Melanoma Recurrence after Mohs Micrographic Surgery with MART-1: A Systematic Review and Meta-analysis

Main Article Content

Tyler Long
Austin Dunn
Mary Arndt
Eric Parlette


melanoma, in situ, cutaneous, invasive, Mohs, micrographic Surgery, MART-1, immunohistochemistry, Dermatology, Dermatological surgery


Background: Surveys suggest wide-spread use of MART-1 in MMS for CM among Mohs surgeons, but no previous systematic review has investigated the efficacy of this specific procedure.

Methods: A systematic search and meta-analysis of retrospective studies on MMS with MART-1 was performed from Pubmed, Medline, and Cochrane databases for articles published from their inception to October 30, 2020. We performed a chi-squared analysis of homogenized data to examine the relationship between recurrence location and rate of recurrence. A risk of bias was obtained with the ROBINS-I tool. [PROSPERO ID: CRD42020221826]

Results: Among the included studies, there were a total of 15 (0.52%) local recurrences of melanoma in-situ and invasive melanoma after MMS with MART-1.

Conclusions: This review has served to demonstrate that MMS with MART-1 immunostaining in frozen sections is a technique that produces satisfactory recurrence rates for melanoma in-situ and invasive melanoma.


1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-1953. doi:10.1002/ijc.31937

2. Balch CM. Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol. 1992;8(6):400-414. doi:10.1002/ssu.2980080611

3. Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80(1):208-250. doi:10.1016/j.jaad.2018.08.055

4. Etzkorn JR, Sobanko JF, Shin TM, et al. Correlation Between Appropriate Use Criteria and the Frequency of Subclinical Spread or Reconstruction With a Flap or Graft for Melanomas Treated With Mohs Surgery With Melanoma Antigen Recognized by T Cells 1 Immunostaining. Dermatol Surg. 2016;42(4):471-476. doi:10.1097/DSS.0000000000000693

5. Fix W, Etzkorn JR, Shin TM, et al. Melanomas of the head and neck have high local recurrence risk features and require tissue rearranging reconstruction more commonly than BCC and SCC: A comparison of indications for microscopic margin control prior to reconstruction in 13,664 tumors [published online ahead of print, 2018 Nov 17]. J Am Acad Dermatol. 2018;S0190-9622(18)32910-4. doi:10.1016/j.jaad.2018.11.020

6. Stonecipher MR, Leshin B, Patrick J, White WL. Management of lentigo maligna and lentigo maligna melanoma with paraffin-embedded tangential sections: utility of immunoperoxidase staining and supplemental vertical sections. J Am Acad Dermatol. 1993;29(4):589-594. doi:10.1016/0190-9622(93)70226-j

7. Dhawan SS, Wolf DJ, Rabinovitz HS, Poulos E. Lentigo maligna. The use of rush permanent sections in therapy. Arch Dermatol. 1990;126(7):928-930. doi:10.1001/archderm.126.7.928

8. Prieto VG, Argenyi ZB, Barnhill RL, et al. Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions? Am J Clin Pathol. 2003;120(2):203-208. doi:10.1309/J1Q0-V35E-UTMV-R193

9. Barlow RJ, White CR, Swanson NA. Mohs’ micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ. Br J Dermatol. 2002;146(2):290-294. doi:10.1046/j.1365-2133.2002.04661.x

10. Cohen LM, McCall MW, Zax RH. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. A follow-up study. Dermatol Surg. 1998;24(6):673-677. doi:10.1111/j.1524-4725.1998.tb04226.x

11. Cohen LM, McCall MW, Hodge SJ, Freedman JD, Callen JP, Zax RH. Successful treatment of lentigo maligna and lentigo maligna melanoma with Mohs’ micrographic surgery aided by rush permanent sections. Cancer. 1994;73(12):2964-2970. doi:10.1002/1097-0142(19940615)73:12<2964::aid-cncr2820731213>;2-o

12. Bene NI, Healy C, Coldiron BM. Mohs micrographic surgery is accurate 95.1% of the time for melanoma in situ: a prospective study of 167 cases. Dermatol Surg. 2008;34(5):660-664. doi:10.1111/j.1524-4725.2007.34124.x

13. Kelley LC, Starkus L. Immunohistochemical staining of lentigo maligna during Mohs micrographic surgery using MART-1. J Am Acad Dermatol. 2002;46(1):78-84. doi:10.1067/mjd.2002.119197

14. Zalla MJ, Lim KK, Dicaudo DJ, Gagnot MM. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg. 2000;26(8):771-784. doi:10.1046/j.1524-4725.2000.00081.x

15. Albertini JG, Elston DM, Libow LF, Smith SB, Farley MF. Mohs micrographic surgery for melanoma: a case series, a comparative study of immunostains, an informative case report, and a unique mapping technique. Dermatol Surg. 2002;28(8):656-665. doi:10.1046/j.1524-4725.2002.02024.x

16. Ellison PM, Zitelli JA, Brodland DG. Mohs micrographic surgery for melanoma: A prospective multicenter study. J Am Acad Dermatol. 2019;81(3):767-774. doi:10.1016/j.jaad.2019.05.057

17. Foxton GC, Elliott TG, Litterick KA. Treating melanoma in situ and lentigo maligna with Mohs micrographic surgery in Australia. Australas J Dermatol. 2019;60(1):33-37. doi:10.1111/ajd.12845

18. Valentín-Nogueras SM, Brodland DG, Zitelli JA, González-Sepúlveda 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):733-744. doi:10.1097/DSS.0000000000000725

19. Heath M, Woody M, Leitenberger J, Latour E, Bar A. Invasive Melanoma and Melanoma in Situ Treated With Modified Mohs Micrographic Surgery With En Face Permanent Sectioning: A 10-Year Retrospective Review. Dermatol Surg. 2020;46(8):1004-1013. doi:10.1097/DSS.0000000000002246

20. Kunishige JH, Doan L, Brodland DG, Zitelli JA. Comparison of surgical margins for lentigo maligna versus melanoma in situ. J Am Acad Dermatol. 2019;81(1):204-212. doi:10.1016/j.jaad.2019.01.051

21. Stigall LE, Brodland DG, Zitelli JA. The use of Mohs micrographic surgery (MMS) for melanoma in situ (MIS) of the trunk and proximal extremities. J Am Acad Dermatol. 2016;75(5):1015-1021. doi:10.1016/j.jaad.2016.06.033

22. Cherpelis BS, Moore R, Ladd S, Chen R, Glass LF. Comparison of MART-1 frozen sections to permanent sections using a rapid 19-minute protocol. Dermatol Surg. 2009;35(2):207-213. doi:10.1111/j.1524-4725.2008.34411.x

23. Siscos SM, Neill BC, Seger EW, Hooton TA, Hocker TLH. The Current State of Mohs Surgery for the Treatment of Melanoma: A Nationwide Cross-Sectional Survey of Mohs Surgeons. Dermatol Surg. 2020;46(10):1267-1271. doi:10.1097/DSS.0000000000002645

24. Lee MP, Sobanko JF, Shin TM, et al. Evolution of Excisional Surgery Practices for Melanoma in the United States [published online ahead of print, 2019 Aug 28]. JAMA Dermatol. 2019;155(11):1244-1251. doi:10.1001/jamadermatol.2019.2346

25. Sharma AN, Foulad DP, Doan L, Lee PK, Atanaskova Mesinkovska N. Mohs surgery for the treatment of lentigo maligna and lentigo maligna melanoma - a systematic review [published online ahead of print, 2019 Nov 20]. J Dermatolog Treat. 2019;1-7. doi:10.1080/09546634.2019.1690624

26. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919; doi:10.1136/bmj.i4919

27. Degesys CA, Powell HB, Hsia L-LB, Merritt BG. Outcomes for Invasive Melanomas Treated With Mohs Micrographic Surgery: A Retrospective Cohort Study. Dermatol Surg. 2019;45(2):223-228. doi:10.1097/DSS.0000000000001658

28. Etzkorn JR, Sobanko JF, Elenitsas R, 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):840-850. doi:10.1016/j.jaad.2015.01.007

29. Shin TM, Shaikh WR, Etzkorn JR, et al. Clinical and pathologic factors associated with subclinical spread of invasive melanoma. J Am Acad Dermatol. 2017;76(4):714-721. doi:10.1016/j.jaad.2016.11.048

30. Shin TM, Etzkorn JR, Sobanko JF, et al. Clinical factors associated with subclinical spread of in situ melanoma. J Am Acad Dermatol. 2017;76(4):707-713. doi:10.1016/j.jaad.2016.10.049

31. Wilson JG, German R, Hamann CR, Vidal NY, LeBoeuf M. Comparison of staged excision and Mohs micrographic surgery with and without MART-1 immunostains for surgical treatment of melanoma of the head, neck, and special sites: A retrospective cohort study. J Am Acad Dermatol. 2021;84(1):192-194. doi:10.1016/j.jaad.2020.04.081

32. Etzkorn JR, Jew OS, Shin TM, Sobanko JF, Neal DE, Miller CJ. Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining for atypical intraepidermal melanocytic proliferation. J Am Acad Dermatol. 2018;79(6):1109-1116.e1. doi:10.1016/j.jaad.2018.06.058

33. Terushkin V, Brodland DG, Sharon DJ, Zitelli JA. Digit-Sparing Mohs Surgery for Melanoma. Dermatol Surg. 2016;42(1):83-93. doi:10.1097/DSS.0000000000000587

34. Rzepecki AK, Hwang CD, Etzkorn JR, et al. The “Rule of 10s” versus the “Rule of 2s”: High complication rates after conventional excision with postoperative margin assessment of specialty site versus trunk and proximal extremity melanomas [published online ahead of print, 2018 Nov 14]. J Am Acad Dermatol. 2018;S0190-9622(18)32892-5. doi:10.1016/j.jaad.2018.11.008

35. Bricca GM, Brodland DG, Ren D, Zitelli JA. Cutaneous head and neck melanoma treated with Mohs micrographic surgery. J Am Acad Dermatol. 2005;52(1):92-100. doi:10.1016/j.jaad.2004.08.038

36. Burnett ME, Brodland DG, Zitelli JA. Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal extremities [published online ahead of print, 2020 Aug 4]. J Am Acad Dermatol. 2020;S0190-9622(20)32316-1. doi:10.1016/j.jaad.2020.07.113

37. Semkova K, Mallipeddi R, Robson A, Palamaras I. Mohs micrographic surgery concordance between Mohs surgeons and dermatopathologists. Dermatol Surg. 2013;39(11):1648-1652. doi:10.1111/dsu.12320

38. Highsmith JT, Highsmith MJ, Monheit GD. Histologic Accuracy of Mohs Micrographic Surgery. Dermatol Surg. 2018;44(3):350-353. doi:10.1097/DSS.0000000000001352

39. Kesty K, Sangueza OP, Leshin B, Albertini JG. Mohs micrographic surgery and dermatopathology concordance; An analysis of 1421 Mohs cases over 17 years [published online ahead of print, 2017 Dec 13]. J Am Acad Dermatol. 2017;S0190-9622(17)32814-1. doi:10.1016/j.jaad.2017.11.055

40. Mariwalla K, Aasi SZ, Glusac EJ, Leffell DJ. Mohs micrographic surgery histopathology concordance. J Am Acad Dermatol. 2009;60(1):94-98. doi:10.1016/j.jaad.2008.09.061

41. Demer, A. M., Hanson, J. L., Maher, I. A., & Liszewski, W. Association of Mohs Micrographic Surgery vs Wide Local Excision With Overall Survival Outcomes for Patients With Melanoma of the Trunk and Extremities. JAMA Dermatol. 2021 Jan 1;157(1):84-89. doi:10.1001/jamadermatol.2020.3950

42. Phan, K., Onggo, J., & Loya, A. Mohs micrographic surgery versus wide local excision for head and neck melanoma- in-situ. J Dermatolog Treat. 2020 Sep;31(6):559-562. doi: 10.1080/09546634.2019.1639605.

43. Daniel, V. T., Crawford, A., Kiefe, C. I., & Mahmoud, B. H. Recurrence and Mortality of Melanoma In Situ of the Trunk or Extremities: A Surveillance, Epidemiology, and End Results Analysis. Dermatol Surg. 2021 Jan 1;47(1):1-5. Doi: 10.1097/DSS.0000000000002417.

44. National Comprehensive Cancer Network. National Comprehensive Cancer Network. NCCN Clin Pract Guidel Oncol Melanoma. 2018;Version 2.

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