Presenter
Jacob A. Houpt
Authors
Jacob A. Houpt 1, Hao Li 1, Lee-Cyn Ang 1, David Ramsay 1, Cynthia Hawkins 2, Qi Zhang 1
1 Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada.
2 Hospital for Sick Children, Toronto, ON, Canada.
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 19-month-old left-hand dominant female was found to have a mass in the left frontoparietal lobe with concern for diffuse leptomeningeal involvement for which surgical resection was undertaken. Despite also undergoing an extensive regimen of chemotherapy, a recurrence was detected along the anterior aspect of the resection cavity 3 years later. Repeat excision was undertaken followed by radiation to the tumour bed. Following the second surgery, she was left with right-sided hemiplegia and hemiparesis.
At 19 years of age (approximately 15 years later), she began experiencing multiple 3-minute episodes of sudden repetitive horizontal eye movement, breathlessness, and facial droop, occasionally preceded by light-headedness and double vision. She was diagnosed with focal epilepsy which proved to be drug-resistant. Electroencephalography identified epileptogenic foci arising from the left frontoparietal resection cavity. Prompted by this, the clinician requests a retrospective review of the pathological diagnoses.
Discussion points
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What is the differential diagnosis?
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What special stains, IHCs, or ancillary testing would be most informative?
Reveal Diagnosis
Atypical teratoid/rhabdoid tumour (AT/RT), WHO Grade 4. The morphological differential includes other embryonal/neuroepithelial tumours (such as medulloblastoma and CNS tumour with BCOR ITD), mesenchymal tumours (such as chordoma, FET::CREB+ intracranial mesenchymal tumour, and CIC-rearranged sarcoma), and germ cell tumours.
Additional relevant investigations and comment.
IHC: loss of SMARCB1/INI1 immunoexpression is seen in over 95% of AT/RT cases, assisting in narrowing the differential diagnosis to AT/RT and poorly-differentiated chordoma given the morphology. The latter can be reliably excluded via lack of brachyury immunoexpression. Characteristically immunopositive IHCs in AT/RT include EMA, vimentin, and smooth muscle actin, though numerous glial and neuronal markers can also be expressed. Periodic acid Schiff special stain might be considered to exclude the presence of cytoplasmic glycogen if Ewing sarcoma is also suspected. SMARCA4 IHC can be undertaken if AT/RT remains a consideration in cases of retained SMARCB1 expression.
Methylation classification: the recurrent tumour was classified with NIH Bethesda v2 as atypical teratoid rhabdoid tumour SHHactivated (with score 0.997).
Copy number profiling: the recurrent tumour was found to harbour gains of chromosomes 1q, 5, and 7, and a loss ofchromosome 18.
Comment: long-term (23 year) survival interval, in particular following local recurrence, is extremely unusual in cases of atypical teratoid/rhabdoid tumours. The retrospective pathological review of this case was requested due to the uncharacteristic/unexpected survival interval and the numerous new tumour entities described (including other SMARCB1-
deficient entities) since the original diagnosis was made.
References
DOI: 10.1002/cncr.27373
DOI: 10.1093/neuonc/noab106
DOI: 10.1093/neuonc/noae064.011
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