CTNNB1 (β-Catenin)-altered Neoplasia

β-catenin (CTNNB1) is a key regulatory molecule of the Wnt signaling pathway, which is important for tissue homeostasis and regulation of cell proliferation, differentiation, and function. Abnormal stabilization and nuclear accumulation of β-catenin as a consequence of missense mutations or alternative molecular mechanisms occurs at a high frequency in a variety of epithelial cancers. In mesenchymal neoplasia, the role of β-catenin has been traditionally considered limited to desmoid-type fibromatosis. However, the spectrum of β-catenin-driven (β-catenin-altered) neoplasia of mesenchymal origin has been steadily widening to include, in addition to desmoid tumors, a variety of benign and intermediate-biology neoplasms of soft tissue (intranodal palisaded myofibroblastoma), head and neck (juvenile nasopharyngeal angiofibroma and sinonasal hemangiopericytoma/glomangiopericytoma), and ovarian (microcystic stromal tumor) origin. In addition, several old and newly reported distinctive site-specific β-catenin-driven parenchymal neoplasms of uncertain histogenesis have been well characterized in recent studies, including solid-pseudopapillary neoplasm of the pancreas and its recently described ovarian counterpart, sclerosing hemangioma of lung and calcifying nested stromal-epithelial tumor of the liver. This review addresses the most relevant pathobiological and differential diagnostic aspects of β-catenin-altered neoplasms with emphasis on site-specific histologic and biological variations. In addition, the morphologic overlap and analogy as well as distinctness between these uncommon tumors will be presented and discussed. Furthermore, a note is made on association of some of these lesions with hereditary tumor syndromes, in particular with the familial adenomatous polyposis coli.