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Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell
Thibault Kervarrec1,2,3, Anne Tallet4, Elodie Miquelestorena-Standley5
1Department of Pathology, Université François Rabelais de Tours, CHU de Tours, avenue de la République, 37170, Chambray-les-tours, France. thibaultkervarrec@yahoo.fr.
Abstract:
In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases associated with a high mutational load are most likely caused by UV radiation. The current study aimed to compare the morphological and immunohistochemical features of 80 virus-positive and 21 virus-negative Merkel cell carcinoma cases. Microscopic evaluation revealed that elongated nuclei-similar to the spindle-shape variant of small cell lung cancer-were less frequent in Merkel cell polyomavirus-positive Merkel cell carcinoma compared to the virus-negative subset (p = 0.005). Moreover, virus-negative cases more frequently displayed a "large-cell neuroendocrine carcinoma" phenotype with larger cell size (p = 0.0026), abundant cytoplasm (p = 4×10-7) and prominent nucleoli (p = 0.002). Analysis of immunohistochemical data revealed frequent positivity for thyroid transcription factor 1 and cytokeratin 7, either absence or overexpression of p53, as well as frequent lack of neurofilament expression in virus-negative cases. By contrast, cytokeratin 8, 18 and 20 and a CD99 with a dot pattern as well as high EMA expression were identified as characteristic features of virus-positive Merkel cell carcinoma. In particular, the CD99 dot-like expression pattern was strongly associated with presence of the Merkel cell polyomavirus in Merkel cell carcinoma (sensitivity = 81%, specificity = 90%, positive likelihood ratio = 8.08). To conclude, virus-positive and -negative Merkel cell carcinoma are characterized by distinct morphological and immunohistochemical features, which implies a significant difference in tumor biology and behavior. Importantly, we identified the CD99 staining pattern as a marker indicating the virus status of this skin cancer.
Insights
Merkel cell carcinoma (MCC) differs based on virus status. Virus-positive MCC shows distinct features from virus-negative MCC, with CD99 staining patterns indicating Merkel cell polyomavirus presence.
Area of Science:
- Oncology
- Dermatopathology
- Virology
Background:
- Merkel cell polyomavirus (MCPyV) is implicated in ~80% of Merkel cell carcinoma (MCC) cases.
- UV radiation is a likely cause for the remaining MCPyV-negative MCC cases, which exhibit high mutational burden.
- Understanding the distinct characteristics of MCPyV-positive and -negative MCC is crucial for diagnosis and treatment.
Purpose of the Study:
- To compare the morphological and immunohistochemical features of MCPyV-positive and -negative MCC.
- To identify specific biomarkers that differentiate between virus-positive and virus-negative MCC.
- To assess the diagnostic utility of the CD99 staining pattern for determining MCPyV status in MCC.
Main Methods:
- Morphological analysis of 80 MCPyV-positive and 21 MCPyV-negative MCC cases.
- Immunohistochemical analysis of various markers, including cytokeratins, p53, neurofilament, EMA, and CD99.
- Statistical analysis to compare features and determine the sensitivity, specificity, and likelihood ratio of the CD99 staining pattern.
Main Results:
- MCPyV-negative MCC cases showed less frequent elongated nuclei and a higher prevalence of a large-cell neuroendocrine carcinoma phenotype with larger cell size, abundant cytoplasm, and prominent nucleoli.
- Immunohistochemistry revealed distinct marker profiles: virus-negative cases showed frequent TTF-1 and CK7 positivity, variable p53 expression, and lack of neurofilament; virus-positive cases were characterized by CK8, 18, 20, high EMA, and a dot-like CD99 pattern.
- A CD99 dot-like expression pattern was strongly associated with MCPyV positivity (81% sensitivity, 90% specificity, 8.08 positive likelihood ratio).
Conclusions:
- MCPyV-positive and -negative MCC exhibit distinct morphological and immunohistochemical features, suggesting differences in tumor biology and behavior.
- The CD99 dot-like staining pattern is a reliable marker for identifying the virus status in MCC.
- These findings aid in differentiating MCC subtypes and may inform future therapeutic strategies.
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