Superficial fibromatoses are genetically distinct from deep fibromatoses

Mod Pathol. 2001 Jul;14(7):695-701. doi: 10.1038/modpathol.3880374.


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 beta-catenin or APC gene mutations have been reported in < or =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 beta-catenin on 29 superficial fibromatoses (22 palmar, 5 plantar, 1 penile, and 1 infantile digital fibromatosis) and 5 deep fibromatoses. Mutations of beta-catenin and APC genes were analyzed in cases of superficial fibromatoses by direct DNA sequencing of the beta-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 beta-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 beta-catenin or APC genes were identified in any of the superficial fibromatoses. In contrast to deep fibromatoses, superficial fibromatoses lack beta-catenin and APC gene mutations; the significance of focal nuclear beta-catenin accumulation is unclear. This difference may account inpart for their divergent clinical manifestations despite their morphologic resemblance to deep fibromatoses.

MeSH terms

  • Adult
  • Aged
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • DNA Mutational Analysis
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Diagnosis, Differential
  • Female
  • Fibroma / genetics
  • Fibroma / metabolism
  • Fibroma / pathology*
  • Genes, APC / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • Trans-Activators
  • beta Catenin