Malignant Melanoma Differential Diagnoses

1. Melanoma Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Available at https://www.cancer.gov/types/skin/hp/melanoma-treatment-pdq#link/_25_toc. October 14, 2022; Accessed: January 26, 2023.

2. Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008 Jul 12. 372(9633):117-26. [QxMD MEDLINE Link].

3. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014 Jul 14. [QxMD MEDLINE Link].

4. Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. 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. 2015 Apr. 16(4):375-84. [QxMD MEDLINE Link].

5. Tawbi HA, et al; RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022 Jan 6. 386 (1):24-34. [QxMD MEDLINE Link].

6. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011 Jun 8. 305(22):2327-34. [QxMD MEDLINE Link]. [Full Text].

7. Dalvin LA, Damento GM, Yawn BP, Abbott BA, Hodge DO, Pulido JS. Parkinson Disease and Melanoma: Confirming and Reexamining an Association. Mayo Clin Proc. 2017 Jul. 92 (7):1070-1079. [QxMD MEDLINE Link]. [Full Text].

8. American Cancer Society. Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: January 26, 2023.

9. Adamson AS, Suarez EA, Welch HG. Estimating Overdiagnosis of Melanoma Using Trends Among Black and White Patients in the US. JAMA Dermatol. 2022 Mar 16. [QxMD MEDLINE Link].

10. Ward WH, Farma JM. Cutaneous Melanoma: Etiology and Therapy. 2017 Dec 21. [QxMD MEDLINE Link]. [Full Text].

11. Cancer Stat Facts: Melanoma of the Skin. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/melan.html. Accessed: January 26, 2023.

12. Shaikh WR, Xiong M, Weinstock MA. The contribution of nodular subtype to melanoma mortality in the United States, 1978 to 2007. Arch Dermatol. 2012 Jan. 148(1):30-6. [QxMD MEDLINE Link].

13. Mocellin S, Pasquali S, Riccardo Rossi C, Nitti D. Validation of the prognostic value of lymph node ratio in patients with cutaneous melanoma: A population-based study of 8,177 cases. Surgery. 2011 Jul. 150(1):83-90. [QxMD MEDLINE Link].

14. Survival Rates for Melanoma Skin Cancer, by Stage. American Cancer Society. Available at https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage.html. March 1, 2022; Accessed: January 26, 2023.

15. Brewer JD, Christenson LJ, Weaver AL, et al. Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis. Arch Dermatol. 2011 Jul. 147(7):790-6. [QxMD MEDLINE Link].

16. Jethanamest D, Vila PM, Sikora AG, Morris LG. Predictors of survival in mucosal melanoma of the head and neck. Ann Surg Oncol. 2011 Oct. 18(10):2748-56. [QxMD MEDLINE Link]. [Full Text].

17. Sandru A, Voinea S, Panaitescu E, Blidaru A. Survival rates of patients with metastatic malignant melanoma. J Med Life. 2014 Oct-Dec. 7 (4):572-6. [QxMD MEDLINE Link]. [Full Text].

18. Kantor J, Kantor DE. Routine dermatologist-performed full-body skin examination and early melanoma detection. Arch Dermatol. 2009 Aug. 145(8):873-6. [QxMD MEDLINE Link].

19. Sabel MS, Wong SL. Review of evidence-based support for pretreatment imaging in melanoma. J Natl Compr Canc Netw. 2009 Mar. 7(3):281-9. [QxMD MEDLINE Link].

20. Xing Y, Bronstein Y, Ross MI, Askew RL, Lee JE, Gershenwald JE, et al. Contemporary diagnostic imaging modalities for the staging and surveillance of melanoma patients: a meta-analysis. J Natl Cancer Inst. 2011 Jan 19. 103(2):129-42. [QxMD MEDLINE Link]. [Full Text].

21. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Version 1.2023 — December 22, 2022; Accessed: January 26, 2023.

22. Gillgren P, Drzewiecki KT, Niin M, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet. 2011 Nov 5. 378(9803):1635-42. [QxMD MEDLINE Link].

23. Hu J, Cai X, Lv JJ, Wan XC, Zeng XY, Feng ML, et al. PRAME Immunohistochemistry as an Adjunct for Differential Diagnosis in Acral Lentiginous Melanoma and Acral Nevi. Hum Pathol. 2021 Nov 17. [QxMD MEDLINE Link].

24. Cesinaro AM, Piana S, Paganelli A, Pedroni G, Santandrea G, Maiorana A. PRAME expression in cellular neurothekeoma: A study of 11 cases. J Cutan Pathol. 2021 Nov 10. [QxMD MEDLINE Link].

25. Ricci C, Franceschini T, Giunchi F, Grillini M, Ambrosi F, Massari F, et al. Immunohistochemical Expression of Preferentially Expressed Antigen in Melanoma (PRAME) in the Uninvolved Background Testis, Germ Cell Neoplasia in Situ, and Germ Cell Tumors of the Testis. Am J Clin Pathol. 2021 Dec 1. [QxMD MEDLINE Link].

26. Farah M, Chung HJ. Diagnostic utility of preferentially expressed antigen in melanoma immunohistochemistry in the evaluation of melanomas with a co-existent nevoid melanocytic population: A single-center retrospective cohort study. J Am Acad Dermatol. 2021 Oct 28. [QxMD MEDLINE Link].

27. Wilson ML. Histopathologic and Molecular Diagnosis of Melanoma. Clin Plast Surg. 2021 Oct. 48 (4):587-598. [QxMD MEDLINE Link].

28. Revythis A, Shah S, Kutka M, Moschetta M, Ozturk MA, Pappas-Gogos G, et al. Unraveling the Wide Spectrum of Melanoma Biomarkers. Diagnostics (Basel). 2021 Jul 26. 11 (8):[QxMD MEDLINE Link]. [Full Text].

29. Rashid S, Tsao H. Recognition, Staging, and Management of Melanoma. Med Clin North Am. 2021 Jul. 105 (4):643-661. [QxMD MEDLINE Link].

30. Deacon DC, Smith EA, Judson-Torres RL. Molecular Biomarkers for Melanoma Screening, Diagnosis and Prognosis: Current State and Future Prospects. Front Med (Lausanne). 2021. 8:642380. [QxMD MEDLINE Link]. [Full Text].

31. Bachter D, Michl C, Buchels H, Vogt H, Balda BR. The predictive value of the sentinel lymph node in malignant melanomas. Recent Results Cancer Res. 2001. 158:129-36. [QxMD MEDLINE Link].

32. Cadili A, McKinnon G, Wright F, Hanna W, Macintosh E, Abhari Z, et al. Validation of a scoring system to predict non-sentinel lymph node metastasis in melanoma. J Surg Oncol. 2010 Mar 1. 101(3):191-4. [QxMD MEDLINE Link].

33. Bronstein Y, Ng CS, Rohren E, Ross MI, Lee JE, Cormier J, et al. PET/CT in the Management of Patients With Stage IIIC and IV Metastatic Melanoma Considered Candidates for Surgery: Evaluation of the Additive Value After Conventional Imaging. AJR Am J Roentgenol. 2012 Apr. 198(4):902-8. [QxMD MEDLINE Link].

34. American Joint Committee on Cancer. Melanoma of the Skin. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Staging Manual. 8th edition. New York: Springer; 2016.

35. McWilliams RR, Rao RD, Buckner JC, Link MJ, Markovic S, Brown PD. Melanoma-induced brain metastases. Expert Rev Anticancer Ther. 2008 May. 8(5):743-55. [QxMD MEDLINE Link].

36. Lee AY, Brady MS. Neoadjuvant immunotherapy for melanoma. J Surg Oncol. 2021 Mar. 123 (3):782-788. [QxMD MEDLINE Link]. [Full Text].

37. Erstad DJ, Witt RG, Wargo JA. Neoadjuvant therapy for melanoma: new and evolving concepts. Clin Adv Hematol Oncol. 2022 Jan. 20 (1):47-55. [QxMD MEDLINE Link].

38. Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017 Jun 8. 376 (23):2211-2222. [QxMD MEDLINE Link].

39. Leiter U, Stadler R, Mauch C, et al. Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial. Journal of Clinical Oncology. 2015. 33 (suppl):Abstract LBA9002. [Full Text].

40. Gould Rothberg BE, Berger AJ, Molinaro AM, Subtil A, Krauthammer MO, Camp RL, et al. Melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol. 2009 Dec 1. 27(34):5772-80. [QxMD MEDLINE Link]. [Full Text].

41. Saberian C, Sperduto P, Davies MA. Targeted therapy strategies for melanoma brain metastasis. Neurooncol Adv. 2021 Nov. 3 (Suppl 5):v75-v85. [QxMD MEDLINE Link]. [Full Text].

42. Khaddour K, Maahs L, Avila-Rodriguez AM, Maamar Y, Samaan S, Ansstas G. Melanoma Targeted Therapies beyond BRAF-Mutant Melanoma: Potential Druggable Mutations and Novel Treatment Approaches. Cancers (Basel). 2021 Nov 22. 13 (22):[QxMD MEDLINE Link]. [Full Text].

43. Varrone F, Mandrich L, Caputo E. Melanoma Immunotherapy and Precision Medicine in the Era of Tumor Micro-Tissue Engineering: Where Are We Now and Where Are We Going?. Cancers (Basel). 2021 Nov 18. 13 (22):[QxMD MEDLINE Link]. [Full Text].

44. Zeng H, Liu F, Zhou H, Zeng C. Individualized Treatment Strategy for Cutaneous Melanoma: Where Are We Now and Where Are We Going?. Front Oncol. 2021. 11:775100. [QxMD MEDLINE Link]. [Full Text].

45. Dietz H, Weinmann SC, Salama AK. Checkpoint Inhibitors in Melanoma Patients with Underlying Autoimmune Disease. Cancer Manag Res. 2021. 13:8199-8208. [QxMD MEDLINE Link]. [Full Text].

46. Boutros A, Bruzzone M, Tanda ET, Croce E, Arecco L, Cecchi F, et al. Health-related quality of life in cancer patients treated with immune checkpoint inhibitors in randomised controlled trials: A systematic review and meta-analysis. Eur J Cancer. 2021 Nov 6. 159:154-166. [QxMD MEDLINE Link].

47. Ferrucci PF, Lens M, Cocorocchio E. Combined BRAF-Targeted Therapy with Immunotherapy in BRAF-Mutated Advanced Melanoma Patients. Curr Oncol Rep. 2021 Nov 4. 23 (12):138. [QxMD MEDLINE Link].

48. Aleksakhina SN, Imyanitov EN. Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives. Int J Mol Sci. 2021 Oct 10. 22 (20):[QxMD MEDLINE Link]. [Full Text].

49. Pisibon C, Ouertani A, Bertolotto C, Ballotti R, Cheli Y. Immune Checkpoints in Cancers: From Signaling to the Clinic. Cancers (Basel). 2021 Sep 12. 13 (18):[QxMD MEDLINE Link]. [Full Text].

50. Teixido C, Castillo P, Martinez-Vila C, Arance A, Alos L. Molecular Markers and Targets in Melanoma. Cells. 2021 Sep 5. 10 (9):[QxMD MEDLINE Link]. [Full Text].

51. Yuan J, Khilnani A, Brody J, Andtbacka RHI, Hu-Lieskovan S, Luke JJ, et al. Current strategies for intratumoural immunotherapy - Beyond immune checkpoint inhibition. Eur J Cancer. 2021 Nov. 157:493-510. [QxMD MEDLINE Link].

52. Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet. 2021 Sep 11. 398 (10304):1002-1014. [QxMD MEDLINE Link].

53. Sevilla-Ortega L, Ferrándiz-Pulido L, Palazón-Carrión N, et al. Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature. Cancers (Basel). 2021 Oct 31. 13 (21):[QxMD MEDLINE Link]. [Full Text].

54. Soldozy S, Mulligan KM, Zheng DX, Levoska MA, Cullison CR, Elarjani T, et al. Oncolytic Virotherapy for Melanoma Brain Metastases, a Potential New Treatment Paradigm?. Brain Sci. 2021 Sep 23. 11 (10):[QxMD MEDLINE Link]. [Full Text].

55. Carr MJ, Sun J, DePalo D, Rothermel LD, Song Y, Straker RJ, et al. Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience. Ann Surg Oncol. 2021 Oct 14. [QxMD MEDLINE Link].

56. Zawit M, Swami U, Awada H, Arnouk J, Milhem M, Zakharia Y. Current status of intralesional agents in treatment of malignant melanoma. Ann Transl Med. 2021 Jun. 9 (12):1038. [QxMD MEDLINE Link]. [Full Text].

57. Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017 Nov 9. 377 (19):1813-1823. [QxMD MEDLINE Link]. [Full Text].

58. Hauschild A, Dummer R, Santinami M, et al. Long-term benefit of adjuvant dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: Five-year analysis of COMBI-AD. J Clin Oncol. 2020. 38:15 suppl:[Full Text].

59. Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018 May 10. 378 (19):1789-1801. [QxMD MEDLINE Link]. [Full Text].

60. Eggermont AM, Blank CU, Mandalà M, et al. Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up. J Clin Oncol. 2020. 38:15 suppl:[Full Text].

61. FDA approves pembrolizumab for adjuvant treatment of Stage IIB or IIC melanoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-stage-iib-or-iic-melanoma. December 6, 2021; Accessed: January 26, 2023.

62. Weber J, et al; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9. 377 (19):1824-1835. [QxMD MEDLINE Link].

63. FDA approves Opdualag for unresectable or metastatic melanoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-opdualag-unresectable-or-metastatic-melanoma. March 21, 2022; Accessed: January 26, 2023.

64. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med. 2016 Nov 10. 375 (19):1845-1855. [QxMD MEDLINE Link]. [Full Text].

65. Nelson, R. FDA approves Imlygic, First Oncolytic Viral Therapy in the US. Medscape Medical News. October 27, 2015. Available at http://www.medscape.com/viewarticle/853345.

66. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1. 33 (25):2780-8. [QxMD MEDLINE Link].

67. Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017 Jun. 66 (6):683-695. [QxMD MEDLINE Link]. [Full Text].

68. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996 Jan. 14(1):7-17. [QxMD MEDLINE Link].

69. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U. Eastern Cooperative Oncology Group. A pooled analysis of Eastern Cooperative Oncology Group and intergroup trials of adjuvant high dose alpha interferon for melanoma. Clin Cancer Res. 2004. 10:1670-77.

70. Pectasides D, Dafni U, Bafaloukos D, Skarlos D, Polyzos A, Tsoutsos D, et al. Randomized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma. J Clin Oncol. 2009 Feb 20. 27(6):939-44. [QxMD MEDLINE Link].

71. Hauschild A, Weichenthal M, Rass K, Linse R, Ulrich J, Stadler R, et al. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma. J Clin Oncol. 2009 Jul 20. 27(21):3496-502. [QxMD MEDLINE Link].

72. Hauschild A, Weichenthal M, Rass K, Linse R, Berking C, Böttjer J, et al. Efficacy of low-dose interferon (alpha)2a 18 versus 60 months of treatment in patients with primary melanoma of >= 1.5 mm tumor thickness: results of a randomized phase III DeCOG trial. J Clin Oncol. 2010 Feb 10. 28 (5):841-6. [QxMD MEDLINE Link].

73. Eggermont AM, Suciu S, Testori A, et al. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012 Jan. 48(2):218-25. [QxMD MEDLINE Link].

74. Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, Hayes FA, et al. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2000 Apr. 18(8):1614-21. [QxMD MEDLINE Link].

75. Lawson DH, Lee S, Zhao F, Tarhini AA, Margolin KA, Ernstoff MS, et al. Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697). J Clin Oncol. 2015 Dec 1. 33 (34):4066-76. [QxMD MEDLINE Link]. [Full Text].

76. Lazarus HM, Ragsdale CE, Gale RP, Lyman GH. Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time?. Front Immunol. 2021. 12:706186. [QxMD MEDLINE Link]. [Full Text].

77. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2. 373 (1):23-34. [QxMD MEDLINE Link]. [Full Text].

78. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30. 364(26):2507-16. [QxMD MEDLINE Link].

79. Chustecka Z. Dabrafenib and Trametinib Approved for Metastatic Melanoma. Medscape Medical News. Available at http://www.medscape.com/viewarticle/804918. Accessed: June 4, 2013.

80. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012 Jul 28. 380(9839):358-65. [QxMD MEDLINE Link].

81. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012 Jul 12. 367(2):107-14. [QxMD MEDLINE Link].

82. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012 Nov. 367(18):1694-703. [QxMD MEDLINE Link]. [Full Text].

83. US Food and Drug Administration. FDA approves Mekinist in combination with Tafinlar for advanced melanoma. FDA. Available at https://wayback.archive-it.org/7993/20170112222928/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm381159.htm. Accessed: January 26, 2023.

84. Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Sep. 17 (9):1248-60. [QxMD MEDLINE Link].

85. Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May. 19 (5):603-615. [QxMD MEDLINE Link].

86. Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF^V600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Jun 13. 395 (10240):1835-1844. [QxMD MEDLINE Link].

87. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015 May 21. 372 (21):2006-17. [QxMD MEDLINE Link].

88. Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, et al. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016 Nov 3. 375 (18):1749-1755. [QxMD MEDLINE Link].

89. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol. 2022 Jan 10. 40 (2):127-137. [QxMD MEDLINE Link].

90. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22. 372 (4):320-30. [QxMD MEDLINE Link]. [Full Text].

91. US Food and Drug Administration. FDA approves Keytruda for advanced melanoma: first PD-1 blocking drug to receive agency approval [press release]. September 4, 2014. Available at https://wayback.archive-it.org/7993/20170112023823/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412802.htm. Accessed: January 26, 2023.

92. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015 Jun 25. 372 (26):2521-32. [QxMD MEDLINE Link].

93. Sarnaik AA, Weber JS. Recent advances using anti-CTLA-4 for the treatment of melanoma. Cancer J. 2009 May-Jun. 15(3):169-73. [QxMD MEDLINE Link].

94. Yervoy (ipilimumab) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2017 July. Available at [Full Text].

95. Hodi FS, O'Day SJ, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19. 363(8):711-23. [QxMD MEDLINE Link].

96. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011 Jun 30. 364(26):2517-26. [QxMD MEDLINE Link].

97. Weber JS, Dummer R, de Pril V, Lebbe C, Stephen Hodi F. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: Detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013 Feb 7. [QxMD MEDLINE Link].

98. FDA approves Opdualag for unresectable or metastatic melanoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-opdualag-unresectable-or-metastatic-melanoma. March 21, 2022; Accessed: January 26, 2023.

99. Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013 Jul 8. [QxMD MEDLINE Link]. [Full Text].

100. Carvajal RD. Another option in our KIT of effective therapies for advanced melanoma. J Clin Oncol. 2013 Aug 12. [QxMD MEDLINE Link]. [Full Text].

101. Guo J, Si L, Kong Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011 Jul 20. 29(21):2904-9. [QxMD MEDLINE Link].

102. Hirai I, Tanese K, Fukuda K, Fusumae T, Nakamura Y, Sato Y, et al. Imatinib mesylate in combination with pembrolizumab in patients with advanced KIT-mutant melanoma following progression on standard therapy: A phase I/II trial and study protocol. Medicine (Baltimore). 2021 Dec 10. 100 (49):e27832. [QxMD MEDLINE Link].

103. In Melanoma, Personalized Treatment Vaccines Show Promise. National Cancer Institute. Available at https://www.cancer.gov/news-events/cancer-currents-blog/2017/melanoma-personalized-vaccine. August 4, 2017; Accessed: January 26, 2023.

104. Ellingsen EB, Bjørheim J, Gaudernack G. Therapeutic cancer vaccination against telomerase: clinical developments in melanoma. Curr Opin Oncol. 2023 Jan 17. [QxMD MEDLINE Link].

105. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000 Jan. 18(1):158-66. [QxMD MEDLINE Link].

106. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul. 17(7):2105-16. [QxMD MEDLINE Link].

107. Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009 Jun 10. 27(17):2823-30. [QxMD MEDLINE Link].

108. Perez DG, Suman VJ, Fitch TR, Amatruda T III, Morton RF, Jilani SZ, et al. Phase II trial of carboplatin, weekly paclitaxel, and weekly bevacizumab in patients with unresectable stage IV melanoma: a North Central Cancer Treatment Group study, N047A. Cancer. Jan 2009. 115(1):119-27.

109. Huncharek M, Kupelnick B. Use of topical sunscreen and the risk of malignant melanoma. Results of a meta-analysis of 9,067 patients. Ann Epidemiol. 2000 Oct 1. 10(7):467. [QxMD MEDLINE Link].

110. Autier P, Boniol M, Dore JF. Sunscreen use and increased duration of intentional sun exposure: still a burning issue. Int J Cancer. 2007 Jul 1. 121(1):1-5. [QxMD MEDLINE Link].

111. Kling J. Study Calls Into Question Sunscreen in Melanoma Prevention. Medscape Medical News. Available at http://www.medscape.com/viewarticle/871438?src=soc_fb_161108-pm_mscpedt_news_pharm. November 4, 2016; Accessed: January 26, 2023.

112. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Ebell M, et al. Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016 Jul 26. 316 (4):429-35. [QxMD MEDLINE Link]. [Full Text].

113. American Academy of Dermatology. Free Skin Cancer Screenings: Skin Cancer Screening Program. Available at https://www.aad.org/public/public-health/skin-cancer-screenings. Accessed: January 26, 2023.

114. [Guideline] Bichakjian CK, Halpern AC, Johnson TM, Foote Hood A, Grichnik JM, Swetter SM, et al. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol. 2011 Nov. 65 (5):1032-47. [QxMD MEDLINE Link]. [Full Text].

115. [Guideline] Swetter SM, Tsao H, Bichakjian CK, Curiel-Lewandrowski C, Elder DE, Gershenwald JE, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019 Jan. 80 (1):208-250. [QxMD MEDLINE Link]. [Full Text].

116. [Guideline] Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, Keilholz U, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019 Dec 1. 30 (12):1884-1901. [QxMD MEDLINE Link]. [Full Text].

117. [Guideline] Garbe C, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC). European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics - Update 2019. Eur J Cancer. 2020 Jan 9. [QxMD MEDLINE Link]. [Full Text].

118. [Guideline] Michielin O, van Akkooi A, Lorigan P, et al. ESMO consensus conference recommendations on the management of locoregional melanoma: the ESMO Guidelines Committee. Ann Oncol. 2020 Jul 22. [QxMD MEDLINE Link]. [Full Text].

119. Kirkland EB, Zitelli JA. Mitotic rate for thin melanomas: should a single mitotic figure warrant a sentinel lymph node biopsy?. Dermatol Surg. 2014 Sep. 40 (9):937-45. [QxMD MEDLINE Link].

120. McClain SE, Shada AL, Barry M, Patterson JW, Slingluff CL Jr. Outcome of sentinel lymph node biopsy and prognostic implications of regression in thin malignant melanoma. Melanoma Res. 2012 Aug. 22 (4):302-9. [QxMD MEDLINE Link].

121. [Guideline] Wong SL, Faries MB, Kennedy EB, Agarwala SS, Akhurst TJ, Ariyan C, et al. Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. Ann Surg Oncol. 2018 Feb. 25 (2):356-377. [QxMD MEDLINE Link].

122. Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol. 2012 Mar. 66 (3):438-44. [QxMD MEDLINE Link].

123. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012 Oct. 67 (4):531-50. [QxMD MEDLINE Link].

124. [Guideline] Garbe C, et al; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC). European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2019. Eur J Cancer. 2019 Dec 19. [QxMD MEDLINE Link]. [Full Text].

125. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019 Oct 17. 381 (16):1535-1546. [QxMD MEDLINE Link]. [Full Text].

126. Tobin RP, Cogswell DT, Cates VM, Davis DM, Borgers JSW, Van Gulick RJ, et al. Targeting MDSC differentiation using ATRA: a phase I/II clinical trial combining pembrolizumab and all-trans retinoic acid for metastatic melanoma. Clin Cancer Res. 2022 Nov 15. [QxMD MEDLINE Link].

127. Rohaan MW, Borch TH, van den Berg JH, et al. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma. N Engl J Med. 2022 Dec 8. 387 (23):2113-2125. [QxMD MEDLINE Link]. [Full Text].

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman, Division of Hematology/Oncology Education, Chair, Cancer Survivorship Program, Associate Chair, Department of Medicine Faculty Development, Mayo Clinic Florida; Vice President, Florida Society of Clinical Oncology

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

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.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Mohsin R Mir, MD Private Practice, Mohs Micrographic Surgery and Dermatologic Surgery, Kelsey-Seybold Clinic; Assistant Professor, Baylor College of Medicine

Mohsin R Mir, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Wesley Wu, MD Mohs Surgeon, Department of Dermatology, VA Puget Sound and University of Washington School of Medicine

Wesley Wu, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

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