Virchows Archiv

, Volume 472, Issue 5, pp 825–837 | Cite as

Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma

  • Thibault Kervarrec
  • Mahtab Samimi
  • Pauline Gaboriaud
  • Tarik Gheit
  • Agnès Beby-Defaux
  • Roland Houben
  • David Schrama
  • Gaëlle Fromont
  • Massimo Tommasino
  • Yannick Le Corre
  • Eva Hainaut-Wierzbicka
  • Francois Aubin
  • Guido Bens
  • Hervé Maillard
  • Adeline Furudoï
  • Patrick Michenet
  • Antoine Touzé
  • Serge Guyétant
Original Article


Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as “combined” or “conventional.” Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of the combined MCC cases suggests similar routes of carcinogenesis for combined and conventional MCC.


Merkel cell carcinoma Merkel cell polyomavirus Combined merkel cell carcinoma Squamous carcinoma Polyomavirus Papillomavirus 



This work was funded by project POCAME, Axe Immunothérapies, Cancéropole Grand Ouest-Région Centre Val de Loire (France) and by the Fond de recherche de la société française de Pathologie 2016.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Institutional review board

The local Ethics Committee of Tours (France) approved the study (no. RCB2009-A01056-51)

Supplementary material

428_2018_2342_MOESM1_ESM.docx (66 kb)
Supplemental table S1 Antibodies and dilution used for immunohistochemistry (DOCX 66 kb)
428_2018_2342_MOESM2_ESM.docx (59 kb)
Supplemental table S2 Primers used (DOCX 59 kb)
428_2018_2342_MOESM3_ESM.docx (14 kb)
Supplemental table S3 Univariate analysis of factors associated with Merkel cell carcinoma recurrence and death (DOCX 14 kb)
428_2018_2342_MOESM4_ESM.docx (49 kb)
Supplemental table S4 Detection of beta papillomavirus (DOCX 48 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Thibault Kervarrec
    • 1
    • 2
    • 3
  • Mahtab Samimi
    • 2
    • 4
  • Pauline Gaboriaud
    • 2
  • Tarik Gheit
    • 5
  • Agnès Beby-Defaux
    • 6
    • 7
  • Roland Houben
    • 3
  • David Schrama
    • 3
  • Gaëlle Fromont
    • 1
  • Massimo Tommasino
    • 4
  • Yannick Le Corre
    • 8
  • Eva Hainaut-Wierzbicka
    • 9
  • Francois Aubin
    • 10
  • Guido Bens
    • 11
  • Hervé Maillard
    • 12
  • Adeline Furudoï
    • 13
  • Patrick Michenet
    • 14
  • Antoine Touzé
    • 2
  • Serge Guyétant
    • 1
    • 2
  1. 1.Department of PathologyUniversité de Tours, Centre Hospitalier Universitaire de ToursTours Cedex 09France
  2. 2.Biologie des infections à polyomavirus team, UMR INRA ISP 1282Université de ToursToursFrance
  3. 3.Department of Dermatology, Venereology and AllergologyUniversity Hospital WürzburgWürzburgGermany
  4. 4.Department of DermatologyUniversité François Rabelais, Centre Hospitalier Universitaire de ToursTours Cedex 09France
  5. 5.Infections and Cancer Biology Group, International Agency for Research on CancerLyonFrance
  6. 6.Université de Poitiers, 2RCT “Récepteurs et régulation des cellules tumorales” teamPoitiersFrance
  7. 7.Department of VirologyUniversité de Poitiers, Centre Hospitalier Universitaire de PoitiersPoitiersFrance
  8. 8.Department of DermatologyLUNAM Université, Centre Hospitalier Universitaire d’AngersAngersFrance
  9. 9.Department of DermatologyUniversité de Poitiers, Centre Hospitalier Universitaire de PoitiersPoitiersFrance
  10. 10.Department of DermatologyUniversité de Franche Comté, Centre Hospitalier Universitaire de BesançonBesançonFrance
  11. 11.Department of DermatologyCentre Hospitalier Régional d’OrléansOrléans cedex 2France
  12. 12.Department of DermatologyCentre Hospitalier Régional du MansLe MansFrance
  13. 13.Department of PathologyUniversité de Bordeaux, Centre Hospitalier Universitaire de BordeauxPessacFrance
  14. 14.Department of PathologyCentre Hospitalier Régional d’OrléansOrléans cedex 2France

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