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Castillo PAuthorCastrejón NAuthorTeixido CAuthorMontironi CAuthorGarcía-Herrera AAuthorAlbero RAuthorMatas JAuthorPuig SAuthorAlos LCorresponding Author

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November 24, 2023
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Combined WNT-activated deep penetrating/plexiform melanocytoma: insights into clinicopathological and molecular characterization

Publicated to:Clinical And Experimental Dermatology. 49 (4): 356-363 - 2024-03-21 49(4), DOI: 10.1093/ced/llad405

Authors: Castillo, Paola; Castrejon, Natalia; Marginet, Marta; Massi, Daniela; Alamon, Francesc; Teixido, Cristina; Montironi, Carla; Garcia-Herrera, Adriana; Albero-Gonzalez, Raquel; Matas, Jessica; Puig, Susana; Alos, Llucia

Affiliations

August Pi & Sunyer Biomed Res Inst IDIBAPS - Author
August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. - Author
European Org Res & Treatment Canc EORTC, Melanoma Grp - Author
Hosp Clin Barcelona, Dept Dermatol - Author
Hosp Clin Barcelona, Dept Opthamol - Author
Hosp Clin Barcelona, Dept Pathol - Author
Univ Barcelona - Author
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Abstract

Background A combined deep-penetrating tumour redefined as WNT-activated deep-penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses. Objectives To review the clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms. Methods The study included 51 patients with combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available) and histological characteristics were reviewed. Immunohistochemistry for β-catenin, LEF1, HMB45, Ki67, p16 and PRAME (preferentially expressed antigen in melanoma) was performed. Atypical forms underwent next-generation sequencing (NGS) panel analysis, including driver genes implicated in DPMs, TERT-promoter (p) mutations and the investigation of the 9p21 locus via fluorescence in situ hybridization. Results Among the 51 patients (32 females and 19 males, age range 4–74 years), 68% with available clinical data (15/22) were initially suspected of having melanoma. Except for one patient, complete excision resulted in no recurrences or metastases. One patient who had an incompletely excised combined DPM developed a lymph node melanoma metastasis 10 years later. In the 51 patients, 10 samples (20%) showed atypical histological features; 7 (14%) exhibited a significant loss of p16 expression; and 2 (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in 11 patients revealed a double mutation BRAFV600E and exon 3 CTNNB1; no TERTp mutations were detected. Conclusions Clinical suspicion of melanoma is common in combined DPMs, but malignant progression is infrequent in tumours lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumours or melanocytomas. © The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved.

Keywords

3-(3,5-dichlorophenyl)-1-methyl-2,5-pyrrolidinedioneAdolescentAdultAgedAntigens, neoplasmBeta cateninBraf geneChildChild, preschoolChromosome 9pClinical featureControlled studyCtnnb1 geneDeep penetrating plexiform melanocytomaEpiluminescence microscopyExcisionFemaleFluorescence in situ hybridizationGeneGene mutationGeneticsHigh throughput sequencingHistopathologyHumanHuman tissueHumansImmunohistochemistryIn situ hybridization, fluorescenceKi 67 antigenKi-67 antigenLymph node metastasisLymphatic metastasisLymphoid enhancer factor 1Major clinical studyMaleMelanocytomaMelanomaMetabolismMiddle agedMutationNevus, epithelioid and spindle cellPathologyPrame protein, humanPreschool childProliferation indexPromoter regionProtein expressionProtein p16Retrospective studyReviewSkin neoplasmsSkin tumorSpitz nevusSuccinimide derivativeSuccinimidesTelomerase reverse transcriptaseTumor antigenWnt proteinYoung adult

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Clinical And Experimental Dermatology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 18/94, thus managing to position itself as a Q1 (Primer Cuartil), in the category Dermatology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.15, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-07, the following number of citations:

  • WoS: 2
  • Scopus: 2
  • Europe PMC: 1

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 8.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Belgium; Italy.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Castillo Fernández, Paola Cecilia) and Last Author (Alos Hernandez, Llucia).

the author responsible for correspondence tasks has been Alos Hernandez, Llucia.