Melanocytic nevi are a category of benign melanocytic proliferations with a number of subtypes. These include congenital melanocytic nevi, blue nevi, acquired melanocytic nevi, and Spitz nevi.
Many of these share common mutations with melanoma progenitor cells, such as BRAF mutations in acquired melanocytic nevi and in melanoma. NRAS and GNAQ mutations are often found in congenital melanocytic nevi and blue nevi. Spitz nevi have HRAS mutations. These are driver mutations which propel the formation of nevi through an initial proliferative phase to terminal senescence which causes the nevus to remain unchanged thereafter. In some cases, more mutations emerge to add to the tumor-inducing properties of the original oncogenic mutations, leading to malignant progression by reversing the senescence.
Melanocytic nevi thus represent benign epidermal nests of melanocytes within the dermis or in other tissues.
Congenital Melanocytic Nevi (CMN)
CMN are almost always found to occur sporadically, and probably result from somatic mutations during fetal life.
Blue nevi represent a category of acquired pigmented nodules or papules arising from dendritic dermal melanocytes through proliferation - they are usually common or cellular variants. Common blue nevi often emerge in adolescence and are small whilst cellular blue nevi may be larger, and occur in adults below 40 years. Both have a deep bluish black color due to the depth of the color-imparting melanocytes in this tumor. The melanin undergoes Tyndall scattering, which results in greater and preferential scattering of blue light with its shorter wavelength, producing the typical blue or gray color of the nevi.
These nevi are benign, and contain large melanocytes which are epithelioid or spindled.
Common Acquired Melanocytic Nevi (CAMN)
CAMN is an acquired benign nevus containing melanocytes, also called ‘signature nevus.’ It has been classified into junctional, compound or dermal nevi, based on the anatomy, the structure, and the histology.
Both genetic and environmental factors influence the occurrence of nevi. They have a slight male preponderance, and affect white-skinned individuals, especially with fair skin and red or blond hair. Ultraviolet rays encourage nevus formation, as is shown by the reduced occurrence of nevi following the use of a sunscreen. The light used for neonatal phototherapy also increases nevus formation in children, because of melanocytic activation for a brief period. Nevi become malignant more often in those which have this in their family.
The origin of melanocytic nevi appears to be from the totipotent neural crest cells migrating to the skin. There they differentiate into intraepidermal melanocytes within junctional nests, with a more epithelioid tendency rather than the common dendritic type of melanocyte.
Clinically, melanocytic nevi are well-defined, rounded lesions with regular borders. Dermoscopic evaluation can also be done to identify the following subtypes:
- Globular or congenital
- Reticular or acquired
- Blue or homogeneous
- Nevi with halos or eczema, and recurrent or combined nevi
Most melanocytic nevi are benign and the patient may be reassured, with surgical excision occurring only if there are atypical features suggesting a melanoma. In such cases, excision under local anesthesia is preferred. Most techniques of cosmetic removal, including laser excision and shave excision, do not go deep enough to allow proper histological assessment of the whole nevus. Moreover, they do not preserve any intact tissue for histopathological examination. In addition, inadequate removal often occurs when the nevus is ablated by laser or cryosurgery. Complete scalpel excision leaves an undesirable scar, on the other hand, which has led to an increasing demand for cosmetic surgical excision.
The total number of CAMN in white skin is the primary determinant of melanoma risk. The more the atypical nevi, both over the whole body and over the buttocks, and the greater the number of nevus excisions performed during the follow-up period, the higher the risk of melanoma.
In all cases, follow up should be undertaken following lesion removal. Furthermore, any recurrence should be carefully evaluated to rule out melanoma. The greatest number of melanocytic nevi are benign, however, and recurrence is rare even following laser surgery.
Reviewed by Afsaneh Khetrapal BSc (Hons)