Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung

Abstract

Background: A new virus called the Merkel Cell Polyomavirus (MCPyV) has recently been found in Merkel Cell Carcinoma (MCC). MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC). So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet.

Methodology/principal findings: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected.

Conclusions/significance: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

Figure 1. Electron micrographs showing viral particles in a sample of patient no. 4.

a) destroyed merkel cell carcinoma cell with viral particles (white arrow) measuring 50 nm, mingled with nuclear fragments and multiple smaller ribosomes (20 nm). b) penetration of virions through the nuclear membrane (white arrows) toward the cytoplasm (on the left). (original magnification; 12000×).