Epithelial elements in superficial angiomyxomas: mimicry of adnexal development, and mesenchymal-to-epithelial...

A subset of superficial angiomyxomas contains epithelial elements. Rarely, especially in Carney's complex patients, arborizing adnexal proliferations are present, with some authors proposing that they could be authentic adnexal neoplasms. Our aim was to determine if the epithelial elements are trapped adnexal epithelium, epithelial outgrowths triggered by myxoid tumour cells or genuinely neoplastic.

We studied the clinicopathological and immunophenotypic features (immunohistochemistry and double immunofluorescence) of 43 superficial angiomyxomas, including one from a Carney's complex patient. We found hair follicle placode/germ formation in 7 cases; elongated and/or branched eccrine elements in 4 cases and solid/cystic infundibular-like hyperplastic epithelium in 10 cases. S100A4-positive mesenchymal condensates surrounded follicular and eccrine epithelial buds close to myxoid tumour cells, but only the latter showed variable PRKAR1A loss. In the Carney's complex case, prominent eccrine duct branching was found mimicking fibrofolliculoma, with vimentin-positive cell aggregates connecting and integrating with the pre-existing epithelium. By double immunofluorescence, they showed cytokeratin and E-cadherin immunoreactivity while still expressing vimentin as evidence of mesenchymal-to-epithelial transition.

Our results suggest that adnexal epithelial elements reproduce their embryogenesis through the involvement of S100A4-positive mesenchymal niches in both follicular and eccrine elements. These niches are close to myxoid cells with PRKAR1A loss, whereas the complex epithelial structures retain PRKAR1A, which suggests that the former induce non-neoplastic growth of the latter. Finally, we provide evidence for the role of mesenchymal-to-epithelial transition in the branching of the eccrine duct epithelium in the Carney's complex case, probably secondary to protein kinase A activation.