1. INTRODUCTION
The estimated cost to the healthcare system to detect one melanoma is approximately $32594, which is largely due to the high biopsy rate of benign lesions. 1 One systematic review and meta‐analysis found that the number needed to treat to identify one melanoma was 22.62 for primary care providers and 9.60 for dermatology providers. 2 Pigmented lesion assays (PLA, “adhesive patch tests”), which are intended to be used on suspicious pigmented lesions that exhibit ≥1 ABCD criteria, noninvasively detect the presence of three genes associated with melanoma (LINC00518, PRAME, and TERT). PLAs have the potential to decrease the skin biopsy burden with a reported sensitivity of 91%–97% and negative predictive value (NPV) ≥99%. 3 , 4 Another tool used in pigmented skin lesion triage, the modified dermoscopy three‐point checklist (3PC), which includes asymmetry, round structures, and blue color, has been shown to have a sensitivity of 96.3% when employed by novice dermoscopists. 5
2. METHODS
Our retrospective case–control study aimed to compare the sensitivities and NPVs of PLA‐testing and the 3PC in the context of suspicious pigmented lesions. We also investigated associations among PLA results, ABCD criteria, and 3PC features. Data was collected from April 2021 to August 2022 from an academic‐tertiary level center.
3. RESULTS
Of 510 total PLA cases, 67 were quantitatively insufficient, meaning that there was not enough genetic material to run the test, and 443 returned with a definitive result. Of those with a definitive PLA result, 117 were biopsied and 34 were melanoma (Table 1). Of the 34 biopsy‐proven melanomas, 12 were PLA− (Table 1). Based on our preliminary results, the PLA test's sensitivity and NPV for melanoma was 64.7% and 96.9%, respectively, when non‐biopsied clinically stable lesions were included as true negatives.
TABLE 1.
Pigmented lesion assays (PLA) results of pigmented lesions that underwent biopsy
| All lesions that underwent PLA testing, excluding QNS | Lesions that underwent PLA‐testing and had associated clinical and dermoscopy photos | |
|---|---|---|
| Melanoma (MM) | ||
| PLA+ (% of MM) | 22 (65%) | 20 (65%) |
| PLA− (% of MM) | 12 (35%) | 11 (35%) |
| Total (% of all biopsied lesions) | 34 (29.1%) | 31 (29.8%) |
| Non‐melanoma skin cancer (NMSC) | ||
| PLA+ (% of NMSC) | 2 (100%) | 2 (100%) |
| PLA− (% of NMSC) | 0 (0%) | 0 (0%) |
| Total (% of all biopsied lesions) | 2 (1.7%) | 2 (1.9%) |
| Atypical melanocytic nevi (AMN) | ||
| PLA+ (% of AMN) | 15 (43%) | 15 (50%) |
| PLA− (% of AMN) | 20 (57%) | 15 (50%) |
| Total (% of all biopsied lesions) | 35 (29.9%) | 30 (28.9%) |
| Benign on biopsy | ||
| PLA+ (% of benign) | 21 (46%) | 18 (44%) |
| PLA− (% of benign) | 25 (54%) | 23 (56%) |
| Total (% of all biopsied lesions) | 46 (39.3%) | 41 (39.4%) |
| All biopsied lesions | ||
| PLA+ (% of all biopsied lesions) | 60 (51.3%) | 55 (52.9%) |
| PLA− (% of all biopsied lesions) | 57 (48.7%) | 49 (47.1%) |
| Total (% of all biopsied lesions) | 117 (100%) | 104 (100%) |
| Not biopsied, clinically stable | ||
| PLA+ (% of not biopsied) | 0 (0%) | 0 (0%) |
| PLA− (% of not biopsied) | 326 (100%) | 289 (100%) |
| Total count (% of not biopsied) | 326 (100%) | 289 (100%) |
| Total | ||
| PLA+ (% of all lesions) | 60 (13.5%) | 55 (14.0%) |
| PLA− (% of all lesions) | 383 (86.5%) | 338 (86.0%) |
| Total count (% of all lesions) | 443 (100%) | 393 (100%) |
Overall, 393 of the 443 PLA cases with definitive results and 104 of the 117 biopsied cases had associated clinical and dermoscopy images (Table 1). Of the 31 melanomas, all exhibited ≥1 3PC feature (Table 2). The sensitivity and NPV of the dermoscopy 3PC for melanoma were both 100% when non‐biopsied clinically stable lesions were included as true negatives.
TABLE 2.
ABCD and dermoscopy three‐point checklist criteria of biopsied lesions with pigmented lesion assays (PLA) results
| PLA result | ≥1 ABCD criteria | Clinical asymmetry | Irregular borders | Multiple colors | Diameter ≥6 mm | ≥1 dermoscopy three‐point checklist criteria | Asymmetry on dermoscopy | Round structures | Blue structures | |
|---|---|---|---|---|---|---|---|---|---|---|
| MMs | ||||||||||
| PLA+ (n = 20) | 95% (n = 19) | 75% (n = 15) | 70% (n = 14) | 75% (n = 15) | 80% (n = 16) | 100% (n = 20) | 95% (n = 19) | 50% (n = 10) | 30% (n = 6) | |
| PLA− (n = 11) | 91% (n = 10) | 55% (n = 6) | 45% (n = 5) | 64% (n = 7) | 64% (n = 7) | 100% (n = 11) | 82% (n = 9) | 9% (n = 1) | 36% (n = 4) | |
| All MMs (n = 31) | 94% (n = 29) | 68% (n = 21) | 61% (n = 19) | 71% (n = 22) | 74% (n = 23) | 100% (n = 31) | 90% (n = 28) | 35% (n = 11) | 32% (n = 10) | |
| AMNs | ||||||||||
| PLA+ (n = 14) | 87% (n = 13) | 60% (n = 9) | 67% (n = 10) | 67% (n = 10) | 60% (n = 9) | 100% (n = 15) | 100% (n = 15) | 20% (n = 3) | 20% (n = 3) | |
| PLA− (n = 16) | 73% (n = 11) | 47% (n = 7) | 33% (n = 5) | 53% (n = 8) | 47% (n = 7) | 87% (n = 13) | 73% (n = 11) | 33% (n = 5) | 20% (n = 3) | |
| All AMNs (n = 30) | 80% (n = 24) | 53% (n = 16) | 50% (n = 15) | 60% (n = 18) | 93% (n = 28) | 93% (n = 28) | 87% (n = 26) | 27% (n = 8) | 20% (n = 6) | |
| Benign | ||||||||||
| PLA+ (n = 18) | 61% (n = 11) | 44% (n = 8) | 33% (n = 6) | 33% (n = 6) | 56% (n = 10) | 100% (n = 18) | 89% (n = 16) | 39% (n = 7) | 28% (n = 5) | |
| PLA− (n = 23) | 91% (n = 21) | 43% (n = 10) | 26% (n = 6) | 43% (n = 10) | 61% (n = 14) | 96% (n = 22) | 91% (n = 21) | 39% (n = 9) | 26% (n = 6) | |
| All benign (n = 41) | 78% (n = 32) | 44% (n = 18) | 29% (n = 12) | 39% (n = 16) | 59% (n = 24) | 98% (n = 40) | 90% (n = 37) | 39% (n = 16) | 27% (n = 11) | |
| Not biopsied, clinically stable | ||||||||||
| PLA− (n = 289) | 79.9% (n = 231) | 49.1% (n = 142) | 48.4% (n = 140) | 46.0% (n = 133) | 52.6% (n = 152) | 95.5% (n = 276) | 87.2% (n = 252) | 33.2% (n = 96) | 11.1% (n = 32) | |
Abbreviations: AMN, atypical melanocytic nevi; MM, melanoma.
Significantly, only 9% of PLA− melanomas exhibited round structures on dermoscopy, whereas 50% of PLA+ melanomas included round structures (p = 0.023) (Table 2). There was no significant difference in ABCD criteria or other 3PC criteria between PLA+ and PLA− melanomas.
4. DISCUSSION
Those who are nonexperts in skin cancer detection may find themselves over‐relying on PLA results, which can lead to delayed diagnosis of provider‐selected skin lesions of concern, given that based on our preliminary results, the PLA test's sensitivity for melanoma was 26.3%–32.3% lower than previously reported values. 3 , 4 The PLA test was negative in 35% of biopsy‐proven melanomas and over half of AMNs. These lesions would be mismanaged if the provider only took into account the PLA result. Fortunately, the dermoscopy 3PC can easily be employed even by nonexpert dermoscopy users and serve as an additional screening tool when monitoring lesions that return PLA−, especially in lesions that lack round structures in dermoscopy. Our study's results confirmed the high sensitivity of the dermoscopy 3PC, which has been previously reported. 5 Pairing PLA testing with simple dermoscopy criteria such as the 3PC can improve pigmented lesion triage and monitoring, even by nonexperts.
The external validity of this study is limited by the small sample size of biopsied lesions and variability among providers reading clinical and dermoscopy images. Future studies are required to explore the utility of more specific dermoscopy features being used for the selection of lesions appropriate for PLA‐testing and monitoring of suspicious lesions with negative PLA results. Additionally, identifying dermoscopy features that may be associated with LINC00518, PRAME, and TERT positivity may help better select lesions for testing.
CONFLICTS OF INTEREST
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Ludzik J, Becker AL, Lee C, Witkowski A. Augmenting pigmented lesion assay results with the three‐point dermoscopy checklist to improve pigmented lesion triage. Skin Res Technol. 2022;28:877–879. 10.1111/srt.13205
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.