Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

Intraoperative Immunohistochemistry During Mohs Micrographic Surgery and Staged Excision Decreases Local Recurrence Rates for Invasive Cutaneous Melanoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes. OBJECTIVE: To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes. MATERIALS AND METHODS: Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality. RESULTS: Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0-0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%-2.8%) [ p < .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high. CONCLUSION: Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma.Trial Registration PROSPERO Identifier: CRD42023435630.

The Impact of Surgical Delay in Primary Cutaneous Melanoma: A Systematic Review.

BACKGROUND AND OBJECTIVES: The prognosis of patients diagnosed with melanoma is highly dependent on staging, early detection, and early intervention. In this systematic review, the authors aimed to investigate the impact of surgical delay (time between diagnostic biopsy and definitive surgical excision) on melanoma-specific outcomes. MATERIAL AND METHODS: A systematic review was conducted from Embase (1974-present), MEDLINE (1946-present), Cochrane Central Register of Controlled Trials (2005-present), Scopus, and Web of Science. A total of 977 studies were included for review after removal of duplicates. A total of 10 studies were included for final analysis. RESULTS: In total, 70% (7/10) of the studies found that longer wait times between initial biopsy and surgical intervention are correlated with lower overall survival. Among the 9 studies that reported overall survival as a percentage, the median and SD overall survival was 82% ± 5.87. CONCLUSION: There is evidence that prolonged surgical delay in patients diagnosed with Stage I cutaneous melanoma is associated with worsened overall mortality, whereas the effect of surgical delay on overall mortality in Stages II and III melanomas is uncertain. Future prospective studies and randomized clinical trials are needed to better define the appropriate surgical wait times between biopsy and surgical treatment.

Disease-Specific Mortality of Dermatofibrosarcoma Protuberans After Mohs Surgery Versus Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE: To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS: A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1-1.2, p : 0.016) versus WLE (0.9%, CI 0.6-1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0-2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0-5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE: The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.

Mohs Micrographic Surgery With Melanocytic Immunostains for T1a/b Invasive Melanoma Yields <1% Local Recurrence and Disease-specific Mortality.

BACKGROUND: The use of Mohs micrographic surgery with melanocytic immunostains (MMS-I) for cutaneous melanoma is increasing. OBJECTIVE: To assess local recurrence, melanoma-specific death rates in patients with invasive melanoma treated with MMS-I. MATERIALS AND METHODS: A single-center retrospective review of patients with invasive melanoma treated with MMS-I from January 2008 to December 2018. RESULTS: Three hundred fifty-two patients (359 melanomas) were included. The median age was 71 years; most patients were male (252%; 71.6%). Most tumors were T1a/b (341, 95%), H/N (322; 89.7%), and lentigo maligna subtype (281, 78.3%). At a median follow-up of 4.3 years, local recurrence rates were 1.4% (5) and 0.9% (3) among all-stage and T1a/b tumors, respectively. There were 3 melanoma-related deaths (0.9%). CONCLUSION: MMS-I is associated with <1% risk of local recurrence and disease-specific mortality for T1a/b melanomas.

Immunohistochemistry-Assisted Mohs Surgery for Invasive Eyelid and Periorbital Cutaneous Melanoma.

BACKGROUND: Prior studies describe wide local excision and "slow Mohs" outcomes for periocular melanoma. Mohs micrographic surgery (MMS) with immunohistochemistry maximizes tissue preservation and offers same-day comprehensive margin evaluation, which facilitates expedited repair, and coordination of oculoplastic reconstruction when necessary. OBJECTIVE: To describe oncologic and reconstructive outcomes of invasive periocular cutaneous melanoma treated with immunohistochemistry-assisted MMS. MATERIALS AND METHODS: Invasive melanoma cases affecting the eyelids or periorbital region treated with MMS between 2008 and 2018 were reviewed. Eyelid tumors and those in adjacent subunits were compared. Main outcome measures were recurrence, melanoma-specific death, and postreconstructive complications. RESULTS: Of 42 cases, 28 were classified as periorbital and 14 as eyelid involving. Most were T1 (37, 88.1%). There was 1 local recurrence in a patient with persistent positive conjunctival margin (2.4%). No local recurrences were observed in cases where negative Mohs margins were achieved, and no melanoma-related deaths occurred. Eyelid tumors were more likely to result in lid margin involving defects and require oculoplastic reconstruction. Eyelid complications developed in 10 cases (23.8%), and 5 (11.9%) required revision surgery. CONCLUSION: Mohs micrographic surgery for periocular melanoma results in low rates of local recurrence and melanoma-specific death. Initial tumor location can aid in reconstructive planning.

Increasing Incidence and Decreasing Mortality of Melanoma in Elderly Adults: An Epidemiologic Study in Olmsted County, Minnesota.

BACKGROUND AND OBJECTIVE: Primary cutaneous melanoma incidence is increasing in elderly individuals. This population-based cohort examines incidence and mortality rates among adults aged 61 years and older with cutaneous melanoma. MATERIALS AND METHODS: Using the Rochester Epidemiology Project, patients aged 61 years of age or older with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970 and December 31, 2020 were identified. RESULTS: The age- and sex-adjusted incidence rate increased from 16.4 (95% CI, 8.2-24.6) per 100,000 person-years in 1970 to 1979 to 201.5 (95% CI, 185.1-217.8) per 100,000 person-years in 2011 to 2020 (12.3-fold increase). There was a 16.0x increase in males and an 8.5× increase in females. Melanoma incidence has stabilized in males (1.2-fold increase, p = .11) and continues to significantly increase in females (2.7-fold increase, p < .001). Older age at diagnosis was significantly associated with an increased risk of death (HR 1.23 per 5-year increase in age at diagnosis, 95% CI, 1.02-1.47). CONCLUSION: Melanoma incidence continues to increase since 1970. The incidence has risen in elderly females, but has stabilized in males. Mortality has decreased throughout this period.

Mohs Micrographic Surgery With Immunohistochemistry for the Treatment of Periocular Melanoma In Situ.

PURPOSE: Mohs micrographic surgery with immunohistochemistry allows for same-day comprehensive margin assessment of melanoma in situ prior to subspecialty reconstruction. This study describes the oncologic and reconstructive outcomes of eyelid and periorbital melanoma in situ and identifies risk factors for complex reconstructive demands. METHODS: Retrospective case series of all patients treated with Mohs micrographic surgery with immunohistochemistry for melanoma in situ affecting the eyelids or periorbital region from 2008 to 2018 at a single institution. Tumors were assigned to the eyelid group if the clinically visible tumor involved the skin inside the orbital rim. Reconstructive variables were compared between the eyelid and periorbital cohorts. RESULTS: There were 24 eyelid and 141 periorbital tumors included. The initial surgical margin for all tumors was 5.34 ± 1.54 mm and multiple Mohs stages were required in 24.2% of cases. Eyelid tumors included more recurrences (p = 0.003), and the average defect size was larger (14.0 ± 13.3 cm2 vs. 7.7 ± 5.4 cm2, p = 0.03). Risk factors for complex reconstruction included: initial tumor diameter >2 cm (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 1.95-7.57) and eyelid involved by initial tumor (OR: 4.88, 95% CI: 1.94-12.28). At an average follow-up of 4.8 years, there were no melanoma-related deaths and 1 local recurrence (0.6% recurrence rate). CONCLUSIONS: Mohs micrographic surgery with immunohistochemistry achieves excellent local control rates for periocular melanoma in situ. An initial surgical margin of 5 mm is frequently insufficient to achieve clear margins. The resulting defects are large, and the complexity of reconstruction can be predicted by tumor size and clinical involvement of eyelid skin.

Local Recurrence Rates of Malignant Melanoma After Mohs Micrographic Surgery Are Lowest With 5- to 10-mm Initial Margins: A Systematic Review and Meta-Analysis.

BACKGROUND: Current consensus guidelines have discouraged the use of sub-0.5-cm (in situ) and sub-1-cm (invasive) margins when performing Mohs micrographic surgery (Mohs) for melanoma, with minimal evidence to guide this recommendation. OBJECTIVE: To compare melanoma local recurrence rates after Mohs based on initial margin size. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted with search terms including Mohs micrographic surgery, surgical margin, recurrent disease, and melanoma. RESULTS: Forty-three studies were included. The 5- to 10-mm margin category had a statistically significant lower local recurrence compared with 1- to 5-mm and 5-mm categories. Recurrence for 1- to 5-mm, 5-mm, 5- to 10-mm, and 10-mm categories were 2.3% (CI 0.8-3.5, p < .001), 1.4% (CI 0.6-2.2, p < .001), 0.3% (CI 0.2-0.5, p < .001), and 6.1% (CI -6.7 - 18.8, p = .349), respectively. Number of stages for 1 to 5, 5, 5 to 10, and 10-mm categories were 1.8, 1.8, 1.6, and 1.6, respectively. There was no statistically significant difference between the groups (p = .694). CONCLUSION: Five- to 10-mm margins were associated with the lowest local recurrence rates. A 5- to 10-mm initial margin should be considered where other factors (tumor characteristics, anatomical or functional considerations) allow.

Incisional Biopsy Technique Is Associated With Decreased Overall Survival for Cutaneous Melanoma.

BACKGROUND: Previous studies examining melanoma biopsy technique have not demonstrated an effect on overall survival. OBJECTIVE: To examine overall survival of patients with cutaneous melanoma diagnosed by shave, punch, incisional, or excisional techniques from the National Cancer Database (NCDB). MATERIALS AND METHODS: Melanoma data from the 2004 to 2016 NCDB data set were analyzed. A Cox proportional hazards model was constructed to assess the risk of 5-year all-cause mortality. RESULTS: In total, 42,272 cases of melanoma were reviewed, with 27,899 (66%) diagnosed by shave biopsy, 8,823 (20.9%) by punch biopsy, and 5,550 (13.1%) by incisional biopsy. Both the univariate and multivariate analyses demonstrated that tumors diagnosed by incisional biopsy had significantly (p = .001) lower overall 5-year survival compared with shave techniques (hazard ratio [HR] = 1.140, 95% confidence interval [CI] 1.055 to 1.231). We found no difference (p = .109) between shave and punch biopsy techniques (HR 1.062, 95% CI 0.987-1.142) or between punch and incisional techniques (HR 1.074, 95% CI 0.979-1.177, p = .131). CONCLUSION: Incisional biopsies were associated with decreased overall 5-year survival in the NCDB. No difference was observed between shave and punch biopsy techniques. These findings support current melanoma management guidelines.

Mohs Micrographic Surgery at Challenging Anatomical Sites.

BACKGROUND: Mohs micrographic surgery (MMS) is often the treatment of choice for skin cancer removal as it maximizes normal tissue sparing and can be paired with a reconstructive approach that optimizes function and cosmesis. Many tumors on the eyelid, nose, ear, and genitals are particularly well suited for MMS but can be challenging for the dermatologic surgeon. OBJECTIVE: To review the complex anatomy, as well as the authors' approach to executing and interpreting Mohs layers, at each of these anatomical sites. METHODS: A review of the literature on MMS of the eyelid, nose, ear, and genitals was performed using the PubMed database and relevant search terms. CONCLUSION: These sites present potential pitfalls for tumor resection and reconstruction, but with the proper technique, the dermatologic surgeon can minimize tumor recurrence and MMS complications. Warning signs for potentially difficult tumor resection can signify when an interdisciplinary approach is warranted.

Benefit of Mohs Micrographic Surgery Over Wide Local Excision for Melanoma of the Head and Neck: A Rational Approach to Treatment.

BACKGROUND: There are limited published data comparing wide local excision (WLE) with Mohs micrographic surgery (MMS) for the treatment of melanoma. OBJECTIVE: To describe a novel treatment algorithm for the surgical management of head and neck melanoma and compare rates of local recurrence for tumors treated with either MMS using immunohistochemistry or WLE. MATERIALS AND METHODS: A 10-year retrospective chart review including all in situ and invasive melanomas of the head and neck treated at one institution from January 2004 to June 2013. RESULTS: Among 388 patients with melanoma, MMS was associated with decreased rates of local recurrence (p = .0012). However, patient and tumor characteristics varied significantly, and WLE subgroup was largely composed of higher stage and risk tumors. Subgroup analysis found that patients with in situ or thin invasive tumors (<0.8 mm) treated with MMS had improved local recurrence outcomes (p = .0049), despite more frequent tumor location on high risk anatomic sites (e.g., central face). In addition, MMS was associated with a favorable delay in time to local recurrence among in situ tumors (HR = 31.8; p = .0148). CONCLUSION: These findings further support the use of MMS for treatment of melanoma of the head and neck and help to validate our proposed clinical decision tree.