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.

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.

Performance of Staging Systems for Non-Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The performance of staging systems in non-head and neck cutaneous squamous cell carcinomas has not been well established. OBJECTIVE: To evaluate the performance of the American Joint Committee on Cancer 8th Edition and Brigham and Women's Hospital staging systems in non-head and neck squamous cell carcinomas. MATERIALS AND METHODS: Eligible tumors were identified and staged from an existing retrospective database. Cumulative incidence function curves of any poor outcome were generated. Distinctiveness, sensitivity, specificity, positive and negative predictive value, and concordance index were calculated. RESULTS: 1,042 primary tumors were included, with 38 resulting in any poor outcome and 16 in any major poor outcome. High-stage tumors represented 2.2% and 3.5% of tumors; these accounted for 10/38 of the poor outcomes (26.3%) and 8/16 of the major poor outcomes (50%). High-stage tumors predicted major poor outcomes with a sensitivity of 0.5 and specificity of 0.99 for the Brigham and Women's Hospital system, and a sensitivity of 0.5 and specificity of 0.97 for the American Joint Committee on Cancer 8th edition system. The concordance index for both was 0.74. CONCLUSION: Current staging systems can be used to predict poor outcomes in cutaneous squamous cell carcinomas off the head and neck.

Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review.

BACKGROUND: Imaging has been shown to impact management and disease outcomes in cutaneous squamous cell carcinoma, but the literature on optimal modalities is lacking. OBJECTIVE: To perform a systematic review evaluating the performance of various imaging studies for the detection of perineural spread, bony invasion, nodal metastasis (NM), and distant metastasis in cutaneous squamous cell carcinoma. MATERIALS AND METHODS: Four databases were searched for relevant terms. Articles were included if they presented primary data on 5 or more subjects with cutaneous squamous cell carcinoma who underwent imaging to detect perineural spread, bony involvement, NM, or distant metastasis. RESULTS: Thirty studies and 1,027 subjects were included in the pooled analysis. Magnetic resonance imaging had a 94.9% sensitivity in detecting perineural spread. Computed tomography (CT) demonstrated a sensitivity of 75.7% and specificity of 98.6% in detecting bony invasion. While ultrasound, positron emission tomography-computed tomography, and CT all performed reasonably well in detecting NM, CT demonstrated the highest sensitivity (96.4%) and specificity (100%). Imaging changed management in up to 33% of cases. CONCLUSION: Imaging is useful in high-risk cutaneous squamous cell carcinoma. Magnetic resonance imaging performs best in the detection of perineural spread, and CT is the most accurate modality to detect bony invasion and NM.

Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study.

BACKGROUND: Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage. OBJECTIVE: To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC. MATERIALS AND METHODS: A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome. RESULTS: There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group. CONCLUSION: Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.

Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins.

ABSTRACT: Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.

Metastatic Spiradenocarcinoma Managed With PD-1 Inhibition.

Spiradenomas are rare skin adnexal tumors, usually benign, appearing in early adulthood. The etiology of this tumor is still debated. The tumor suppressor gene CYLD, responsible for the Brooke-Spiegler syndrome, causes spiradenomas, trichoepitheliomas, and cylindromas. With time, spiradenomas can degenerate into aggressive spiradenocarcinomas. With only 117 malignant cases reported, treatment recommendations are based on case reports and expert opinion. There is no standard of care beyond surgical resection for localized disease and no guidelines for management of metastatic disease. With the advent of immunotherapy and PD-1 inhibition, we present the first reported case of a metastatic spiradenocarcinoma managed with pembrolizumab.

Safety and Efficacy of Oral Benzodiazepines for Periprocedural Anxiolysis: A Systematic Review.

BACKGROUND: Oral benzodiazepines (BZDs) are useful tools for periprocedural anxiolysis. The United States Food and Drug Administration (FDA) recently issued a black-box warning of their risks of abuse and dependence. We performed a systematic review evaluating the safety and efficacy of oral BZDs for periprocedural anxiolysis in outpatient dermatologic, plastic surgery, dental, and ophthalmologic procedures performed under local anesthesia. METHODS: A systematic review of 5 databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Oral benzodiazepine safety and efficacy data were extracted from eligible articles. RESULTS: A total of 43 articles and 4,060 subjects were included. Oral BZDs consistently imparted a positive anxiolytic effect and demonstrated superior or equivalent scores in patient satisfaction, surgeon satisfaction, pain, and anxiety to comparator groups in most studies. Thirty-five subjects experienced transient hypoxia, and 2 experienced transient hypertension. A total of 195 mild, self-limited adverse effects were reported. None of the studies addressed the risks of abuse and dependence in this clinical setting. CONCLUSION: Short-term use of oral BZDs for periprocedural anxiolysis seems to be safe and effective. The 2020 FDA black-box warning should not deter their appropriate use in dermatologic surgery and other low-risk outpatient procedures.

Utility of Debulk Specimens During Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Limited literature exists regarding whether intraoperative analysis of frozen debulk specimens during Mohs micrographic surgery (MMS) improves identification of high-risk features (HRF) of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: Primary: identification of new HRF on debulk specimens. Secondary: CSCC upstaged after considering debulk data. MATERIALS AND METHODS: A single-center, retrospective cohort study of patients with biopsy-proven CSCC treated by MMS with intraoperative frozen debulk analysis. Restricted (poor differentiation, new perineural invasion ≥0.1 mm, and Breslow depth >6 mm) and nonrestricted (any worsened tumor differentiation, any new perineural invasion, and Breslow depth >2 mm) analyses were performed. RESULTS: In restricted analysis, 3.94% of cases had 1 new HRF on debulk analysis. In nonrestricted analysis, 32.9% of cases had ≥1 new HRF; 7.6% increased by 2 HRF. Approximately 2.0% of cases were upstaged by American Joint Committee on Cancer system, eighth edition criteria, 1.4% by Brigham and Women's Hospital. Tumor size ≥2 cm, male sex, and moderate differentiation on biopsy were significantly associated with new HRF identified on debulk analysis. CONCLUSION: Intraoperative frozen debulk analysis can reveal HRF of CSCC not seen on biopsy or MMS stages, particularly among tumors ≥2 cm. American Joint Committee on Cancer system, eighth edition T2 tumors were most likely to be upstaged. Identification of new HRF on debulk analysis can improve CSCC staging and may impact patient treatment and follow-up.

Characterization of the 2019 Micrographic Surgery and Dermatologic Oncology Standardized Letter of Recommendation.

BACKGROUND: Traditional letters of recommendation used for postgraduate medical training applications have multiple limitations, including a lack of clarity, inflated and overly flattering assessments, and low reliability between interpreting faculty. A micrographic surgery and dermatologic oncology (MSDO) standardized letter of recommendation (SLOR) was created to improve the efficiency, validity, and stratification of applicants to dermatology fellowship training programs. OBJECTIVE: To analyze the MSDO SLOR for trends in grading based on letter-writer and applicant characteristics and to evaluate its ability to demonstrate differences between applicants. METHODS: Standardized letter of recommendations received by 4 fellowship programs from the 2019 San Francisco Match application cycle were reviewed retrospectively. RESULTS: Two hundred forty-nine SLORs were analyzed from 140 applicants. Grade inflation and limited variability in scores were evident. Higher scores correlated with the length of the relationships between letter-writers and applicants and with female letter-writer gender. There was no applicant gender or ethnicity bias detected. CONCLUSION: Despite score inflation, the MSDO SLOR allows for differentiation between fellowship applicants. Future studies are needed to further evaluate the reliability of the SLOR and find ways to improve its content.

Preferences for Prophylactic Oral Antibiotic Use in Dermatologic Surgery: A Multicenter Discrete Choice Experiment.

BACKGROUND: Antibiotics are often prescribed after dermatologic surgery for infection prophylaxis, but patient preferences about prophylactic antibiotics are not well understood. OBJECTIVE: To understand patient preferences about taking antibiotics to prevent surgical site infection (SSI) relative to antibiotic efficacy and antibiotic-associated adverse drug reactions. MATERIALS AND METHODS: Multi-center, prospective discrete choice experiment (DCE). RESULTS: Three hundred thirty-eight respondents completed the survey and DCE. 54.8% of respondents preferred to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (1% risk gastrointestinal upset, 0.5% risk itchy skin rash, 0.01% risk emergency department visit). Even if an antibiotic could eliminate SSI risk (0% risk SSI) and had a low adverse drug reaction profile, 26.7% of respondents prefer not to take prophylactic oral antibiotics. CONCLUSION: Risk-benefit thresholds for taking antibiotics to prevent SSI vary widely. Clinical trials are needed to better characterize the effectiveness and risks of oral antibiotic SSI prophylaxis to guide decision-making. Future studies should also evaluate whether shared decision-making can improve the patient experience.

Postoperative Infections in Dermatologic Surgery: The Role of Wound Cultures.

BACKGROUND: Dermatologic surgery is associated with low postoperative infection rates, averaging from approximately 1% to 4.25%. Often, postoperative infections are treated empirically based on clinical diagnosis of infection, given it can take 48 to 72 hours for a wound culture to identify a pathogen. OBJECTIVE: We aimed to evaluate the efficacy of empiric antibiotics in dermatologic surgery postoperative infections and if wound cultures change postoperative antibiotic therapy. METHODS: A 7-center, retrospective analysis of postoperative infections, with culture data, in dermatologic surgery patients was performed. RESULTS: Of 91 cases of clinically diagnosed postoperative infection, 82.4% (n = 75) were successfully treated with empiric oral antibiotics (95% confidence interval [0.73-0.89], p < .0001). In 16 (17.6%) cases, initial empiric antibiotics were unsuccessful, and wound culture results altered antibiotic therapy in 9 cases (9.9%) with 6 (6.6%) of these cases requiring additional coverage for methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: Empiric antibiotic treatment is usually appropriate for patients with postoperative surgical-site infections with wound cultures altering antibiotic management in a minority of cases. When empiric antibiotics fail, lack of MRSA coverage is usually the cause; therefore, providers should be aware of local MRSA prevalence and susceptibilities.

Examining the Relevance to Patients of Complications in the American College of Mohs Surgery Registry: Results of a Delphi Consensus Process.

BACKGROUND: Surgical registries are valuable tools for tracking outcomes. Incorporating patient input allows registries to address the interests of this important stakeholder group. OBJECTIVE: The aim of this study was to identify a list of "patient-selected complications" and to explore the relevance to patients of previously published physician-identified complications. METHODS: Delphi process with 2 rounds using patients to identify complications that are highly relevant for tracking by the proposed American College of Mohs Surgery (ACMS) National Registry. RESULTS: Complications that physicians identified as highly relevant (death from any cause, hospitalization related to the procedure, functional loss attributable to surgery, bleeding requiring a second procedure, and surgical site infection) were each rated as highly relevant by patients. Patients also identified scarring, recurrence, and wound dehiscence as highly relevant outcomes for registry tracking. CONCLUSION: Incorporating patient input into the ACMS registry design process identified 2 additional complication outcomes to be considered for inclusion within the registry-wound dehiscence and scarring. Patient input also corroborated the relevance of complications previously identified by ACMS physicians for inclusion in the registry. Furthermore, the importance of tracking local recurrence was confirmed from a patient-centered perspective.