Desmoid tumor with ossification in chest wall: Possible involvement of BAMBI promoter hypermethylation in metaplastic bone formation

Introduction: Desmoid-type fibromatosis, originating from mesenchymal cells with myofibroblastic features, is a locally aggressive and frequently recurring infiltrative lesion. One such sporadic case with metaplastic ossification in the chest wall is presented. Materials and Methods: A 43-year-old man was referred to the hospital with a gradually enlarging hard mass in the left anterolateral chest wall. A thoracotomy was carried out, and histopathological specimens were used for immunohistochemical, genetic, and methylation studies. Results: Accumulation of altered P-catenin associated with a somatic heterozygous activating mutation in codon 41 was detected in the typical desmoid-type fibromatosis and at the ossifying focus. Among factors related to bone formation and the classical wnt-beta-catenin signaling pathway, BMP and activin membrane-bound inhibitor (BAMBI) expression was specifically downregulated at the ossifying focus. Hypermethylation of the BAMBI promoter was observed in microdissected tissue from the ossifying focus but not in that from the typical desmoid-type fibromatosis. Conclusions: Because both BMP and classical Wnt/beta-catenin/LEF1 signaling cooperatively and mutually induce differentiation of mesenchymal cells into osteoblastic cells and promote bone formation, the epigenetic event leading to the enhanced responsiveness to BMP signaling may play a crucial role in the formation of metaplastic bone.