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.

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.

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.

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.

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.

Mohs surgery for early-stage Merkel cell carcinoma (MCC) achieves local control better than wide local excision ± radiation therapy with no increase in MCC-specific death.

BACKGROUND: Merkel cell carcinoma (MCC) of the skin is most commonly treated with wide local excision (WLE) with or without adjuvant radiation therapy (RT). Mohs micrographic surgery (MMS) as monotherapy may offer an alternative treatment modality. The purpose of this study is to describe outcomes of patients with primary Stage I/II MCC treated with MMS alone and no RT. METHODS: A retrospectively collected sample of 56 MCCs treated with MMS was studied over an 18-year period. Tumor and treatment characteristics were described, and follow-up was assessed. RESULTS: A total of 56 primary Stage I/II MCCs in 53 patients were treated with MMS as monotherapy from April 2001 through July 2019. Patients were followed for an average of 4.6 years (median 2.7 years, range 0.8 to 16.9 years), of which 19 (33.9%) had follow-up of 5 years or more. There were no local recurrences due to inadequate excision. The 5-year Kaplan-Meier MCC-specific survival for AJCC8 Stage I and AJCC8 Stage IIA were 91.2% and 68.6%, respectively. CONCLUSION: In comparison to historical controls, Mohs surgery offers a survival that is at least as good as WLE +/- RT, with the added benefits of no need for adjuvant RT or the need for further surgery for treatment of local recurrence.

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.

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.

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.

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.

Clinical outcomes in high-risk squamous cell carcinoma patients treated with Mohs micrographic surgery alone.

BACKGROUND: There is little evidence to predict patient outcomes after the treatment of high-risk cutaneous SCC (hrSCC) using Mohs micrographic surgery (MMS). OBJECTIVE: We sought to report the rates of poor outcomes in patients with hrSCC treated by MMS alone and to determine if any specific clinical factors may be more predictive of these outcomes. METHODS: We conducted a retrospective chart review of all patients with hrSCC who were treated in our clinic between October 2011 and December 2015. RESULTS: We identified 647 hrSCC tumors that met the inclusion criteria. During the follow-up period, there were 19 local recurrences (2.9%), 31 nodal metastases (4.8%), 7 distant metastases (1.1%), and 7 disease-specific deaths (1.1%). Two factors, poor differentiation and invasion beyond the subcutaneous fat, were positively associated with local recurrence, nodal metastasis, and disease-specific death through multivariate analysis. CONCLUSIONS: Invasion beyond the subcutaneous fat and poor histologic differentiation may carry a greater risk of poor outcomes than other factors in hrSCC. MMS alone provides excellent marginal control with low rates of local recurrence, nodal metastasis, and disease-specific death.