Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses

Abstract

Whereas deep fibromatoses (abdominal, extra-abdominal, mesenteric) display locally aggressive behavior, superficial fibromatoses typically remain small and less likely to recur despite essentially identical morphology. Somatic β-catenin or APC gene mutations have been reported in ≤74% of sporadic deep fibromatoses and in virtually 100% of Gardner syndrome–associated fibromatoses, whereas genetic events in superficial fibromatoses remain less well characterized. We performed immunohistochemical staining for β-catenin on 29 superficial fibromatoses (22 palmar, 5 plantar, 1 penile, and 1 infantile digital fibromatosis) and 5 deep fibromatoses. Mutations of β-catenin and APC genes were analyzed in cases of superficial fibromatoses by direct DNA sequencing of the β-catenin gene on Exon 3 encompassing the GSK-3 36 phosphorylation region and of the APC gene on the mutation cluster region. Nuclear accumulation of β-catenin was present in 86% (25/29) of superficial fibromatosis cases ranging from 5 to 100% of nuclei (mean, 13%; median, 10%), though in a minority of nuclei in most examples. Deep fibromatoses had 60 to 100% nuclear staining in all five cases. No somatic mutations of β-catenin or APC genes were identified in any of the superficial fibromatoses. In contrast to deep fibromatoses, superficial fibromatoses lack β-catenin and APC gene mutations; the significance of focal nuclear β-catenin accumulation is unclear. This difference may account inpart for their divergent clinical manifestations despite their morphologic resemblance to deep fibromatoses.