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A primary DICER1-sarcoma with KRAS and TP53 mutations in a child with suspected ECCL

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Abstract

A child had been followed since infancy by our multi-disciplinary neuro-oncology clinic with annual magnetic resonance imaging (MRI) under the presumed diagnosis of encephalocraniocutaneous lipomatosis (ECCL), with clinical features including nevus psiloliparus, scalp lipoma, nodular skin tag on and coloboma of the eyelid, cortical atrophy and meningeal angiomatosis. At the age of 4, she was found to have a large temporoparietal lesion causing elevated intracranial pressure requiring surgical resection. Histopathological exam of the tumor was suggestive of an intracranial sarcoma. Sequencing analysis of the tumor revealed mutations in DICER1, KRAS and TP53. Subsequent germline testing confirmed DICER1 syndrome and revealed an insignificant FGFR1 variant at a low frequency. Methylation profile of the tumor showed the tumor clustered most closely with sarcoma (rhabdomyosarcoma-like), confirming this tumor to be a primary DICER1-sarcoma. Compared to the previously reported cases, our unique case of primary DICER1-sarcoma also demonstrated neurofilament and chromogranin positivity, and genomic instability with loss of chromosome 4p, 4q, 8p, 11p, and 19p, as well as gains in chromosome 7p, 9p, 9q, 13q, and 15q on copy variant analysis. The detailed sequencing and methylation information discovered in this unique case of DICER1-sarcoma will hopefully help further our understanding of this rare and emerging entity.

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Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

CNS:

Central nervous system

CT:

Computed tomography

ECCL:

Encephocraniocutaneous lipomatosis

MRI:

Magnetic resonance imaging

RMS:

Rhabdomyosarcoma

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Acknowledgements

We wish to thank Ms. Bruna Capretta for her administrative assistance.

Funding

The authors have no funding to declare.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Toronto, Toronto, ON, Canada

    Kaiyun Yang, Justin Wang & Gelareh Zadeh

  2. Princess Margaret Cancer Center, MacFeeters-Hamilton Center for Neuro-Oncology Research, University of Toronto, Toronto, ON, Canada

    Justin Wang, Vikas Patil, Yasin Mamatjan, Qingxia Wei & Gelareh Zadeh

  3. Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada

    Nisha Kanwar

  4. Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Anita Villani & David Malkin

  5. Division of Neurosurgery, Department of Surgery, McMaster University, Hamilton, ON, Canada

    Olufemi Ajani

  6. Division of Hematology/Oncology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada

    Adam Fleming

  7. Department of Engineering, Thompson Rivers University, Kamloops, BC, Canada

    Yasin Mamatjan

  8. Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, Toronto, ON, Canada

    Adam Shlien

  9. Neuropathology Section, Department of Pathology and Molecular Medicine/Neuropathology, Hamilton General Hospital, McMaster University, 237 Barton Street, Hamilton, ON, L8L 2X2, Canada

    John Provias

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  1. Kaiyun Yang
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  2. Justin Wang
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  10. David Malkin
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Contributions

KY, JW, VP, YM, QW and GZ contributed to the analysis and interpretation of the methylation profile. NK, AV, DM and AS contributed to the analysis and interpretation the sequencing data. KY and JP contributed to the histopatholoical exam of the tumor. OA and AF participated in the clinical care of this patient. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kaiyun Yang or John Provias.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

Institutional ethical approval is not required for the case report.

Consent for publication

The parents have consented to the molecular studies and genetic sequencing of the specimens, and the publication of this case report.

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Yang, K., Wang, J., Kanwar, N. et al. A primary DICER1-sarcoma with KRAS and TP53 mutations in a child with suspected ECCL. Brain Tumor Pathol 39, 225–231 (2022). https://doi.org/10.1007/s10014-022-00437-2

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  • DOI: https://doi.org/10.1007/s10014-022-00437-2

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