Presenter
Jacob A. Houpt
Authors
Jacob A. Houpt 1, Tommaso Romagnoli 1, Christopher Howlett 1, Shayna Zelcer 2, Lee-Cyn Ang1
1 Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada
2 Division of Haematology/Oncology, Western University, London, ON, Canada
Clinical Summary
A 4-year-old left-hand dominant boy with a two-week history of morning headaches and vomiting, constipation, and lethargy. A CT scan of the head revealed a right frontal cystic lesion with a peripherally enhancing nodule, for which he was treated with two resections (the second after local recurrence), chemotherapy, and consolidative radiotherapy. Four months from initial diagnosis, he developed dizziness, unsteadiness, and right leg numbness and weakness, with imaging demonstrating a second cystic/solid lesion in the deep left cerebellum. This new lesion was also treated with surgical resection, and prompted a second course of radiotherapy.
Shortly after this third surgery, the patient began experiencing episodes of repetitive protrusions of the tongue and jerking movements of the eyes. He also had right facial rigidity and tight flexion of the left arm. His admitting neurologist attributed this presentation to dystonia rather than seizure activity.
Following travel for focal proton radiotherapy, the patient returned to hospital with a 48-hour history of severe abdominal pain, constipation, and distention. He unfortunately passed away 3 days after admission.
Discussion points
- What is the differential diagnosis for the original tumour, and what special stains, IHCs, or ancillary testing would be most informative?
- What are possible causes of the patient’s neurological findings after his 3rd surgery, and what autopsy findings could explain them?
- What is the likely cause of the abdominal symptoms?
Reveal Diagnosis
Diagnosis:
Original tumour: CIC-rearranged sarcoma, with CIC::DUX4-fusion. The differential would include Ewing sarcoma, intracranial
mesenchymal tumour FET::CREB fusion-positive, and primary intracranial sarcoma DICER1-mutant.
Neurological presentation: oculo-palatal tremor and dystonia, with potential causes including neuronal and tract degeneration
involving areas of the triangle of Mollaret (secondary to surgery, residual tumour, or inflammation induced by either),
hydrocephalus due to tumour involvement of the foramen of Luschka, or medication effect. Relevant autopsy findings include
degeneration of the dentate nucleus, contralateral inferior olivary complex, and superior and inferior cerebellar peduncles, as
well as the recurrent/residual tumour and associated post-surgical reactive changes.
Abdominal symptoms: Abdominal pain, distention, and constipation was caused by diffuse peritoneal seeding secondary to
recent initiation of VP shunt therapy, which led to involvement of the bowel by innumerable metastatic deposits.
Additional relevant investigations and comment.
IHC: CD99 and vimentin are often positive, but WT1+, ETV4+, and NKX2.2- are findings most useful for distinguishing from
Ewing sarcoma. SMARCB1- can help to rule-out AT/RT, and NUT IHC can be useful in cases of CIC::NUTM1-fusion.
Fusion panel: used to confirm the CIC::DUX4-fusion, or other fusion partners.
Methylation profiling: following an initial diagnosis as high-grade neuroepithelial tumour (HGNET), methylation profiling favoured
CIC-rearranged sarcoma, which then prompted specific fusion testing.
References (optional)
DOI: 10.7759/cureus.11109
DOI: 10.1016/j.parkreldis.2020.05.028
DOI:10.1002/mdc3.12193
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