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<p>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” <i>DICER1</i> variant that likely leads to impaired miRNA biogenesis in all cells. This lesion contained a hotspot <i>CTNNB1</i> c.134C &gt; 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 <i>APC</i> or <i>CTNNB1</i>, leading to increased WNT pathway signaling. In fetal lung tumors linked to <i>DICER1</i> hotspot variants, <i>APC</i> and/or <i>CTNNB1</i> somatic mutations are found in most cases, suggesting a synergistic effect with <i>DICER1</i> 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.</p>

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Desmoid fibromatosis in a child with DICER1-related tumor predisposition

  • 期刊论文

  • 发表日期：

    2025年7月12日

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  • Paul Scott Thorner,
  • Anne-Laure Chong,
  • Sung Mi Jung,
  • Gabriel P. P. Fox,
  • Martin Corbally,
  • William D. Foulkes

摘要

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.