What Are Nevus Cells?

Nevus cells are simply melanocytes—pigment-producing cells derived from the neural crest that have aggregated into nests within the skin. 1

Cellular Identity and Origin

Nevus cells are melanocytes that express the same molecular markers and biochemical characteristics as normal epidermal melanocytes, including E-cadherin, DDR-1, integrin α6, and the ability to produce melanin through tyrosinase-mediated conversion of tyrosine to melanin. 2, 1
These cells may originate from multiple sources: epidermal melanoblasts or potentially dermal stem cells (DSCs), as evidenced by expression of both epidermal melanocyte markers and DSC markers like NGFRp-75 and nestin. 2, 3
The term "nevus cell" was introduced nearly a century ago, but modern morphological and biochemical evidence confirms they are fundamentally melanocytes that have undergone clonal proliferation and organized into characteristic nests. 1

Nevus cells organize into distinct architectural patterns based on their location within the skin: junctional nevi contain nevus cell nests at the dermal-epidermal junction, dermal nevi have nests entirely within the dermis, and compound nevi exhibit both patterns. 4, 3
In congenital melanocytic nevi (CMN), nevus cells are collections of melanocytes with variable extension to adipose tissue, muscles, and around adnexa, distinguishing them from acquired nevi. 4
The depth and distribution of nevus cells can extend beyond typical superficial locations, with some deposits occurring along leptomeninges, cerebral cortex, or brain parenchyma in neurocutaneous melanosis. 4

Benign nevus cells typically exhibit minimal proliferative activity, as demonstrated by low Ki67 expression and absence of dual Ki67/MART-1 positivity in mature dermal components. 4
Capsular nevi in lymph nodes show single MART-1 positivity without Ki67 expression, reflecting lack of cellular proliferation and indicating maturation of nevus cells—a key distinction from metastatic melanoma. 4
Deep dermal nevus cells in benign lesions demonstrate maturation with loss of HMB45 expression, whereas persistent HMB45 positivity and Ki67 activity throughout the dermis suggests malignant transformation. 4

Nevus cells harbor oncogenic driver mutations that trigger initial clonal proliferation: BRAF mutations predominate in acquired melanocytic nevi, NRAS mutations in congenital melanocytic nevi, and GNAQ mutations in blue nevi. 5
Following the initial proliferative phase driven by these mutations, nevus cells execute a senescence program that terminates growth, explaining the benign behavior of most nevi. 5
Nevus cells typically show homogeneous p16 expression on immunohistochemistry, representing heterozygous loss of chromosome 9p or intact chromosome 9, which contributes to growth arrest and distinguishes them from melanoma cells that show complete or heterogeneous loss of p16. 4

Nevus cells in acquired melanocytic nevi first appear around 1 year of age, peak in number during the second or third decades, and gradually disappear by the seventh to ninth decades. 3
These cells may proliferate or become more prominent in response to sun exposure, hormonal changes during puberty or pregnancy, immunosuppression, or chemotherapy. 3
Benign nevus cells undergo predictable changes over time: pigmentation may become more mottled or speckled, surface characteristics can become more raised, hypertrichotic, verrucous, or papillated, without indicating malignant transformation. 6, 7

Nevus cells at special anatomic sites (acral, genital, ear, conjunctivae, scalp, breast, flexural skin) can demonstrate unusual features including asymmetry, irregular nesting, pagetoid spread, and cytologic atypia, yet remain benign—critical to recognize to avoid overtreatment. 8
Dual-color immunohistochemistry using melanocytic markers (MART-1) with proliferation markers (Ki67 or PHH3) specifically identifies nevus cell proliferation activity while excluding non-melanocytic cells, improving diagnostic accuracy. 4