Current Problems in Cancer
Volume 34, Issue 1 , Pages 47-64 , January 2010

Merkel Cell Carcinoma: Pathologic Findings and Prognostic Factors

References 

  1. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105(1):107–110
  2. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma (Diagnosis and treatment). Dermatol Surg. 1995;21(8):669–683
  3. Tang CK, Toker C. Trabecular carcinoma of the skin: an ultrastructural study. Cancer. 1978;42(5):2311–2321
  4. De Wolf-Peeters C, Marien K, Mebis J. A cutaneous apudoma or Merkel cell tumor (A morphologically recognizable tumor with a biological and histological malignant aspect in contrast with its clinical behaviour). Cancer. 1980;46:1810–1816
  5. Winkelmann R. The Merkel cell system and a comparison between it and the neurosecretory or APUD cell system. J Invest Dermatol. 1977;69:41–46
  6. Merkel F. Tastzellen and Tastkoerperchen bei Den Hausthieren und beim menschen. Arch Mikrosc Anat. 1875;11:636–652
  7. Warner T, Uno H, Hafez GR. Merkel cells and Merkel cell tumor ultrastructure, immunocytochemistry and review of the literature. Cancer. 1983;52:238–245
  8. Halata Z, Grim M, Bauman K. Friedrich Sigmund Merkel and His “Merkel Cell,” morphology, development, and physiology: review and new results. Anat Rec A Discov Mol Cell Evol Biol. 2003;271:225–239
  9. Hoefler H, Kerl H, Rauch HJ, Denk H. New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma. Am J Dermatopathol. 1984;6:525–530
  10. Al-Ahmadie HA, Mutasim DF, Mutema GK. A case of intraepidermal Merkel cell carcinoma within squamous cell carcinoma in-situ: Merkel cell carcinoma in-situ?. Am J Dermatopathol. 2004;26(3):230–233
  11. Ferringer T, Rogers HC, Metcalf JS. Merkel cell carcinoma in situ. J Cutan Pathol. 2005;32(2):162–165
  12. 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):376–385
  13. Pilotti S, Rilke F, Lombardi L. Neuroendocrine (Merkel cell) carcinoma of the skin. Am J Surg Pathol. 1982;6(3):243–254
  14. 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):612–619
  15. Connelly T, Cribier B, Brown TJ, Yanguas I. Complete spontaneous regression of Merkel cell carcinoma: a review of the 10 reported cases. Dermatol Surg. 2000;26:853–856
  16. Sais G, Admella C, Soler T. Spontaneous regression in primary cutaneous neuroendocrine (Merkel cell) carcinoma: a rare immune phenomenon?. J Eur Acad Dermatol Venereol. 2002;16:81–94
  17. Poulsen M. Merkel-cell carcinoma of the skin. Lancet Oncol. 2004;5:593–599
  18. Smith KJ, Skelton HG, Holland TT, Morgan AM, Lupton GP. Neuroendocrine (Merkel cell) carcinoma with an intraepidermal component. Am J Dermatopathol. 1993;15(6):528–533
  19. Rocamora A, Badía 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;16:1163–1168
  20. Skelton H, 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):734–739
  21. Gilman S, Morrison R, Hurt M. Epidermotropic neuroendocrine carcinoma (Immunohistochemical differentiation from simulators, including malignant melanoma). J Cutan Pathol. 1991;18:120–127
  22. Brown HA, Sawyer DM, Woo T. Intraepidermal Merkel cell carcinoma with no dermal involvement. Am J Dermatopathol. 2000;22(1):65–69
  23. Hashimoto K, et al. Pagetoid Merkel cell carcinoma: epidermal origin of the tumor. J Cutan Pathol. 1998;25:572–579
  24. Walsh N. Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof. Hum Pathol. 2001;32:680
  25. Hwang JH, Alanen K, Dabbs KD, Danyluk J, Silverman S. Merkel cell carcinoma with squamous and sarcomatous differentiation. J Cutan Pathol. 2008;35(10):955–959
  26. Isimbaldi G, Sironi M, Taccagni G. Tripartite differentiation (squamous, glandular and melanocytic) of a primary cutaneous neuroendocrine carcinoma. Am J Dermatopathol. 1993;15:260–264
  27. Scurry J, Brand A, Planner R, Dowling J, Rode J. Vulvar Merkel cell tumor with glandular and squamous differentiation. Gynecol Oncol. 1996;62:292–297
  28. 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. 1998;12:768–772
  29. Silva EG, Mackay B, Goepfert H, Burgess MA, Fields RS. Endocrine carcinoma of the skin (Merkel cell carcinoma). Pathol Annu. 1984;19:1–30
  30. Fernandez-Figueras MT, Puig L, Gilaberte M, Gómez-Plaza Mdel C, Rex J, Ferrándiz C, et al. Merkel cell (primary neuroendocrine) carcinoma of the skin with nodal metastasis showing rhabdomyosarcomatous differentiation. J Cutan Pathol. 2002;29(10):619–622
  31. Boutilier R, Desormeau L, Cragg F, Roberts P, Walsh N. Merkel cell carcinoma: squamous and atypical fibroxanthoma-like differentiation in successive local tumor recurrences. Am J Dermatopathol. 2001;23:46–49
  32. Youker S, Billingsley E. Combined Merkel cell carcinoma and atypical fibroxanthoma. J Cutan Med Surg. 2005;9:6–9
  33. Cooper L, Debono R, Alsanjari N, Al-Nafussi A. Merkel cell tumour with leiomyosarcomatous differentiation. Histopathology. 2000;36:540–543
  34. Tan KB, Murali R, Karim RZ, Dutta D, Dutta R, McCarthy SW, et al. Merkel cell carcinoma with fibrosarcomatous differentiation. Pathology. 2008;40(3):314–316
  35. Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23(10):2300–2309
  36. Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113(9):2549–2558
  37. 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):734–739
  38. Vesely MJ, Murray DJ, Neligan PC, Novak CB, Gullane PJ, Ghazarian D. Complete spontaneous regression in Merkel cell carcinoma. J Plast Reconstr Aesthet Surg. 2008;61(2):165–171
  39. Burack J, Altschuler EL, Sustained remission of metastatic Merkel cell carcinoma with treatment of HIV infection. J R Soc Med. 2003;96:238–239
  40. Muirhead R, Ritchie D. Partial regression of Merkel cell carcinoma in response to withdrawal of azathioprine in an immunosuppression-induced case of metastatic Merkel cell carcinoma. Clin Oncol (R Coll Radiol). 2007;19:96
  41. Friedlaender MM, Rubinger D, Rosenbaum E, Amir G, Siguencia E. Temporary regression of Merkel cell carcinoma metastases after cessation of cyclosporine. Transplantation. 2002;73(11):1849–1850
  42. Bickle K, Glass LF, Messina JL, Fenske NA, Siegrist K. Merkel cell carcinoma: a clinical, histopathologic, and immunohistochemical review. Semin Cutan Med Surg. 2004;23(1):46–53
  43. Johansson L, Tennvall J, Akerman M. Immunohistochemical examination of 25 cases of Merkel cell carcinoma: a comparison with small cell carcinoma of the lung and oesophagus, and a review of the literature. APMIS. 1990;98(8):741–752
  44. Moll R, Löwe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas. Am J Pathol. 1992;140:427–447
  45. Bobos M, Hytiroglou P, Kostopoulos I, Karkavelas G, Papadimitriou CS. Immunohistochemical distinction between Merkel cell carcinoma and small cell carcinoma of the lung. Am J Dermatopathol. 2006;28(2):99–104
  46. Hanly A, Elgart G, Jorda M. Analysis of thyroid transcription factor-1 and cytokeratin 20 separates Merkel cell carcinoma from small cell carcinoma of the lung. J Cutan Pathol. 2000;27:118–120
  47. Visscher D, Cooper PH, Zarbo RJ, Crissman JD. Cutaneous neuroendocrine (Merkel cell) carcinoma: an immunophenotypic, clinicopathologic, and flow cytometric study. Mod Pathol. 1989;2:331–338
  48. Layfield L, Ulich T, Liao S, Barr R, Cheng L, Lewin KL. Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products. J Cutan Pathol. 1986;13:268–273
  49. Kurokawa M, Nabeshima K, Akiyama Y, Maeda S, Nishida T, Nakayama F, et al. CD56: a useful marker for diagnosing Merkel cell carcinoma. J Dermatol Sci. 2003;31:219–224
  50. Fernandez-Figueras MT, Puig L, Musulen E, Gilaberte M, Ferrándiz C, Lerma E, et al. Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma. Histopathology. 2005;46(6):614–621
  51. Llombart B, Monteagudo C, López-Guerrero JA, Carda C, Jorda E, Sanmartín O, et al. Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers. Histopathology. 2005;46(6):622–634
  52. Tucci MG, Lucarini G, Giangiacomi M, Zizzi A, Criante P, Ricotti G, et al. Immunohistochemical study of apoptosis markers and involvement of chemokine CXCR4 in skin Merkel cell carcinoma. J Eur Acad Dermatol Venereol. 2006;20(10):1220–1225
  53. Kennedy MM, Blessing K, King G, Kerr KM. Expression of Bcl-2 and p53 in Merkel cell carcinoma (An immunohistochemical study). Am J Dermatopathol. 1996;18(3):273–277
  54. Feinmesser M, Halpern M, Fenig E, Tsabari C, Hodak E, Sulkes J, 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):1367–1372
  55. Kim J, McNiff JM. Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma. Mod Pathol. 2008;21(6):764–769
  56. 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):640–647
  57. Brunner M, Thurnher D, Pammer J, Heiduschka G, Petzelbauer P, Schmid C, et al. Expression of hedgehog signaling molecules in Merkel cell carcinoma. Head Neck. 2009;33:333–340
  58. Ng L, Beer TW, Murray K. Vascular density has prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(5):442–445
  59. Brunner M, Thurnher D, Pammer J, Geleff S, Heiduschka G, Reinisch CM, et al. Expression of VEGF-A/C, VEGF-R2, PDGF-alpha/beta, c-kit, EGFR, Her-2/Neu, Mcl-1 and BMI-1 in Merkel cell carcinoma. Mod Pathol. 2008;21(7):876–884
  60. Su LD, Fullen DR, Lowe L, Uherova P, Schnitzer B, Valdez R. CD117 (KIT receptor) expression in Merkel cell carcinoma. Am J Dermatopathol. 2002;24(4):289–293
  61. Camp RL, Neumeister V, Rimm DL. A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol. 2008;26(34):5630–5637
  62. Blom A, Kolb F, Lumbroso J, Duvillard P, Mamelle G, Morzli K, et al. [Significance of sentinel lymph node biopsy in Merkel cell carcinoma (Analysis of 11 cases]). Ann Dermatol Venereol. 2003;130(4):417–422
  63. Allen PJ, Busam K, Hill AD, Stojadinovic A, Coit DG, et al. Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma. Cancer. 2001;92(6):1650–1655
  64. Su LD, Lowe L, Bradford CR, Yahanda AI, Johnson TM, Sondak VK. Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. J Am Acad Dermatol. 2002;46(5):661–666
  65. Sidhu GS, Chandra P, Cassai ND. Merkel cells, normal and neoplastic: an update. Ultrastruct Pathol. 2005;29(3-4):287–294
  66. Sidhu GS, Feiner H, Flotte TJ, Mullins JD, Schaefler K, Schultenover SJ. Merkel cell neoplasms (Histology, electron microscopy, biology, and histogenesis). Am J Dermatopathol. 1980;2(2):101–119
  67. Dey P, Jogai S, Amir T, Temim L. Fine-needle aspiration cytology of Merkel cell carcinoma. Diagn Cytopathol. 2004;31(5):364–365
  68. Collins BT, Elmberger PG, Tani EM, Bjornhagen V, Ramos RR. Fine-needle aspiration of Merkel cell carcinoma of the skin with cytomorphology and immunocytochemical correlation. Diagn Cytopathol. 1998;18(4):251–257
  69. Domagala W, Lubinski J, Lasota J, Giryn I, Weber K, Osborn M. Neuroendocrine (Merkel-cell) carcinoma of the skin (Cytology, intermediate filament typing and ultrastructure of tumor cells in fine needle aspirates). Acta Cytol. 1987;31:267–275
  70. Farinola MA, Weir EG, Ali SZ. CD56 expression of neuroendocrine neoplasms on immunophenotyping by flow cytometry: a novel diagnostic approach to fine-needle aspiration biopsy. Cancer. 2003;99(4):240–246
  71. Buresh CJ, Oliai BR, Miller RT. Reactivity with TdT in Merkel cell carcinoma: a potential diagnostic pitfall. Am J Clin Pathol. 2008;129(6):894–898

PII: S0147-0272(10)00019-X

doi: 10.1016/j.currproblcancer.2010.02.002

Current Problems in Cancer
Volume 34, Issue 1 , Pages 47-64 , January 2010

Article Tools

* Image Usage & Resolution