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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

ABSTRACT: In this retrospective review of 100 patients with primary invasive acral melanoma, we examined whether narrow-margin excision is warranted for acral melanoma. Patients treated with surgical margins recommended by the National Comprehensive Cancer Network (R-group) were compared to those treated with narrow margins (N-group). A total of 65 patients underwent narrow-margin excision. Positive margin status or local recurrence rarely occurred regardless of the excision margins, whereas fatal events frequently occurred, particularly among the patients with T4 melanoma. The mortality rates of N- and R-group with T1-3 melanomas were similar (1.36 and 1.28 per 100 person-years, respectively). However, patients with T4 melanoma treated with narrow-margin excision had a higher mortality rate (11.44 vs. 5.03 per 100 person-years). Kaplan-Meier analyses showed a worse prognosis in the N-group (p = 0.045) but this group had thicker Breslow thickness (4.21 mm vs. 2.03 mm, p = 0.0013). A multivariate analysis showed that Breslow thickness was an independent risk factor, but surgical margin was not a risk factor for melanoma-specific survival or disease-free survival. In conclusion, although we could not find a difference between the narrow-margin excision and recommended-margin excision in this study, we suggest following current recommendations of guidelines. Our study warrants the prospective collection of data on acral melanoma to better define the prognosis of this infrequent type of melanoma.

SUBMITTER: Ito T

PROVIDER: S-EPMC7408916 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

Ito Takamichi T Kaku-Ito Yumiko Y Wada-Ohno Maiko M Furue Masutaka M

Journal of clinical medicine 20200716 7

In this retrospective review of 100 patients with primary invasive acral melanoma, we examined whether narrow-margin excision is warranted for acral melanoma. Patients treated with surgical margins recommended by the National Comprehensive Cancer Network (R-group) were compared to those treated with narrow margins (N-group). A total of 65 patients underwent narrow-margin excision. Positive margin status or local recurrence rarely occurred regardless of the excision margins, whereas fatal events ...[more]

PMID: 32708762

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Project description:BackgroundAcral melanoma is a rare type of melanoma that affects world populations irrespective of skin color and has worse survival than other cutaneous melanomas. It has relatively few single nucleotide mutations without the UV signature of cutaneous melanomas, but instead has a genetic landscape characterized by structural rearrangements and amplifications. BRAF mutations are less common than in other cutaneous melanomas, and knowledge about alternative therapeutic targets is incomplete.MethodsTo identify alternative therapeutic targets, we performed targeted deep-sequencing on 122 acral melanomas. We confirmed the loss of the tumor suppressors p16 and NF1 by immunohistochemistry in select cases.ResultsIn addition to BRAF (21.3%), NRAS (27.9%), and KIT (11.5%) mutations, we identified a broad array of MAPK pathway activating alterations, including fusions of BRAF (2.5%), NTRK3 (2.5%), ALK (0.8%), and PRKCA (0.8%), which can be targeted by available inhibitors. Inactivation of NF1 occurred in 18 cases (14.8%). Inactivation of the NF1 cooperating factor SPRED1 occurred in eight cases (6.6%) as an alternative mechanism of disrupting the negative regulation of RAS. Amplifications recurrently affected narrow loci containing PAK1 and GAB2 (n = 27, 22.1%), CDK4 (n = 27, 22.1%), CCND1 (n = 24, 19.7%), EP300 (n = 20, 16.4%), YAP1 (n = 15, 12.3%), MDM2 (n = 13, 10.7%), and TERT (n = 13, 10.7%) providing additional and possibly complementary therapeutic targets. Acral melanomas with BRAFV600E mutations harbored fewer genomic amplifications and were more common in patients with European ancestry.ConclusionOur findings support a new, molecularly based subclassification of acral melanoma with potential therapeutic implications: BRAFV600E mutant acral melanomas with characteristics similar to nonacral melanomas that could benefit from BRAF inhibitor therapy, and non-BRAFV600E mutant acral melanomas. Acral melanomas without BRAFV600E mutations harbor a broad array of therapeutically relevant alterations. Expanded molecular profiling would increase the detection of potentially targetable alterations for this subtype of acral melanoma.

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Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

Publications

Narrow-Margin Excision for Invasive Acral Melanoma: Is It Acceptable?

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