Abstract
To the Editor,
Acanthosis nigricans (AN) is a skin condition that causes dark, velvety plaques to appear on the body, most often in intertriginous areas such as the neck, axillae, groin, infra-mammary regions. 1 It is most commonly associated with insulin resistance and observed in patients with diabetes, obesity, or metabolic syndrome. 2 It can also be caused by hormonal disorders such as polycystic ovarian syndrome, autoimmune diseases like Hashimoto’s thyroiditis, genetic conditions, and certain drugs. 3 Although AN is frequently linked to many benign disorders, in rare situations, it may be of paraneoplastic nature and suggest the presence of an undiagnosed malignancy. 4 Therefore, in otherwise unexplained cases, its appearance should merit a full oncologic evaluation. We thus contribute to the literature by performing a contemporary systematic review of occurrences of paraneoplastic AN.
Our systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO. A search of PubMed, MEDLINE, Embase databases was performed on April 15, 2025 using relevant search terms and synonyms (Supplementary Table 1). The paraneoplastic nature of each AN case was based on author attribution. Primary research in describing paraneoplastic AN while providing sufficient clinical information was included (Supplementary Figure 1). Two independent reviewers each screened potential articles against the inclusion criteria, and 3 authors extracted data.
After the removal of duplicate titles, we identified a total of 1392 unique studies, with 205 ultimately meeting all inclusion criteria. These articles reported on 219 patients, of which 105 (48.0%) were female (Supplementary Table 2). The mean age of these patients was 54.7 ± 15.7 years. A total of 20 unique locations of solid primary neoplasms were documented, with gastric (31, 14.2%) and lung (31, 14.2%) cancers being the most frequently associated with paraneoplastic AN (Supplementary Table 3). Hematological malignancies including lymphomas (11, 5.0%) and, more rarely, leukemias (2, 0.9%) have also been linked to AN. Similarly to benign AN, paraneoplastic AN most commonly affects intertriginous areas such as the neck (141, 64.4%), axillae (165, 75.3%), inframammary folds (60, 27.4%), and inguinal folds (94, 42.9%). Most cases of paraneoplastic AN appeared prior to the discovery of the underlying malignancy (148, 67.6%), with a mean interval of 11.3 ± 12.8 months between AN appearance and cancer diagnosis. Paraneoplastic AN often mirrored the tumor’s evolution pattern such as progressing with tumor progression (25, 11.4%), regressing with tumor regression (64, 29.2%), or reappearing upon tumor recurrence (11, 5.0%). While the exact pathogenesis of paraneoplastic AN remains unknown, it is hypothesized that malignant cells secrete tumor-derived growth factors that stimulate epidermal cell proliferation, which results in hyperkeratosis and papillomatosis. 5
The main limitations of this article are the retrospective nature of literature reviews, the heterogeneity of the articles as well as the lack of consistency in data reporting and granularity across included studies. Furthermore, our review is mostly comprised of case reports and case series, therefore limiting the quality of evidence. Despite these shortcomings, we believe that our results can aid the development of workup guidelines for an occult malignancy in patients with unexplained AN.
Supplemental Material
sj-docx-1-cms-10.1177_12034754251404449 – Supplemental material for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review
Supplemental material, sj-docx-1-cms-10.1177_12034754251404449 for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review by Shu Yu Qian, Jordan A. Goyal, Kailey Qin and Ilya Mukovozov in Journal of Cutaneous Medicine and Surgery
Supplemental Material
sj-docx-2-cms-10.1177_12034754251404449 – Supplemental material for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review
Supplemental material, sj-docx-2-cms-10.1177_12034754251404449 for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review by Shu Yu Qian, Jordan A. Goyal, Kailey Qin and Ilya Mukovozov in Journal of Cutaneous Medicine and Surgery
Supplemental Material
sj-docx-3-cms-10.1177_12034754251404449 – Supplemental material for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review
Supplemental material, sj-docx-3-cms-10.1177_12034754251404449 for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review by Shu Yu Qian, Jordan A. Goyal, Kailey Qin and Ilya Mukovozov in Journal of Cutaneous Medicine and Surgery
Supplemental Material
sj-docx-4-cms-10.1177_12034754251404449 – Supplemental material for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review
Supplemental material, sj-docx-4-cms-10.1177_12034754251404449 for Clinical Characteristics of Paraneoplastic Acanthosis Nigricans: A Systematic Review by Shu Yu Qian, Jordan A. Goyal, Kailey Qin and Ilya Mukovozov in Journal of Cutaneous Medicine and Surgery
Footnotes
Acknowledgements
We thank Alex Zhao for his assistance for reference reviewing.
Data Availability Statement
The data that support the findings of this study are contained within the article and the supplementary files.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Considerations
Not applicable.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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