Faculty Bibliography

Importance: The 31 gene-expression profiling test (31-GEP) has been shown to provide useful prognostic information in patients with cutaneous melanoma. The test dichotomizes patients into lower risk (Class 1) or higher risk (Class 2) for melanoma metastasis. Previous studies have demonstrated the clinical utility of the test in impacting dermatologists’ management decisions. Physician assistants and nurse practitioners (PA/NPs) account for a significant portion of dermatologic providers. The impact of a 31-GEP assay on clinical management has not been evaluated in this group.

BACKGROUND:Accuracy of US cancer statistics depends on physicians' knowledge of and adherence to reporting mandates. Significant knowledge and practice gaps have been documented in regards to melanoma reporting requirements. OBJECTIVE:To determine whether the gaps in dermatologists' knowledge and practice of melanoma reporting persist. MATERIALS AND METHODS/METHODS:The authors performed a survey of US dermatologists attending a national conference. The proportion aware of the melanoma reporting mandate and the proportion who routinely report newly diagnosed cases were calculated. RESULTS:Ninety-one percent (158/174) of those sampled completed the survey. Forty-nine percent correctly identified melanoma as being a disease of mandated reporting. Only 34% reported newly diagnosed cases to their state registry. Dermatologists seeing low melanoma volumes were less likely to routinely report newly diagnosed cases to registries than those seeing high volumes (22.9% vs 45.4%, p = .004). Those in practice for ≤10 years were less likely to be aware of the mandate than those in practice longer (32.6% vs 57.0%, p = .006). CONCLUSION/CONCLUSIONS:Most of the dermatologists remain unaware of melanoma reporting requirements. Resultant underestimates of the true incidence of melanoma could have resource allocation implications. Interventions aimed at improving knowledge of the mandate should focus on younger clinicians and those with lower melanoma case volumes.

Background and objectives: The incidence of cutaneous malignancy in the United States continues to rise. Mohs micrographic surgery is increasingly utilized to treat both nonmelanoma skin cancer (NSMC) and melanoma. This tissue-sparing method produces the highest cure rates while leading to an esthetic result. However, due to the need for intraoperative pathologic assessment, these procedures can be time-consuming and may average several hours. New technology aimed at more quickly assessing specimen margins for malignant cells has the potential to cut down on operative times and improve efficiency. Bioimpedance has been shown to be a promising method of detecting malignant cells in other cancers, specifically breast cancer and prostate cancer. The purpose of this study was to assess the ability of a novel ex vivo bioimpedance system (MarginScan; NovaScan, Milwaukee, Wisconsin) to detect malignant cells at the margins of removed NMSC Mohs specimens.
Method(s): A total of 151 specimens of NMSC removed during Mohs micrographic surgery were evaluated both using traditional pathologic methods and bioimpedance.
Result(s): Overall, 44/151 (29%) of specimens displayed positive margins by pathology and 45/151 (30%) margin specimens were probable, highly probable, or suspicious for malignant cells by bioimpedance. There were 2 false negative and 1 false positive results by the bioimpedance method, indicating an overall concordance rate of 98.0% between bioimpedance and pathologic assessment. The sensitivity and specificity of the bioimpedance method were 95.1% and 99.1%, respectively. The positive and negative predictive values were 97.7% and 98.1%, respectively.
Conclusion(s): Ex vivo measurement of bioimpedance in NMSC specimens removed during Mohs micrographic surgery appears to have a high rate of concordance for diagnosing margin positivity compared with traditional pathologic assessment. This technique may present a viable alternative to microscopic evaluation of positive margins in NMSC Mohs specimens.
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Background: Genetic evaluation of melanoma is becoming increasingly important. A 31-gene expression profiling (31-GEP) test (Decision-DX; Castle Biosciences, Friendswood, Texas) to predict metastatic risk in patients with cutaneous malignant melanoma (CMM) has previously been validated and is available for clinical use. The impact of this test on clinical decision making has been studied. However, little is known about which clinical factors impact dermatologists' decisions to utilize the test.
Objective(s): To determine which factors impact clinicians' decisions to utilize the 31-GEP test for metastatic risk stratification in patients with CMM. Design, setting, and participants: 181 dermatologists attending a national conference completed a series of questions based around four clinical vignettes using an audience response system. The vignettes and associated questions were designed to determine the impact of three factors-Breslow thickness, ulceration, and sentinel lymph node biopsy (SLNBx) status-on the decision to order the test.
Main Outcomes and Measures: Percentage of respondents who would order the 31-GEP test in the various clinical scenarios was quantified. Chi-squared testing assessed differences in the proportion of respondents who would order the test at baseline and in the presence of ulceration or a negative SLNBx.
Result(s): For tumors with a Breslow thickness >=0.5 mm, a majority of respondents reported that they would recommend the 31-GEP test. Ulceration was associated with a statistically significant increase in the percentage of clinicians who would recommend the assay for all but the thickest (>=2.1 mm) tumors. For a thin tumor (0.26 mm), the presence of ulceration changed the percentage of clinicians who would order the test from a minority to a majority (22% to 67%; P <.001). A negative SLNBx was only associated with a statistically significant increase in the percentage of clinicians who would recommend the test for the thinnest tumors (22% to 34%; P =.033). Conclusions and relevance: Ulceration appears to be the most important factor impacting clinicians when deciding to order the 31-GEP test. Despite the fact that 2/thirds of CMM patients who develop metastases initially have a negative SLNBx, negative SLNBx status does not seem to be a significant stimulus to ordering the test. Given this finding, future research should aim to better understand the reasons for choosing to use this technology in this SLNBx negative population.
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Background: More than 90% of ~2.5 million surgical biopsies performed to rule out melanoma in the U.S. alone are benign and classified as neither invasive melanomas nor melanomas in situ by histopathology. A recently described adhesive patch skin biopsy based noninvasive gene expression test (pigmented lesion assay; PLA) demonstrated utility and differentiated benign from malignant pigmented skin lesions with a test performance that exceeded visual inspection (VI) and a sensitivity that matching the criterion standard of dermatopathology. However, cost and outcome implications of using this molecular test versus VI have not been evaluated.
Objective(s): To determine potential cost savings and impact on outcome of PLA use versus VI in patients with pigmented cutaneous lesions suggestive of melanoma. Design and setting: Health economic analyses were performed from average U.S. insurance reimbursement values, comparing the real-world impact of the PLA with VI. Data sources were from published clinical validation and utility studies as well as from routine use of the test in U.S. dermatology practices, augmented by fee schedules of CMS.
Result(s): The biopsy ratio declined from 12.5 for VI to 2.4 for PLA use; correspondingly, the number needed to excise (NNE) declined from 2.85 for VI to 1.37 for PLA use. The 1.77-fold increase in specificity of PLA over VI also resulted in lower costs for initial biopsy ($211), subsequent excisions ($86), surveillance management ($77), and management of melanoma ($508). There was $31 average savings from avoidance of lost work productivity, and improvement in patient experience as assessed by quality adjusted life years (gain of 0.016 years). Conclusions and relevance: The higher accuracy of PLA use versus VI resulted in fewer unnecessary procedures and office visits, while not compromising early melanoma detection. The consequence effects are potentially reduced direct medical costs, reduced work productivity loss, and improved patient experience and care.
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Background: The topical adhesive 2-octyl cyanoacrylate has been used as an alternative to sutures for closure of skin in a variety of surgical procedures. While there have been benefits in terms of ease of application and cosmetic result, a high incidence of allergic contact dermatitis and exothermic reactions has been a barrier to use. Objectives. To investigate the feasibility of using a novel formulation of 2-octyl cyanoacrylate (Actabond-Bergen Medical Products, Morris Plains, New Jersey) for skin closure after surgical excision of cutaneous lesions.
Method(s): We examined the results of office-based surgical excision procedures using a novel formulation of 2-octyl cyanoacrylate for skin closure. Photographs were taken preoperatively, intraoperatively (open wound, before adhesive application, following adhesive application), and 2 weeks after surgery. At follow-up, all incisions were examined for cosmetic result, skin edge separation, erythema, and abscess formation. Patient satisfaction was also assessed.
Result(s): Ten lesions in 9 consecutive patients undergoing cutaneous excision by two surgeons were included in the study. The average age of included patients was 42. Lesions were excised from the trunk (6) and extremities (4). Lesion types included 3 dysplastic nevi, 3 sebaceous cysts, 3 lipomas, and 1 squamous cell carcinoma. At 2-week follow-up, all wounds were healed without any signs of dehiscence or infection. All wounds demonstrated esthetic closure without suture tracts. None of the patients developed allergic contact dermatitis or burns. On a 1-10 scale, respondents' average satisfaction with the method was 7.7. For patients who had previous skin suture closures, 83% preferred adhesive. Conclusion and relevance. A novel formulation of 2-octyl cyanoacrylate topical adhesive demonstrated feasibility as a potential alternative to the use of sutures for skin closure. In this small case series, all patients had an excellent esthetic result with no complications. Compared with previous iterations of 2-octyl cyanoacrylate, there were no allergic or exothermic reactions in this pilot series. Larger studies need to be performed to further determine advantages that may exist using this closure method compared with standard techniques.
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The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.