Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas originating from peripheral nerves (1). Approximately 50% of patients with MPNST also have neurofibromatosis type 1 (NF1), often due to malignant transformation from plexiform neurofibroma (2, 3). Like most sarcomas, MPNST has a high probability of local recurrence and metastatic spread. Unfortunately, no targeted therapies have proven effective to date, resulting in a relatively poor prognosis (4).

Previous studies found that deletion of the CDKN2A gene is the most common secondary mutation based on NF1 loss, followed by TP53 mutation (3, 5). In addition, PRC2, SUZ12, and EED mutation is also frequently observed in MPNST, and loss of H3K27me3 contributes to MPNST progression (6). These clues reveal the potential treatment of BRD4 and BET inhibition in MPNST (7).

Many researchers have provided new insights into MPNST since the onset of the 20th century. Yearly, many articles are published about MPNST, exploring and demonstrating clinical management, the tumorigenesis mechanism, and candidate molecular targets. However, no bibliometric analyses of MPNST-related studies have been published to date. It is vital for researchers and surgeons to be aware of the qualitative and quantitative characteristics of influential research in MPNST so that they can contextualize their clinical practices and aid in shaping future research. As a result, we conducted a bibliometric analysis of the MPNST literature to provide narrative synthesis and evaluate research trends.

An analysis of bibliometric indicators indicated the research trends in this area and enabled the detection of changes, which will not only provide scientific guidance for future research work but also help us understand more about MPNST recently. The present study investigated 1400 publications from 2000 to 2022. As a relatively rare tumor, it is not surprising that few papers have been published on MPNST. However, inspiringly, the number of published articles has significantly increased. Compared to 2000, the number of articles published in 2021 is about five times higher. Consequently, the field of MPNST is currently gaining research attention. There was a downward trend in the average number of citations per article in MPNST, but this is not an accurate representation of article quality. Citations are more likely to increase with longer time after publication.

Among MPNST researchers, American authors dominate both article production and citations. However, Mautner (University Medical Center Hamburg-Eppendorf) was the author who published the most articles and received the most citations. What is more, he also led the H-index, G-index, and M-index. Clearly, his research has been highly productive as well as profound in its impact. Carroll and Perry are the second and third most productive authors. Among the top 10 high-impact authors, two are from University Medical Center Hamburg-Eppendorf, and two are from the University of California-San Francisco. Research in MPNST has been greatly enriched by those institutions.

With regards to number of publications, the USA dominates the list by a long way. In addition, they have the most experience in multi-country cooperation. Among the top 10 most productive countries, India and Korea are most likely to publish research by authors from a single country. It is likely that this multi-country collaborative research will become a trend and make a more significant contribution to MPNST research in the future.

Modern Pathology published 69 MPNST articles leading all other journals. Cancer Research received 877 citations and was the top-cited journal, while PNAS had the highest average citations per publication (237.50) with only two publications on MPNST. That is mainly attributed to the article titled “tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors” published in PNAS in 2005. This article was cited 446 times and has become the second most cited MPNST article since 2000. It is encouraging to note that by analyzing the productive and highly cited journals in MPNST, we found that most of the top 10 journals in MPNST are in the JIF Q1 division, including well-known and influential journals like Nature Genetics (IF: 41.307) and Journal of Clinical Oncology> (IF:50.717). As a result, much attention is being focused on MPNST-related research.

Compared to other bibliometric analyses in oncology (11–13), most of the research also analyzed the productive authors, relevant institutions, preferred journals, and high-citation articles to summarize the research trend. However, MPNST is a relatively rare tumor and a gain of knowledge from a small number of cases is limited. Institutions focused on the treatment of MPNST have the advantage of more extensive clinical data and biobanking. Cooperation with those outstanding institutions could be helpful. MPNST research led and influenced by these institutions will probably be the trend and will help to further discover the pathogenesis and predictive factors important for the prognosis in this rare disease.

Using neutral conjunction of top keywords and literature, the following research hotspots were identified:

1) Tumorigenesis in MPNST: MPNST still lacks a specific treatment because its mechanisms are unclear. Thus, finding the trigger genes for MPNST tumorigenesis is vital for discovering new therapies. Berghmans et al. demonstrated in 2005 that mutant tp53 zebrafish develop MPNST, and this paper became the second most cited publication in MPNST since 2000 (9). Lee et al. found PRC2 is recurrently inactivated through EED or SUZ12 loss in MPNST (6). Patel discovered that inhibition of the BET bromodomain triggers apoptosis in MPNST (14).

2) Clinical management: De Raedt et al. observed that NF1 microdeletion patients have an elevated risk of MPNST (2), and Tucker et al. reported a similar trend (15). Zou et al. analyzed 140 MPNST patients (72 were NF1-related, 68 were sporadic) and found MPNST ≥10 cm at diagnosis, partial resection, and metastasis development were significant negative predictors (16). Mautner et al. showed the difference in MRI between neurofibroma and MPNST (17). Warbey et al. indicated the value of [F-18]FDG PET/CT in diagnosing MPNST (18). Hagel et al. found patients were significantly younger at diagnosis (p < 0.001) and had a significantly shorter survival time than sporadic patients (19).

3) Predictive biomarkers: Zhang et al. performed genome-wide or targeted sequencing on 50 cases. Of the 50 cases, 16 MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation (20). Prieto-Granada et al. assessed 68 MPNST biospecimens and concluded that H3K27me3 has good sensitivity and robust specificity for diagnosing MPNST (21). Endo et al. found that p-mTOR and p-S6RP were both indicators of poor prognosis (22).

The bibliometric analysis helped improve understanding the research trends and hot spots in MPNST, and the visual presentation clarified the collaboration between authors and institutions. Moreover, our analysis of hotspot burst time and highly cited articles will provide further insights into the MPNST research and guide future research ( Figure 6 ). Despite its strengths, the study does have some limitations. First, unless an article is included in the WOS database, it will not be included in this analysis. Since this analysis is based on the WOS database, more convenience is provided, but some of the detail was sacrificed in the process. Additionally, we searched for articles containing MPNST in the title, so some MPNST research publications might be overlooked if the term does not appear in their titles. The suggestion of cooperation institutions should not simplify ranked by the number of publications or citations, because each institution has respective interests, strengths and weaknesses. The recommendation needs to be judged upon the situation.

A steady increase in the number of publications on MPNST was observed from 2000 to 2022. The most influential author is Mautner (University Medical Center Hamburg-Eppendorf). The USA, Japan, and China were the three most productive countries. The journal Modern Pathology features the most MPNST publications, while those in the journal Cancer Research were the most frequently cited. The University of Texas MD Anderson Cancer Center may be a good partner to collaborate with. Recent research trends in MPNST have focused on tumorigenesis, clinical management, and predictive biomarkers.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

CG and XjH designed the experiments; XfH and ZF performed the Bibliometric Analysis; QG and SW check the data; JW and YS performed visualization in data; XfH wrote this manuscript. All authors contributed to the article and approved the submitted version.