Melanoma In Situ

  • Charles Thomas DarraghEmail author
  • Anna S. Clayton


Melanoma in situ (MIS) is defined as a malignant melanocytic tumor restricted to the epidermis. According to recent database statistics, it is the fastest-growing cancer in the United States with a 9.5% annual incidence increase. Melanoma in situ is not a dangerous tumor and is classified as stage 0. Patients diagnosed with MIS have the same life expectancy as the general population. It is important to remember the ABCDEs of melanoma when evaluating for lesions suspicious of melanoma in situ. There are several clinical subtypes, most notably lentigo maligna, which is found on sun-damaged sites. Diagnosis of MIS is made with histopathology, often with accompanying immunohistochemical stains including SOX 10 and Melan-A. It can be very difficult to determine severely sun-damaged skin versus MIS lesions under the microscope, and this remains a challenge for dermatopathologists. Once a diagnosis of MIS is made, it can be treated with several surgical options. These options include wide local excision, Mohs micrographic surgery, and staged excision or “slow Mohs.” In certain circumstances, imiquimod or radiation could be considered for adjuvant therapy. After diagnosis of MIS, patients should be followed closely with every 3- to 6-month skin checks.


Melanoma in situ ABCDEs Lentigo maligna Mohs micrographic surgery Wide local excision Staged excision Imiquimod Dermoscopy Sox 10 Dermatopathology 


  1. 1.
    Rapini RP. Practical dermatopathology. 2nd ed. Edinburgh: Elsevier/Saunders; 2012. p. 450.Google Scholar
  2. 2.
    Mocellin S, Nitti D. Cutaneous melanoma in situ: translational evidence from a large population-based study. Oncologist. 2011;16(6):896–903.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Higgins HW 2nd, Lee KC, Galan A, Leffell DJ. Melanoma in situ: part I. Epidemiology, screening, and clinical features. J Am Acad Dermatol. 2015;73(2):181–90. quiz 91-2.CrossRefPubMedGoogle Scholar
  4. 4.
    Coory M, Baade P, Aitken J, Smithers M, McLeod GR, Ring I. Trends for in situ and invasive melanoma in Queensland, Australia, 1982–2002. Cancer Causes Control. 2006;17(1):21–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Helvind NM, Holmich LR, Smith S, Glud M, Andersen KK, Dalton SO, et al. Incidence of in situ and invasive melanoma in Denmark from 1985 through 2012: a National Database Study of 24,059 melanoma cases. JAMA Dermatol. 2015;151(10):1087–95.CrossRefPubMedGoogle Scholar
  6. 6.
    Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ. 2005;331(7515):481.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol. 2009;129(7):1666–74.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol. 2010;146(3):265–72.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Wei EX, Qureshi AA, Han J, Li TY, Cho E, Lin JY, et al. Trends in the diagnosis and clinical features of melanoma in situ (MIS) in US men and women: a prospective, observational study. J Am Acad Dermatol. 2016;75(4):698–705.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Tiodorovic-Zivkovic D, Argenziano G, Lallas A, Thomas L, Ignjatovic A, Rabinovitz H, et al. Age, gender, and topography influence the clinical and dermoscopic appearance of lentigo maligna. J Am Acad Dermatol. 2015;72(5):801–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Lesage C, Barbe C, Le Clainche A, Lesage FX, Bernard P, Grange F. Sex-related location of head and neck melanoma strongly argues for a major role of sun exposure in cars and photoprotection by hair. J Invest Dermatol. 2013;133(5):1205.CrossRefPubMedGoogle Scholar
  12. 12.
    Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1995;33(6):923–36. quiz 37-40.CrossRefPubMedGoogle Scholar
  13. 13.
    Australian Cancer Network Melanoma Guidelines Revision Working Party. Clinical practice guidelines for the managment of melanoma in Australia and New Zealand. Cancer Council Australia and Australian Cancer Network, Sydney and New Zealand Guidelines Group, Wellington; 2008.Google Scholar
  14. 14.
    NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Melanoma Version 1.2017 [web page]. 2017. www.nccn.orgJanuary. [updated January 2017].
  15. 15.
    Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. Available from:
  16. 16.
    Bartoli C, Bono A, Clemente C, Del Prato ID, Zurrida S, Cascinelli N. Clinical diagnosis and therapy of cutaneous melanoma in situ. Cancer. 1996;77(5):888–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Rosina P, Tessari G, Giordano MV, Girolomoni G. Clinical and diagnostic features of in situ melanoma and superficial spreading melanoma: a hospital based study. J Eur Acad Dermatol Venereol. 2012;26(2):153–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Ara M, Maillo C, Martin R, Grasa MP, Carapeto FJ. Recurrent lentigo maligna as amelanotic lentigo maligna melanoma. J Eur Acad Dermatol Venereol. 2002;16(5):506–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol. 2000;42(5 Pt 1):731–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Jung HJ, Kweon SS, Lee JB, Lee SC, Yun SJ. A clinicopathologic analysis of 177 acral melanomas in Koreans: relevance of spreading pattern and physical stress. JAMA Dermatol. 2013;149(11):1281–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Higgins HW 2nd, Lee KC, Galan A, Leffell DJ. Melanoma in situ: Part II. Histopathology, treatment, and clinical management. J Am Acad Dermatol. 2015;73(2):193–203; quiz −4.CrossRefPubMedGoogle Scholar
  22. 22.
    Goydos JS, Shoen SL. Acral Lentiginous Melanoma. Cancer Treat Res. 2016;167:321–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Silverstein D, Mariwalla K. Biopsy of the pigmented lesions. Dermatol Clin. 2012;30(3):435–43.CrossRefPubMedGoogle Scholar
  24. 24.
    Mendese G, Maloney M, Bordeaux J. To scoop or not to scoop: the diagnostic and therapeutic utility of the scoop-shave biopsy for pigmented lesions. Dermatol Surg. 2014;40(10):1077–83.CrossRefPubMedGoogle Scholar
  25. 25.
    Appert DL, Otley CC, Phillips PK, Roenigk RK. Role of multiple scouting biopsies before Mohs micrographic surgery for extramammary Paget's disease. Dermatol Surg. 2005;31(11 Pt 1):1417–22.PubMedGoogle Scholar
  26. 26.
    Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622–34.CrossRefPubMedGoogle Scholar
  27. 27.
    Ackerman AB, Briggs PL, Bravo F. Differential diagnosis in dermatopathology III. Philadelphia: Lea & Febiger; 1993. pp. xii, 202.Google Scholar
  28. 28.
    Weyers W, Bonczkowitz M, Weyers I, Bittinger A, Schill WB. Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin. Assessment of the significance of histopathologic criteria for differential diagnosis. Am J Dermatopathol. 1996;18(6):560–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Buonaccorsi JN, Prieto VG, Torres-Cabala C, Suster S, Plaza JA. Diagnostic utility and comparative immunohistochemical analysis of MITF-1 and SOX10 to distinguish melanoma in situ and actinic keratosis: a clinicopathological and immunohistochemical study of 70 cases. Am J Dermatopathol. 2014;36(2):124–30.CrossRefPubMedGoogle Scholar
  30. 30.
    El Shabrawi-Caelen L, Kerl H, Cerroni L. Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis. Am J Dermatopathol. 2004;26(5):364–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Charles CA, Yee VS, Dusza SW, Marghoob AA, Oliveria SA, Kopf A, et al. Variation in the diagnosis, treatment, and management of melanoma in situ: a survey of US dermatologists. Arch Dermatol. 2005;141(6):723–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Gardner KH, Hill DE, Wright AC, Brewer JD, Arpey CJ, Otley CC, et al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg. 2015;41(10):1122–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Egnatios GL, Dueck AC, Macdonald JB, Laman SD, Warschaw KE, DiCaudo DJ, et al. The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma. Am J Surg. 2011;202(6):771–7; discussion 7–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol. 2012;66(3):438–44.CrossRefPubMedGoogle Scholar
  35. 35.
    de Vries K, Greveling K, Prens LM, Munte K, Koljenovic S, van Doorn MB, et al. Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision. Br J Dermatol. 2016;174(3):588–93.CrossRefPubMedGoogle Scholar
  36. 36.
    Felton S, Taylor RS, Srivastava D. Excision margins for melanoma in situ on the head and neck. Dermatol Surg. 2016;42(3):327–34.CrossRefPubMedGoogle Scholar
  37. 37.
    Welch A, Reid T, Knox J, Wilson ML. Excision of melanoma in situ on nonchronically sun-exposed skin using 5-mm surgical margins. J Am Acad Dermatol. 2014;71(4):834–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Abdelmalek M, Loosemore MP, Hurt MA, Hruza G. Geometric staged excision for the treatment of lentigo maligna and lentigo maligna melanoma: a long-term experience with literature review. Arch Dermatol. 2012;148(5):599–604.CrossRefPubMedGoogle Scholar
  39. 39.
    Johnson TM, Headington JT, Baker SR, Lowe L. Usefulness of the staged excision for lentigo maligna and lentigo maligna melanoma: the “square” procedure. J Am Acad Dermatol. 1997;37(5 Pt 1):758–64.CrossRefPubMedGoogle Scholar
  40. 40.
    Gaudy-Marqueste C, Perchenet AS, Tasei AM, Madjlessi N, Magalon G, Richard MA, et al. The “spaghetti technique”: an alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma). J Am Acad Dermatol. 2011;64(1):113–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Viola KV, Rezzadeh KS, Gonsalves L, Patel P, Gross CP, Yoo J, et al. National utilization patterns of Mohs micrographic surgery for invasive melanoma and melanoma in situ. J Am Acad Dermatol. 2015;72(6):1060–5.CrossRefPubMedGoogle Scholar
  42. 42.
    Zitelli JA, Moy RL, Abell E. The reliability of frozen sections in the evaluation of surgical margins for melanoma. J Am Acad Dermatol. 1991;24(1):102–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Valentin-Nogueras SM, Brodland DG, Zitelli JA, Gonzalez-Sepulveda L, Nazario CM. Mohs micrographic surgery using MART-1 immunostain in the treatment of invasive melanoma and melanoma in situ. Dermatol Surg. 2016;42(6):733–44.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Etzkorn JR, Sobanko JF, Elenitsas R, Newman JG, Goldbach H, Shin TM, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72(5):840–50.CrossRefPubMedGoogle Scholar
  45. 45.
    Mora AN, Karia PS, Nguyen BM. A quantitative systematic review of the efficacy of imiquimod monotherapy for lentigo maligna and an analysis of factors that affect tumor clearance. J Am Acad Dermatol. 2015;73(2):205–12.CrossRefPubMedGoogle Scholar
  46. 46.
    Pandit AS, Geiger EJ, Ariyan S, Narayan D, Choi JN. Using topical imiquimod for the management of positive in situ margins after melanoma resection. Cancer Med. 2015;4(4):507–12.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hyde MA, Hadley ML, Tristani-Firouzi P, Goldgar D, Bowen GM. A randomized trial of the off-label use of imiquimod, 5%, cream with vs without tazarotene, 0.1%, gel for the treatment of lentigo maligna, followed by conservative staged excisions. Arch Dermatol. 2012;148(5):592–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Fogarty GB, Hong A, Scolyer RA, Lin E, Haydu L, Guitera P, et al. Radiotherapy for lentigo maligna: a literature review and recommendations for treatment. Br J Dermatol. 2014;170(1):52–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Marsden JR, Newton-Bishop JA, Burrows L, Cook M, Corrie PG, Cox NH, et al. Revised U.K. guidelines for the management of cutaneous melanoma 2010. Br J Dermatol. 2010;163(2):238–56.CrossRefPubMedGoogle Scholar
  50. 50.
    DiFronzo LA, Wanek LA, Morton DL. Earlier diagnosis of second primary melanoma confirms the benefits of patient education and routine postoperative follow-up. Cancer. 2001;91(8):1520–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Balamurugan A, Rees JR, Kosary C, Rim SH, Li J, Stewart SL. Subsequent primary cancers among men and women with in situ and invasive melanoma of the skin. J Am Acad Dermatol. 2011;65(5 Suppl 1):S69–77.PubMedGoogle Scholar
  52. 52.
    Pomerantz H, Huang D, Weinstock MA. Risk of subsequent melanoma after melanoma in situ and invasive melanoma: a population-based study from 1973 to 2011. J Am Acad Dermatol. 2015;72(5):794–800.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dermatology, Vanderbilt University of MedicineNashvilleUSA

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