Dysplastic nevi with severe atypia: Long-term outcomes in patients with and without re-excision

Engeln, Kathleen; Peters, Kaitlin; Ho, Jonhan; Jedrych, Jaroslaw; Winger, Daniel G.; Ferris, Laura K.; Patton, Timothy

doi:10.1016/j.jaad.2016.08.054

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…[2][3][4] While some melanomas do arise within dysplastic nevi, the majority do not, and some propose that routine re-excision of all SDN may not be necessary. 5,6 Improved ability to stratify the malignant potential in these borderline lesions could spare patients unnecessary procedures.…”

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confidence: 99%

Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses

et al. 2020

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Background: Strategies to non-invasively detect cutaneous melanoma generally focus on differentiating melanoma from non-melanoma lesions. However, given the variabilities in practice and lack of guidelines, it is important for clinicians to understand how such strategies and technologies perform on borderline lesions of uncertain clinical behavior. Objective: To evaluate LINC and PRAME gene expression and the presence of somatic mutations in BRAF, NRAS, and/or TERT in severely dysplastic nevi (SDN) and to assess, how combining gene expression and mutation analyses may impact test performance.Materials and Methods: One hundred three eligible skin lesions clinically suspicious for melanoma were non-invasively sampled via adhesive patches to enable genomic analyses. Afterward, these same lesions were immediately surgically biopsied to enable comparisons of genomic analyses with histopathologic diagnoses rendered by a panel of three dermatopathologists. Twenty-three of these lesions analyzed were deemed borderline lesions of SDN histology by at least one dermatopathologist. RNA-based gene expression positivity by Pigmented Lesion Assay (PLA) analysis was defined by detectable levels of LINC and/or PRAME. DNA-based mutation positivity was defined as detection of somatic mutations in BRAF (non-V600E), NRAS, and/or the TERT promoter. Results: Adding TERT mutation analyses to PLA gene expression increases the test’s sensitivity to rule out melanoma from 93% to 97% in this study. In addition, 61% of PLA positive lesions that were not diagnosed as melanoma were found to have severe histologic atypia. PLA-positive lesions histopathologically diagnosed as melanomas harbored TERT mutations in 70% of cases while both SDN and non-melanoma lesions including nevi without severe histologic atypia harbored TERT mutations in 4% of cases. BRAF non-V600E and NRAS mutations were only found in the melanoma group and adding these mutations did not further enhance the test’s sensitivity. Conclusions and Relevance: PLA positivity increases with histologic atypia of pigmented skin lesions. Combining TERT mutation analyses with melanoma-associated gene expression provides additional genetic information to further non-invasively risk-stratify pigmented lesions. These findings furthermore support that pigmented lesions exist on a spectrum of genomic atypia that may prove useful in identifying borderline lesions beyond their morphological appearance.

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confidence: 99%

Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses

et al. 2020

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“…In Engeln et al . that evaluated exclusively HDN with severe atypia, two (1%) patients were diagnosed with melanoma upon re‐excision and none developed metastatic melanoma at follow‐up of 10 years . In Fleming et al ., among mild‐to‐moderate HDN with a mean follow‐up of 5·5 years (range 14 to 93 years), six of the 304 (2%) in the observation developed melanoma .…”

Section: Resultsmentioning

confidence: 99%

“…Only one study was not conducted in the U.S.A. (it was in New Zealand). More than half (seven of 12, 58%) of the included studies had primary outcomes focused on the development of melanoma at the site of HDN biopsy, with a third of studies assessing recurrence of HDN (four of 12, 33%), and one study assessing both outcomes (one of 12, 8%) . Half of the studies did not provide any demographic information about the study population …”

Section: Resultsmentioning

confidence: 99%

“…The duration of follow‐up time was not specified at all in a quarter of the studies, a minimum duration of follow‐up was specified in three studies (at least 2 years; at least 5 years) and a maximum duration of follow‐up was specified in part of one study (less than 5 years) . When quantified, follow‐up was less than 5 years (range 2–16 weeks; mean 3·56 years, range 1·17–8·72 years) in two studies, it was between 5 and 10 years in two studies (mean ± SD 5·5 ± 4·6 years; mean 6·17 years, range 5·03–9·78 years) and greater than 10 years in two studies (median 11·9 years, interquartile range 9–14·8 years; mean 17·4 years, range: 0–29·9 years).…”

Section: Resultsmentioning

confidence: 99%

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Surgical re-excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes

et al. 2018

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“…Given the above considerations, the histopathologic diagnosis of a dysplastic nevus impacts patient management. While it is generally accepted that mildly atypical dysplastic nevi which do not resemble melanoma do not require further treatment [ 7 ], recent studies have shown low recurrence rates of dysplastic nevi with moderate atypia and positive histologic margins [ 9 , 11 ] and of dysplastic nevi with severe atypia [ 12 ], thus suggesting that re-excision may not be required [ 9 , 11 , 12 ]. Others advocate an upfront clear margin policy in the re-excision of dysplastic nevi with a margin biopsy of 2.0 mm [ 13 ] or with complete shave removal with clear margins [ 14 ].…”

Section: The Re-excision Controversymentioning

confidence: 99%

The “Dysplastic Nevus” Conundrum: A Look Back, a Peek Forward

Stefanato

2018

Dermatopathology

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Dysplastic nevi with severe atypia: Long-term outcomes in patients with and without re-excision

Cited by 16 publications

References 22 publications

Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses

Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses

Surgical re-excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes

The “Dysplastic Nevus” Conundrum: A Look Back, a Peek Forward

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