Superficial mesenchymal tumours expressing epithelial markers on immunohistochemistry: Diagnostic clues and pitfalls

The diagnosis of mesenchymal neoplasms arising in the superficial soft tissue can be challenging as some entities are rare and show overlapping features. Moreover, the spectrum of mesenchymal tumours has expanded recently to include potential new entities, some of which have been described after the 5th edition of the World Health Organisation (WHO) classification of soft tissue and bone tumours published in 2020. In the skin and superficial soft tissue, tumours of epidermal, melanocytic and appendageal origin are more commonly encountered than mesenchymal neoplasms. However, specific entities from the latter category can occasionally express epithelial markers on immunohistochemistry, some of them in a strong and diffuse manner. It is therefore crucial to be aware of diagnostic pitfalls when encountering cytokeratin positivity in superficial soft tissue neoplasms. This article provides an overview on the differential diagnosis of these mesenchymal tumours that can sporadically occur also in the skin, including myoepithelial neoplasms, epithelioid sarcoma, keratin positive giant cell tumour of soft tissue / xanthogranulomatous epithelial tumour, superficial CD34-positive fibroblastic tumour / PRDM10rearranged soft tissue tumour, and perineurioma.

Automated summary

The diagnosis of mesenchymal neoplasms in superficial soft tissue is challenging due to their rarity and overlapping features. The classification of these tumors has expanded to include potential new entities that were described after the publication of the 5th edition of WHO classification in 2020. Although non-mesenchymal tumors are more common in the skin and superficial soft tissue, specific entities in the mesenchymal category can express epithelial markers, highlighting the importance of being aware of diagnostic pitfalls. This article provides an overview on the differential diagnosis of these mesenchymal tumors in the skin.