Polyomavirus-Positive Merkel Cell Carcinoma Derived from a Trichoblastoma Suggests an Epithelial Origin of this Merkel Cell Carcinoma

J Invest Dermatol. 2020 May;140(5):976-985. doi: 10.1016/j.jid.2019.09.026. Epub 2019 Nov 22.

Abstract

Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells. To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing. Although MCPyV was found to be integrated only in the MCC part, six somatic mutations were shared by both tumor components. The mutational overlap between the trichoblastoma and MCPyV-positive MCC parts of the combined tumor implies that MCPyV integration occurred in an epithelial tumor cell before MCC development. Therefore, our report demonstrates that MCPyV-positive MCC can derive from the epithelial lineage.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinogenesis
  • Carcinoma, Merkel Cell / diagnosis*
  • Cell Differentiation
  • Cell Lineage
  • Hair Follicle / pathology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mutation / genetics
  • Neoplasms / diagnosis*
  • Polyomavirus / physiology*
  • Polyomavirus Infections / diagnosis*
  • Skin / pathology*
  • Skin / virology
  • Skin Neoplasms / diagnosis*
  • Tumor Virus Infections
  • Virus Integration