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Melanom der Vulva

  • Thomas Eigentler
Chapter

Zusammenfassung

Das maligne Melanom ist ein hochmaligner, von Melanozyten ausgehender Tumor. Insgesamt findet sich in bis zu 10 % aller Melanommanifestationen der Frau eine Lokalisation im Urogenitaltrakt. Trotz der absoluten Seltenheit stellen Vulvamelanome die dritthäufigste Gruppe maligner Neoplasien der Vulva dar. Die wichtigste Maßnahme der Früherkennung ist die klinische Inspektion, die Therapie der Wahl die operative Exzision. Die Nachsorge sollte aufgrund des Rezidiv- und Metastasierungsrisikos in den ersten Jahren intensiviert erfolgen. Im Stadium der Fernmetastasierung stehen immunologische Therapiekonzepte im Vordergrund.

Literatur

  1. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS (2015) Talimogene Laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 33(25):2780–2788CrossRefGoogle Scholar
  2. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 ajcc melanoma staging and classification. J Clin Oncol 27(36):6199–6206CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cameron DA, Cornbleet MC, Mackie RM, Hunter JA, Gore M, Hancock B, Smyth JF, Scottish Melanoma G (2001) Adjuvant interferon alpha 2b in high risk melanoma – the Scottish study. Bri J Cancer 84(9):1146–1149CrossRefGoogle Scholar
  4. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK (2011) Kit as a therapeutic target in metastatic melanoma. JAMA 305(22):2327–2334CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chung AF, Woodruff JM, Lewis JL Jr (1975) Malignant melanoma of the vulva: a report of 44 cases. Obstet Gynecol 45(6):638–646CrossRefPubMedGoogle Scholar
  6. Creagan ET, Cupps RE, Ivins JC, Pritchard DJ, Sim FH, Soule EH, O’Fallon JR (1978) Adjuvant radiation therapy for regional nodal metastases from malignant melanoma: a randomized, prospective study. Cancer 42(5):2206–2210CrossRefPubMedGoogle Scholar
  7. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954CrossRefGoogle Scholar
  8. Douglas JG, Margolin K (2002) The treatment of brain metastases from malignant melanoma. Semin Oncol 29(5):518–524CrossRefPubMedGoogle Scholar
  9. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Konto C, Hoos A, de Pril V, Gurunath RK, de Schaetzen G, Suciu S, Testori A (2015) Adjuvant Ipilimumab versus placebo after complete resection of high-risk stage III melanoma (eortc 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 16(5):522–530CrossRefPubMedGoogle Scholar
  10. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A (2016) Prolonged survival in stage III melanoma with Ipilimumab adjuvant therapy. N Engl J Med 375(19):1845–1855CrossRefPubMedPubMedCentralGoogle Scholar
  11. Eigentler TK, Garbe C (2009) Malignes Melanom. In: Hiddemann W, Bartram CR (Hrsg) Die Onkologie, Teil 2: Solide Tumoren – Lymphome – Leukämien. Springer, HeidelbergGoogle Scholar
  12. Eigentler TK, Caroli UM, Radny P, Garbe C (2003) Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 4(12):748–759CrossRefGoogle Scholar
  13. Eigentler TK, Figl A, Krex D, Mohr P, Mauch C, Rass K, Bostroem A, Heese O, Koelbl O, Garbe C, Schadendorf D (2011) Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma. Cancer 117(8):1697–1703CrossRefGoogle Scholar
  14. Eigentler TK, Muhlenbein C, Follmann M, Schadendorf D, Garbe C (2017) S3-Leitlinie Diagnostik, Therapie und Nachsorge des Melanoms – update 2015/2016, Kurzversion 2.0. J Dtsch Dermatol Ges 15(6):e1–e41CrossRefPubMedGoogle Scholar
  15. Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, Jahkola T, Bowles TL, Testori A, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, Wouters M, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Rossi CR, Neves RI, Trocha SD, Wright F, Byrd DR, Matter M, Hsueh E, MacKenzie-Ross A, Johnson DB, Terheyden P, Berger AC, Huston TL, Wayne JD, Smithers BM, Neuman HB, Schneebaum S, Gershenwald JE, Ariyan CE, Desai DC, Jacobs L, McMasters KM, Gesierich A, Hersey P, Bines SD, Kane JM, Barth RJ, McKinnon G, Farma JM, Schultz E, Vidal-Sicart S, Hoefer RA, Lewis JM, Scheri R, Kelley MC, Nieweg OE, Noyes RD, Hoon DSB, Wang HJ, Elashoff DA, Elashoff RM (2017) Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 376(23):2211–2222CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ferraioli D, Lamblin G, Mathevet P, Hetu J, Berakdar I, Beurrier F, Chopin N (2016) Genital melanoma: prognosis factors and treatment modality. Arch Gynecol Obstet 294(5):1037–1045CrossRefPubMedGoogle Scholar
  17. Filippetti R, Pitocco R (2015) Amelanotic vulvar melanoma: a case report. Am J Dermatopathol 37(6):e75–77CrossRefPubMedGoogle Scholar
  18. Garbe C (2000) Differenzialdiagnose pigmentierter Hautveränderungen und Melanombehandlung am unteren Genitaltrakt der Frau. Onkologe 6(11):1083–1090CrossRefGoogle Scholar
  19. Gershenwald JE, Scolyer RA, Hess KR, Thompson JF, Long GV, Ross MI, Lazar AJ, Atkins MB, Balch CM, Barnhill RL, Bilimoria KY, Brierley JD, Buzaid AC, Byrd DR, Chapman PB, Cochran AJ, Coit DG, Eggermont AM, Elder DE, Faries MB, Flaherty KT, Garbe C, Gardner JM, Gimotty PA, Halpern AC, Haydu LE, Johnson T, Kirkwood JM, Lee AWM, McArthur GA, Mihm MC, Prieto VG, Sober AJ, Wahl RL, Wong SL, Sondak VK (2016) Melanoma of the skin. AJCC Cancer Staging Manual. Springer, Heidelberg, S 563–585Google Scholar
  20. Grob JJ, Dreno B, de la Salmoniere P, Delaunay M, Cupissol D, Guillot B, Souteyrand P, Sassolas B, Cesarini JP, Lionnet S, Lok C, Chastang C, Bonerandi JJ (1998) Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet 351 (9120): 1905–1910Google Scholar
  21. Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S (2011) Phase II, open-label, single-arm trial of Imatinib Mesylate in patients with metastatic melanoma harboring c-kit mutation or amplification. J Clin Oncol 29(21):2904–2909CrossRefPubMedGoogle Scholar
  22. Hancock BW, Wheatley K, Harris S, Ives N, Harrison G, Horsman JM, Middleton MR, Thatcher N, Lorigan PC, Marsden JR, Burrows L, Gore M (2004) Adjuvant interferon in high-risk melanoma: The Aim High Study – United Kingdom Coordinating Committee on cancer research randomized study of adjuvant low-dose extended-duration interferon alfa-2a in high-risk resected malignant melanoma. J Clin Oncol 22(1):53–61CrossRefPubMedGoogle Scholar
  23. Heinzelmann-Schwarz VA, Nixdorf S, Valadan M, Diczbalis M, Olivier J, Otton G, Fedier A, Hacker NF, Scurry JP (2014) A clinicopathological review of 33 patients with vulvar melanoma identifies c-kit as a prognostic marker. Int J Mol Med 33(4):784–794CrossRefPubMedPubMedCentralGoogle Scholar
  24. Henderson MA, Burmeister BH, Ainslie J, Fisher R, Di Iulio J, Smithers BM, Hong A, Shannon K, Scolyer RA, Carruthers S, Coventry BJ, Babington S, Duprat J, Hoekstra HJ, Thompson JF (2015) Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (anzmtg 01.02/trog 02.01): 6-year follow-up of a phase 3, randomised controlled trial. Lancet Oncol 16(9):1049–1060CrossRefPubMedGoogle Scholar
  25. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, Eertwegh AJ van den, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with Ipilimumab in patients with metastatic melanoma. N Eng J Med 363(8):711–723CrossRefGoogle Scholar
  26. Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA (2016) Combined Nivolumab and Ipilimumab versus Ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 17(11):1558–1568CrossRefPubMedPubMedCentralGoogle Scholar
  27. Ives NJ, Suciu S, Eggermont AMM, Kirkwood J, Lorigan P, Markovic SN, Garbe C, Wheatley K (2017) Adjuvant interferon-alpha for the treatment of high-risk melanoma: an individual patient data meta-analysis. Eur J Cancer 82:171–183CrossRefPubMedGoogle Scholar
  28. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial est 1684. J Clin Oncol 14(1):7–17CrossRefPubMedGoogle Scholar
  29. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS, Smith TJ, Rao U, Steele M, Blum RH (2000) High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial e1690/s9111/c9190. J Clin Oncol 18(12):2444–2458CrossRefPubMedGoogle Scholar
  30. Kirkwood JM, Ibrahim J, Lawson DH, Atkins MB, Agarwala SS, Collins K, Mascari R, Morrissey DM, Chapman PB (2001) High-dose interferon alfa-2b does not diminish antibody response to gm2 vaccination in patients with resected melanoma: results of the multicenter Eastern Cooperative Oncology Group phase II trial. J Clin Oncol 19(5):1430–1436CrossRefPubMedGoogle Scholar
  31. Larkin J, Hodi FS, Wolchok JD (2015) Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(13):1270–1271CrossRefPubMedGoogle Scholar
  32. Leitao MM Jr (2014) Management of vulvar and vaginal melanomas: current and future strategies. Am Soc Clin Oncol Educ Book, e277–281Google Scholar
  33. Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer N, Berking C, Sunderkotter C, Kaatz M, Schulte KW, Lehmann P, Vogt T, Ulrich J, Herbst R, Gehring W, Simon JC, Keim U, Martus P, Garbe C (2016) Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (decog-slt): a multicentre, randomised, phase 3 trial. Lancet Oncol 17(6):757–767CrossRefPubMedGoogle Scholar
  34. Lens MB, Dawes M, Goodacre T, Newton-Bishop JA (2002) Elective lymph node dissection in patients with melanoma: systematic review and meta-analysis of randomized controlled trials. Arch Surg 137(4):458–461CrossRefPubMedGoogle Scholar
  35. Leo F, Cagini L, Rocmans P, Cappello M, Geel AN, Maggi G, Goldstraw P, Pastorino U (2000) Lung metastases from melanoma: when is surgical treatment warranted? Br J Cancer 83(5):569–572CrossRefPubMedPubMedCentralGoogle Scholar
  36. Mai R, Zhou S, Zhong W, Rong S, Cong Z, Li Y, Xie Q, Chen H, Li X, Liu S, Cheng Y, Huang Y, Zhou Y, Zhang G (2015) Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials. Oncotarget 6(29):28502–28512CrossRefPubMedPubMedCentralGoogle Scholar
  37. Mert I, Semaan A, Winer I, Morris RT, Ali-Fehmi R (2013) Vulvar/vaginal melanoma: an updated surveillance epidemiology and end results database review, comparison with cutaneous melanoma and significance of racial disparities. Int J Gynecol Cancer 23(6):1118–1125CrossRefPubMedGoogle Scholar
  38. Morton DL, Wanek L, Nizze JA, Elashoff RM, Wong JH (1991) Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the john wayne cancer clinic. Ann Surg 214 (4): 491–499, discussion 499–501Google Scholar
  39. Oiso N, Yoshida M, Kawara S, Kawada A (2010) Amelanotic vulvar melanoma with intratumor histological heterogeneity. J Dermatol 37(6):537–541CrossRefPubMedGoogle Scholar
  40. Omholt K, Grafstrom E, Kanter-Lewensohn L, Hansson J, Ragnarsson-Olding BK (2011) Kit pathway alterations in mucosal melanomas of the vulva and other sites. Clin Cancer Res 17(12):3933–3942CrossRefPubMedGoogle Scholar
  41. Pehamberger H, Soyer HP, Steiner A, Kofler R, Binder M, Mischer P, Pachinger W, Aubock J, Fritsch P, Kerl H, Wolff K (1998) Adjuvant interferon alfa-2a treatment in resected primary stage ii cutaneous melanoma. Austrian malignant melanoma cooperative group. J Clin Oncol 16(4):1425–1429CrossRefPubMedGoogle Scholar
  42. Piura B (2008) Management of primary melanoma of the female urogenital tract. Lancet Oncol 9(10):973–981CrossRefPubMedGoogle Scholar
  43. Pleunis N, Schuurman MS, Van Rossum MM, Bulten J, Massuger LF, De Hullu JA, Van der Aa MA (2016) Rare vulvar malignancies incidence, treatment and survival in the Netherlands. Gynecol Oncol 142(3):440–445CrossRefPubMedGoogle Scholar
  44. Podratz KC, Gaffey TA, Symmonds RE, Johansen KL, O’Brien PC (1983) Melanoma of the vulva: an update. Gynecol Oncol 16(2):153–168CrossRefPubMedGoogle Scholar
  45. Ragnarsson-Olding BK, Kanter-Lewensohn LR, Lagerlof B, Nilsson BR, Ringborg UK (1999) Malignant melanoma of the vulva in a nationwide, 25-year study of 219 swedish females: clinical observations and histopathologic features. Cancer 86(7):1273–1284CrossRefPubMedGoogle Scholar
  46. Raigani S, Cohen S, Boland GM (2017) The role of surgery for melanoma in an era of effective systemic therapy. Curr Oncol Rep 19(3):17CrossRefPubMedGoogle Scholar
  47. Rate WR, Solin LJ, Turrisi AT (1988) Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression. Int J Radiat Oncol Biol Phys 15(4):859–864CrossRefPubMedGoogle Scholar
  48. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O’Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A (2015) Pembrolizumab versus investigator-choice chemotherapy for Ipilimumab-refractory melanoma (keynote-002): a randomised, controlled, phase 2 trial. Lancet Oncol 16(8):908–918CrossRefGoogle Scholar
  49. Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, Algazi A, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C (2016) Association of Pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 315(15):1600–1609CrossRefPubMedGoogle Scholar
  50. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus Dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526CrossRefGoogle Scholar
  51. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015a) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372(4):320–330CrossRefGoogle Scholar
  52. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 Investigators (2015b) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372(26):2521–2532CrossRefGoogle Scholar
  53. Rock B (1992) Pigmented lesions of the vulva. Dermatol Clin 10(2):361–370CrossRefPubMedGoogle Scholar
  54. Schuurman MS, Einden LCG van den, Massuger LFAG, Kiemeney LA, Aa MA van der, Hullu JA de (2013) Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 49(18):3872–3880CrossRefPubMedGoogle Scholar
  55. Seegenschmiedt MH, Keilholz L, Pieritz A, Altendorf-Hofmann A, Urban A, Schell H, Hohenberger W, Sauer R (1999) Locally recurrent and metastatic malignant melanoma. Long-term results and prognostic factors after percutaneous radiotherapy. Strahlenther Onkol 175(9):450–457CrossRefPubMedGoogle Scholar
  56. Stang A, Streller B, Eisinger B, Jockel KH (2005) Population-based incidence rates of malignant melanoma of the vulva in Germany. Gynecol Oncol 96(1):216–221CrossRefPubMedGoogle Scholar
  57. Stevens G, McKay MJ (2006) Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma. Lancet Oncol 7(7):575–583CrossRefPubMedGoogle Scholar
  58. Tcheung WJ, Selim MA, Herndon JE 2nd, Abernethy AP, Nelson KC (2012) Clinicopathologic study of 85 cases of melanoma of the female genitalia. J Am Acad Dermatol 67(4):598–605CrossRefPubMedGoogle Scholar
  59. Ulmer A, Dietl J, Schaumburg-Lever G, Fierlbeck G (1996) Amelanotic malignant melanoma of the vulva. Case report and review of the literature. Arch Gynecol Obstet 259(1):45–50CrossRefPubMedGoogle Scholar
  60. Weber JS, DʼAngelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH Jr, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-ctla-4 treatment (checkmate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16(4):375–384CrossRefGoogle Scholar
  61. Wechter ME, Reynolds RK, Haefner HK, Lowe L, Gruber SB, Schwartz JL, Johnston CM, Johnson TM (2004) Vulvar melanoma: review of diagnosis, staging, and therapy. J Low Genit Tract Dis 8(1):58–69CrossRefPubMedGoogle Scholar
  62. Zambo K, Szabo Z, Schmidt E, Koppan M, Repasy I, Bodis J (2007) Is the clinical staging system a good choice in the staging of vulvar malignancies? Eur J Nucl Med Mol Imaging 34 (11): 1878–1879, author reply 1880Google Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Universitäts-HautklinikTübingenDeutschland

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