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Malignant Melanoma Differential Diagnoses

  • Author: Winston W Tan, MD, FACP; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Feb 11, 2016
 
 

Diagnostic Considerations

Differentials to consider in the diagnosis of malignant melanoma include the following conditions:

  • Benign melanocytic lesions
  • Dysplastic nevus
  • Squamous cell carcinoma
  • Metastatic tumors to the skin
  • Blue nevus
  • Epithelioid (Spitz) tumor
  • Pigmented spindle cell tumor
  • Halo nevus
  • Atypical fibroxanthoma
  • Pigmented actinic keratosis
  • Sebaceous carcinoma
  • Histiocytoid hemangioma

Also see Lentigo Maligna Melanoma, Oral Malignant Melanoma, and Head and Neck Mucosal Melanomas.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

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 of Education, Division of Hematology/Oncology, Mayo Clinic Florida

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

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.

Chief Editor

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.

Additional Contributors

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.

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

  2. 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. [Medline].

  3. 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. [Medline].

  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. [Medline].

  5. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001 Aug 15. 19(16):3635-48. [Medline].

  6. American Joint Committee on Cancer. AJCC Staging Manual. 6th edition. 2002.

  7. American Cancer Society. Cancer Facts & Figures 2015. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf. Accessed: April 30, 2015.

  8. 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. [Medline].

  9. Murali R, Desilva C, Thompson JF, Scolyer RA. Factors predicting recurrence and survival in sentinel lymph node-positive melanoma patients. Ann Surg. 2011 Jun. 253(6):1155-64. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. 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. [Medline]. [Full Text].

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

  14. 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. [Medline].

  15. 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. [Medline]. [Full Text].

  16. 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. [Medline].

  17. Grotz TE, Markovic SN, Erickson LA, et al. Mayo Clinic consensus recommendations for the depth of excision in primary cutaneous melanoma. Mayo Clin Proc. 2011 Jun. 86(6):522-8. [Medline]. [Full Text].

  18. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma Version 3.2015. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed: April 30, 2105.

  19. 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. [Medline].

  20. 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. [Medline].

  21. Wong SL, Balch CM, Hurley P, Agarwala SS, Akhurst TJ, Cochran A, et al. Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline. Ann Surg Oncol. 2012 Jul 6. [Medline].

  22. 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].

  23. 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. [Medline].

  24. 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. [Medline].

  25. 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. [Medline]. [Full Text].

  26. 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. [Medline].

  27. 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.

  28. 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. [Medline].

  29. 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. [Medline].

  30. Hauschild A, Weichenthal M, Rass K, Linse R, Berking C, Bottjer 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. [Medline].

  31. 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. [Medline].

  32. 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. [Medline].

  33. 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. [Medline].

  34. Fecher LA, Flaherty KT. Where are we with adjuvant therapy of stage III and IV melanoma in 2009?. J Natl Compr Canc Netw. 2009 Mar. 7(3):295-304. [Medline].

  35. Lens MB, Reiman T, Husain AF. Use of tamoxifen in the treatment of malignant melanoma. Cancer. 2003 Oct 1. 98(7):1355-61. [Medline].

  36. 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. [Medline].

  37. 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. [Medline].

  38. 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. [Medline].

  39. 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.

  40. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010 Aug 26. 363(9):809-19. [Medline].

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

  42. 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. [Medline].

  43. 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. [Medline].

  44. 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. [Medline].

  45. 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. [Medline].

  46. 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. [Medline]. [Full Text].

  47. US Food and Drug Administration. FDA approves Mekinist in combination with Tafinlar for advanced melanoma. FDA. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm381159.htm. Accessed: January 16, 2014.

  48. Mulcahy N. FDA Approves First Combination Therapy for Melanoma. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/818930. Accessed: January 14, 2014.

  49. Larkin J, et al. Update of progression-free survival (PFS) and correlative biomarker analysis from coBRIM: Phase III study of cobimetinib (cobi) plus vemurafenib (vem) in advanced BRAF-mutated melanoma. Abstract 9006. Presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. May 29 – June 2, 2015. Chicago, IL. Available at http://meetinglibrary.asco.org/content/144759-156. Accessed: December 4, 2015.

  50. 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. [Medline]. [Full Text].

  51. 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. [Medline].

  52. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol. 2001 May 1. 19(9):2370-80. [Medline].

  53. Sasse AD, Sasse EC, Clark LG, Ulloa L, Clark OA. Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma. Cochrane Database Syst Rev. 2007 Jan 24. CD005413. [Medline].

  54. Mulcahy N. Imatinib is yet another option in advanced melanoma. Medscape Medical News. August 13, 2013. [Full Text].

  55. 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. [Medline]. [Full Text].

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

  57. 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. [Medline].

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

  59. 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. [Medline].

  60. 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. [Medline].

  61. Boggs W. Immune-related problems due to ipilimumab emerge early, resolve with discontinuation. Medscape Medical News. February 12, 2013. Available at http://www.medscape.com/viewarticle/779186. Accessed: March 4, 2013.

  62. 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. [Medline].

  63. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 May. 16 (5):522-30. [Medline].

  64. 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 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412802.htm. Accessed: September 9, 2014.

  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. [Medline].

  67. 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. [Medline].

  68. 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. [Medline].

  69. Hancock BW, Wheatley K, Harris S, Ives N, Harrison G, Horsman JM, et al. 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. 2004 Jan 1. 22(1):53-61. [Medline].

  70. Maio M, Mackiewicz A, Testori A, Trefzer U, Ferraresi V, Jassem J, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010 Apr 1. 28(10):1780-7. [Medline].

  71. 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. [Medline]. [Full Text].

  72. 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. [Medline].

  73. 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. [Medline]. [Full Text].

  74. Spain L, Larkin J. Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma. Expert Opin Biol Ther. 2016 Feb 1. 1-8. [Medline].

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A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation.
Malignant melanoma. Image courtesy of Hon Pak, MD.
Lentigo maligna melanoma, right lower cheek. The centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ). Image courtesy of Susan M. Swetter, MD.
 
 
 
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