Value of Merkel cell Polyomavirus DNA Detection in Routine Pathology

Abstract

To the Editor: With great interest, we studied the recently published article from Duncavage et al1 “Merkel Cell Polyomavirus-A Specific Marker for Merkel Cell Carcinoma in Histologically Similar Tumors”. We agree that molecular pathologic investigation for Merkel cell polyomavirus (MCPyV) of tumors, which are histologically similar to Merkel cell carcinoma (MCC) is a very interesting and important issue. It is beyond debate that analysis of MCPyV prevalence in other skin conditions than MCC is necessary to get insight in the relevance of MCPyV infection. Our group is intensively working in this field, and we discuss the value of MCPyV detection as a diagnostic tool in routine histopathology in the light of the latest literature. Duncavage et al1 screened 74 cases of visceral high-grade neuroendocrine tumors (which are histologically similar to MCC) for MCPyV DNA by means of polymerase chain reaction (PCR). They detected MCPyV DNA just in 1 case (1.4%). Interestingly this case is, “upon detailed review, actually a misclassified case of metastatic MCC”, displaying the problem of distinguishing these entities. Therefore they suggest PCR-based testing for MCPyV DNA as helpful and specific marker in differentiating those histologically similar tumors. Furthermore, they report and discuss frequent absence of MCPyV DNA in several cutaneous and extracutaneous neoplasms.1 We agree with Duncavage et al1 that detection of MCPyV DNA is highly dependent upon a number of different methodical parameters such as tissue fixation, methods of DNA extraction and specific sequence detection, such as PCR method, selection of PCR primer sets, and last but not least dependent upon the amount of available tissue. Among others, Duncavage et al1 investigated 16 small cell carcinomas of the lung reporting absence of MCPyV DNA. We analyzed in a prior study, 30 small cell carcinomas of the lung and detected MCPyV DNA in 2 of 30 patients (7.5%), in 3 of 35 samples (2 of these 3 samples were from the same patient), respectively.2 Furthermore, there is enough evidence that MCPyV DNA is a common and frequent finding in tissues of immunosuppressed and immunocompetent individuals as well. MCPyV DNA was found in several benign, semimalignant and malignant skin tumors as well as in inflammatory skin diseases and clinical healthy skin from non-MCC patients.3-12Table 1 summarizes an incomplete selection of results from various research groups analyzing MCPyV DNA prevalence in different entities. For example, prevalence of MCPyV DNA in basal cell carcinomas was investigated from 4 independent research groups and taken together MCPyV DNA was detected in 66 of 221 samples (29.9%), ranging from 0% to 72%.3,5,6,8 We think, this situation nicely shows that MCPyV DNA analysis is most likely dependent on various before mentioned technical parameters, resulting in variable MCPyV DNA detection rates. Nevertheless, almost any of these studies point to the fact that MCPyV is ubiquitously present, even detectable in healthy and non-MCC tissue. Of special interest is that various groups reported significant differences in MCPyV viral load with usually higher copy numbers in MCC tissues and lower ones in non-MCC tissues, representing a possible parameter for differentiation.5,6,9 However, one must consider that most routine pathology laboratories use standard PCR-based methods for MCPyV detection as a qualitative test without analyzing quantitative viral load.TABLE 1: Prevalence of MCPyV DNA in Different Entities Analyzed by PCR-Based MethodsIn summary, latest reports proved that MCPyV DNA is abundantly detectable in tissues of various entities including clinical healthy skin (Table 1). Therefore, a qualitative proof of MCPyV DNA in a tissue sample is by far not specific for MCC. To us, the value of an ancillary MCPyV DNA-analysis in the differential diagnosis of MCC and similar tumors is questionable, and results have to be interpreted in the context of the recent literature suggesting a high prevalence of MCPyV. ACKNOWLEDGMENTS This study was in part supported by the Dr. H. Legerlotz, the R. Bartling and the M. Lackas Foundation. Christian Andres, MD* Benedetta Belloni, MD* *Department of Dermatology and Allergy, Ludwig-Maximilians-Universität München, Munich, Germany Michael J. Flaig, MD† †Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany