title: Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma.
abstract: Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P < .001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.
authors.affiliation: Division of Molecular Pathology, Faculty of Medicine, Tottori University, 86 Nishi-Cho, Yonago, Tottori, 683-8503, Japan. s.quamoto@gmail.com
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwamoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Higaki
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Kanai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sano
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kato
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Murakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horie
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000473:pathology* / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D011120:Polyomavirus / Q000302:isolation & purification; D027601:Polyomavirus Infections / Q000150:complications*; D012878:Skin Neoplasms / Q000473:pathology* / Q000821:virology*