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Dermatologic Manifestations of Merkel Cell Carcinoma Follow-up

  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
Updated: Sep 14, 2015


Photoprotection (eg, sunscreen, behavioral prevention) may help prevent Merkel cell carcinoma (MCC), but this is not proven. Also see Sunscreens and Photoprotection.



Complications secondary to metastasis depend on the anatomic sites of involvement.



Partial or complete spontaneous regression (reminiscent of that sometimes seen in melanoma) is a well documented but rare phenomenon in Merkel cell carcinoma and may be more common in women than in men.[44] Even some metastases may remit spontaneously. Regression is accompanied by dense lymphocytic infiltrates, primarily of the CD8 phenotype, and proceeds via apoptosis (as documented ultrastructurally and by the in situ DNA nick end labeling [TUNEL] technique).

Local cutaneous recurrence occurs after wide excision in 30-40% of patients with clinical stage I Merkel cell carcinoma; local invasion of contiguous organs (eg, intracranial) is also possible. Regional lymph node metastasis occurs in 50-79% of patients, and distant metastasis occurs in more than 30% of patients; major sites include liver, bone, central nervous system, lung, and skin.

Overall, the mortality rate is 30-50% in 2 years; few studies include longer-term follow-up. Women appear to have a better survival rate than men. Histopathologic features associated with a lower survival rate include small cell size, high mitotic rate, subcutaneous invasion, diffuse growth pattern, heavy lymphocytic infiltrates, increased vascular density, lymphovascular invasion, mast cell count, and tumor size greater than 5 mm.[13, 45]  


Patient Education

For patient education resources, see the Cancer and Tumors Center, as well as Skin Cancer and Skin Biopsy.

Contributor Information and Disclosures

Christopher R Shea, MD Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago, The Pritzker School of Medicine

Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology, Association of Professors of Dermatology, International Society of Dermatopathology, Arthur Purdy Stout Society, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society

Disclosure: Nothing to disclose.


Victor G Prieto, MD, PhD Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Society of Dermatopathology, College of American Pathologists, American Association for the Advancement of Science, International Society of Dermatopathology, European Society of Pathology, American Medical Association, American Society for Clinical Pathology, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Received grant/research funds from Genentech for investigator.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Susan M Swetter, MD Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, Women's Dermatologic Society, American Society of Clinical Oncology, Society for Melanoma Research, Eastern Cooperative Oncology Group, American Medical Association, Pacific Dermatologic Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

  1. Maricich SM, Wellnitz SA, Nelson AM, Lesniak DR, Gerling GJ, Lumpkin EA, et al. Merkel cells are essential for light-touch responses. Science. June 2009. 324:1580-2. [Medline].

  2. Van Keymeulen A, Mascre G, Youseff KK, Harel I, Michaux C, De Geest N, et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol. October 2009. 187:91-100. [Medline].

  3. Leonard JH, Hayard N. Loss of heterozygosity of chromosome 13 in Merkel cell carcinoma. Genes Chromosomes Cancer. 1997 Sep. 20(1):93-7. [Medline].

  4. Leonard JH, Williams G, Walters MK, Nancarrow DJ, Rabbitts PH. Deletion mapping of the short arm of chromosome 3 in Merkel cell carcinoma. Genes Chromosomes Cancer. 1996 Feb. 15(2):102-7. [Medline].

  5. Van Gele M, Speleman F, Vandesompele J, Van Roy N, Leonard JH. Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma detected by comparative genomic hybridization. Cancer Res. 1998 Apr 1. 58(7):1503-8. [Medline].

  6. Van Gele M, Van Roy N, Ronan SG, et al. Molecular analysis of 1p36 breakpoints in two Merkel cell carcinomas. Genes Chromosomes Cancer. 1998 Sep. 23(1):67-71. [Medline].

  7. Vortmeyer AO, Merino MJ, Böni R, Liotta LA, Cavazzana A, Zhuang Z. Genetic changes associated with primary Merkel cell carcinoma. Am J Clin Pathol. 1998 May. 109(5):565-70. [Medline].

  8. Paulson KG, Lemos BD, Feng B, Jaimes N, Peñas PF, Bi X, et al. Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc. J Invest Dermatol. June 2009. 129:1547-55. [Medline].

  9. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005 Jan 1. 89(1):1-4. [Medline].

  10. E. Nicolaidou, A. Mikrova, C. Antoniou, A.D. Katsambas. Advances in Merkel cell carcinoma pathogenesis and management: a recently discovered virus, a new international consensus staging system and new diagnostic codes. Br J Dermatol. January 2012. 166:16-21. [Medline].

  11. Lyhne D, Lock-Andersen J, Dahlstrøm K, Drzewiecki KT, Balslev E, Muhic A, et al. Rising incidence of Merkel cell carcinoma. J Plast Surg Hand Surg. December 2011. 45:274-80. [Medline].

  12. Pitale M, Sessions RB, Husain S. An analysis of prognostic factors in cutaneous neuroendocrine carcinoma. Laryngoscope. 1992 Mar. 102(3):244-9. [Medline].

  13. Mott RT, Smoller BR, Morgan MB. Merkel cell carcinoma: a clinicopathologic study with prognostic implications. J Cutan Pathol. 2004 Mar. 31(3):217-23. [Medline].

  14. Gipponi M. Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms. Minerva Chir. 2005 Aug. 60(4):217-33. [Medline].

  15. Gupta SG, Wang LC, Penas PF, Gellenthin M, Lee SJ, Nghiem P. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol. 2006 Jun. 142(6):685-90. [Medline].

  16. Schmalbach CE, Lowe L, Teknos TN, Johnson TM, Bradford CR. Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma. Arch Otolaryngol Head Neck Surg. 2005 Jul. 131(7):610-4. [Medline].

  17. Wasserberg N, Schachter J, Fenig E, Feinmesser M, Gutman H. Applicability of the sentinel node technique to Merkel cell carcinoma. Dermatol Surg. 2000 Feb. 26(2):138-41. [Medline].

  18. Marcoval J, Ferreres JR, Penín RM, Pérez D, Viñals JM. Merkel Cell Carcinoma: Differences between Sun-Exposed and Non-Sun-Exposed Variants - A Clinical Analysis of 36 Cases. Dermatology. 2014 Sep 25. [Medline].

  19. Gooptu C, Woollons A, Ross J, et al. Merkel cell carcinoma arising after therapeutic immunosuppression. Br J Dermatol. 1997 Oct. 137(4):637-41. [Medline].

  20. Ma JE, Brewer JD. Merkel cell carcinoma in immunosuppressed patients. Cancers (Basel). 2014 Jun 27. 6(3):1328-50. [Medline]. [Full Text].

  21. Shaw M, Warren S, Groben P, Gulley ML. No evidence of Epstein-Barr virus association with Merkel cell carcinoma. J Cutan Pathol. 2006 Sep. 33(9):624-8. [Medline].

  22. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008 Feb 22. 319(5866):1096-100. [Medline]. [Full Text].

  23. Verhaegen ME, Mangelberger D, Harms PW, et al. Merkel Cell Polyomavirus Small T Antigen is Oncogenic in Transgenic Mice. J Invest Dermatol. 2014 Oct 14. [Medline].

  24. Knight LM, Stakaityte G, Wood JJ, et al. Merkel cell polyomavirus small T antigen mediates microtubule destabilisation to promote cell motility and migration. J Virol. 2014 Oct 15. [Medline].

  25. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972 Jan. 105(1):107-10. [Medline].

  26. Hashimoto K, Lee MW, D'Annunzio DR, Balle MR, Narisawa Y. Pagetoid Merkel cell carcinoma: epidermal origin of the tumor. J Cutan Pathol. 1998 Nov. 25(10):572-9. [Medline].

  27. 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 Oct. 12(10):768-72. [Medline].

  28. Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol. 1998 Nov. 39(5 Pt 2):882-7. [Medline].

  29. Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev. 1999 Feb. 8(2):153-8. [Medline].

  30. Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Mod Pathol. 1995 May. 8(4):384-8. [Medline].

  31. Haugg AM, Rennspiess D, Hausen AZ, Speel EJ, Cathomas G, Becker JC, et al. Fluorescence in situ hybridization and qPCR to detect Merkel cell polyomavirus physical status and load in Merkel cell carcinomas. Int J Cancer. 2014 Dec 15. 135(12):2804-15. [Medline].

  32. 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 Jan. 6(1):3-9. [Medline].

  33. 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 Apr. 18(4):251-7. [Medline].

  34. Lemos BD, Storer BE, Iyer JG, Phillips JL, Bichakjian CK, Fang LC, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. 2010 Nov. 63(5):751-61. [Medline]. [Full Text].

  35. Voog E, Biron P, Martin JP, Blay JY. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer. 1999 Jun 15. 85(12):2589-95. [Medline].

  36. Decker RH, Wilson LD. Role of radiotherapy in the management of merkel cell carcinoma of the skin. J Natl Compr Canc Netw. 2006 Aug. 4(7):713-8. [Medline].

  37. Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1995 Jan 15. 31(2):325-31. [Medline].

  38. Senchenkov A, Barnes SA, Moran SL. Predictors of survival and recurrence in the surgical treatment of merkel cell carcinoma of the extremities. J Surg Oncol. 2007 Mar 1. 95(3):229-34. [Medline].

  39. Veness MJ, Perera L, McCourt J, et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg. 2005 May. 75(5):275-81. [Medline].

  40. [Guideline] Lebbe C, Becker JC, Grob JJ, et al. Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer. 2015 Aug 6. [Medline].

  41. O'Connor WJ, Roenigk RK, Brodland DG. Merkel cell carcinoma. Comparison of Mohs micrographic surgery and wide excision in eighty-six patients. Dermatol Surg. 1997 Oct. 23(10):929-33. [Medline].

  42. Leong SP. Selective sentinel lymphadenectomy for malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma. Cancer Treat Res. 2005. 127:39-76. [Medline].

  43. Kokoska ER, Kokoska MS, Collins BT, Stapleton DR, Wade TP. Early aggressive treatment for Merkel cell carcinoma improves outcome. Am J Surg. 1997 Dec. 174(6):688-93. [Medline].

  44. Takenaka H, Kishimoto S, Shibagaki R, Nagata M, Yasuno H. Merkel cell carcinoma with partial spontaneous regression: an immunohistochemical, ultrastructural, and TUNEL labeling study. Am J Dermatopathol. 1997 Dec. 19(6):614-8. [Medline].

  45. Ng L, Beer TW, Murray K. Vascular density has prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008 Oct. 30(5):442-5. [Medline].

  46. 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 Dec. 10(6):376-85. [Medline].

Large, violaceous nodule of Merkel cell carcinoma on the antecubital fossa. Courtesy of Dr. Jonathan Cook.
Histologic appearance of nodular Merkel cell carcinoma. Dermal nodule with a cohesive, expansile growth of basophilic cells.
High-power view demonstrates an open chromatin pattern and a high mitotic index.
Pseudorosette formation in Merkel cell carcinoma.
Merkel cell carcinoma with a focus of squamous differentiation.
Prominent in situ nested component of Merkel cell carcinoma, simulating malignant melanoma.
Electron micrograph of Merkel cell carcinoma showing a dense core granule (arrow).
Electron micrograph of Merkel cell carcinoma showing whorled bundles of intermediate filaments (arrow) near nucleus in Merkel cell carcinoma.
Dotlike paranuclear pattern of cytokeratin immunolocalization.
Table 1. Tumor Status
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis In situ primary tumor
T1 Primary tumor 2 cm or less in greatest dimension
T2 Primary tumor >2 cm but not >5 cm in greatest dimension
T3 Primary tumor >5 cm in greatest dimension
T4 Primary tumor invades bone, muscle, fascia, or cartilage
Table 2. Node Status
Nx Regional nodes cannot be assessed
N0 No regional node metastasis
cN0 Nodes not clinically detectable
cN1 Nodes clinically detectable
pN0 Nodes negative by pathologic examination
pNx Nodes not examined pathologically
N1a Micrometastasis
N1b Macrometastasis
N2 In-transit metastasis
Table 3. Metastasis Status
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Distant skin, distant subcutaneous tissues, or distant lymph nodes
M1b Lung
M1c All other visceral sites
Table 4. Stage Grouping
Stage Stage grouping
0 Tis N0 M0
IA T1 pN0 M0
IB T1 cN0 M0
IIA T2/T3 pN0 M0
IIB T2/T3 cN0 M0
IIC T4 N0 M0
IIIA Any T N1a M0
IIIB Any T N1b/N2 M0
IV Any T Any N M1
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