Faculty Bibliography

Survival outcomes in melanoma, and their association with mutations in the telomerase reverse transcriptase (TERT) promoter, remain uncertain. In addition, few studies have examined whether these associations are affected by a nearby common germline polymorphism, or vary based on melanoma histopathological subtype. We analyzed 408 primary tumors from a prospective melanoma cohort for somatic TERT^-124[C>T] and TERT^-146[C>T] mutations, the germline polymorphism rs2853669, and BRAF^V600 and NRAS^Q61 mutations. We tested the associations between these variants and clinicopathologic factors and survival outcomes. TERT^-124[C>T] was associated with thicker tumors, ulceration, mitoses (>0/mm²), nodular histotype and CNS involvement. In a multivariable model controlling for AJCC stage, TERT^-124[C>T] was an independent predictor of shorter recurrence-free survival (RFS) (HR=2.58, p=0.001), and overall survival (HR=2.47, p=0.029). Patients with the germline variant and TERT^-124[C>T] mutant melanomas had significantly shorter RFS than those patients lacking either or both sequence variants (p<0.04). The impact of the germline variant appeared to be more pronounced in superficial spreading compared to nodular melanoma. No associations were found between survival and TERT^-146[C>T], BRAF or NRAS mutations. These findings strongly suggest that TERT^-124[C>T] mutation is a biomarker of aggressive primary melanomas, an effect that may be modulated by rs2853669.

BACKGROUND:MoleMap NZ is a novel New Zealand based store-and-forward telemedicine service to detect melanoma. It utilizes expert review of total body photography and close-up and dermoscopic images of skin lesions suspicious for malignancy. OBJECTIVE:The purpose of this study was to assess the effectiveness of MoleMap NZ as a melanoma early detection program. METHODS:We conducted a review of 2,108 melanocytic lesions recommended for biopsy/excision by MoleMap NZ dermoscopists from January 2015-December 2016. RESULTS:Pathologic diagnoses were available for 1,571 lesions. Of these, 1,303 (83%) lesions were benign and 260 (17%) lesions were diagnosed as melanoma, for a melanoma-specific benign-to-malignant ratio of 5.0 to 1. The number-needed-to-biopsy one melanoma was 6. Among melanomas with available tumor thickness data (n=137), 92% were <0.8mm (range: in situ - 3.1mm), with in-situ melanomas comprising 74%. LIMITATIONS/CONCLUSIONS:Only lesions recommended for excision were analyzed. Pathology results were available for 75% of these cases. Tumor thickness data was available for 53% of melanomas diagnosed. CONCLUSION/CONCLUSIONS:This real-world study of MoleMap NZ, a community-based teledermoscopy program, suggests that it has the potential to increase patients' access to specialist expertise via telemedicine. Additional studies are needed to more accurately define its efficacy.

A diagnosis of late stage melanoma is associated with significant mortality. From a public health perspective, knowledge of geographic disparities in late-stage diagnoses can inform efforts to facilitate the diagnosis of earlier stage, highly curable melanomas. We conducted a county-level analysis of melanoma in New York State to identify communities that may benefit from pilot health interventions to reduce the burden of late stage melanoma. From 1995 to 2016, late-stage melanoma incidence increased from 1.5 to 2.8 cases/100,000 in NY State. We found statistically significant associations between decreased county-level health system access (including physician density and resident educational status), and increased county incidence and proportion of late-stage disease among diagnosed cases (p<0.001 for both). Increased county-level socioeconomic status (SES), (including measures of resident wealth and medical insurance status), was positively associated with greater late-stage incidence (p<0.001). However, decreased county-level SES was positively associated with a greater proportion of late-stage disease among cases at diagnosis (p=0.009). Counties with reduced access to physician services and lower SES may be suitable for pilot interventions promoting recognition and diagnosis of early stage melanomas to reduce late stage diagnoses and associated mortality.

Nevisense is an FDA-cleared device to aid in diagnosing melanoma. Using a non-invasive probe, the device measures electrical impedance spectroscopy (EIS) of target skin lesions. While EIS has demonstrated high sensitivity in diagnosing melanoma, its impact on a clinician's diagnostic confidence remains unknown. We conducted a pilot study evaluating whether the addition of EIS scores to clinical and dermoscopic images increases diagnostic confidence, accuracy, sensitivity, and specificity for students and dermatologists when evaluating lesions clinically suspicious for melanoma. Three pigmented lesions specialists and three 4^th year medical students completed an online survey to evaluate 34 melanocytic lesions suspicious for melanoma. For each lesion, participants provided their diagnosis, biopsy recommendation, and confidence in diagnosing a lesion as benign or malignant based on history and clinical and dermoscopic images, and again after receiving an EIS score. Addition of EIS scores increased mean biopsy sensitivity for melanoma/severe dysplastic nevi (DN) from 70% to 84% (p =.014) and mean diagnostic accuracy from 74% to 86% (p =.005). Mean diagnostic confidence increased for 29/34 lesions, of which 26 were accurately diagnosed by >=4 evaluators. Increases in diagnostic confidence were significant for common melanocytic nevi, DN, and melanoma, for both students and dermatologists (all p <.05). Use of EIS may increase clinicians' confidence to provide greater reassurance regarding dermoscopically equivocal lesions such as DN. EIS thus has the potential to help clinicians better alleviate patients' anxieties during skin exams. EIS may also improve management of melanocytic lesions suspicious for melanoma among novice and expert diagnosticians, though further investigation is needed to determine if these findings translate to clinical settings. NB: All authors except for Ms. Fried are team members for a separate study utilizing a Nevisense device, loaned to NYU by Scibase.
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