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This study identifies a new type of superficial fibroma, CTNNB1-mutated superficial fibroma, which resembles Gardner fibroma but has different genetic underpinnings and behavior. These findings help distinguish them from other fibromas and aggressive desmoid tumors.

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Area of Science:

  • Oncology
  • Dermatopathology
  • Molecular Pathology

Background:

  • Superficial fibromas are diverse mesenchymal tumors, some linked to genetic syndromes like Gardner syndrome (familial adenomatosis polyposis).
  • Gardner fibroma, associated with APC mutations, is a benign superficial tumor. Patients are at increased risk for desmoid fibromatosis (DTF), a locally aggressive neoplasm.
  • Most DTFs arise sporadically due to CTNNB1 mutations, but a superficial, non-syndromic CTNNB1-mutated fibroma equivalent to Gardner fibroma was previously undefined.

Observation:

  • Two cases of subcutaneous tumors with a hypocellular, collagen-rich, Gardner fibroma-like histology are presented.
  • These tumors exhibited pathogenic, somatic CTNNB1 mutations.
  • Histological, immunohistochemical, and molecular profiles were analyzed to differentiate these lesions.

Findings:

  • The presented tumors are characterized by a Gardner fibroma-like appearance and somatic CTNNB1 mutations.
  • These CTNNB1-mutated superficial fibromas are distinct from syndromic Gardner fibromas and locally aggressive desmoid fibromatosis.
  • Key differences lie in histological features, immunohistochemical profiles, molecular drivers, biological behavior, and prognosis.

Implications:

  • This work defines CTNNB1-mutated superficial fibromas as a distinct entity, serving as a sporadic counterpart to syndromic Gardner fibromas.
  • Accurate differentiation is crucial for appropriate management, prognosis, and therapeutic strategies, distinguishing them from benign fibromas and aggressive desmoid tumors.
  • Understanding the molecular basis (CTNNB1 mutations) provides insights into fibroma tumorigenesis and potential targeted therapies.