What is the origin of the Merkel cell and Merkel cell carcinoma (MCC)?

Answer

The origin of Merkel cells is unclear, as they share both epidermal and neuroendocrine features. Research suggests that they may be derived from pluripotential stem cells of the dermis or, as an alternative, from neural crest cells. Cytologic and immunohistochemical data support both contentions.

Merkel cells display paranuclear staining for cytokeratins, which are also found in other neuroendocrine tumors. Osmiophilic granules contain neuropeptide, such as neuron-specific enolase, chromogranins, and synaptophysin. Evidence suggests that Merkel cells communicate with nerve terminals by means of a glutamatergic pathway, implying that they may have a neuroendocrine origin.

The general assumption is that MCC originates from Merkel cells, though this does not appear to be entirely correct. For example, MCC develops almost exclusively in the dermis, whereas the overwhelming majority of Merkel cells are found in the epidermis, a site rarely involved with MCC. Some suggest that the cells of origin may be immature pluripotential stem cells found in the dermis. These stem cells share phenotypic similarities with Merkel cells, though they do not appear to communicate with nerve terminals. It is postulated that these cells may acquire neuroendocrine features during malignant transformation.

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Pellitteri PK, Takes RP, Lewis JS Jr, et al. Merkel cell carcinoma of the head and neck. Head Neck. 2012 Sep. 34(9):1346-54. [Medline].
Brady M, Spiker AM. Cancer, Skin, Merkel Cell. 2018 Jan. [Medline]. [Full Text].
Muller-Richter UDA, Gesierich A, Kubler AC, Hartmann S, Brands RC. Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment. Ann Surg Oncol. 2017 Oct. 24 (11):3430-7. [Medline]. [Full Text].
Hoetzenecker W, Guenova E, Bottinger TU, Hafner HM, Breuninger H. Mapping of specific sentinel node locations for skin cancer of the head. Eur J Dermatol. 2011 May-Jun. 21(3):354-8. [Medline].
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].
Kassem A, Schopflin A, Diaz C, Weyers W, Stickeler E, Werner M. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 2008 Jul 1. 68(13):5009-13. [Medline].
Becker JC, Houben R, Ugurel S, Trefzer U, Pfohler C, Schrama D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol. 2009 Jan. 129(1):248-50. [Medline].
Sastre-Garau X, Peter M, Avril MF, Laude H, Couturier J, Rozenberg F. Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis. J Pathol. 2009 May. 218(1):48-56. [Medline].
Houben R, Shuda M, Weinkam R, Schrama D, Feng H, Chang Y. Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens. J Virol. 2010 Jul. 84(14):7064-72. [Medline].
Houben R, Adam C, Baeurle A, Hesbacher S, Grimm J, Angermeyer S. An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells. Int J Cancer. 2012 Feb 15. 130(4):847-56. [Medline].
Jung HS, Choi YL, Choi JS, Roh JH, Pyon JK, Woo KJ. Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell carcinomas by PCR and immunohistochemistry. Histol Histopathol. 2011 Oct. 26(10):1231-41. [Medline].
Willmes C, Adam C, Alb M, Volkert L, Houben R, Becker JC. Type I and II IFNs inhibit Merkel cell carcinoma via modulation of the Merkel cell polyomavirus T antigens. Cancer Res. 2012 Apr 15. 72(8):2120-8. [Medline].
Chen T, Hedman L, Mattila PS, et al. Serological evidence of Merkel cell polyomavirus primary infections in childhood. J Clin Virol. 2011 Feb. 50(2):125-9. [Medline].
Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer. 2009 Sep 15. 125(6):1250-6. [Medline].
Iwasaki T, Matsushita M, Kuwamoto S, Kato M, Murakami I, Higaki-Mori H. Usefulness of significant morphologic characteristics in distinguishing between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinomas. Hum Pathol. 2013 May 10. [Medline].
Amber K, McLeod MP, Nouri K. The Merkel cell polyomavirus and its involvement in Merkel cell carcinoma. Dermatol Surg. 2013 Feb. 39(2):232-8. [Medline].
Erovic BM, Al Habeeb A, Harris L, Goldstein DP, Ghazarian D, Irish JC. Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma. Head Neck. 2013 Feb. 35(2):184-9. [Medline].
Colgan MB, Tarantola TI, Weaver AL, Wiseman GA, Roenigk RK, Brewer JD. The predictive value of imaging studies in evaluating regional lymph node involvement in Merkel cell carcinoma. J Am Acad Dermatol. 2012 Dec. 67(6):1250-6. [Medline].
Hawryluk EB, O'Regan KN, Sheehy N, Guo Y, Dorosario A, Sakellis CG. Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women's Cancer Center. J Am Acad Dermatol. 2013 Apr. 68(4):592-9. [Medline].
Enzenhofer E, Ubl P, Czerny C, Erovic BM. Imaging in patients with merkel cell carcinoma. J Skin Cancer. 2013. 2013:973123. [Medline].
Knopf A, Bas M, Hofauer B, Mansour N, Stark T. Clinicopathological characteristics of head and neck Merkel cell carcinomas. Head Neck. 2017 Jan. 39 (1):92-7. [Medline].
Tarantola TI, Vallow LA, Halyard MY, Weenig RH, Warschaw KE, Grotz TE. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol. 2013 Mar. 68(3):425-32. [Medline].
Smith VA, MaDan OP, Lentsch EJ. Tumor location is an independent prognostic factor in head and neck Merkel cell carcinoma. Otolaryngol Head Neck Surg. 2012 Mar. 146(3):403-8. [Medline].
Lim CS, Whalley D, Haydu LE, Murali R, Tippett J, Thompson JF. Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma. Ann Surg Oncol. 2012 Oct. 19(11):3325-34. [Medline].
Asioli S, Righi A, Volante M, Eusebi V, Bussolati G. p63 expression as a new prognostic marker in Merkel cell carcinoma. Cancer. 2007 Aug 1. 110(3):640-7. [Medline].
Vlahova L, Doerflinger Y, Houben R, Becker JC, Schrama D, Weiss C. P-cadherin expression in Merkel cell carcinomas is associated with prolonged recurrence-free survival. Br J Dermatol. 2012 May. 166(5):1043-52. [Medline].
Ott MJ, Tanabe KK, Gadd MA, et al. Multimodality management of Merkel cell carcinoma. Arch Surg. 1999 Apr. 134(4):388-92; discussion 392-3. [Medline].
Perez MC, de Pinho FR, Holstein A, et al. Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?. Ann Surg Oncol. 2018 Oct. 25 (11):3334-40. [Medline].
Papadiochos I, Patrikidou A, Patsatsi A, Mangoudi D, Thuau H, Vahtsevanos K. Head and neck Merkel cell carcinoma: a retrospective case series and critical literature review with emphasis on treatment and prognosis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Feb. 125 (2):126-39. [Medline].
Bishop AJ, Garden AS, Gunn GB, et al. Merkel cell carcinoma of the head and neck: favorable outcomes with radiotherapy. Head Neck. 2016 Apr. 38 Suppl 1:E452-8. [Medline].
Strom T, Naghavi AO, Messina JL, et al. Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck. Head Neck. 2017 Jan. 39 (1):48-55. [Medline].
Pape E, Rezvoy N, Penel N, et al. Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients. J Am Acad Dermatol. 2011 Nov. 65(5):983-90. [Medline].
Lewis KG, Weinstock MA, Weaver AL, Otley CC. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006 Jun. 142(6):693-700. [Medline].
Chen MM, Roman SA, Sosa JA, et al. The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients. JAMA Otolaryngol Head Neck Surg. 2015 Feb. 141(2):137-41. [Medline].
Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct. 17 (10):1374-1385. [Medline].
Willmes C, Adam C, Alb M, Volkert L, Houben R, Becker JC. Type I and II IFNs inhibit Merkel cell carcinoma via modulation of the Merkel cell polyomavirus T antigens. Cancer Res. 2012 Apr 15. 72(8):2120-8. [Medline].
Zeng Q, Gomez BP, Viscidi RP, et al. Development of a DNA vaccine targeting Merkel cell polyomavirus. Vaccine. 2012 Feb 8. 30(7):1322-9. [Medline].

Media Gallery

Large, violaceous nodule of a Merkel cell carcinoma on the antecubital fossa (photo courtesy of Dr Jonathan Cook).
Histologic appearance of nodular Merkel cell carcinoma. This dermal nodule has a cohesive, expansile growth of basophilic cells.
Note the small, round, basophilic cells arranged in sheets, rests, or trabeculae in this Merkel cell carcinoma. The cells possess hyperchromatic nuclei, minimal cytoplasm, and frequent mitotic and apoptotic figures (hematoxylin-eosin stain).
Electron photomicrograph of a Merkel cell carcinoma shows a dense core granule (arrow).

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Author

Arjun S Joshi, MD Assistant Professor of Surgery, Division of Otolaryngology–Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Arjun S Joshi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Medical Association, American Thyroid Association

Disclosure: Nothing to disclose.

Coauthor(s)

Neil S Nayak George Washington University School of Medicine and Health Sciences

Disclosure: Nothing to disclose.

John Boone, MD Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor

John Boone, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nader Sadeghi, MD, FRCSC Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, McGill University Faculty of Medicine; Chief Otolaryngologist, MUHC; Director, McGill Head and Neck Cancer Program, Royal Victoria Hospital, Canada

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Thyroid Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;The Physicians Edge;Sync-n-Scale;mCharts<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; .

Additional Contributors

Mark K Wax, MD Professor and Program Director, Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University; Service Chief, Department of Surgery, Section of Otolaryngology, Veterans Affairs Medical Center

Mark K Wax, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Head and Neck Society, Canadian Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American College of Surgeons, American Rhinologic Society, American Society for Laser Medicine and Surgery, North American Skull Base Society, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

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