CTNNB1 Mutational analysis enhances diagnostic precision in β-catenin-negative desmoid fibromatosis: a...

Diagnostic challenges remain in desmoid fibromatosis (DF) due to somewhat frequent β-catenin immunohistochemical negativity, risking misclassification and overtreatment. The present study evaluates the role of CTNNB1 molecular testing in optimizing diagnosis. A single-center, large retrospective analysis of 780 patients with DF was performed. The incidence of DF was higher in females, particularly within the adult demographic. 77.3% of DF cases exhibited nuclear β-catenin positivity.The majority of cases that were β-catenin nuclear negative underwent CTNNB1 exon 3 Sanger sequencing.Molecular analysis revealed that 74.1% of β-catenin negative cases harbored CTNNB1 mutations, primarily at codon 41 (p.T41A). Patients with wild-type CTNNB1 were significantly older. Notably, β-catenin IHC showed higher positivity in resected specimens (79.7%) compared to biopsies (62.0%), whereas CTNNB1 mutational detection was higher in biopsies (93.5%) than resections (76.8%). Codon 41 mutations correlated with higher β-catenin IHC positivity than codon 45 mutations. A subsequent analysis of age demonstrated that DF in the abdominal wall, retroperitoneal cavity, and trunk was more likely to occur in the adult group. Four novel mutations (p.S45_G48del, p.T41V, p.S23N, and p.G34E) were identified. CTNNB1 mutational testing is indispensable for the diagnosis of β-catenin-negative DF, especially in older patients, where IHC limitations are pronounced. Identifying CTNNB1 gene mutations provides an accurate diagnosis in challenging cases without immunohistochemical support, facilitating the development of more effective treatment strategies.