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Archives of Dermatological Research
Published in: Archives of Dermatological Research 10/2018

01-12-2018 | Original Paper

Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers

Authors: Laura Cristina Gironi, Enrico Colombo, Barbara Pasini, Roberto Giorgione, Pamela Farinelli, Francesca Zottarelli, Elia Esposto, Elisa Zavattaro, Elias Allara, Paola Ogliara, Marta Betti, Irma Dianzani, Paola Savoia

Published in: Archives of Dermatological Research | Issue 10/2018

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Abstract

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.
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Metadata
Title
Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers
Authors
Laura Cristina Gironi
Enrico Colombo
Barbara Pasini
Roberto Giorgione
Pamela Farinelli
Francesca Zottarelli
Elia Esposto
Elisa Zavattaro
Elias Allara
Paola Ogliara
Marta Betti
Irma Dianzani
Paola Savoia
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 10/2018
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-018-1866-0

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