Desmoid-type fibromatosis: from morphology to molecular genetics

Abstract 

Desmoid fibromatosis is a locally aggressive myofibroblastic neoplasm that may occur at abdominal, intra-abdominal and extra-abdominal locations. Most cases occur sporadically; however, a minority of cases is associated with familial adenomatous polyposis (Gardner syndrome). Morphologically, desmoid fibromatosis is an infiltrative, bland spindle cell proliferation set in a collagenized stroma. The characteristic immunophenotype is represented by expression of smooth muscle actin and β-catenin. Genetically, two distinct molecular events involve two different proteins, both members of the WNT signalling pathway. In fact, familial desmoids display germline inactivating mutations in the adenomatous polyposis coli (APC) gene, whereas most sporadic desmoids harbour activating mutations in exon 3 of the CTNNB1 gene that encodes β-catenin. As desmoid fibromatosis represents a major therapeutic challenge, further clarification of the molecular oncogenesis of this disease may offer a rationale to develop innovative therapeutic approaches.

Keywords: adenomatous polyposis coli, β-catenin, desmoid fibromatosis, Gardner syndrome, APC