Faculty Bibliography

Cutaneous surgery has become critical to comprehensive dermatologic care, and dermatologists must therefore be equipped to manage the risks associated with surgical procedures. As complications may occur at any point along the continuum of care, assessing, managing and preventing risk from beginning to end becomes essential. This review focuses on preventing surgical complications pre- and post-operatively as well as during the surgical procedure.

The growth of molecular technologies analyzing skin cells and inherited genetic variations has the potential to address current gaps in both diagnostic accuracy and prognostication in melanoma patients or in individuals at risk for developing melanoma. In part II of this continuing medical education article, novel molecular technologies are reviewed. These have been developed as adjunct tools for melanoma management and include the Pigmented Lesion Assay (PLA), myPath Melanoma, and DecisionDx-Melanoma tests, and genetic testing in patients with a strong familial melanoma history. These tests are commercially available and marketed as ancillary tools for clinical decision-making, diagnosis, and prognosis. Here we review fundamental principles behind each test, discuss peer-reviewed literature assessing their performance, and highlight the utility and limitations of each assay. The goal of this article is to provide a comprehensive, evidence-based foundation for clinicians regarding management of patients with difficult pigmented lesions.

Managing the balance between accurately identifying early stage melanomas while avoiding obtaining biopsy specimens of benign lesions (ie, overbiopsy) is the major challenge of melanoma detection. Decision making can be especially difficult in patients with extensive atypical nevi. Recognizing that the primary screening modality for melanoma is subjective examination, studies have shown a tendency toward overbiopsy. Even low-risk routine surgical procedures are associated with morbidity, mounting health care costs, and patient anxiety. Recent advancements in noninvasive diagnostic modalities have helped improve diagnostic accuracy, especially when managing melanocytic lesions of uncertain diagnosis. Breakthroughs in artificial intelligence have also shown exciting potential in changing the landscape of melanoma detection. In the first article in this continuing medical education series, we review novel diagnostic technologies, such as automated 2- and 3-dimensional total body imaging with sequential digital dermoscopic imaging, reflectance confocal microscopy, and electrical impedance spectroscopy, and we explore the logistics and implications of potentially integrating artificial intelligence into existing melanoma management paradigms.

BACKGROUND:The American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared to the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared to AJCC7. METHODS:We analyzed a cohort of 1,315 prospectively enrolled patients. We assessed primary tumor and nodal classification of stage I-III patients using AJCC7 and AJCC8 to assign disease stages at diagnosis. We compared recurrence-free (RFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. We then compared concordance indices of discriminatory prognostic ability and area under the curve (AUC) of 5-year survival to predict RFS/OS. All statistical tests were two-sided. RESULTS:Stage IIC continued to have worse outcomes than those for stage IIIA patients, with 5-year RFS of 26.5% (95%CI=12.8-55.1%) vs. 56.0% (95%CI=37.0-84.7%) by AJCC8 (P = 0.002). For stage I, removing mitotic index as T classification factor decreased its prognostic value, although not statistically significantly (RFS C-index=0.63 [95%CI=0.56-0.69] to 0.56 [95%CI=0.49-0.63], P = 0.07; OS C-index=0.48 [95%CI=0.38-0.58] to 0.48 [95%CI=0.41-0.56], P = 0.90). For stage II, prognostication remained constant (RFS C-index=0.65 [95%CI=0.57-0.72]; OS C-index=0.61 [95%CI=0.50-0.72]), and. For stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index=0.65 [95%CI=0.60-0.70] to 0.70 [95%CI=0.66-0.75], P = 0.01). CONCLUSIONS:Compared with AJCC7, we demonstrate that AJCC8 enables more accurate prognosis for patients with stage III melanoma. Restaging a large cohort of patients can enhance the analysis of active clinical trials.

Despite major improvements in combatting metastatic melanoma since the advent of immunotherapy, the overall survival for patients with advanced disease remains low. Recently, there is a growing number of reports supporting an "obesity paradox," in which patients who are overweight or mildly obese may exhibit a survival benefit in patients who received immune checkpoint inhibitors. We studied the relationship between body mass index and progression-free survival and overall survival in a cohort of 423 metastatic melanoma patients receiving immunotherapy, enrolled and prospectively followed up in the NYU Interdisciplinary Melanoma Cooperative Group database. We analyzed this association stratified by first vs. second or greater-line of treatment and treatment type adjusting for age, gender, stage, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, number of metastatic sites, and body mass index classification changes. In our cohort, the patients who were overweight or obese did not have different progression-free survival than patients with normal body mass index. Stratifying this cohort by first vs. non-first line immunotherapy revealed a moderate but insignificant association between being overweight or obese and better progression-free survival in patients who received first line. Conversely, an association with worse progression-free survival was observed in patients who received non-first line immune checkpoint inhibitors. Specifically, overweight and obese patients receiving combination immunotherapy had a statistically significant survival benefit, whereas patients receiving the other treatment types showed heterogeneous trends. We caution the scientific community to consider several important points prior to drawing conclusions that could potentially influence patient care, including preclinical data associating obesity with aggressive tumor biology, the lack of congruence amongst several investigations, and the limited reproduced comprehensiveness of these studies.

Background/Objectives/UNASSIGNED:Although total body skin examination (TBSE) is the primary screening mechanism for melanoma, there is no consensus on which anatomic sites a screening TBSE should include. We sought to establish which anatomic sites are examined during routine (>90%) TBSEs of patients at high risk for skin cancer. Methods/UNASSIGNED:A Google survey was emailed to 173 international dermatologist skin cancer specialists. Results/UNASSIGNED:More than 75% of participants reported routinely examining the scalp, ears, face and neck, trunk, breasts, inframammary areas, axillae, extremities, palms and soles, nails, interdigital spaces, and buttocks. The least frequently inspected anatomic sites included genitalia, with male genitalia more frequently examined than female (penis n = 39; 52%; labia majora n = 21; 28%; P = 0.003), the perianal region (n = 26; 34.7%), and the ocular conjunctiva and oral mucosa (n = 35; 46.7%). Participants cited not screening these areas because of perceived patient discomfort, low prevalence of malignancy, and the expectation that other specialists examine the area. Conclusions/UNASSIGNED:The role of routine surveillance of neglected anatomic sites is unclear and warrants further discussion weighing potential mortality benefit against the incidence of melanoma in obscure sites, morbidity of intervention in sensitive sites, cost-effectiveness, and potential for patient discomfort.

IMPORTANCE/OBJECTIVE:Dermoscopic triage algorithms have been shown to improve beginners' abilities for identifying pigmented skin lesions requiring biopsy. OBJECTIVE:To estimate the diagnostic accuracy of the Triage Amalgamated Dermoscopic Algorithm (TADA) for pigmented and nonpigmented skin cancers. Secondarily, to compare TADAs performance to those of existing triage algorithms for the identification of pigmented skin cancers. DESIGN/METHODS:Cross-sectional, observational, reader study that took place at a beginner and intermediate level dermoscopy course. PARTICIPANTS/METHODS:Two hundred medical professionals of various specialties attended the course and 120 voluntarily joined the study (60% participation rate). EXPOSURES/UNASSIGNED:After receiving basic dermoscopy training, participants evaluated 50 polarized, dermoscopic images of pigmented (22 benign, 18 malignant) and nonpigmented (1 benign, 9 malignant) skin lesions using TADA. Pigmented lesions were also evaluated using the Three-Point Checklist and AC Rule. With TADA, participants first determined if a lesion was an unequivocal angioma, dermatofibroma, or seborrheic keratosis, which would exclude it from further evaluation. All other lesions were assessed for architectural disorder, starburst pattern, blue-black or gray color, shiny white structures, negative network, ulcer/erosion, or vessels. Any one feature indicated suspicion for malignancy. RESULTS:Most participants were dermatologists (n=64, 53.3%) or primary care physicians (n=41, 34.2%), and many lacked previous dermoscopy training (n=52, 43.3%). TADA's sensitivity and specificity for all skin cancers was 94.6% (95% CI=93.4-95.7%) and 72.5% (95% CI=70.1-74.7%), respectively. For pigmented skin cancers, the sensitivity and specificity were 94.0% (95% CI=92.9-95.0%) and 75.5% (95% CI=73.8-77.2%). This compared to 71.9% (95%CI=69.8-73.9%) and 81.4% (95%CI=79.7-83.0%) for the Three-Point Checklist and 88.6% (95%CI=87.1-89.9%) and 78.7% (95%CI=76.9-80.3%) for the AC Rule. CONCLUSIONS:These results suggest that TADA compares favorably to existing triage algorithms and might be a useful triage tool with high sensitivity and specificity for pigmented and nonpigmented skin cancers. Further studies are needed to validate these preliminary observations.