Beyond the Surface: Porokeratotic Eccrine Nevus as a Marker of Genetic Mosaicism and Potential Malignancy

Abstract

Background: Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare skin condition that usually appears as clusters of thickened, wart-like bumps tracing the body’s natural skin lines. While it’s generally considered harmless, there’s growing evidence that it may sometimes evolve into skin cancer, particularly squamous cell carcinoma. Recent research suggests that the condition may stem from mosaic mutations in the GJB2 gene specifically affecting a protein called connexin 26, which plays a key role in how skin cells and sweat glands communicate.

Objective: This narrative review aims to be the first comprehensive synthesis that brings together what we currently know about PEODDN, from how it looks and behaves to the genetic factors behind it and the risk of it turning cancerous. A central focus is the role of connexin 26 dysfunction in breaking down the normal interactions between skin layers and sweat gland ducts. We also highlight a major gap in the research: there’s still no clear model linking the underlying genetic changes to the skin changes we see under the microscope, how the condition progresses over time, or the likelihood of cancer.

Methods: We conducted a comprehensive review of studies published from 2015 to 2025, using databases like PubMed, Scopus, and Web of Science. We focused on articles that explored the genetics, clinical features, risk of malignancy, or treatments for PEODDN. Only English-language studies with full-text access were included. Our aim was to identify patterns, highlight knowledge gaps, and suggest directions for future research.

Results: Across the literature, mosaic mutations in GJB2 and the resulting issues with connexin 26 emerge as a recurring theme in how this condition starts and possibly leads to cancer. Yet, despite numerous case studies, there’s still no unified explanation that connects these genetic findings to the clinical course or cancer risk. There are no formal guidelines for monitoring patients, and current treatments mainly surgical removal or laser therapy offer mixed results.

Conclusion: This review offers a new way of looking at PEODDN by tying together its clinical, genetic, and cancer-related aspects. We propose a working model that connects connexin dysfunction to both the development of lesions and the possibility of malignancy. There’s a clear need for standardized diagnostic tools, long-term monitoring protocols, and genetic counseling for patients with widespread or unusual presentations.