Surreal illustration of skin moles following Blaschko lines with DNA strands, representing genetic origins of epidermal nevi.

Skin Moles and Keratinocytic Nevi: What You Need to Know

Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"A comprehensive guide to understanding epidermal nevi, their genetic origins, and associated syndromes."

Skin moles, clinically known as nevi, are common. Epidermal nevi, specifically, are benign, tumor-like malformations that originate from the epidermis and sometimes the skin's adnexal structures (like hair follicles and sweat glands). Historically, these nevi have been categorized by their appearance. However, recent genetic research has begun to shed light on their origins and links to other health conditions.

This article dives into the world of epidermal nevi, focusing on keratinocytic nevi. We'll explore how these skin lesions develop, what genetic factors are involved, and what associated syndromes you should be aware of. This is the first part of a series, focusing specifically on nevi derived from the epidermis.

Whether you're someone with a newfound interest in skin health, have noticed a mole that concerns you, or simply want to expand your knowledge, this guide offers accessible insights into the nature, genetics, and potential implications of keratinocytic nevi.

What are Keratinocytic Nevi and How Do They Develop?

Surreal illustration of skin moles following Blaschko lines with DNA strands, representing genetic origins of epidermal nevi.

A hamartoma, the origin of skin nevi, is a benign, tumor-like malformation that arises due to an abnormal mixture of mature tissue elements. Unlike neoplasms, hamartomas don't involve autonomous, uncontrolled growth. When these occur in the skin, they're called nevi.

The development of keratinocytic nevi is linked to genetic mutations or epigenetic changes affecting skin cell clones during embryonic development. This leads to mosaicism, where an individual has two or more genetically distinct cell populations. Several mechanisms contribute to this mosaicism:

Somatic mutations in autosomal dominant genes: These mutations, which would be lethal in a zygote, persist in a mosaic form, affecting only a group of cells that survive due to proximity to normal cells. These mutations often involve the PI3K and MAP-kinase pathways, crucial for cell survival and proliferation.
Nonlethal mutations in autosomal genes: These mutations cause extensive skin disease when present in the zygote but can manifest in mosaic form following a postzygotic mutation. This can lead to exclusively mosaic involvement in otherwise healthy individuals (type 1 Happle mosaicism) or occur in patients already presenting a generalized form of the disease (type 2 mosaicism).
Mosaic mutations or epigenetic changes: These occur in genes linked to polygenic inflammatory diseases.
Functional mosaicism: This is linked to random X chromosome inactivation in women, also known as lyonization.

Interestingly, the same genetic mutation can result in different appearances of keratinocytic nevi. Conversely, mutations in different genes can lead to similar-looking lesions, highlighting the complex relationship between genotype and phenotype. Most epidermal nevi follow Blaschko lines, reflecting patterns of embryonic skin development, though exceptions exist. The timing of the mutation influences the location and extent of the nevus, with early mosaicism resulting in more widespread lesions often associated with extracutaneous involvement.

Key Takeaways and Next Steps in Understanding Keratinocytic Nevi

Keratinocytic nevi are complex skin lesions arising from genetic mosaicism during development. While typically benign, understanding their genetic basis and potential associations with syndromes is crucial.

If you notice a new or changing mole, particularly one that follows a linear pattern or is associated with other unusual symptoms, consult a dermatologist. Genetic testing and careful clinical evaluation can help determine the nature of the lesion and any associated risks.

This article serves as a starting point. As research progresses, our understanding of epidermal nevi and their genetic underpinnings will continue to evolve, leading to improved diagnostics and management strategies. Stay informed and proactive about your skin health.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.adengl.2018.07.019, Alternate LINK

Title: Epidermal Nevi And Related Syndromes — Part 1: Keratinocytic Nevi

Subject: Dermatology

Journal: Actas Dermo-Sifiliográficas (English Edition)

Publisher: Elsevier BV

Authors: J. Garcias-Ladaria, M. Cuadrado Rosón, M. Pascual-López

Published: 2018-10-01

Everything You Need To Know

What exactly are keratinocytic nevi, and where do they come from?

Keratinocytic nevi are benign skin lesions that stem from genetic mosaicism during embryonic development. This mosaicism occurs when some skin cells have different genetic makeups than others in the same individual. These nevi are derived from the epidermis and can sometimes involve skin structures like hair follicles and sweat glands. While generally non-cancerous, understanding their genetic origins is essential, especially considering potential links to other syndromes. These nevi often appear along Blaschko lines, which reflect patterns of embryonic skin development.

What genetic mechanisms are responsible for the development of keratinocytic nevi?

The development of keratinocytic nevi is closely tied to genetic mutations or epigenetic modifications during embryonic development, leading to mosaicism. Several mechanisms cause mosaicism, including somatic mutations in autosomal dominant genes (affecting the PI3K and MAP-kinase pathways), nonlethal mutations in autosomal genes (resulting in type 1 or type 2 Happle mosaicism), mosaic mutations in genes related to polygenic inflammatory diseases, and functional mosaicism linked to X chromosome inactivation in women (lyonization). The timing of these mutations affects the location and extent of the nevus.

How do somatic mutations in autosomal dominant genes impact the formation of keratinocytic nevi?

Somatic mutations in autosomal dominant genes play a significant role in the formation of keratinocytic nevi. These mutations, which would be lethal if present in the zygote, survive in a mosaic form because they only affect a group of cells. These mutations often involve the PI3K and MAP-kinase pathways, which are crucial for cell survival and proliferation. These pathways regulate cell growth, differentiation, and apoptosis. When these pathways are disrupted by somatic mutations, it can lead to the uncontrolled growth of keratinocytes, contributing to the development of nevi.

Is it possible for different genetic mutations to cause similar-looking keratinocytic nevi, and vice versa?

Mutations in different genes can indeed lead to similar-looking keratinocytic nevi. Conversely, the same genetic mutation can result in different appearances. This phenomenon underscores the complex relationship between genotype and phenotype in the context of epidermal nevi. The ultimate appearance of a nevus is influenced not only by the specific gene mutated but also by other factors such as the timing of the mutation during development, the location of the affected cells, and the individual's overall genetic background.

How does mosaicism specifically influence the development and appearance of keratinocytic nevi?

Mosaicism influences the development and appearance of keratinocytic nevi in several ways. Early mosaicism, which occurs very early in embryonic development, typically results in more widespread lesions that may be associated with extracutaneous involvement, meaning they affect tissues beyond the skin. The location of the nevus will depend on when and where the mutation happened in development. Functional mosaicism, specifically lyonization (random X chromosome inactivation in women), also plays a key role in the variable presentation of keratinocytic nevi in females.