Genomic Analysis Aids in the Management of Dermoscopically Atypical Pigmented Lesions.

BACKGROUND: Numerous melanoma-specific dermoscopic features have been described in invasive melanomas, while fewer features are found in melanoma in situ (MIS) and atypical nevi (ATN). Consensus regarding which features are critical for the differentiation of MIS from ATN has not been reached. PURPOSE: Determine 1) whether there are dermoscopic features that differentiate early MIS from ATN, and 2) whether non-invasive assessment of genomic biomarkers (LINC00518 and PRAME) can aid in patient management. METHODS: From 2018 to 2023, 56 melanomas were evaluated for 5 clinical and 13 dermoscopic features and melanoma-associated genomic biomarkers. Two groups of ATN with positive and negative genomic biomarkers were randomly selected for comparison. RESULTS: All melanomas in this study expressed one or both melanoma-associated genomic markers. MIS had an average of 3.90 (range, 2-7) of the 13 dermoscopic features, while invasive melanomas had an average of 4.44 (range, 3-6). Sixteen of 40 (40%) MIS and 3 of 16 (18.8%) invasive melanomas had 3 or fewer dermoscopic features. These findings were comparable to those observed in both ATN groups. The most common dermoscopic features were absent or diminished pigment network, regression structures, and granularity. This combination of features was most helpful in identifying lesions for genomic testing. CONCLUSIONS: Clinical and dermoscopic features alone could not differentiate MIS from ATN. Non-invasive genomic testing helped differentiate lower from higher-risk lesions and aid in clinical management decisions. Genomic testing was particularly helpful in patients with large numbers of lesions with several being considered for biopsy based on clinical and dermoscopic examination. J Drugs Dermatol. 2024;23(9):717-723. doi:10.36849/JDD.8454.

Corrigendum: Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large US registry study.

The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.

Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study.

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.

Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions.

About 3 million surgical pigmented skin lesion biopsies are performed each year in the USA alone to diagnose fewer than 200 000 new cases of invasive melanoma and melanoma in situ using the current standard of care that includes visual assessment and histopathology. A recently described noninvasive adhesive patch-based gene expression rule-out test [pigmented lesion assay (PLA)] may be helpful in identifying high-risk pigmented skin lesions to aid with surgical biopsy decisions. The main objective of this utility study was to determine the real-world clinical performance of PLA use and assess how the PLA changes physician behavior in an observational cohort analysis of 381 patients assessed with the PLA. All (100%) of 51 PLA(+) test results were clinically managed with surgical biopsy. Of these, 19 (37%) were melanomas, corresponding to a number needed to biopsy of 2.7 and a biopsy ratio of 1.7. All melanomas were histopathologically classified as melanoma in situ or stage 1. Nearly all (99%) of 330 PLA(-) test results were clinically managed with surveillance. None of the three follow-up biopsies performed in the following 3-6 months, were diagnosed as melanoma histopathologically. The estimated sensitivity and specificity of the PLA from these data sets are 95 and 91%, respectively. Overall, 93% of PLA results positive for both LINC00518 and PRAME were diagnosed histopathologically as melanoma. PRAME-only and LINC00518-only lesions were melanomas histopathologically in 50 and 7%, respectively. The PLA alters clinical management of pigmented lesions and shows high clinical performance. The likelihood of positive histopathologic diagnosis of melanoma is higher in PLA results that are positive for both LINC00518 and PRAME.

Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy.

Importance: Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. Objective: To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions. Design, Setting, and Participants: In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015. Interventions: Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided. Main Outcomes and Measures: Biopsy sensitivity and specificity with vs without PLA data. Results: Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P < .001) with PLA data. Conclusions and Relevance: The noninvasive PLA enables dermatologists to significantly improve biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.

Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians.

Skin cancer most commonly affects Caucasians and rarely affects individuals of African, Asian, Latin-American, and American-Indian descent. Although skin cancer is rare in these groups, the diagnosis may be associated with significant morbidity and mortality. Many factors may account for this discrepancy. Skin cancers in these groups may have atypical presentations. Melanoma usually involves areas not exposed to the sun, including palmoplantar skin and mucosal surfaces with the acral lentiginous melanoma being the most common histologic subtype. Basal cell carcinomas may involve sun-exposed areas such as the head and neck, while squamous cell carcinomas tend to involve unexposed areas in these groups. Because of the low index of suspicion in both the medical community and the ethnic groups, diagnosis is often delayed resulting in an advanced presentation and a worse prognosis.

A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris.

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.

Advanced presentation of melanoma in African Americans.

BACKGROUND: Melanoma in African Americans is rare, and the diagnosis is often delayed, leading to advanced presentation and poor prognosis. OBJECTIVE: The purpose of this retrospective study is to determine whether African American patients diagnosed with melanoma at the Washington Hospital Center were initially seen with more advanced disease than white patients. METHODS: A retrospective chart review was performed on 36 African American patients who were diagnosed and/or treated for melanoma at the Washington Hospital Center between 1981 and 2000. Data obtained included patient age at presentation, sex, Breslow's depth and histologic subtype, stage at presentation, and tumor location. These data were compared with information obtained from white patients with melanoma during this period. RESULTS: A total of 649 African American and white patients were treated for melanoma at the Washington Hospital Center between 1981 and 2000. Of these, 36 (6.1%) patients were African American. African American patients were more likely to initially be seen with stage III/IV disease (32.1%) compared with (12.7%) the white patients initially seen with these disease stages. Of the white patients 60.4% were initially seen with melanoma in situ/stage I disease compared with 39.3% of the African American patients. The 5-year survival rate was 58.8% in African Americans compared with 84.8% in whites. CONCLUSIONS: In our series, African Americans are more likely than whites to be initially seen with advanced disease and have a subsequent worse prognosis. Physician training and patient education campaigns are crucial to improving the poor prognosis associated with melanoma in the African American community.