Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Pinch Grafts Versus Second Intention Wound Healing for Mohs Micrographic Surgery Defects Below the Knee: A Prospective Randomized Trial.

BACKGROUND: The surgical management of leg wounds following skin cancer extirpation is challenging. Pinch grafting (PG) is a technique that has been rarely described in the reconstruction of acute surgical wounds. OBJECTIVE: The purpose of this study was to evaluate whether PG resulted in faster healing times for below the knee wounds following Mohs micrographic surgery (MMS) when compared with second intention healing (SIH). MATERIALS AND METHODS: This was a prospective randomized trial of patients with post-Mohs micrographic surgical wounds of the lower extremity who were randomized either to receive pinch grafts or to heal by second intention. Patients were followed through a combination of in-person and virtual visits until their wounds were completely reepithelialized. RESULTS: Median time to wound healing was 36 days in the PG group versus 56 days for the SIH group, representing a 56% improvement in healing time. There were no differences in complications between the 2 groups with trends toward decreased rates of pain and infection in the PG group. CONCLUSION: PG is an effective simple method to hasten the healing of lower extremity wounds following MMS.

Clinical Characteristics of Marginally Recurrent Melanoma After Primary Excision: A Multisite Retrospective Analysis of 140 Cases Referred for Mohs Surgery.

BACKGROUND: Marginally recurrent melanoma (MRM) manifests immediately adjacent to or within a scar and arises from incomplete tumor clearance after primary treatment. Little is known about the progression and treatment of MRM after all forms of excision. OBJECTIVE: To determine the invasive growth potential, tumor-stage progression, and outcomes of those with MRM. METHODS: One hundred forty patients with MRM were collected from 5 practice databases. All patients were treated with Mohs micrographic surgery. They were evaluated for Breslow depth and tumor stage change from the time of primary treatment and recurrent treatment. RESULTS: Of 101 cases initially treated as melanoma in situ, 13 (12.9%) marginally recurred with invasive disease at the time of Mohs micrographic surgery. The median thickness of these recurrent melanomas was 0.58 mm. Of 39 cases initially treated as invasive melanoma, 10 (25.6%) marginally recurred with a greater Breslow depth. The median increase in thickness from initial treatment to recurrence was 1.31 mm. CONCLUSION: Marginally recurrent melanoma retains its invasive growth potential. This can lead to Breslow depth increase, tumor-stage progression, and a worse prognosis on recurrence. Obtaining tumor-free margins is critical in initial and recurrence treatments.

Mohs for Melanoma: A Review of MART-1 Frozen Section Interpretation.

BACKGROUND: Mohs surgery for melanoma has been performed for many decades, but advances in the use of immunohistochemistry with frozen sections during Mohs surgery have allowed for more accurate, reliable, and efficient margin assessment with improved local control of the disease. OBJECTIVE: To describe the use of MART-1 in treating melanoma with Mohs surgery and serve as a primer for the Mohs surgeon adding melanoma cases to their repertoire. MATERIALS AND METHODS: Review of the literature and discussion of experience with Mohs for melanoma. RESULTS: Practical approach and pitfalls when assessing margins using MART-1 immunohistochemistry during Mohs surgery for the treatment of melanoma. CONCLUSION: Mohs for melanoma is an expanding field-education of Mohs surgeons and increasing the practice of this technique has the potential to improve patient outcomes.

Clinical outcomes of high-risk cutaneous squamous cell carcinomas treated with Mohs surgery alone: An analysis of local recurrence, regional nodal metastases, progression-free survival, and disease-specific death.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) continues to increase, and it is now predicted that the number of deaths from cSCC will surpass that of melanoma within the next 5 years. Although most cSCCs are successfully treated, there exists an important subset of high-risk tumors that have the highest propensity for local recurrence (LR), nodal metastasis (NM), and disease-specific death (DSD). OBJECTIVE: We investigated the clinical outcomes of high-risk cSCCs treated with Mohs surgery (MS) alone, analyzing LR, NM, distant metastasis, and DSD. In addition, we analyzed progression-free survival and DSD in patients who underwent salvage head/neck dissection for regional NMs. METHODS: Retrospective review of all high-risk cSCC treated in our clinics between January 1, 2000, and January 1, 2020, with follow-up through April 1, 2020. SETTING: Two university-affiliated, private-practice MS referral centers. RESULTS: In total, 581 high-risk primary cSCCs were identified in 527 patients, of which follow-up data were obtained for 579 tumors. The 5-year disease-specific survival was 95.7%, with a mean survival time of 18.6 years. The 5-year LR-free survival was 96.9%, the regional NM-free survival was 93.8%, and the distant metastasis-free survival was 97.3%. The 5- and 10-year progression-free survival rates from metastatic disease were 92.6 and 90.0%, respectively. In patients who experienced regional NMs and underwent salvage head and neck dissection with or without radiation, the 2-year disease-specific survival was 90.5%. CONCLUSION: Our cohort, which is the largest high-risk cSCC cohort treated with MS to date, experienced lower rates of LR, NM, and DSD than those reported with historical reference controls using both the Brigham and Women's Hospital and American Joint Committee on Cancer, Eighth Edition, staging systems. We demonstrated that MS confers a disease-specific survival advantage over historical wide local excision for high-risk tumors. Moreover, by improving local tumor control, MS appears to reduce the frequency of regional metastatic disease and may confer a survival advantage even for patients who develop regional metastases.

Outcomes of invasive melanoma of the head and neck treated with Mohs micrographic surgery - A multicenter study.

BACKGROUND: There are no randomized controlled trials to guide surgical margins for invasive head and neck (H&N) melanoma using conventional excision. Mohs micrographic surgery (MMS) has shown improved local recurrence rates and survival for invasive H&N melanomas. OBJECTIVE: Determine local recurrence (LR), nodal recurrence, and distant recurrence rates, and disease specific survival for invasive melanoma of the H&N treated with MMS. METHODS: A retrospective multicenter study of 785 cases of invasive H&N melanoma treated with MMS using frozen sections with melanoma antigen recognized by T-cells 1 immunohistochemical staining was performed to evaluate long-term outcomes over 12-years. RESULTS: 785 melanomas (thickness: 0.3 mm-8.5 mm) were treated with MMS. LR, nodal recurrence, and distant recurrence rates were 0.51% (4/785), 1.0% (8/785), and 1.1% (9/785) respectively. For T1, T2, T3, and T4 tumors LR was 0.16% (1/636), 1.18% (1/85), 2.22% (1/45), and 5.26% (1/19), respectively. Five and 10-year disease specific survival were 96.8% (95% CI 95.0% to 98.5%) and 93.4% (95% CI 88.5% to 98.3%). LIMITATIONS: A nonrandomized retrospective study. CONCLUSION: MMS achieves significant improvements in LR compared to a meta-analysis of historical cohorts of patients treated with conventional excision. MMS should be considered an important surgical option for invasive H&N melanoma.

The Controversy and Value of Mohs Micrographic Surgery for Melanoma and Melanoma in Situ on the Trunk and Extremities.

BACKGROUND: The use of Mohs surgery for melanoma on the trunk and extremities is not supported in the guidelines of dermatology, but is widely used in the real world. OBJECTIVE: The purpose of this article is to expose the value of Mohs surgery for melanoma on the trunk and extremities for consideration of updating the guidelines. MATERIALS AND METHODS: This was a retrospective review of a prospectively maintained database 7 to identify patients whose melanomas would likely have recurred using standard surgical margins. A prediction model was used to evaluate the value of Mohs surgery. RESULTS: The model predicted that 2,847 (2%) patients with melanoma on the trunk and extremities would likely recur each year with standard surgical margins even after re-excision when positive margins were identified, compared with 0.1% after Mohs surgery. This likely would result in the upstaging of 27% of melanoma in situ patients and 13% of patients with invasive melanoma. The upstaging would also result in a decrease in melanoma-specific survival and the death of 1% of patients with true local recurrences of melanoma. CONCLUSION: Mohs surgery has value for melanoma on the trunk and extremities by minimizing local recurrence and death from disease progression.

Cost effectiveness of intermediate-risk squamous cell carcinoma treated with Mohs micrographic surgery compared with wide local excision.

BACKGROUND: The efficacy of Mohs micrographic surgery (MMS) in treating cutaneous squamous cell carcinoma has been demonstrated. The cost effectiveness of MMS has rarely been studied to support the perceived higher cost. OBJECTIVE: Perform a cost-effectiveness analysis to determine whether MMS is cost effective over wide local excision (WLE) for Brigham and Women's Hospital tumor stage T2a cutaneous squamous cell carcinoma over a 5-year period. METHODS: A Markov model with a 5-year time horizon was created using variables from published data. Costs in United States dollars and quality-adjusted life-years (QALY) were calculated. RESULTS: MMS was $333.83 less expensive ($4365.57 [95% CI, $3664.68-$6901.66] vs $4699.41 [95% CI, $3782.94-$10,019.31]) than WLE. MMS gained 2.22 weeks of perfect health (3.776 QALY [95% CI, 3.774-3.777] for MMS and 3.733 QALY [95% CI, 3.728-3.777]) over 5 years. The incremental cost-effectiveness ratio was -$7,822.19. MMS had a 99.9% probability of being more cost effective than WLE. Annualized savings of choosing MMS over WLE would be $200 million and over 25,000 QALY. MMS could cost 3.1 times its current rate and remain cost effective. LIMITATIONS: Relied on data from external retrospective sources. CONCLUSION: MMS is less costly and more effective than WLE and should be strongly considered for stage T2a cSCC, given improvements in costs and QALY.

Correlation of basal cell carcinoma subtype with histologically confirmed subclinical extension during Mohs micrographic surgery: A prospective multicenter study.

BACKGROUND: Traditionally "aggressive" histologic subtypes (HSs) of basal cell carcinoma (BCC) are more likely to quantitatively exhibit subclinical extension (SCE), requiring more stages during Mohs micrographic surgery (MMS) and, therefore, larger margins upon excision. However, the tendency for SCE has never been compared between HSs of BCC in a prospective manner. OBJECTIVE: To prospectively correlate the HS of BCC with the likelihood of SCE as defined by the number of MMS stages required to clear the tumor. METHODS: In a prospective, multicenter study involving 17 Mohs surgeons in 16 different practices across the United States, data regarding 1686 cases of BCC undergoing MMS were collected. Patient demographics, tumor characteristics, number of MMS stages required for tumor clearance, and specific BCC subtypes noted on both index biopsy and the final MMS stage were recorded. RESULTS: Analysis of the average number of MMS stages for each HS required to clear tumor revealed 2 distinct degrees of SCE (P < .0001): high (higher than average) risk of SCE (1.9 stages, 1.0 SD) and low (lower than average) risk of SCE (1.6 stages, 0.9 SD). Subtypes of BCC within the high category were morpheaform (2.1), infiltrative (1.9), metatypical (1.9), mixed (1.8), and superficial (1.8). The low category included BCC subtypes of basosquamous (1.6), micronodular (1.6), nodular (1.6), and unspecified (1.5). Three hundred twenty-four cases (22.0%) manifested HS drift or a change in subtype from index biopsy to the final MMS stage. Superficial BCC was the only subtype that showed an increase in prevalence from index biopsy to the final MMS stage (from 16.0% to 25.8%; P < .0002). LIMITATIONS: HSs from index biopsy may not be representative of all HSs present, resulting in sampling bias. CONCLUSION: SCE of superficial BCC was as likely as SCE of BCC subtypes that are considered "aggressive" and are deemed "appropriate" for MMS by the appropriate use criteria. Our study also found that when HS drift occurs, the most likely subtype to extend subclinically is superficial BCC.

Development and validation of a nomogram incorporating gene expression profiling and clinical factors for accurate prediction of metastasis in patients with cutaneous melanoma following Mohs micrographic surgery.

BACKGROUND: There is a need to improve prognostic accuracy for patients with cutaneous melanoma. A 31-gene expression profile (31-GEP) test uses the molecular biology of primary tumors to identify individual patient metastatic risk. OBJECTIVE: Develop a nomogram incorporating 31-GEP with relevant clinical factors to improve prognostic accuracy. METHODS: In an IRB-approved study, 1124 patients from 9 Mohs micrographic surgery centers were prospectively enrolled, treated with Mohs micrographic surgery, and underwent 31-GEP testing. Data from 684 of those patients with at least 1-year follow-up or a metastatic event were included in nomogram development to predict metastatic risk. RESULTS: Logistic regression modeling of 31-GEP results and T stage provided the simplest nomogram with the lowest Bayesian information criteria score. Validation in an archival cohort (n = 901) demonstrated a significant linear correlation between observed and nomogram-predicted risk of metastasis. The resulting nomogram more accurately predicts the risk for cutaneous melanoma metastasis than T stage or 31-GEP alone. LIMITATIONS: The patient population is representative of Mohs micrographic surgery centers. Sentinel lymph node biopsy was not performed for most patients and could not be used in the nomogram. CONCLUSIONS: Integration of 31-GEP and T stage can gain clinically useful prognostic information from data obtained noninvasively.

Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test.

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan-Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for class 1 and ≥50% for class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.

Plain language summary Cutaneous squamous cell carcinoma is a common skin cancer, with approximately 2 million cases diagnosed each year in the USA. Because substantial numbers of patients experience metastasis, which can result in death, accurate metastatic risk assessment is important. Clinicians use clinicopathologic factors to determine risk for disease progression. However, traditional methods miss pinpointing many patients who experience metastasis and sometimes categorize patients as at risk who do not develop metastasis, indicating that additional tools are needed. A molecular test, the 40-gene expression profile (40-GEP), was developed to predict metastatic risk based on the biology of the tumor. This study demonstrates that the 40-GEP, either as an independent tool or together with traditional methods, accurately identifies patients' risk of metastasis. Using the 40-GEP could improve patient management to improve patient outcomes.

Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities.

BACKGROUND: Microscopic evaluation of the entire surgical margin during excision of cutaneous malignancies results in the highest rates of complete excision and lowest rates of true local scar recurrence. Few studies demonstrate the outcomes of Mohs micrographic surgery specifically for invasive melanoma of the trunk and proximal portion of the extremities. OBJECTIVE: To evaluate the long-term efficacy of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities, including true local scar recurrence rate, distant recurrence-free survival, and disease-specific survival. METHODS: Prospectively collected study of 1416 cases of invasive melanoma of the trunk and proximal portion of the extremities was performed to evaluate long-term outcomes. RESULTS: True local scar recurrences occurred in our cohort at a rate of 0.14% (2/1416), after a mean follow-up period of 75 months and were not associated with tumor depth. The rate of satellite/in-transit recurrences and the disease-specific survival stratified by tumor thickness were superior to historical control values. LIMITATIONS: We used a nonrandomized, single institution, retrospective design. CONCLUSIONS: Mohs micrographic surgery of primary cutaneous invasive melanoma on the trunk and proximal portion of the extremities resulted in local control of 99.86% of tumors and an overall disease-specific death rate superior to that of wide local excision.

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma.

BACKGROUND: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. OBJECTIVE: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324). RESULTS: A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems. LIMITATIONS: Potential understaging of cases could affect metastasis rate accuracy. CONCLUSION: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

Opioid Prescribing Recommendations After Mohs Micrographic Surgery and Reconstruction: A Delphi Consensus.

BACKGROUND: Prescription opioids play a large role in the opioid epidemic. Even short-term prescriptions provided postoperatively can lead to dependence. OBJECTIVE: To provide opioid prescription recommendations after Mohs micrographic surgery (MMS) and reconstruction. METHODS: This was a multi-institutional Delphi consensus study consisting of a panel of members of the American College of Mohs Surgery from various practice settings. Participants were first asked to describe scenarios in which they prescribe opioids at various frequencies. These scenarios then underwent 2 Delphi ratings rounds that aimed to identify situations in which opioid prescriptions should, or should not, be routinely prescribed. Consensus was set at ≥80% agreement. Prescription recommendations were then distributed to the panelists for feedback and approval. RESULTS: Twenty-three Mohs surgeons participated in the study. There was no scenario in which consensus was met to routinely provide an opioid prescription. However, there were several scenarios in which consensus were met to not routinely prescribe an opioid. CONCLUSION: Opioids should not be routinely prescribed to every patient undergoing MMS. Prescription recommendations for opioids after MMS and reconstruction may decrease the exposure to these drugs and help combat the opioid epidemic.

Long-term clinical outcomes of patients with invasive cutaneous squamous cell carcinoma treated with Mohs micrographic surgery: A 5-year, multicenter, prospective cohort study.

BACKGROUND: Outcomes for patients with cutaneous squamous cell carcinoma (CSCC) treated with Mohs micrographic surgery (MS) in the United States have never been prospectively defined. Risk factors as they relate to outcomes are primarily derived from single-institution, retrospective data without regard for treatment modality. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital T staging systems have not been prospectively validated. OBJECTIVE: To prospectively quantify outcomes by T stage and verify historically high-risk features as they pertain to outcomes in MS-treated CSCC. METHODS: A 5-year, prospective, multicenter analysis of patients undergoing MS for invasive CSCC was conducted. RESULTS: The study enrolled 647 patients with 745 tumors. The 5-year local recurrence (LR)-free survival, nodal metastasis (NM)-free survival, and disease-specific survival were 99.3%, 99.2%, and 99.4%, respectively. Both staging systems were predictive of NM, disease-specific death, and all-cause death; neither was predictive of LR. Although Breslow depth was statistically associated with LR, NM, and disease-specific death, incidental perineural invasion was not. LIMITATIONS: The Brigham and Women's Hospital and the American Joint Committee on Cancer Staging Manual, Eighth Edition T staging systems were published after study enrollment, therefore T stages were retrospectively applied using the prospectively collected data. CONCLUSION: MS is a highly effective treatment for CSCC and may mitigate factors typically considered high risk. Uniform reporting of Breslow depth should be considered in CSCC. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital staging system are useful prognosticators but are not predictive of LR after MS.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Comparison of surgical margins for lentigo maligna versus melanoma in situ.

BACKGROUND: Multiple studies have shown a 5-mm surgical margin to be inadequate for excision of melanoma in situ. Some have suggested that a wider margin is needed only for the lentigo maligna subtype. OBJECTIVE: To compare subclinical extension of lentigo maligna with that of melanoma in situ. The secondary objective was to investigate the effect of other factors on extent of subclinical extension. METHODS: A prospectively collected series of noninvasive melanomas was studied. Original pathology reports were used to identify lentigo maligna and compare data for that subtype with data for the remaining melanomas in situ. RESULTS: A total of 1506 lentigo maligna cases and 829 melanomas in situ were included. To obtain a 97% clearance rate, both lentigo maligna and melanoma in situ required a 12-mm margin on the head and neck and a 9-mm margin on the trunk and extremities. Only 79% of lentigo maligna and 83% of melanoma in situ were successfully excised with a 6-mm margin (P = .12). Local recurrence was identified in 0.26% (5 facial, 1 scalp, and 1 acral), with a mean follow-up time of 5.7 years. LIMITATIONS: Margins less than 6 mm were not studied. The use of lentigo maligna diagnosis was not used by all dermatopathologists consistently. The degree of surrounding photodamage was not assessed. CONCLUSION: Subclinical extension of lentigo maligna and melanoma in situ are similar. Standard surgical excision of all melanoma in situ subtypes, including lentigo maligna, should include at least 9 mm of normal-appearing skin, which is similar to the amount recommended for early invasive melanoma. Lesions on the head and neck or those with a diameter greater than 1 cm may require even wider margins and are best treated with Mohs micrographic surgery. The perception that lentigo maligna has wider subclinical extension may be related to its frequent location on the head and neck, where photodamage can camouflage the clinical border.

Mohs micrographic surgery for melanoma: A prospective multicenter study.

BACKGROUND: Single-institution studies show that frozen section Mohs micrographic surgery (MMS) is an effective treatment modality for cutaneous melanoma, but no multi-institutional studies have been published. OBJECTIVE: To characterize the use of MMS in the treatment of melanoma at 3 academic and 8 private practices throughout the United States, to recommend excision margins when 100% histologic margin evaluation is not used, and to compare actual costs of tumor removal with MMS vs standard surgical excision. METHODS: Prospective, multicenter, cohort study of 562 melanomas treated with MMS with melanoma antigen recognized by T cells 1 immunostaining. RESULTS: Primary trunk and extremity melanomas (noninvasive and invasive melanoma) achieved histologically negative margins in 97% of tumors with 10-mm margins, whereas 12-mm margins were necessary to achieve histologically negative margins in 97% of head and neck melanomas. Overall average cost per tumor treated was $1328.46. LIMITATIONS: Nonrandomized and noncontrolled study. CONCLUSIONS: MMS with melanoma antigen recognized by T cells 1 immunostaining safely provides tissue conservation and same-day reconstruction of histologically verified tumor-free margins in a convenient, single-day procedure. When comprehensive margin evaluation is not used, initial surgical margins of at least 10 mm for primary trunk/extremity and 12 mm for head/neck melanomas should be used to achieve histologically negative margins 97% of the time.