2025 – Case 1

by | Sep 26, 2025 | 2025 Diagnostic Case Studies

Presenter

Madison Gray

Bio

Dr Gray is a staff neuropathologist at the CHUM in Montreal and an assistant professor in the department of Pathology and Cellular Biology at the Université de Montréal. He completed medical school at the University of Ottawa and a PhD at SickKids & the University of Toronto before finishing his neuropathology training at the University of Western Ontario.

Authors

Madison T. Gray 1 2, Sarah Lapointe 3 4, Romain Cayrol 1 2

 1 Neuropathology service, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
2 Department of Pathology and Cellular Biology, Université de Montréal, Montreal, QC, Canada
3 Department of Medicine, Centre Hospitalier de l’Université de Montréal
4 Department of Neurosciences, Université de Montréal

Conflict of Interest

I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose.

Clinical Summary

A 51-year-old previously healthy woman presented to our institution with diplopia secondary to a bilateral CN VI palsy. Family history was not notable for CNS or epithelial neoplasms. Imaging showed a 3 x 2 x 2 cm contrast-enhancing tumor of the pineal region with aqueductal compression and triventricular hydrocephalus. A ventriculoscopy and partial resection of the lesion was performed. Methylation profiling matched to a distinct tumour class but routine sequencing results were disconcordant.

Discussion points

  1. Differential diagnosis
  2. Immunohistochemical and molecular workup?
  3. Pathogenesis of this and similar lesions?
H&E-stained slide
Slide stained for ATRX
Reveal Diagnosis
High-grade glioma with SDH deficiency, NEC

Additional relevant investigations and comment:
An initial targeted next-generation sequencing (NGS) panel found a TP53 mutation (p.Arg248Gln) but no IDH1 or IDH2 alterations.
DNA methylation profiling classified the tumor within the methylation classes “diffuse glioma, IDH-mutant family ” (DKFZ v12.8,score 0.973) and “astrocytoma, IDH-mutant; high grade” (NIH Bethesda v2, score 0.981).
FH immunostaining was retained and 2SC expression was not increased (data not shown).
Broader NGS testing (Illumina Trusight RNA Pan-Cancer), however, showed a mutation in SDHA (p.Arg585Trp, VAF 0.43) previously observed in other SDH-related neoplasms.
To determine the integrity of the SDH complex, we performed SDHB immunostaining which showed loss of expression in tumor cells suggesting a defect in the SDH holoenzyme.

References (optional)
2025 AANP DSS case 3 (Dan Marker, UPitt) –
https://neuro2.pathology.pitt.edu/dsa/api/v1/file/685882c56737e900a0d9dc36/download?

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