Central nervous system tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 6).
  2. Reinhardt A, Stichel D, Schrimpf D, et al. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol. 2018;136(2):273-291.
  3. Jaunmuktane Z, Capper D, Jones DTW, et al. Methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre. Acta Neuropathol Commun. 2019;7(1):24.
  4. Gareton A, Tauziède-Espariat A, Dangouloff-Ros V, et al. The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population. Acta Neuropathol. 2020;139(2):287-303.
  5. Priesterbach‐Ackley LP, Boldt HB, Petersen JK, et al. Brain tumour diagnostics using a DNA methylation‐based classifier as a diagnostic support tool. Neuropathol Appl Neurobiol. 2020;46(5):478-492.
Kathryn Eschbacher profile square

Kathryn Eschbacher, M.D.
Fellow, Anatomic Pathology/Neuropathology
Mayo Clinic

Jorge Trejo-Lopez, M.D.
Senior Associate Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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