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Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes

Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications

Walsh, Noreen M. MD, FRCPC, FRCPath (UK)*,†,‡; Castonguay, Mathieu C. MD, FRCPC*,†; Carter, Michael D. MD, PhD, FRCPC*,†; Pasternak, Sylvia MD, MSc, FRCPC*,†,‡; Ly, Thai Yen MD, FRCPC*,†; Doucette, Steve MSc†,§; Hanly, John G. MD, FRCPC*,†,‡; Saggini, Andrea MD¶,‖; Cerroni, Lorenzo MD

The American Journal of Dermatopathology: November 2019 - Volume 41 - Issue 11 - p 819–825
doi: 10.1097/DAD.0000000000001390
Original Study

Abstract: We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

*Department of Pathology, Queen Elizabeth II Health Sciences Center, Nova Scotia Health Authority (Central Zone), Halifax, Nova Scotia, Canada;

Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada;

Department of Medicine, Queen Elizabeth II Health Sciences Center, Nova Scotia Health Authority (Central Zone), Halifax, Nova Scotia, Canada;

§Research Methods Unit, Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada;

Anatomical Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; and

Research Unit Dermatopathology, Department of Dermatology, Medical University of Graz, Graz, Austria.

Correspondence: Noreen M. Walsh, MD, FRCPC, FRCPath (UK), Division of Anatomical Pathology, Rm 721, Nova Scotia Health Authority (QEII Site), Mackenzie Building, 5788 University Avenue, Halifax, NS B3H 1V8, Canada (e-mail:

Supported by research grants from the Nova Scotia Health Authority Research Fund and the DPLM Fund for Molecular Pathology housed at the QE II Foundation.

The authors declare no conflicts of interest.

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