Skip to main content
SpringerLink
Log in

Histopathologic Diagnosis

  • Chapter
  • First Online:
Merkel Cell Carcinoma

  • 751 Accesses

Abstract

Merkel cells are cutaneous neuroendocrine cells that function as cutaneous mechanoreceptors. They reside in the basal epidermis, mucosal epithelium, and follicular epithelium and have a non-descript appearance that resembles neighboring keratinocytes in conventional microscopic sections. Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma) arises from the malignant transformation of Merkel cells or Merkel cell progenitors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Szeder V, Grim M, Halata Z, Sieber-Blum M. Neural crest origin of mammalian Merkel cells. Dev Biol. 2003;253(2):258–63.

    Article  PubMed  CAS  Google Scholar 

  2. Van Keymeulen A, Mascre G, Youseff KK, et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol. 2009;187(1):91–100.

    Article  PubMed  Google Scholar 

  3. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105(1):107–10.

    Article  PubMed  CAS  Google Scholar 

  4. Tang CK, Toker C. Trabecular carcinoma of the skin: an ultrastructural study. Cancer. 1978;42(5):2311–21.

    Article  PubMed  CAS  Google Scholar 

  5. De Wolff-Peeters C, Marien K, Mebis J, Desmet V. A cutaneous APUDoma or Merkel cell tumor? A morphologically recognizable tumor with a biological and histological malignant aspect in contrast with its clinical behavior. Cancer. 1980;46(8):1810–6.

    Article  PubMed  Google Scholar 

  6. Hoefler H, Kerl H, Rauch HJ, Denk H. New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma. Am J Dermatopathol. 1984;6(6):525–30.

    Article  PubMed  CAS  Google Scholar 

  7. Rocamora A, Badia N, Vives R, Carrillo R, Ulloa J, Ledo A. Epidermotropic primary neuroendocrine (Merkel cell) carcinoma of the skin with Pautrier-like microabscesses. Report of three cases and review of the literature. J Am Acad Dermatol. 1987;16(6):1163–8.

    Article  PubMed  CAS  Google Scholar 

  8. Leong AS, Phillips GE, Pieterse AS, Milios J. Criteria for the diagnosis of primary endocrine carcinoma of the skin (Merkel cell carcinoma). A histological, immunohistochemical and ultrastructural study of 13 cases. Pathology. 1986;18(4):393–9.

    Article  PubMed  CAS  Google Scholar 

  9. Kuwamoto S, Higaki H, Kanai K, et al. Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma. Hum Pathol. 2011;42(5):632–40.

    Article  PubMed  CAS  Google Scholar 

  10. Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg. 2011;254(3):465–73; discussion 473–465.

    Article  PubMed  Google Scholar 

  11. Kukko HM, Koljonen VS, Tukiainen EJ, Haglund CH, Bohling TO. Vascular invasion is an early event in pathogenesis of Merkel cell carcinoma. Mod Pathol. 2010;23(8):1151–6.

    Article  PubMed  Google Scholar 

  12. Ball NJ, Tanhuanco-Kho G. Merkel cell carcinoma frequently shows histologic features of basal cell carcinoma: a study of 30 cases. J Cutan Pathol. 2007;34(8):612–9.

    Article  PubMed  Google Scholar 

  13. Plaza JA, Suster S. The Toker tumor: spectrum of morphologic features in primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma). Ann Diagn Pathol. 2006;10(6):376–85.

    Article  PubMed  Google Scholar 

  14. Leong AS, Dixon BR. Bidirectional differentiation in a large cell pleomorphic primary endocrine carcinoma of the skin (a variant of malignant Merkel cell tumour). Pathology. 1986;18(2):256–61.

    Article  PubMed  CAS  Google Scholar 

  15. Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113(9):2549–58.

    Article  PubMed  Google Scholar 

  16. Fields RC, Busam KJ, Chou JF, et al. Recurrence and survival in patients undergoing sentinel lymph node biopsy for merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol. 2011;18(9):2529–37.

    Article  PubMed  Google Scholar 

  17. Koljonen V, Bohling T, Virolainen S. Tumor burden of sentinel lymph node metastasis in Merkel cell carcinoma. J Cutan Pathol. 2011;38(6):508–13.

    Article  PubMed  Google Scholar 

  18. Larramendy ML, Koljonen V, Bohling T, Tukiainen E, Knuutila S. Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas. Mod Pathol. 2004;17(5):561–7.

    Article  PubMed  CAS  Google Scholar 

  19. Paulson KG, Lemos BD, Feng B, et al. Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc. J Invest Dermatol. 2009;129(6):1547–55.

    Article  PubMed  CAS  Google Scholar 

  20. Ahronowitz IZ, Daud AI, Leong SP, et al. An isolated Merkel cell carcinoma metastasis at a distant cutaneous site presenting as a second ‘primary’ tumor. J Cutan Pathol. 2011;38(10):801–7.

    PubMed  Google Scholar 

  21. Skelton HG, Smith KJ, Hitchcock CL, McCarthy WF, Lupton GP, Graham JH. Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival. J Am Acad Dermatol. 1997;37(5 Pt 1):734–9.

    Article  PubMed  CAS  Google Scholar 

  22. Sarma DP, Heagley DE, Chalupa J, Cox M, Shehan JM. An unusual clinical presentation of merkel cell carcinoma: a case report. Case Report Med. 2010;2010:905414.

    Google Scholar 

  23. Walsh NM. Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof. Hum Pathol. 2001;32(7):680–9.

    Article  PubMed  CAS  Google Scholar 

  24. Battistella M, Durand L, Jouary T, Peltre B, Cribier B. Primary cutaneous neuroendocrine carcinoma within a cystic trichoblastoma: a nonfortuitous association? Am J Dermatopathol. 2011;33(4):383–7.

    Article  PubMed  Google Scholar 

  25. Barroeta JE, Farkas T. Merkel cell carcinoma and chronic lymphocytic leukemia (collision tumor) of the arm: a diagnosis by fine-needle aspiration biopsy. Diagn Cytopathol. 2007;35(5):293–5.

    Article  PubMed  Google Scholar 

  26. Forman SB, Vidmar DA, Ferringer TC. Collision tumor composed of Merkel cell carcinoma and lentigo maligna melanoma. J Cutan Pathol. 2008;35(2):203–6.

    PubMed  Google Scholar 

  27. Youker SR, Billingsley EM. Combined Merkel cell carcinoma and atypical fibroxanthoma. J Cutan Med Surg. 2005;9(1):6–9.

    Article  PubMed  Google Scholar 

  28. Tanahashi J, Kashima K, Daa T, Yada N, Fujiwara S, Yokoyama S. Merkel cell carcinoma co-existent with sebaceous carcinoma of the eyelid. J Cutan Pathol. 2009;36(9):983–6.

    Article  PubMed  Google Scholar 

  29. Tilkorn DJ, Lehnhardt M, Hauser J, et al. Merkel cell carcinoma metastasis and dermatofibrosarcoma protuberans presenting as a collision tumour: a case report and review of the literature. J Med Case Reports. 2009;3:7493.

    Article  Google Scholar 

  30. Gould E, Albores-Saavedra J, Dubner B, Smith W, Payne CM. Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study. Am J Surg Pathol. 1988;12(10):768–72.

    Article  PubMed  CAS  Google Scholar 

  31. Hallman JR, Shaw JA, Geisinger KR, Loggie BW, White WL. Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases. Acta Cytol. 2000;44(2):185–93.

    Article  PubMed  CAS  Google Scholar 

  32. Adhikari LA, McCalmont TH, Folpe AL. Merkel cell carcinoma with heterologous rhabdomyoblastic differentiation: the role of immunohistochemistry for Merkel cell polyomavirus large T-antigen in confirmation. J Cutan Pathol. 2012;39(1):47–51.

    Article  PubMed  Google Scholar 

  33. Cooper L, Debono R, Alsanjari N, Al-Nafussi A. Merkel cell tumour with leiomyosarcomatous differentiation. Histopathology. 2000;36(6):540–3.

    Article  PubMed  CAS  Google Scholar 

  34. Tan KB, Murali R, Karim RZ, et al. Merkel cell carcinoma with fibrosarcomatous differentiation. Pathology. 2008;40(3):314–6.

    Article  PubMed  Google Scholar 

  35. Vanchinathan V, Marinelli EC, Kartha RV, Uzieblo A, Ranchod M, Sundram UN. A malignant cutaneous neuroendocrine tumor with features of Merkel cell carcinoma and differentiating neuroblastoma. Am J Dermatopathol. 2009;31(2):193–6.

    Article  PubMed  Google Scholar 

  36. Kossard S, Wittal R, Killingsworth M. Merkel cell carcinoma with a desmoplastic portion. Am J Dermatopathol. 1995;17(5):517–22.

    Article  PubMed  CAS  Google Scholar 

  37. Hashimoto K, Lee MW, D’Annunzio DR, Balle MR, Narisawa Y. Pagetoid Merkel cell carcinoma: epidermal origin of the tumor. J Cutan Pathol. 1998;25(10):572–9.

    Article  PubMed  CAS  Google Scholar 

  38. Vazmitel M, Michal M, Kazakov DV. Merkel cell carcinoma and Azzopardi phenomenon. Am J Dermatopathol. 2007;29(3):314–5.

    Article  PubMed  Google Scholar 

  39. Acebo E, Vidaurrazaga N, Varas C, Burgos-Bretones JJ, Diaz-Perez JL. Merkel cell carcinoma: a clinicopathological study of 11 cases. J Eur Acad Dermatol Venereol. 2005;19(5):546–51.

    Article  PubMed  CAS  Google Scholar 

  40. George E, Swanson PE, Wick MR. Neuroendocrine differentiation in basal cell carcinoma. An immunohistochemical study. Am J Dermatopathol. 1989;11(2):131–5.

    Article  PubMed  CAS  Google Scholar 

  41. Rosso R, Paulli M, Carnevali L. Neuroendocrine carcinoma of the skin with lymphoepithelioma-like features. Am J Dermatopathol. 1998;20(5):483–6.

    Article  PubMed  CAS  Google Scholar 

  42. Rund CR, Fischer EG. Perinuclear dot-like cytokeratin 20 staining in small cell neuroendocrine carcinoma of the ovary (pulmonary-type). Appl Immunohistochem Mol Morphol. 2006;14(2):244–8.

    Article  PubMed  Google Scholar 

  43. Wong A, McCalmont T. Neurofilament is superior to CK20 for the identification of Merkel cell carcinoma: A review of 351 cases. J Cutan Pathol. 2012;39(1):97.

    Google Scholar 

  44. Shah IA, Netto D, Schlageter MO, Muth C, Fox I, Manne RK. Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma. Mod Pathol. 1993;6(1):3–9.

    PubMed  CAS  Google Scholar 

  45. Calder KB, Coplowitz S, Schlauder S, Morgan MB. A case series and immunophenotypic analysis of CK20-/CK7+ primary neuroendocrine carcinoma of the skin. J Cutan Pathol. 2007;34(12):918–23.

    Article  PubMed  Google Scholar 

  46. Wick MR, Millns JL, Sibley RK, Pittelkow MR, Winkelmann RK. Secondary neuroendocrine carcinomas of the skin. An immunohistochemical comparison with primary neuroendocrine carcinoma of the skin (“Merkel cell” carcinoma). J Am Acad Dermatol. 1985;13(1):134–42.

    Article  PubMed  CAS  Google Scholar 

  47. Bastian BC, Kreipe HH, Brocker EB. Primary neuroendocrine carcinoma of the skin with an unusual follicular lymphocytic infiltrate of the dermis. Am J Dermatopathol. 1996;18(6):625–8.

    Article  PubMed  CAS  Google Scholar 

  48. Machado I, Navarro S, Lopez-Guerrero JA, Alberghini M, Picci P, Llombart-Bosch A. Epithelial marker expression does not rule out a diagnosis of Ewing’s sarcoma family of tumours. Virchows Arch. 2011;459(4):409–14.

    Article  PubMed  CAS  Google Scholar 

  49. Van Gele M, Leonard JH, Van Roy N, et al. Combined karyotyping, CGH and M-FISH analysis allows detailed characterization of unidentified chromosomal rearrangements in Merkel cell carcinoma. Int J Cancer. 2002;101(2):137–45.

    Article  PubMed  Google Scholar 

  50. Van Gele M, Boyle GM, Cook AL, et al. Gene-expression profiling reveals distinct expression patterns for classic versus variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma. Oncogene. 2004;23(15):2732–42.

    Article  PubMed  Google Scholar 

  51. Paulson KG, Iyer JG, Tegeder AR, et al. Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J Clin Oncol. 2011;29(12):1539–46.

    Article  PubMed  CAS  Google Scholar 

  52. Mott RT, Smoller BR, Morgan MB. Merkel cell carcinoma: a clinicopathologic study with prognostic implications. J Cutan Pathol. 2004;31(3):217–23.

    Article  PubMed  Google Scholar 

  53. Asioli S, Righi A, Volante M, Eusebi V, Bussolati G. p63 expression as a new prognostic marker in Merkel cell carcinoma. Cancer. 2007;110(3):640–7.

    Article  PubMed  Google Scholar 

  54. Hall B, Pincus L, Yu S, Oh D, Wilson A, McCalmont T. Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome. J Cutan Pathol. 2012;39(10):911–7.

    Article  PubMed  Google Scholar 

  55. Ng L, Beer TW, Murray K. Vascular density has prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(5):442–5.

    Article  PubMed  Google Scholar 

  56. Llombart B, Monteagudo C, Lopez-Guerrero JA, et al. Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers. Histopathology. 2005;46(6):622–34.

    Article  PubMed  CAS  Google Scholar 

  57. Koljonen V, Tukiainen E, Haglund C, Bohling T. Proliferative activity detected by Ki67 correlates with poor outcome in Merkel cell carcinoma. Histopathology. 2006;49(5):551–3.

    Article  PubMed  CAS  Google Scholar 

  58. Sihto H, Kukko H, Koljonen V, Sankila R, Bohling T, Joensuu H. Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma. J Natl Cancer Inst. 2009;101(13):938–45.

    Article  PubMed  CAS  Google Scholar 

  59. Sihto H, Kukko H, Koljonen V, Sankila R, Bohling T, Joensuu H. Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Cancer Res. 2011;17(14):4806–13.

    Article  PubMed  CAS  Google Scholar 

  60. Schrama D, Peitsch WK, Zapatka M, et al. Merkel cell polyomavirus status is not associated with clinical course of Merkel cell carcinoma. J Invest Dermatol. 2011;131(8):1631–8.

    Article  PubMed  CAS  Google Scholar 

  61. Werling AM, Doerflinger Y, Brandner JM, et al. Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching. Histopathology. 2011;58(2):286–303.

    Article  PubMed  Google Scholar 

  62. Vlahova L, Doerflinger Y, Houben R, et al. P-cadherin expression in Merkel cell carcinomas is associated with prolonged recurrence-free survival. Br J Dermatol. 2012;166(5):1043–52.

    Article  PubMed  CAS  Google Scholar 

  63. Bhatia K, Goedert JJ, Modali R, Preiss L, Ayers LW. Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression. Int J Cancer. 2010;126(9):2240–6.

    PubMed  CAS  Google Scholar 

  64. Houben R, Schrama D, Alb M, et al. Comparable expression and phosphorylation of the retinoblastoma protein in Merkel cell polyoma virus-positive and negative Merkel cell carcinoma. Int J Cancer. 2010;126(3):796–8.

    Article  PubMed  CAS  Google Scholar 

  65. Waltari M, Sihto H, Kukko H, et al. Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma. Int J Cancer. 2011;129(3):619–28.

    Article  PubMed  CAS  Google Scholar 

  66. Carson HJ, Reddy V, Taxy JB. Proliferation markers and prognosis in Merkel cell carcinoma. J Cutan Pathol. 1998;25(1):16–9.

    Article  PubMed  CAS  Google Scholar 

  67. Feinmesser M, Halpern M, Fenig E, et al. Expression of the apoptosis-related oncogenes bcl-2, bax, and p53 in Merkel cell carcinoma: can they predict treatment response and clinical outcome? Hum Pathol. 1999;30(11):1367–72.

    Article  PubMed  CAS  Google Scholar 

  68. Kim J, McNiff JM. Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma. Mod Pathol. 2008;21(6):764–9.

    Article  PubMed  CAS  Google Scholar 

  69. Beer TW, Ng LB, Murray K. Mast cells have prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(1):27–30.

    Article  PubMed  Google Scholar 

  70. Lill C, Schneider S, Pammer J, et al. Significant correlation of peptidyl-prolyl isomerase overexpression in merkel cell carcinoma with overall survival of patients. Head Neck. 2010;33(9):1294–300.

    Article  PubMed  Google Scholar 

  71. Woegerbauer M, Thurnher D, Houben R, et al. Expression of the tetraspanins CD9, CD37, CD63, and CD151 in Merkel cell carcinoma: strong evidence for a posttranscriptional fine-tuning of CD9 gene expression. Mod Pathol. 2010;23(5):751–62.

    Article  PubMed  CAS  Google Scholar 

  72. Brunner M, Thurnher D, Pammer J, et al. Expression of hedgehog signaling molecules in Merkel cell carcinoma. Head Neck. 2010;32(3):333–40.

    PubMed  Google Scholar 

  73. Pryor JG, Simon RA, Bourne PA, Spaulding BO, Scott GA, Xu H. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas. Hum Pathol. 2009;40(2):238–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Missouri, One Hospital Dr., MA111, Columbus, MO, 65212, USA

    Jeffrey North

  2. Department of Pathology (Dermatopathology), University of California, San Francisco, 1701 Divisadero Street, Suite 280, San Francisco, CA, 94115, USA

    Timothy H. McCalmont

Authors
  1. Jeffrey North
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy H. McCalmont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey North .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Northwestern University, Chicago, 60611, Illinois, USA

    Murad Alam

  2. University Hospitals Case Medical Center, Department of Dermatology, Case Western Reserve University, Cleveland, 44106, Ohio, USA

    Jeremy S. Bordeaux

  3. Department of Dermatology, University of California, San Francisco, San Francisco, 94115, California, USA

    Siegrid S. Yu

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

North, J., McCalmont, T.H. (2013). Histopathologic Diagnosis. In: Alam, M., Bordeaux, J., Yu, S. (eds) Merkel Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6608-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6608-6_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6607-9

  • Online ISBN: 978-1-4614-6608-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation