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The Desmoid Tumor Research Foundation

July 2025

Desmoid fibromatosis in a child with DICER1-related tumor predisposition

Author Information

Paul Scott Thorner 1, Anne-Laure Chong 2 3, Sung Mi Jung 4, Gabriel P P Fox 5 6, Martin Corbally 7, William D Foulkes 8 9 10 11 12

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 2Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. 3Cancer Axis, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada. 4Department of Pathology, McGill University, Montreal, QC, Canada. 5Department of Pediatrics, King Hamad University Hospital, Muharraq, Bahrain. 6Department of Pediatrics, The Royal College of Surgeons in Ireland, Muharraq, Bahrain. 7Department of General Surgery, King Hamad University Hospital, Muharraq, Bahrain. 8Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. william.foulkes@mcgill.ca. 9Cancer Axis, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada. william.foulkes@mcgill.ca. 10Department of Human Genetics, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca. 11Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca. 12Division of Medical Genetics, Department of Specialized Medicine, The Lady Davis Institute, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, H3T 1E2, Canada. william.foulkes@mcgill.ca.

Publication

Virchows Arch

Summary

DICER1-related tumor predisposition is an inherited disorder, generally pediatric in onset, featuring a characteristic array of mainly mesenchymal tumors. We report a chest wall desmoid fibromatosis, occurring in a child who uniquely carries a germline "hotspot" DICER1 variant that likely leads to impaired miRNA biogenesis in all cells. This lesion contained a hotspot CTNNB1 c.134C > T, (p.S45F) exon 3 somatic mutation and immunohistochemistry showed nuclear accumulation of β-catenin. Desmoid fibromatosis is known to be associated with dysregulation of β-catenin, resulting from altered APC or CTNNB1, leading to increased WNT pathway signaling. In fetal lung tumors linked to DICER1 hotspot variants, APC and/or CTNNB1 somatic mutations are found in most cases, suggesting a synergistic effect with DICER1 hotspot mutation to increase WNT pathway signaling. We postulate a similar mechanism is involved in this case and that desmoid fibromatosis is a rare mesenchymal lesion that could be part of DICER1-related tumor predisposition.

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