title: Small cell carcinoma in the parotid harboring Merkel cell polyomavirus.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI.
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Fisher
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.affiliation: School of Dentistry, Indiana University, Indianapolis, IN.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Edwards
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Department of Dermatology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Bichakjian
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI.
authors.forename: Erika
authors.initials: E
authors.lastname: Benavides
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI. Electronic address: tdanciu@umich.edu.
authors.forename: Theodora E
authors.initials: TE
authors.lastname: Danciu
mesh_terms: D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000628:therapy / Q000821:virology*; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059965:Merkel cell polyomavirus / Q000302:isolation & purification*; D008875:Middle Aged; D010307:Parotid Neoplasms / Q000628:therapy / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction