The importance of surgical margins in melanoma

Optimization of margins to minimize morbidity and maximize local control is critical to the success of surgical management of primary melanomas. This article synthesizes the historical perspectives and key clinical trials that have contributed to the evolution of resection margins for melanoma, focusing on the importance of surgical margins in the context of an era of improvements in systemic therapy and greater use of minimally invasive techniques. J. Surg. Oncol. 2016;113:339–345. © 2015 Wiley Periodicals, Inc.

[1]  M. Wiseman,et al.  Topical 5% Imiquimod in the Treatment of Lentigo Maligna , 2012, Journal of cutaneous medicine and surgery.

[2]  F. Sim,et al.  Adjuvant radiation therapy for regional nodal metastases from malignant melanoma. A randomized, prospective study , 1978, Cancer.

[3]  J. Aitken,et al.  Clinical practice guidelines for the management of melanoma in Australia and New Zealand , 2008 .

[4]  Grant W. Carlson,et al.  1 or 2 cm Margins of Excision for T2 Melanomas: Do They Impact Recurrence or Survival? , 2012, Annals of Surgical Oncology.

[5]  N. Cascinelli,et al.  Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma. , 1991, Archives of surgery.

[6]  V. Sondak,et al.  Pathology review of thin melanoma and melanoma in situ in a multidisciplinary melanoma clinic: impact on treatment decisions. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D. McCready,et al.  Primary excision margins and sentinel lymph node biopsy in clinically node-negative melanoma of the trunk or extremities. , 2011, Clinical oncology (Royal College of Radiologists (Great Britain)).

[8]  Jeffrey E. Lee,et al.  Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma , 1998, Annals of Surgical Oncology.

[9]  Joel L Cohen,et al.  Melanoma In Situ Treated Successfully Using Imiquimod After Nonclearance with Surgery: Review of the Literature , 2012, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[10]  Yao-Tseng Chen,et al.  Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma. , 1998, The American journal of surgical pathology.

[11]  J. Coebergh,et al.  Melanoma incidence has risen in Europe , 2005, BMJ : British Medical Journal.

[12]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[13]  L. Hughes,et al.  Suture or graft? Changing trends in melanoma wound closure. , 1988, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[14]  M. Hansen,et al.  Tumor thickness and lymphocytic infiltration in malignant melanoma of the head and neck. , 1974, American journal of surgery.

[15]  C. O'brien,et al.  Experience with 998 cutaneous melanomas of the head and neck over 30 years. , 1991, American journal of surgery.

[16]  Raymond L. Barnhill,et al.  Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. , 2001 .

[17]  S. Chimenti,et al.  Treatment of lentigo maligna with tazarotene 0.1% gel. , 2004, Journal of the American Academy of Dermatology.

[18]  B. Hanusa,et al.  Mohs micrographic surgery for the treatment of primary cutaneous melanoma. , 1997, Journal of the American Academy of Dermatology.

[19]  J. Wayne,et al.  Reducing margins of wide local excision in head and neck melanoma for function and cosmesis: 5‐year local recurrence‐free survival , 2015, Journal of surgical oncology.

[20]  C. Ingvar,et al.  Long term results of a randomized study by the Swedish Melanoma Study Group on 2‐cm versus 5‐cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8–2.0 mm , 2000, Cancer.

[21]  R. F. Ryan,et al.  A role for topical 5‐fluorouracil therapy in melanoma , 1988, Journal of surgical oncology.

[22]  L. Hughes,et al.  A policy of selective excision for primary cutaneous malignant melanoma. , 1985, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[23]  Stage I melanoma of the skin: the problem of resection margins. W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma. , 1980, European journal of cancer.

[24]  D. Morton,et al.  Is adjuvant radiotherapy necessary after positive lymph node dissection in head and neck melanomas? , 2000, Annals of Surgical Oncology.

[25]  P. Duray,et al.  Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions? , 2003, American journal of clinical pathology.

[26]  Blessing,et al.  Comparison of immunohistochemical staining of the novel antibody melan‐A with S100 protein and HMB‐45 in malignant melanoma and melanoma variants , 1998, Histopathology.

[27]  M. Lens,et al.  Excision margins for primary cutaneous melanoma: updated pooled analysis of randomized controlled trials. , 2007, Archives of surgery.

[28]  R. Braun,et al.  Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma. , 2011, Swiss medical weekly.

[29]  U. Ringborg,et al.  Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor thickness of 0.8 to 2.0 mm: A randomized study by the Swedish Melanoma Study Group , 1996, Cancer.

[30]  S. Florell,et al.  Lentigo Maligna/Lentigo Maligna Melanoma: Current State of Diagnosis and Treatment , 2006, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[31]  B. Brown,et al.  Excision of underlying fascia with a primary malignant melanoma: effect on recurrence and survival rates. , 1982, Surgery.

[32]  C. Balch,et al.  Head and Neck Melanoma in 534 Clinical Stage I Patients: A Prognostic Factors Analysis and Results of Surgical Treatment , 1984, Annals of surgery.

[33]  W. Tope,et al.  Mohs Micrographic Surgery for Lentigo Maligna and Lentigo Maligna Melanoma using Mel‐5 Immunostaining: University of Minnesota Experience , 2006, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[34]  K. Shannon,et al.  Adjuvant Postoperative Radiotherapy to the Cervical Lymph Nodes in Cutaneous Melanoma: Is There Any Benefit for High-Risk Patients? , 2008, Annals of Surgical Oncology.

[35]  M. Heenen,et al.  RECURRENT LENTIGO MALIGNA MELANOMA: REGRESSION ASSOCIATED WITH LOCAL AZELAIC ACID 20% , 2002, International journal of clinical practice.

[36]  P. Nathan,et al.  Revised U.K. guidelines for the management of cutaneous melanoma 2010 , 2010, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[37]  A. Kopf,et al.  Treatment of lentigo maligna and lentigo maligna melanoma. , 1979, The Journal of dermatologic surgery and oncology.

[38]  M. Mihm,et al.  Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. , 1993, Annals of surgery.

[39]  C. Garbe,et al.  Imiquimod in the treatment of extensive recurrent lentigo maligna. , 2005, Journal of the American Academy of Dermatology.

[40]  M. Mihm,et al.  Conservative surgical management of superficially invasive cutaneous melanoma , 1984, Cancer.

[41]  C. Balch,et al.  Efficacy of 2 cm surgical margins for intermediate thickness melanomas (1 to 4 mm): Results of a multi-institutional randomized surgical trial , 1995 .

[42]  D. Brodland,et al.  Margins for standard excision of melanoma in situ. , 2013, Journal of the American Academy of Dermatology.

[43]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[44]  S. Steinberg,et al.  Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Goldman Li The surgical therapy of malignant melanomas. , 1975 .

[46]  M. Singer,et al.  Is Head and Neck Melanoma Different from Trunk and Extremity Melanomas with Respect to Sentinel Lymph Node Status and Clinical Outcome? , 2013, Annals of Surgical Oncology.

[47]  M. Weichenthal,et al.  Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma” , 2013, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[48]  Deirdre M. Jones,et al.  An Assessment of Histological Margins and Recurrence of Melanoma In Situ , 2015, Plastic and reconstructive surgery. Global open.

[49]  K. Shannon,et al.  The Importance of Adequate Primary Tumor Excision Margins and Sentinel Node Biopsy in Achieving Optimal Locoregional Control for Patients With Thick Primary Melanomas , 2013, Annals of surgery.

[50]  C. Balch,et al.  Tumor thickness as a guide to surgical management of clinical stage I melanoma patients , 1979, Cancer.

[51]  R. Fisher,et al.  Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial. , 2012, The Lancet. Oncology.

[52]  Mcbride Cm,et al.  Excision of underlying fascia with a primary malignant melanoma: effect on recurrence and survival rates. , 1982 .

[53]  C. Balch,et al.  Thin Stage I Primary Cutaneous Malignant Melanoma , 1988 .

[54]  Z. Lj,et al.  Suture or graft? Changing trends in melanoma wound closure. , 1988 .

[55]  C. Gross,et al.  National utilization patterns of Mohs micrographic surgery for invasive melanoma and melanoma in situ. , 2015, Journal of the American Academy of Dermatology.

[56]  B. Coldiron,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. , 2012, Journal of the American Academy of Dermatology.

[57]  R. Barlow,et al.  Topical imiquimod immunotherapy in the management of lentigo maligna , 2004, Clinical and experimental dermatology.

[58]  M. Trotter Melanoma Margin Assessment. , 2009, Surgical pathology clinics.

[59]  A. Hauschild,et al.  Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[60]  L. Mack,et al.  Controversies in the management of metastatic melanoma to regional lymphatic basins , 2004, Journal of surgical oncology.

[61]  J. Berth-Jones,et al.  Imiquimod: a novel treatment for lentigo maligna , 2000, The British journal of dermatology.

[62]  A. Garden,et al.  Postoperative radiotherapy for cutaneous melanoma of the head and neck region. , 1994, International journal of radiation oncology, biology, physics.

[63]  Erik J. Geiger,et al.  Using topical imiquimod for the management of positive in situ margins after melanoma resection , 2015, Cancer medicine.

[64]  W. Coleman,et al.  Treatment of lentigo maligna and lentigo maligna melanoma. , 1980, The Journal of dermatologic surgery and oncology.

[65]  C. Hanke,et al.  Mohs micrographic surgery: Facts and controversies. , 2010, Clinics in dermatology.

[66]  B. Pockaj,et al.  Desmoplastic melanoma – the step‐child in the melanoma family? , 2011, Journal of surgical oncology.

[67]  A. Breslow,et al.  Optimal size of resection margin for thin cutaneous melanoma. , 1977, Surgery, gynecology & obstetrics.

[68]  The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma , 1985, Cancer.

[69]  C. Balch,et al.  Local recurrence in malignant melanoma: Long-term results of the multiinstitutional randomized surgical trial , 2006, Annals of Surgical Oncology.

[70]  M. Mihm,et al.  Narrower margins for clinical stage I malignant melanoma. , 1982, The New England journal of medicine.

[71]  P. Hutchinson,et al.  A follow-up study to investigate the efficacy of initial treatment of lentigo maligna with surgical excision. , 2002, British journal of plastic surgery.

[72]  J. Thomas,et al.  Excision margins in high-risk malignant melanoma. , 2004, The New England journal of medicine.

[73]  S. Waltman,et al.  Glaucoma and HL-A antigens , 1975, The Lancet.

[74]  B. Cummings,et al.  0‐7‐21 radiotherapy in nodular melanoma , 1983, Cancer.

[75]  C. Ingvar,et al.  2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial , 2011, The Lancet.

[76]  D. Ren,et al.  Cutaneous head and neck melanoma treated with Mohs micrographic surgery. , 2005, Journal of the American Academy of Dermatology.

[77]  W. Clark,et al.  Optimal Resection Margin for Cutaneous Malignant Melanoma , 1983, Plastic and reconstructive surgery.

[78]  Christopher J. Miller,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. , 2015, Journal of the American Academy of Dermatology.

[79]  D. Goldgar,et al.  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. , 2012, Archives of dermatology.

[80]  R. Fisher,et al.  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. , 2015, The Lancet. Oncology.

[81]  F. Mohs Chemosurgical treatment of melanoma; a microscopically controlled method of excision. , 1951, Archives of dermatology and syphilology.

[82]  C. Balch,et al.  Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm. , 1988, The New England journal of medicine.

[83]  R. Ceilley,et al.  Staged excision versus Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. , 2007, Journal of the American Academy of Dermatology.

[84]  N. Swanson,et al.  Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ , 2002, The British journal of dermatology.

[85]  M. Clarke Meta-analyses of adjuvant therapies for women with early breast cancer: the Early Breast Cancer Trialists' Collaborative Group overview. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[86]  P. G. Lang,et al.  Desmoplastic Neurotropic Melanoma: A Clinicopathologic Analysis of 128 Cases , 2009 .

[87]  J. Callen,et al.  Successful treatment of lentigo maligna and lentigo maligna melanoma with mohs' micrographic surgery aided by rush permanent sections , 1994, Cancer.

[88]  G. Fisher,et al.  Treatment of melanoma in situ on sun-damaged skin with topical 5% imiquimod cream complicated by the development of invasive disease. , 2003, Archives of dermatology.

[89]  C. Balch,et al.  The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma , 1985, Cancer.

[90]  D. DiCaudo,et al.  Mohs micrographic excision of melanoma using immunostains. , 2000, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[91]  J. Carucci,et al.  Intralesional interferon alfa for treatment of recurrent lentigo maligna of the eyelid in a patient with primary acquired melanosis. , 2000, Archives of dermatology.