Superficial fibromas with CTNNB1 mutation

Abstract

Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.