Moh’s micrographic surgery (MMS) has very high rates of local control and cure for basal cell and squamous cell carcinoma. When appropriately performed, cure rates exceed 98%, especially for smaller lesions¹. The role of MMS for treatment of melanoma is less clear. MMS is predicated on the use of close margins to clear disease, while preserving normal anatomy. This is contrary to the classic teaching of wide margins for clearance of melanoma. We thus ask, is MMS appropriate for melanoma, and in what circumstances?

Techniques:

MMS is performed most frequently in the office setting by a dermatologic surgeon. The skin lesion is debulked, and a thin margin is then taken circumferentially and deep to the tumor. This tissue is processed with H and E staining, in a manner to assess nearly the entirety of the margin, rather than the breadloaf technique which is prone to sampling error. Residual tumor is identified, and the process is repeated until clear margins are achieved. Often, the resection is performed typically in a single office visit, and reconstruction can be immediate or staged, depending on the defect. The process is illustrated here²:

MMS for melanoma has a few technical differences. The debulk and acquisition of the margins are similar. However, the margins are sent to a pathologist for rushed, but otherwise typical, permanent section analysis. The patient is dressed and sent home until the results are finalized, indicating the need for additional stages. This is known as the “slow Moh’s” approach. Some MMS surgeons use rapid MART-1 stains in the Moh’s lab to speed up the process, and offer single-day MMS in select cases³. Regardless of the technique, it is typically recommended to send the debulked central component for permanent section analysis to obtain complete staging information.

On the other hand, wide local excision (WLE) is the current standard of care for in-situ and invasive melanoma. The meaning of “wide” depends of course of the depth of the tumor. According to the National Comprehensive Cancer Network (NCCN), wide margins are as follows⁴:

Obtaining these margins is often done in the operating room, and with delayed reconstruction once complete circumferential and deep margin clearance is verified.

Pros and Cons

A pros and cons comparison between MMS and WLE is summarized in this table by Beaulieu and colleagues⁵. The article can be found here, and the table here.

In brief, the pros of WLE include the wealth of data demonstrating efficacy, use of permanent section analysis of the specimen, and the relative short duration of the procedure compared to MMS. The primary drawbacks of WLE include the time between the procedure and the final pathology reporting, and the idea that WLE is not necessarily designed to be tissue sparing.

On the contrary, MMS is noted to provide point-of-care pathologic information, with presumed 100% margin analysis. However, there is uncertainty of “clear margins” with in the setting of satellitosis, and the extent / distance of a clear margin is not verified due to the tumor debulking process.

Another drawback of MMS in melanoma is a logistical one with regards to sentinel lymph node biopsy (SLNB). In many cases, SLNB can be performed in the same setting as WLE, typically under general anesthesia, with radionuclide / methylene blue injection into the skin lesion prior to the WLE. With MMS, this workflow is not possible. The SLNB would have to be done in a separate operative encounter prior to MMS. Post-MMS reconstruction may then require an additional operative encounter of course.  Alternatively, SLNB may be performed after MMS, but this would require injection of the tracer into the margin of the excised lesion, or the resultant scar. The concern here is the alteration of dermal lymphatic drainage after MMS which may alter the reliability of the SLNB procedure.  Though the details are out of the scope of this blog post, the importance of properly performed SLNB has been clearly established in multiple studies, both from a prognostic and therapeutic standpoint. To alter or degrade the prognostic and therapeutic effect of SLNB when performing MMS in lieu of WLE may actually be detrimental to some patients at high risk of occult nodal disease at presentation. In addition, the potential need for multiple operative encounters and anesthetic episodes can lead to increased costs and time for the patient.

The Evidence

High quality evidence addressing the use of MMS for melanoma is a bit lacking. Studies largely consist of retrospective, non-randomized, or single arm prospective observational trials.

Most data report results with treatment of melanoma in-situ (MIS), specifically lentigo maligna (LM).

• De Vries et al, have demonstrated 100% local control rates in a retrospective cohort of LM patients treated with MMS. Average follow-up was 60 months⁶.
• Hou et al demonstrated similar rates of local control for MMS compared to WLE in a non-randomized prospective trial of LM patients. Larger lesions of the head and neck, with indistinct borders, were preferentially treated with MMS, and demonstrated 1.9% rate of recurrence⁷.
• Nosrati et al report retrospective analysis of 277 patients with MIS treated with MMS and 385 patients treated with conventional WLE, demonstrating no significant differences in local recurrence rates, overall survival, or melanoma-specific survival. Median follow-up was 8.6 years⁸.

Some studies report the use of MMS in invasive disease as well.

• Bricca and colleagues report favorable local recurrence rates for invasive melanoma treated with MMS compared to WLE. This data even suggests superior local control with MMS rather than WLE, for MIS and thin melanoma. Local recurrence was noted to be 0.3 and 0% for MIS and melanoma <0.76 mm respectively, when treated with MMS, versus recurrence rates of 20 and 7.3% when treated with WLE⁹. This study is severely limited by use of historical control rates for patients undergoing WLE.
• A prospective study by Ellison and colleagues demonstrated excellent local control rates in a cohort of 562 tumors, including invasive disease, mostly involving the head and neck¹⁰. However, the authors report the need for 10 to 12 mm margins for optimal local control, even if MMS technique is used.

The Guidelines

Institutional guidance is provided regarding the use of MMS in melanoma. The NCCN cutaneous melanoma guidelines (2.2021) state:

Mohs micrographic surgery (MMS) is not recommended for primary treatment of invasive cutaneous melanoma. It may be considered selectively for minimally invasive melanomas when standard margins cannot be achieved in anatomically constrained areas, along with other surgical methods that provide comprehensive histologic assessment, such as staged excision with permanent sections for dermatopathology review.

In the “Guidelines of care for the management of primary cutaneous melanoma”, a working group of the American Academy of Dermatology (AAD) acknowledges the recommendation to maintain at least 1 cm margins for invasive disease when possible¹¹. MMS may be used for clearance of melanoma-in-situ, specifically of the lentigo maligna subtype (as distinguished from acral lentiginous).

In Conclusion

Take home points:

• MMS is not recommended for invasive melanoma, and not supported by the NCCN or AAD guidelines.
• Data regarding long term outcomes of MMS are evolving and the guidelines are under revision.
• Regarding MIS specifically, complete circumferential and peripheral margin assessment (CCPMA) is ideal, and this can be accomplished with either en face rush permanent section analysis of margins, as well as MMS.

In practice, the current data and institutional guidelines recommend against the use of MMS for melanoma which is known or suspected to be invasive. This is due to a lack of clear oncologic equipoise when compared to WLE. Also, MMS may confound and complicate the performance and validity of SLNB, which is a critical component of treating certain invasive lesions. If purely in-situ disease is known or suspected, MMS seems to have a role here. In addition, a common scenario is the presence of residual in-situ disease at the margins of invasive disease cleared by WLE. MMS may be helpful to address this when WLE re-resection to clear the in-situ finding is not feasible or accepted by the patient. In many cases where MMS may play a role, these decisions are optimally made after consultation with both an oncologic head and neck melanoma surgeon and MMS surgeon, who can recommend the appropriate approach after weighing risks and benefits in select cases on an individualized basis.

References:

1. Mansouri B, Bicknell LM, Hill D, Walker GD, Fiala K, Housewright C. Mohs Micrographic Surgery for the Management of Cutaneous Malignancies. Facial Plast Surg Clin North Am. 2017 Aug;25(3):291-301.
2. Prickett KA, Ramsey ML. Mohs Micrographic Surgery. [Updated 2021 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441833/
3. 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 Oct;46(10):1267-1271.
4. NCCN Clinical Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 2.2021 — February 19, 2021.
5. Beaulieu D, et al. Current perspectives on Mohs micrographic surgery for melanoma. Clin Cosmet Investig Dermatol. 2018; 11: 309–320.
6. de Vries K, Greveling K, Prens LM, et al. Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision. Br J Dermatol 2016;174:588-593.
7. Hou JL, Reed KB, Knudson RM, et al. Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort. Dermatol Surg 2015;41:211-218.
8. Nosrati A, Berliner JG, Goel S, McGuire J, Morhenn V, de Souza JR, Yeniay Y, Singh R, Lee K, Nakamura M, Wu RR, Griffin A, Grimes B, Linos E, Chren MM, Grekin R, Wei ML. Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision. JAMA Dermatol. 2017 May 1;153(5):436-441.
9. Bricca GM, et al. Cutaneous head and neck melanoma treated with Mohs micrographic surgery. J Am Acad Dematol. 2005 Dec;52(1):92-100.
10. Ellison PM, Zitelli JA, Brodland DG. Mohs micrographic surgery for melanoma: A prospective multicenter study. J Am Acad Dermatol. 2019 Sep;81(3):767-774.
11. Melanoma Work Group. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019 Jan;80(1):208-250.

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Bharat Yarlagadda

Dr. Bharat Yarlagadda is a head and neck surgeon at the Lahey Hospital and Medical Center in Burlington, MA and an assistant professor in the Department of Otolaryngology - Head and Neck Surgery at Boston University School of Medicine. He completed Otolaryngology residency at the Boston Medical Center, and head and neck fellowship at the Massachusetts Eye and Ear Infirmary. His research is focused on surgical simulation as well as quality improvement and outcomes.

Latest posts by Bharat Yarlagadda (see all)

• The Role of Moh’s Surgery in the Treatment of Melanoma - April 8, 2021