'Difficult to diagnose' desmoid tumours: a potential role for CTNNB1 mutational analysis.

AIMS: The utility of CTNNB1 (encoding β-catenin) genotyping for diagnosing sporadic desmoid tumours (DT) when traditional clinicopathological parameters were inconclusive was evaluated.

METHODS AND RESULTS: Cases included were: (i) new primary lesions where initial DT diagnosis was inconclusive; and (ii) possible recurrent DT versus scar. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained via needle biopsy or a surgical excision (57 specimens) as part of initial assessment. DNA extraction, CTNNB1 exon 3 amplification and sequencing were conducted in a Clinical Laboratory Improvement Amendments of 1988 (CLIA)-approved molecular diagnostics laboratory. For patients with no previous DT history (n = 47) sequencing identified mutations in 30 (64%), substantiating DT diagnosis. In biopsies with non-mutated (NM) CTNNB1 (n = 17) the test was inconclusive; in seven of these, a diagnosis of DT was strongly favoured in the subsequent surgical resection specimen. Ten patients with previously resected DT were evaluated; mutation was identified in six cases (60%), indicating DT over scar. In two (20%) with primary tumours harbouring CTNNB1 mutation no mutation was found, favouring scar over DT; the other two NM-CTNNB1 cases (20%) were inconclusive.

CONCLUSIONS: CTNNB1 genotyping can be very useful in 'difficult to diagnose' lesions when the differential diagnosis includes DT. Recognizing inherent test limitations, the presence of CTNNB1 mutation can inform the therapeutic approach.