What are the recommended safety margins for radical excision of a primary melanoma (in situ)?
Background
As for invasive melanoma, the treatment for melanoma in situ, including lentigo maligna (LM), is complete surgical excision with clear margins. For excision to be successful, a margin of clinically normal skin must be included because macroscopically invisible tumour often exists at the margins. Use of magnification, bright light and possibly Wood's lighting or confocal microscopy for preoperative marking are useful methods for improving the accurate definition of detectable margins.
Evidence
There are no RCTs and limited case series data to help direct excision of melanoma in situ.[1] Given this lack of evidence, in 1992 consensus guidelines were published suggesting that 5 mm excision margins should be adequate for melanoma in situ. However, recent studies have shown that 5 mm margins might be inadequate in some situations and can lead to significant rates of disease recurrence, particularly for head and neck disease.
In many cases, in-situ melanoma margins can be accurately determined pre-operatively by careful examination and an adequate margin of ≥ 5mm can be confirmed by pathology. In some cases Mohs surgery or staged serial excision may have a role, but the accuracy is lesion dependant and operator dependant. Unfortunately Mohs surgery currently is not universally available or affordable in Australia. Most international guidelines suggest 5 mm margins for melanoma in situ.[2][3] The BMJ Best Practice monograph on melanoma[4] states that “For melanoma in situ the recommended surgical margin is 0.5 cm. Some studies have found that this margin will be inadequate in some (up to 50% of) cases of melanoma in situ and particularly lentigo maligna. Options for dealing with this include: (a) wide excision with 1-cm margin; (b) staged excision with careful margin assessment; and (c) Mohs surgery.” The 2010 UK guidelines state 5 mm margins to achieve complete histological clearance.[5] The 2011 US guidelines go further recommending 5 mm-1 cm margins and state that "wider margins may be necessary for lentigo maligna subtypes".[6]
Evidence summary and recommendations
| Evidence summary | Level | References |
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| There is case series evidence suggesting that 5 mm margins are often adequate to treat melanoma in situ. However, in some cases of melanoma in situ 5mm margins are inadequate and may lead to significant rates of disease recurrence. | IV | [7], [8], [9], [10], [11], [12] |
Recommendations
Evidence-based recommendation
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Grade |
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 Melanoma in situ of non-lentigo maligna type is likely to be completely excised with 5mm margins whereas lentigo maligna may require wider excision. Minimum clearances from all margins should be stated/assessed. Consideration should be given to further excision if necessary; positive histological margins are unacceptable. |
D |
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Excisions should have vertical edges to ensure consistent margins. |
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For all melanomas, minimum clearances from all margins should be stated/assessed. When necessary, further excision should be performed in order to achieve the appropriate margin of clearance. |
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Excision biopsy of the complete lesion with a narrow (2mm) margin is appropriate for definitive diagnosis of primary melanoma. Once the diagnosis of melanoma has been made, re-excision of the lesion (biopsy site) should then be performed in order to achieve the definitive, wider margins that are recommended in these guidelines. |
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Depth of excision in usual clinical practice is excision down to but not including the deep fascia unless it is involved or has been reached during the diagnostic excision. For body sites where there is particularly deep subcutis, it is usual practice to excise to a depth equal to the recommended lateral (radial) excision margins for that specific melanoma; in these cases it is not deemed necessary to excise right down to fascia. |
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Where tissue flexibility is limited, a flap repair or skin graft may be necessary subsequent to an adequate margin of removal. |
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Most primary melanomas can be treated as an outpatient under local anaesthesia or as a day-case. |
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Patients should be informed that surgical excision may be followed by wound infection, bleeding, haematoma, failure of the skin graft or flap, risk of numbness, a non-cosmetic scar, dehiscence and the possibility of further surgery. |
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Some tumours may be incompletely excised despite using the above-recommended margins. These include melanomas occurring in severely sun-damaged skin (e.g. LM) and those with difficult-to-define margins (eg amelanotic and desmoplastic melanomas). In these categories, the presence of atypical melanocytes at the margins of excision should be detected by comprehensive histological examination (including immunohistochemical staining) and followed by wider excision as appropriate. Alternatively, staged serial excision (also known as ‘slow Mohs’ surgery) may be utilised to achieve complete histological clearance of melanoma in situ/lentigo maligna. Pre-operative mapping of the extent of some lesions with confocal microscopy may be useful and is available in some centres. Referral to a specialist melanoma centre or discussion in a multidisciplinary meeting should be considered for difficult or complicated cases. |
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Amelanotic melanoma can present significant difficulties for defining a margin with up to one third of subungual and nodular melanomas being non-pigmented. This may dictate choice of a wider margin, or further re-excision, where practicable. |
Supplement. Moh's surgery and staged serial excision
A large prospective study[7] assessed complete clearance of 1120 melanomas in situ excised by Mohs micrographic surgery with frozen-section examination of the margin. Six millimetre margins were adequate for complete clearance in 86% of all tumours; 9 mm margins were adequate for complete clearance in 98.9% of all tumours. A 1.2 cm margin yielded 99.4% clearance, 1.5 cm margin yielded 99.6% clearance, and 3 cm margin yielded 100% clearance. The authors state that “the frequently recommended 5 mm margin for melanoma is inadequate. Standard surgical excision of melanoma in situ should include 9 mm of normal-appearing skin, similar to that recommended for early invasive melanoma”. This study includes a mixture of cases of melanoma in situ, both LM and non-lentigo maligna type, and it is possible that LM requires a wider margin than other melanomas in situ.
A retrospective review of 192 cases of melanoma in situ[8] found that LM required wider margins for complete excision than did non-lentigo maligna melanoma in situ.
In another retrospective study of 117 LM and lentigo maligna melanoma (LMM) cases treated with a staged margin-controlled excision technique,[9] the mean total surgical margin required for excision of LM was 7.1 mm and was 10.3 mm for LMM. Of the tumours diagnosed as LM on initial biopsy specimen, 16% were found to have unsuspected invasion. Total surgical margin was associated with initial clinical lesion diameter. The authors concluded that the standard excision margins for LM and LMM are often inadequate and occult invasive melanoma occurs in LM. Dermatoscopy and confocal microscopy may be useful in defining margins before excision of melanoma in situ.
A retrospective review of 343 cases of melanoma in situ on the head and neck treated by Mohs micrographic surgery[10] showed that 65% of cases were cleared by a 5 mm margin whilst 15 mm margins were needed to obtain a 97% clearance rate. The authors concluded that “melanoma in situ on the head and neck can spread significantly beyond the clinical margins and demonstrates the importance of confirming clearance histologically before closure procedures. Mohs surgery has the advantage of total margin evaluation and where available it may be reasonable to start with 5 mm margins. Where Mohs surgery is not a treatment option, the authors would advocate larger excision margins of ≥ 10 mm.”
In a study of 51 cases of facial LM and thin (<1 mm) LMM, with LMM present in nine lesions (average Breslow depth, 0.65 mm),[11] peripheral margin control was performed with repeated margin excision until histological clearance of the lesion. Margins required for clearance of LM and LMM averaged 1.0 and 1.3 cm, respectively. No recurrences were identified with long-term follow-up. Immediate reconstruction was performed in all cases.
In another retrospective review of 293 cases of LM and LMM treated by geometric staged excision,[12] the mean margin to clearance after excision was 6.6 mm for LM and 8.2 mm for LMM. Of concern, 26.6% of LM would not have been adequately excised using traditional 5 mm margins. The rate of recurrence of after geometric staged excision was 1.7% with a mean of 32.3 months of follow up. A total of 11.7% of LMM was initially diagnosed as LM on biopsy, with the invasive component discovered only after excision.
Zitelli comments that “Many surgeons shudder at the thought of such wide margins on the head and neck, and therefore it is important to note that Mohs surgery using MART 1 immunostains offers a way to keep more narrow margins for the majority of patients yet still have the ability to identify the outlier patients with wide subclinical extensions of MIS. The importance of clearing MIS on the first procedure is that recurrence appears as invasive melanoma of 1-mm thickness in 23% of recurrences.”[13]
References
- ↑ Tzellos T, Kyrgidis A, Mocellin S, Chan AW, Pilati P, Apalla Z. Interventions for melanoma in situ, including lentigo maligna. Cochrane Database Syst Rev 2014 Dec 19;12:CD010308 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25526608.
- ↑ Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, et al. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline--Update 2012. Eur J Cancer 2012 Oct;48(15):2375-90 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22981501.
- ↑ Dummer R, Hauschild A, Lindenblatt N, Pentheroudakis G, Keilholz U, on behalf of the ESMO Guidelines Committee. ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Onco; 2015.
- ↑ BMJ Best Practice. BMJ Best practice monograph on melanoma. [homepage on the internet] BMJ Publishing Group; 2016 Jan 18 [cited 2016 Jan 18; updated 2016]. Available from: http://bestpractice.bmj.com/best-practice/monograph/268.html.
- ↑ 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 Aug;163(2):238-56 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20608932.
- ↑ 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21868127.
- ↑ 7.0 7.1 Kunishige JH, Brodland DG, Zitelli JA. Surgical margins for melanoma in situ. J Am Acad Dermatol 2012 Mar;66(3):438-44 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22196979.
- ↑ 8.0 8.1 Akhtar S, Bhat W, Magdum A, Stanley PR. Surgical excision margins for melanoma in situ. J Plast Reconstr Aesthet Surg 2014 Mar;67(3):320-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24444795.
- ↑ 9.0 9.1 Hazan C, Dusza SW, Delgado R, Busam KJ, Halpern AC, Nehal KS. Staged excision for lentigo maligna and lentigo maligna melanoma: A retrospective analysis of 117 cases. J Am Acad Dermatol 2008 Jan;58(1):142-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18029055.
- ↑ 10.0 10.1 Felton S, Taylor RS, Srivastava D. Excision Margins for Melanoma In Situ on the Head and Neck. Dermatol Surg 2016 Mar;42(3):327-334 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26866286.
- ↑ 11.0 11.1 Jejurikar SS, Borschel GH, Johnson TM, Lowe L, Brown DL. Immediate, optimal reconstruction of facial lentigo maligna and melanoma following total peripheral margin control. Plast Reconstr Surg 2007 Oct;120(5):1249-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17898597.
- ↑ 12.0 12.1 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 May;148(5):599-604 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22782151.
- ↑ Zitelli J. Excision margins for melanoma in situ on the head and neck. [homepage on the internet] Practice Update; 2016 [cited 2016 Apr 15]. Available from: http://www.practiceupdate.com/content/excision-margins-for-melanoma-in-situ-on-the-head-and-neck/36098#commentarea.
Appendices
