Merkelzellkarzinom

ZUSAMMENFASSUNG

Das Merkelzellkarzinom ist ein aggressiver neuroendokriner Tumor, welcher durch schnelles Wachstum und frühzeitige Metastasierung charakterisiert ist. Das mediane Erkrankungsalter liegt zwischen 75–80 Jahren. Mit Zunahme des durchschnittlichen Bevölkerungsalters tritt der einstmals seltene Tumor immer häufiger auf. Neben den klassischen Therapiesäulen Chirurgie, Strahlentherapie und Chemotherapie spielt die Immunonkologie auch beim Merkelzellkarzinom eine zunehmend wichtige Rolle.

ABSTRACT

Merkel cell carcinoma represents a neuroendocrine tumour which can grow rapidly and metastasizes early. The median age of patients is 75–80 years. Given the continuously rising population age Merkel cell carcinoma is diagnosed more often. Besides surgery, radiotherapy and chemotherapy immunooncology plays an important role in the treatment of this aggressive tumour.

Publication History

Article published online:
31 March 2023

• Literatur

• 1 Heath M, Jaimes N, Lemos B. et al Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2008; 58: 375-381 DOI: 10.1016/j.jaad.2007.11.020.
• 2 Hitchcock CL, Bland KI, Laney RG. et al Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg 1988; 207: 201-207 DOI: 10.1097/00000658-198802000-00015.
• 3 Lemos BD, Storer BE, Iyer JG. 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; 63: 751-761 DOI: 10.1016/j.jaad.2010.02.056.
• 4 Albores-Saavedra J, Batich K, Chable-Montero F. et al Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol 2010; 37: 20-27 DOI: 10.1111/j.1600-0560.2009.01370.x.
• 5 Harms KL, Healy MA, Nghiem P. et al Analysis of Prognostic Factors from 9387 Merkel Cell Carcinoma Cases Forms the Basis for the New 8th Edition AJCC Staging System. Ann Surg Oncol 2016; 23: 3564-3571 DOI: 10.1245/s10434-016-5266-4.
• 6 Sridharan V, Muralidhar V, Margalit DN. et al Merkel Cell Carcinoma: A Population Analysis on Survival. J Natl Compr Canc Netw 2016; 14: 1247-1257 DOI: 10.6004/jnccn.2016.0134.
• 7 Allen PJ, Bowne WB, Jaques DP. et al Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005; 23: 2300-2309 DOI: 10.1200/JCO.2005.02.329.
• 8 Harrington C, Kwan W. Radiotherapy and Conservative Surgery in the Locoregional Management of Merkel Cell Carcinoma: The British Columbia Cancer Agency Experience. Ann Surg Oncol 2016; 23: 573-578 DOI: 10.1245/s10434-015-4812-9.
• 9 Zaar O, Gillstedt M, Lindelöf B. et al Merkel cell carcinoma incidence is increasing in Sweden. J Eur Acad Dermatol Venereol 2016; 30: 1708-1713 DOI: 10.1111/jdv.13698.
• 10 Youlden DR, Soyer HP, Youl PH. et al Incidence and survival for Merkel cell carcinoma in Queensland, Australia, 1993–2010. JAMA Dermatol 2014; 150: 864-872 DOI: 10.1001/jamadermatol.2014.124.
• 11 Feng H, Shuda M, Chang Y. et al Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319: 1096-1100 DOI: 10.1126/science.1152586.
• 12 Rollison DE, Giuliano AR, Becker JC. New virus associated with merkel cell carcinoma development. J Natl Compr Canc Netw 2010; 08: 874-880 DOI: 10.6004/jnccn.2010.0064.
• 13 Batinica M, Akgül B, Silling S. et al Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma. J Dermatol Sci 2015; 79: 43-49 DOI: 10.1016/j.jdermsci.2015.04.002.
• 14 Santos-Juanes J, Fernández-Vega I, Fuentes N. et al Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and metaanalysis. Br J Dermatol 2015; 173: 42-49 DOI: 10.1111/bjd.13870.
• 15 Paulson KG, Lewis CW, Redman MW. et al Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study. Cancer 2017; 123: 1464-1474 DOI: 10.1002/cncr.30475.
• 16 Soltani AM, Allan BJ, Best MJ. et al Merkel cell carcinoma of the hand and upper extremity: current trends and outcomes. J Plast Reconstr Aesthet Surg 2014; 67: e71-e77 DOI: 10.1016/j.bjps.2013.09.030.
• 17 Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol 2003; 49: 832-841 DOI: 10.1016/s0190-9622(03)02108-x.
• 18 Lanoy E, Costagliola D, Engels EA. Skin cancers associated with HIV infection and solid-organ transplantation among elderly adults. Int J Cancer 2010; 126: 1724-1731 DOI: 10.1002/ijc.24931.
• 19 Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev 1999; 08: 153-158
• 20 Garneski KM, Warcola AH, Feng Q. et al Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009; 129: 246-248 DOI: 10.1038/jid.2008.229.
• 21 Pastrana DV, Tolstov YL, Becker JC. et al Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog 2009; 05: e1000578 DOI: 10.1371/journal.ppat.1000578.
• 22 Erstad DJ, Cusack JC. Mutational analysis of merkel cell carcinoma. Cancers (Basel) 2014; 06: 2116-2136 DOI: 10.3390/cancers6042116.
• 23 Nghiem PT, Bhatia S, Lipson EJ. et al PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med 2016; 374: 2542-2552 DOI: 10.1056/NEJMoa1603702.
• 24 Moshiri AS, Doumani R, Yelistratova L. et al Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection. J Invest Dermatol 2017; 137: 819-827 DOI: 10.1016/j.jid.2016.10.028.
• 25 Becker JC, Kauczok CS, Ugurel S. et al Merkel cell carcinoma: molecular pathogenesis, clinical features and therapy. J Dtsch Dermatol Ges 2008; 06: 709-719 DOI: 10.1111/j.1610-0387.2008.06830.x.
• 26 Schadendorf D, Lebbé C, Zur Hausen A. et al Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs. Eur J Cancer 2017; 71: 53-69 DOI: 10.1016/j.ejca.2016.10.022.
• 27 Gupta SG, Wang LC, Peñas PF. et al 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; 142: 685-690 DOI: 10.1001/archderm.142.6.685.
• 28 Foote M, Veness M, Zarate D. et al Merkel cell carcinoma: the prognostic implications of an occult primary in stage IIIB (nodal) disease. J Am Acad Dermatol 2012; 67: 395-399 DOI: 10.1016/j.jaad.2011.09.009.
• 29 Ben-Haim S, Garkaby J, Primashvili N. et al Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT. Nucl Med Commun 2016; 37: 865-873 DOI: 10.1097/MNM.0000000000000523.
• 30 Poulsen M, Macfarlane D, Veness M. et al Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03. J Med Imaging Radiat Oncol 2018; 62: 412-419 DOI: 10.1111/1754-9485.12705.
• 31 Byrne K, Siva S, Chait L. et al 15-Year Experience of 18F-FDG PET Imaging in Response Assessment and Restaging After Definitive Treatment of Merkel Cell Carcinoma. J Nucl Med 2015; 56: 1328-1333 DOI: 10.2967/jnumed.115.158261.
• 32 George A, Girault S, Testard A. et al The impact of (18)F-FDG-PET/CT on Merkel cell carcinoma management: a retrospective study of 66 scans from a single institution. Nucl Med Commun 2014; 35: 282-290 DOI: 10.1097/MNM.0000000000000039.
• 33 Siva S, Byrne K, Seel M. et al 18F-FDG PET provides high-impact and powerful prognostic stratification in the staging of Merkel cell carcinoma: a 15-year institutional experience. J Nucl Med 2013; 54: 1223-1229 DOI: 10.2967/jnumed.112.116814.
• 34 Haymerle G, Fochtmann A, Kunstfeld R. et al Merkel cell carcinoma: Overall survival after open biopsy versus wide local excision. Head Neck 2016; 38 (Suppl. 01) E1014-E1018 DOI: 10.1002/hed.24148.
• 35 Wright GP, Holtzman MP. Surgical resection improves median overall survival with marginal improvement in long-term survival when compared with definitive radiotherapy in Merkel cell carcinoma: A propensity score matched analysis of the National Cancer Database. Am J Surg 2018; 215: 384-387 DOI: 10.1016/j.amjsurg.2017.10.045.
• 36 Schwartz JL, Bichakjian CK, Lowe L. et al Clinicopathologic features of primary Merkel cell carcinoma: a detailed descriptive analysis of a large contemporary cohort. Dermatol Surg 2013; 39: 1009-1016 DOI: 10.1111/dsu.12194.
• 37 Lim CS, Whalley D, Haydu LE. et al Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma. Ann Surg Oncol 2012; 19: 3325-3334 DOI: 10.1245/s10434-012-2509-x.
• 38 Gunaratne DA, Howle JR, Veness MJ. Sentinel lymph node biopsy in Merkel cell carcinoma: a 15-year institutional experience and statistical analysis of 721 reported cases. Br J Dermatol 2016; 174: 273-281 DOI: 10.1111/bjd.14240.
• 39 Servy A, Maubec E, Sugier PE. et al Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy. Ann Oncol 2016; 27: 914-919 DOI: 10.1093/annonc/mdw035.
• 40 Tai P. A practical update of surgical management of merkel cell carcinoma of the skin. ISRN Surg 2013; 2013: 850797 DOI: 10.1155/2013/850797.
• 41 Cowey CL, Mahnke L, Espirito J. et al Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA. Future Oncol 2017; 13: 1699-1710 DOI: 10.2217/fon-2017-0187.
• 42 Iyer JG, Blom A, Doumani R. et al Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma. Cancer Med 2016; 05: 2294-2301 DOI: 10.1002/cam4.815.
• 43 Becker JC, Lorenz E, Ugurel S. et al Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe. Oncotarget 2017; 08: 79731-79741 DOI: 10.18632/oncotarget.19218.
• 44 Cornejo C, Miller CJ. Merkel Cell Carcinoma: Updates on Staging and Management. Dermatol Clin 2019; 37: 269-277 DOI: 10.1016/j.det.2019.03.001.
• 45 Kaufman HL, Russell J, Hamid O. et al Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17: 1374-1385 DOI: 10.1016/S1470-2045(16)30364-3.
• 46 Becker JC, Eigentler T, Frerich B. et al S2k-Leitlinie Merkelzellkarzinom (MZK, MCC, neuroendokrines Karzinom der Haut) – Update 2018. J Dtsch Dermatol Ges 2019; 17: 562-577 DOI: 10.1111/ddg.13841_g.