Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2023;13(4):e2023266 1 Publication Trends and Hot Topics in Dysplastic Nevus Research: A 30-Year Bibliometric Analysis Hazal Izol Özmen1 1 Department of Pathology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey Key words: dysplastic nevus, melanoma, bibliometric analysis, co-citation analysis, CiteSpace Citation: İzol Özmen H. Publication Trends and Hot Topics in Dysplastic Nevus Research: a 30-Year Bibliometric Analysis. Dermatol Pract Concept. 2023;13(4):e2023266. DOI: https://doi.org/10.5826/dpc.1304a266 Accepted: June 11, 2023; Published: October 2023 Copyright: ©2023 İzol Özmen. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Hazal İzol Özmen, Basaksehir Cam and Sakura City Hospital, Pathology Department, 34480, İstanbul/Turkey. Phone: 00905436922677 E-mail: hazalizol91@gmail.com Introduction: Dysplastic nevi are pigmented lesions that exhibit clinical and histological features of both common nevi and melanoma. In recent years, there has been an increase in publications on dysplastic nevi. Bibliometric analysis is a method of evaluating trends in large number of publications and identifying popular topics. Objectives: The objective of this study is to provide an overview of the landscape of publications related to dysplastic nevi, visualize trends and identify popular topics in the literature. Methods: Thomson Reuters’ Web of Science database was searched with the following query in title, abstract or keywords: TS = (“dysplastic nevus” OR “clark nevus” OR “atypical nevus” OR “dysplastic nevi” OR “clark nevi” OR “atypical nevi”). Time span was set to 1992-2022. Document type was set to Article. Titles, authors, abstracts, institutions, countries, journals, references, and the citation infor- mation were recorded. Results: Although the number of publications has declined over time, the USA remains the leading contributor to published articles. Key clusters of frequently used keywords were identified. The Jour- nal of the American Academy of Dermatology had the highest number of published titles. Country and journal analysis were supplemented by co-citation and co-cited reference cluster analysis. Burst analyses revealed authors like Kittler, Argenziano, and Gandini as significant contributors, with their works receiving strong citation bursts extending until the end of the study period. Conclusions: This bibliometric analysis revealed trends and interest pockets in the literature pertain- ing to dysplastic nevi and melanoma. This study aids in understanding the current research landscape and highlights potential future directions in this field. ABSTRACT 2 Review | Dermatol Pract Concept. 2023;13(4):e2023266 Introduction Dysplastic nevi are characterized by their large size (6 mm or more in diameter) and irregular, asymmetric, pigmented macules with varying colors. Clinically, these features may be similar to those of melanoma and a biopsy might be war- ranted to confirm the diagnosis [1,2]. Dysplastic nevus syndrome is characterized by a pro- pensity for the affected person to have a large number of nevi, which appear abnormal clinically and have histolog- ically dysplastic features. It was originally considered to be a hereditary condition; however, currently most cases are thought to occur sporadically or as a single isolated lesion [3]. The diagnosis of dysplastic nevus syndrome is significant because it suggests an increased risk for developing mela- noma, especially in those with the familial form of the syn- drome [4]. In the recent two decades, there has been increasing in- terest on the relationship and correlation between dysplastic nevi and melanoma. With a growing literature, while major trends are usually discernible, the smaller trends and pockets of interest or “hot topics” can be overlooked. Bibliometric analysis is a method of evaluating trends in large number of publications and making sense of the underlying data. This might be in the form of identifying popular topics or key- words and visualizing the network of citations, journals and other pertinent data. Objectives This paper aims to provide a robust overview of the field, identifying pivotal papers, influential authors, countries, journals and significant research themes. Methods Informed consent was not obtained for this study as only publicly available information was used. The search was conducted in Thomson Reuters’ Web of Science (WoS) data- base using the following criteria: TS = (“dysplastic nev*” OR “clark nev*” OR “atypical nev*”) in title, abstract or key- words. The document type was set to “Articles,” and the in- dexes were set to “SCI-EXPANDED.” The search was limited to articles published in English between 1992 and 2022. Du- plicate results were removed. A total of 1,404 unique articles were found. Titles, authors, abstracts, institutions, countries, journals, references, and citation information were recorded. The obtained data was imported to CiteSpace 6.1.R6, 64-Bit (Drexel University) [5] and VOSviewer 1.6.15 [6]. Keyword, authorship and citation burst analysis was per- formed. Network of keywords and organizations were an- alyzed and visualized with VOSviewer. Co-citation analysis and clustering was performed with CiteSpace. Clusters were analyzed with silhouette, centrality and sigma values, and labeled using different labeling methods (Latent Semantic Indexing (LSI), Log-Likelihood Ratio (LLR), Mutual Infor- mation (MI)). A p value of less than 0.05 was considered significant. Results Figure 1 shows the number of publications and citations per year from 1992 to 2022. Interestingly, the number of publi- cations appears to have decreased in recent years, with the lowest count of 22 in 2022 The linear regression analysis of the number of publications versus year yielded a nega- tive slope of -0.4117, suggesting a decrease in the number of publications over time (P < 0.01). Author keyword visualiza- tion was created using VOSviewer (Figure 2). Nine clusters of frequently used together keywords were identified. Country Analysis Table 1 displays the top 10 countries with the most pub- lished articles from the year 1992 to 2022. The USA stands out as the leading country in this regard, with a total of 676 published articles. This number is significantly larger than the number of articles published by any other country on the list, with Italy, the second-highest country, publishing 161 articles, or approximately a quarter of the number published by the USA. Figure 3 shows the top 10 countries with the strongest citation burst. The country with the highest strength of cita- tion burst was Canada, with a strength of 8.64 from 2007 to 2015. The most recent citation bursts were observed for Spain, Romania, France, and Poland, all persisting until the concluding date of this study. Journal Analysis The Journal of the American Academy of Dermatology leads with the highest number of published titles at 120. The Jour- nal of Cutaneous Pathology follows with 68 titles, and the Archives of Dermatology with 63 titles. Table 2 presents the top 10 most co-cited journals in terms of frequency. The Journal of the American Academy of Dermatology leads the list with 894, followed by Archives of Dermatology (JAMA Dermatology) with 825 and the Journal of Investigative Dermatology with 754. Notably, the British Journal of Cancer, despite having the lowest citation Review | Dermatol Pract Concept. 2023;13(4):e2023266 3 Figure 1. Number of publications and citations by year. Figure 2. Network map of author keywords. 4 Review | Dermatol Pract Concept. 2023;13(4):e2023266 Table 1. Top 10 most publishing countries between 1992-2022. Ranks Country No. of articles Centrality 1 USA 676 0.43 2 ITALY 161 0.24 3 GERMANY 86 0.28 4 CANADA 55 0.01 5 AUSTRALIA 54 0.07 6 NETHERLANDS 36 0.01 7 SPAIN 34 0.17 8 FRANCE 24 0.08 9 SWEDEN 20 0.00 10 AUSTRIA 18 0.01 Figure 3. Top 10 countries with the strongest citation bursts. Table 2. Top 10 most co-cited journals ranked according to co-citation counts. Ranks Co-citation count Journal Impact Factor (IF) 2021 Centrality 1 894 Journal of the American Academy of Dermatology 12.077 <0.01 2 825 Archives of Dermatology (JAMA Dermatology) 3.033 <0.01 3 754 Journal of Investigative Dermatology 7.590 <0.01 4 578 British Journal of Dermatology 11.113 <0.01 5 563 Cancer Research 13.312 0.01 6 516 Cancer 6.921 <0.01 7 506 Melanoma Research 3.199 <0.01 8 481 International Journal of Cancer 7.316 0.01 9 455 New England Journal of Medicine 176.079 0.01 10 381 British Journal of Cancer 9.082 0.02 frequency among the top 10 journals, has the highest cen- trality score (0.02), which indicates a relatively higher influ- ence or connectivity within the network. Co-Citation and Co-Cited Reference Cluster Analysis Co-citation analysis was performed using a scale factor (k) of 25. The validity of the references was checked to ensure accurate results. A total of 23,801 references (99.1337%) were deemed valid, while only 208 references (0.8663%) were invalid. The resulting merged network included 1,353 nodes and 5,402 links. The reference co-citation analysis revealed the central pa- pers in the field of melanoma research (Table 3). The paper of Gandini et al was the most cited and held the highest cen- trality, indicating its pivotal role in this research field. Paper of Landi et al and of Goldstein et al on high-risk melanoma susceptibility genes both had a centrality of 0.20, also em- phasizing their influential positions [7-9]. Clustering of the co-cited references revealed 21 clusters. The largest cluster (Cluster 0) centered on ‘melanocytic nevi’ included 130 articles from around 1990. Table 4 summa- rizes the characteristics of the clusters along with different Review | Dermatol Pract Concept. 2023;13(4):e2023266 5 Table 3. Reference co-citation analysis ranked by centrality. Ranks Co-citation count Centrality Year Lead author, title 1 26 0.24 2005 Gandini S, “Meta-analysis of risk factors for cutaneous melanoma” 2 10 0.20 2002 Landi MT, “DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma” 3 6 0.20 2006 Goldstein AM, “High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL” 4 4 0.20 2009 Chang YM, “A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes” 5 8 0.19 1998 Bataille V, “The association between naevi and melanoma in populations with different levels of sun exposure: a joint case-control study of melanoma in the UK and Australia” 6 20 0.17 1996 Zuo L, “Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma” 7 14 0.17 2002 Bishop DT, “Geographical variation in the penetrance of CDKN2A mutations for melanoma” 8 6 0.16 2009 Bishop DT, “Genome-wide association study identifies three loci associated with melanoma risk” 9 13 0.15 2013 Goldstein AM, “Dysplastic nevi and melanoma” 10 8 0.15 1999 Aitken J, “CDKN2A variants in a population-based sample of Queensland families with melanoma” Table 4. Top 10 Cluster groups with relevant characteristics according to keywords. Cluster Size Silhouette Label (LSI) Label (LLR, p-value) Label (MI score) Average Year 0 130 0.876 melanocytic nevi melanocytic nevi (213.09, p<0.001) different body site (0.88) 1990 1 122 0.85 melanocytic lesion melanocytic lesion (235.12, p<0.001) skin tumor (1.66) 2002 2 108 0.915 familial melanoma familial melanoma (423.98, p<0.001) familial melanoma mlm (0.79) 1992 3 108 0.875 familial melanoma cdkn2a mutation (163.4, p<0.001) cutaneous malignant melanoma risk (0.54) 2000 4 104 0.922 dysplastic nevi dysplastic nevus (156.51, p<0.001) clinical use (0.45) 2009 5 97 0.928 dysplastic nevi severe atypia (155.34, p<0.001) melanoma antigen (0.45) 2015 6 73 0.9 melanoma-prone families melanoma risk (142.34, p<0.001) cdkn2a-mutated melanoma families (0.3) 2005 7 72 0.92 high risk high risk (204.41, p<0.001) patient-initiated mobile teledermoscopy (0.34) 2011 8 59 0.908 cutaneous melanoma hereditary melanoma (187.53, p<0.001) chronic sun exposure (0.38) 1995 9 53 0.965 diagnosing skin diagnosing skin (84.42, p<0.001) telemedicine support (0.04) 2018 labeling methods. Figure 4 is a visual representation of the clusters with lighter colors indicating a more recent average year of references within the cluster. Table 5 presents the most cited member of each cluster. The top three publications with the highest sigma scores in the dataset were established. Topping the list is the study by Gandini et al. in 2005, titled “Meta-analysis of risk fac- tors for cutaneous melanoma,” with a sigma score of 20.45 6 Review | Dermatol Pract Concept. 2023;13(4):e2023266 Figure 4. Clustered network map of co-cited references with log-likelihood ratio labels. located in Cluster 6 [7]. Following closely is the publi- cation by Zuo in 1996, titled “Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma,” with a sigma score of 5.09 located in Cluster 2 [10]. Another significant publication, with a sigma score of 4.89 located in Cluster 1, is the study by Tucker in 1997, titled “Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma [11].” Cited Author Burst Analysis Figure 5 shows top 10 cited authors with the strongest cita- tion bursts. The author with the highest strength of burst is Gandini, with a strength of 28.08 from 2008 to 2022. The longest burst was by Argenziano and Kittler, lasting from 2006 to 2022, and 2004 to 2022, respectively. The most recent bursts are also by Argenziano, Kittler, and Gandini, continuing into the end date of the study. Discussion Dysplastic nevus, also called atypical or Clark nevus, can be precursor to melanoma, as the observation that 36% of melanomas have dysplastic nevi near the invasive tumor supports [12]. Signs that a dysplastic nevus may have tran- sitioned into a melanoma include asymmetry in contour, a noticeable increase in pigment variations, or a grayish tint indicating regression. These malignancies typically arise at a younger age (mid-thirties), are sometimes multiple, and are often found on the trunk [1]. Review | Dermatol Pract Concept. 2023;13(4):e2023266 7 Table 5. Top co-cited member of each cluster. Cluster Cluster Label Lead Author, Year,Title 0 melanocytic nevi Halpern AC, 1991, “Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma: a case-control study” 1 melanocytic lesion Tucker MA, 1997, “Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma” 2 familial melanoma Bal SJ, 1989, “Mapping the Gene for Hereditary Cutaneous Malignant Melanoma– Dysplastic Nevus to Chromosome Lp” 3 cdkn2a mutation Soufir N, 1998, “Prevalence of p16 and CDK4 Germline Mutations in 48 Melanoma- Prone Families in France” 4 dysplastic nevus Balch CM, 2009, “Final version of 2009 AJCC melanoma staging and classification” 5 severe atypia Elmore JG, 2017, “Pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study” 6 melanoma risk Gandini S, 2005, “Meta-analysis of risk factors for cutaneous melanoma” 7 high risk Vestergaard ME, 2008, “Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting” 8 hereditary melanoma Kelly JW, 1997, “A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance” 9 diagnosing skin Esteva A, 2017, “Dermatologist-level classification of skin cancer with deep neural networks” Figure 5. Top 10 authors with the strongest citation bursts. Molecularly, dysplastic nevi have a profile intermediate between benign nevi and malignant melanoma. There are certain described gene mutations that are present in dysplas- tic nevi and two genes – MC1R and BRAF - are present in the cluster analysis of our dataset. The melanocortin 1 re- ceptor (MC1R) gene encodes the receptor of melanocortin- stimulating hormone, which is found on the surface of mela- nocytes. MC1R phenotypic traits make an individual more susceptible to ultraviolet (UV) damage, leading to melanoma even without excessive UV exposure. People with MC1R gene variants tend to develop melanoma more frequently and at an earlier age than the general population. However, it is important to note that the risk of melanoma due to MC1R mutations is still lower than that associated with mutations in CDKN2A and CDK4 [13-14]. It is also shown that MC1R variants are strongly associated with BRAF mutations in non- chronic sun-induced damage melanomas [14,15]. The cluster timeline analysis shows that the co-cited refer- ences of both genes were popular in the same timeframe and relatively less popular since then. There has also been specific genetic findings on patients with dysplastic nevus syndrome, which dysplastic nevus syndrome is inherited as an autosomal dominant with in- complete penetrance. About 40% of families with the dys- plastic nevus syndrome have mutations in the CDKN2A gene [1,16,17]. A new gene linked to the development of atypical 8 Review | Dermatol Pract Concept. 2023;13(4):e2023266 a significant influence in the field. Furthermore, it also tops the list of the most co-cited journals. Interestingly, the cen- trality scores, reflective of influence and connectivity within the scientific network, present an intriguing contrast. De- spite high citation frequencies, the Journal of the American Academy of Dermatology, the Archives of Dermatology, and the Journal of Investigative Dermatology all show centrality scores of less than 0.01. In contrast, the British Journal of Cancer stands out with the highest centrality score (0.02) among the top 10 journals, despite having the lowest cita- tion frequency. One method used in bibliometric analysis is called “co-citation analysis”. Co-citation means citing of two sources by the same article. Since related literature is usually cited together, the network of co-cited sources can present a new angle in analyzing the underlying research trends. This makes it an excellent tool for unveiling the hidden structure and thematic patterns in a vast corpus of literature. Further- more, by analyzing centrality measures, it becomes possible to reveal the most influential works or ‘landmark’ papers in that field. In addition, co-citation analysis can help detect emerging trends and shifts in a scientific field by tracking changes in co-citation patterns over time, thus providing guidance in future research directions [24]. The co-citation and co-cited reference cluster analysis in this study provides critical insights into the key works and authors within melanoma research. In this context, centrality and sigma values provide unique perspectives, particularly when compared to traditional literature review methodol- ogies. Centrality is a metric used in network analysis that quantifies the importance of a node within the network. A work with a high centrality score is considered influential, not necessarily because of the frequency of citations, but due to its pivotal role in connecting various other works or researchers [25]. Sigma, on the other hand, is a metric in co-citation analysis that combines both the frequency of co-citation and the centrality of a work within the co-citation network. A high sigma value implies that a publication is both highly co-cited and centrally located in the co-citation network [26]. By examining Tables 3 and 4, a researcher can gain a clear understanding of the most influential papers and authors in the field, the key ideas that these papers intro- duced, and how these ideas have shaped the development and trajectory of the field. This can be invaluable for identi- fying research gaps, determining future research directions, and understanding the context and significance of one own research within the broader field. Burst analyses of countries and cited authors were per- formed in this study. In the traditional method of literature review, one of the metrics to understand the influence of a work is the total citation count, as more influential works are cited more often than others. However, since older nevi has also been found on the 7q21.3 chromosome, called CDK6 [18]. It has been shown that there is loss of heterozy- gosity in the p16INK4a and p53 genes in sporadic dysplastic nevi [19]. The patients with dysplastic nevus syndrome have increased risk of developing other malignancies such as pan- creatic cancer [13,20]. While there is a recognized connection between dysplas- tic nevi and melanoma, it’s crucial to note that only about 20% to 30% of melanomas evolve from preexisting nevi. The rate of a single nevus transforming into a malignant form is estimated to be less than 3 in 1000 annually. Given that the majority of dysplastic and typical nevi do not de- velop into melanoma, preventive removal of melanocytic nevi is not typically advised [21]. Presently, the understanding is that nevi with mild to moderate histological dysplasia are not direct precursors to melanoma and, hence, do not require re-excision if diagnosed through intended full (not partial) biopsies that remove the whole visible lesion. Nevertheless, nevi that exhibit severe dysplasia ought to be completely removed due to their shared histopathological characteristics with melanomas, which can potentially lead to diagnostic errors. There is ongoing debate regarding whether severe dysplastic nevi with just narrowly clear biopsy margins can be safely observed [21]. This paper aims to provide a robust overview of the field, identifying pivotal papers, influential authors, countries, journals and significant research themes using bibliometric techniques. Bibliometric analysis allows researchers to make sense of the large amount of data using scientific methods. It also provides points of view that traditional review of lit- erature cannot reveal. This study aimed to identify hotspots and popular topics in this area using bibliographic analysis. WoS by Thomson-Rheuters, Scopus by Elsevier and Google Scholar are the three mainly used databases literature and bibliometric research. However, the accuracy of the data presented by Google Scholar has been questioned [22]. WoS and Scopus are the main databases currently used for biblio- metric analysis and citation data [23], with WoS including articles before 2000 as well. With 676 published articles, the USA has been the most prolific contributor to the scientific literature during this pe- riod. Its centrality score of 0.43, the highest among the coun- tries examined, underscores the central role the USA plays in the global scientific collaboration network. The most recent citation bursts in Spain, Romania, France, and Poland reflect emerging trends in influential research from these countries. Observing these shifts in citation bursts could offer insights into evolving research strengths and future research trends, highlighting these countries as potential rising players in the international research landscape. Leading with the highest number of published titles, the Journal of the American Academy of Dermatology exhibits Review | Dermatol Pract Concept. 2023;13(4):e2023266 9 References 1. Calonje JE, Brenn T, Lazar AJ, Billings S. McKee’s Pathology of the Skin, 2 Volume Set E-Book. Elsevier Health Sciences; 2018:1234-1289. 2. Gardner JM. Survival guide to Dermatopathology. Innovative Pathology Press; 2020:106-109. 3. Barnhill RL. Current status of the dysplastic melanocytic ne- vus. J Cutan Pathol. 1991;18(3):147–159. DOI: 10.1111/j.1600 -0560.1991.tb00147.x. PMID: 1918502. 4. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma. Jama. 1997;277(18):1439–1444. PMID: 9145715. 5. Chen C. CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature. J Am Soc Inf Sci Technol. 2006;57:359–77. DOI: 10.1002/asi.20317. 6. Van Eck N, Waltman L. 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In this study, Bale and Cannonbright had the strongest citation bursts early on from 1992 to 2000. On the other hand, authors such as Kittler, Argenziano and Gandini continuing up until the end of the selected study date. This provides a temporal overview of the popularity of authors for researchers at a quick glance and suggests whose work is more relevant recently. Despite the effectiveness of bibliometric analysis, it is es- sential to be mindful of its limitations. First, the data derived from scientific databases such as Scopus and Web of Science can contain errors. These inaccuracies can influence any sub- sequent analysis. Furthermore, the very methodology of bib- liometrics poses inherent constraints. Specifically, drawing qualitative interpretations from bibliometric analysis can be misleading, given its fundamentally quantitative nature. As such, caution should be exercised when drawing qualitative inferences from bibliometric findings [25]. Conclusions The present bibliometric study provides a comprehensive overview of dysplastic nevi and melanoma research field over the past three decades. Despite a noticeable decrease in the number of publications over the years, the focus on this topic remains significant due to the established correla- tion between dysplastic nevi and melanoma. The US holds a central role in this field, contributing the highest number of publications, yet recent citation bursts in Spain, Roma- nia, France, and Poland indicate growing contributions from these countries. Co-citation analysis revealed influential works and au- thors in the field, with Gandini et al 2005 [7] paper holding the highest centrality, reflecting its pivotal role in the research landscape. Journals including the Journal of the American Academy of Dermatology, Archives of Dermatology, and Journal of Investigative Dermatology dominate the publish- ing sphere in this area. 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