Clayton A Fisher1, Paul W Harms2, Jonathan B McHugh3, Paul C Edwards4, Javed Siddiqui5, Nallasivam Palanisamy5, Christopher K Bichakjian6, Erika Benavides1, Theodora E Danciu7. 1. School of Dentistry, University of Michigan, Ann Arbor, MI. 2. Department of Pathology, University of Michigan Health System, Ann Arbor, MI; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI. 3. Department of Pathology, University of Michigan Health System, Ann Arbor, MI. 4. School of Dentistry, Indiana University, Indianapolis, IN. 5. Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI. 6. Department of Dermatology, University of Michigan Health System, Ann Arbor, MI. 7. School of Dentistry, University of Michigan, Ann Arbor, MI. Electronic address: tdanciu@umich.edu.
Abstract
OBJECTIVE: This study aimed to document three new cases of primary small cell carcinoma (SmCC) of the parotid and examine immunohistochemical and quantitative real-time polymerase chain reaction (qPCR) data of the recently developed Merkel cell polyomavirus (MCPyV) within these tumors. STUDY DESIGN: Immunohistochemistry for neuroendocrine markers (chromogranin A, CD56, CD57, neuron-specific enolase [NSE], thyroid transcription factor 1 [TTF-1]), epithelial markers (CK20, CK7, CAM 5.2), and MCPyV large T antigen (LTAg) were examined. qPCR and Sanger sequencing were performed to confirm the presence of the MCPyV LTAg gene. RESULTS: Two males and one female, average age 76 years, presented with left parotid masses. Clinical examinations, histories, and imaging studies were negative for cutaneous Merkel cell carcinoma (MCC), pulmonary and extrapulmonary SmCC, or any other malignancy. Immunohistochemical analysis demonstrated positive immunoreactivity for CK20 in a perinuclear dotlike pattern (3/3), CAM 5.2 (3/3), (2/3), NSE (3/3), CD56 (2/3), and CD57 (3/3). Two cases stained positive for MCPyV, showing moderate to strong, diffuse positivity, confirmed with qPCR. PCR-Sanger sequencing of LTAg exon 2 showed greater than 97% similarity to the MCPyV reference genome in both cases. CONCLUSION: Our findings expand the number of reported cases classified as primary parotid SmCC that harbors MCPyV and underscore the similarity between cutaneous MCC and parotid SmCC. Further investigation is needed to determine whether immune-based therapeutic strategies targeting MCPyV in MCC are also effective in the setting of parotid SmCC harboring MCPyV.
OBJECTIVE: This study aimed to document three new cases of primary small cell carcinoma (SmCC) of the parotid and examine immunohistochemical and quantitative real-time polymerase chain reaction (qPCR) data of the recently developed Merkel cell polyomavirus (MCPyV) within these tumors. STUDY DESIGN: Immunohistochemistry for neuroendocrine markers (chromogranin A, CD56, CD57, neuron-specific enolase [NSE], thyroid transcription factor 1 [TTF-1]), epithelial markers (CK20, CK7, CAM 5.2), and MCPyV large T antigen (LTAg) were examined. qPCR and Sanger sequencing were performed to confirm the presence of the MCPyV LTAg gene. RESULTS: Two males and one female, average age 76 years, presented with left parotid masses. Clinical examinations, histories, and imaging studies were negative for cutaneous Merkel cell carcinoma (MCC), pulmonary and extrapulmonary SmCC, or any other malignancy. Immunohistochemical analysis demonstrated positive immunoreactivity for CK20 in a perinuclear dotlike pattern (3/3), CAM 5.2 (3/3), (2/3), NSE (3/3), CD56 (2/3), and CD57 (3/3). Two cases stained positive for MCPyV, showing moderate to strong, diffuse positivity, confirmed with qPCR. PCR-Sanger sequencing of LTAg exon 2 showed greater than 97% similarity to the MCPyV reference genome in both cases. CONCLUSION: Our findings expand the number of reported cases classified as primary parotid SmCC that harbors MCPyV and underscore the similarity between cutaneous MCC and parotid SmCC. Further investigation is needed to determine whether immune-based therapeutic strategies targeting MCPyV in MCC are also effective in the setting of parotid SmCC harboring MCPyV.
Authors: Andrew G Miner; Rajiv M Patel; Deborah Wilson; Gary W Procop; Eugen Minca; Douglas R Fullen; Paul W Harms; Steven D Billings Journal: Mod Pathol Date: 2016-01 Impact factor: 7.842
Authors: Kelly L Harms; Lorena Lazo de la Vega; Daniel H Hovelson; Samantha Rahrig; Andi K Cani; Chia-Jen Liu; Douglas R Fullen; Min Wang; Aleodor A Andea; Christopher K Bichakjian; Timothy M Johnson; Scott A Tomlins; Paul W Harms Journal: JAMA Dermatol Date: 2017-06-01 Impact factor: 10.282
Authors: Paul W Harms; Angela M B Collie; Daniel H Hovelson; Andi K Cani; Monique E Verhaegen; Rajiv M Patel; Douglas R Fullen; Kei Omata; Andrzej A Dlugosz; Scott A Tomlins; Steven D Billings Journal: Mod Pathol Date: 2016-01-08 Impact factor: 7.842
Authors: Paul William Harms; Pankaj Vats; Monique Elise Verhaegen; Dan R Robinson; Yi-Mi Wu; Saravana Mohan Dhanasekaran; Nallasivam Palanisamy; Javed Siddiqui; Xuhong Cao; Fengyun Su; Rui Wang; Hong Xiao; Lakshmi P Kunju; Rohit Mehra; Scott A Tomlins; Douglas Randall Fullen; Christopher Keram Bichakjian; Timothy M Johnson; Andrzej Antoni Dlugosz; Arul M Chinnaiyan Journal: Cancer Res Date: 2015-08-03 Impact factor: 12.701