Ordinary melanocytic nevi are acquired lesions that typically appear early in life. Nevi may occur at any anatomic site affecting males and females alike. One epidemiologic study found an average of 36 ordinary nevi (2 mm in diameter or greater) on Caucasian patients who visited a dermatology clinic, but acknowledged that the number is highly variable among individuals [15]. Nevi may present as pigmented macules and papules that over time may become less pigmented. Most ordinary nevi are small, symmetrical, have a smooth border, and are evenly pigmented.

It is generally accepted that ordinary acquired nevi undergo a process of growth first within the epidermis (junctional nevus), followed by penetration into the dermis (compound nevus) [16]. Over time, the intraepidermal portion is lost and the lesion resides wholly in the dermis (intradermal nevus). This process usually is accompanied by gradual loss of pigmentation and by elevation of the lesion as melanocytes expand the dermis. Over the course of many years, some nevi undergo complete involution.

The clinical evolution of an ordinary nevus is associated with changes in its microscopic appearance as well. Junctional nevi contain melanocytes disposed singly and/or grouped into nests within the epidermis. The melanocytes have either an epithelioid or dendritic appearance. Many cells contain abundant cytoplasmic melanin. Nuclei may be enlarged and contain nucleoli, but are uniform in appearance and do not display significant pleomorphism or hyperchromasia. Compound and intradermal nevi display characteristic features of so-called “maturation” in the dermis. Nests of epithelioid melanocytes in the superficial dermis transition into areas with smaller nests and more dispersed smaller epithelioid or fusiform cells in the deeper dermis (Fig. 8.2a). Individual nest do not exhibit cellular crowding, and larger, confluent sheets of cells are uncommon. The change in architecture and cytologic morphology with progressive descent into the dermis is accompanied by visible loss of cytoplasmic melanin and by reduction in cellular size (Fig. 8.2b). Although a few mitotic figures may be present in the superficial dermal component of a nevus, few if any are present in the deeper portion. One study found that the nevi of younger patients were more likely to contain superficial dermal mitotic figures [17]. Ordinary benign melanocytic nevi are thus distinguished from nevoid melanomas by their lack of a sheet-like growth pattern, and by their cellular crowding, significant nuclear pleomorphism, and low mitotic rate. The only possible exception is that of nevi occurring in pregnant women, since they may have mitotic figures in the lesion (please see below).

In comparison to nevoid melanoma, ordinary nevi display an immunophenotype of maturation and low proliferative activity in their dermal component. Labeling for gp100 is limited to the intraepidermal (if present) and superficial nested, more pigmented dermal portions of the lesion (Fig. 8.2c). Patchy labeling throughout the lesion or labeling of cells toward the base is not observed. Importantly, any labeling present toward the base of a nevus should be interpreted with extreme caution since some melanophages may display immunoreactivity for gp100 as well as other melanosomal glycoproteins [18]. Similarly, labeling for Ki-67 is largely restricted to melanocytes in the epidermis and in the superficial dermal nests. Labeling (if present) is symmetrically distributed across the superficial portion. Very few, if any, melanocytes toward the base of a nevus are labeled (Fig. 8.2d) [14].

Over time, ordinary melanocytic nevi may undergo changes that make their distinction from nevoid melanoma even more difficult. One example of this phenomenon is the so-called “ancient nevus” named for its histological similarities to ancient schwannoma [19, 20]. These nevi are almost exclusively long-standing papules on chronically sun-damaged skin. Head and neck are the most frequent sites of involvement. Based upon the usual clinical presentation and biological behavior of these lesions, most consider this histological change to be the result of cellular senescence within an otherwise ordinary benign melanocytic nevus.

Observation at low magnification usually reveals the architectural features typical of a predominantly intradermal nevus in a background related to chronic sun exposure. These background actinic changes include variable degrees of epidermal atrophy, increased basal layer pigmentation, venous telangiectasia, perilesional collagen sclerosis, and solar elastosis (Fig. 8.3a). Intraepidermal melanocytes may be increased in number and uniformly distributed along the pigmented basal layer extending peripheral to the nevus, a feature reflective of the background actinic changes and not part of the nevus per se. Dermal melanocytes are nested in the superficial dermis, but are more dispersed at deeper levels in a typical architectural pattern of maturation. On higher magnification; however, ancient nevi contain scattered enlarged pleomorphic cells with hyperchromatic nuclei similar to those seen in nevoid melanoma (Fig. 8.3b). Nucleoli and/or nuclear pseudo-inclusions may be present in the atypical cells. The atypical melanocytes are haphazardly distributed in the lesion, giving the appearance of an altered pattern of maturation. However, unlike nevoid melanoma, ancient/senescent nevi are less cellular, and the atypical cells fewer in number. Few if any mitotic figures are present in the lesion, and those present are located in the upper regions of the lesion, a feature compatible with the theory that these lesions are in a state of cellular senescence.

Although ancient/senescent nevi are less cellular and contain fewer atypical cells, their degree of cytologic atypia may be so severe as to warrant serious consideration of a nevoid melanoma or of a melanoma arising in association with a preexisting benign melanocytic nevus (see below). Fortunately, the gp100 and Ki-67 immunohistochemical features of ancient/senescent nevi are identical to those of ordinary nevi, exhibiting a typical maturation phenotype and low proliferation rate in the dermal melanocytes.

Numerous studies have documented that long-standing ordinary melanocytic nevi may undergo dramatic clinical changes during pregnancy [21]. Nevi in pregnancy may grow rapidly, develop irregular borders, and/or display irregularities of pigmentation [22]. These changes are particularly concerning given that malignant melanoma during pregnancy is often biologically more aggressive. Many believe that these clinical and biological features are related to hormonal fluctuations associated with normal pregnancy. Identification of estrogen receptor-beta expression by melanocytes and melanoma cells has given support to this theory [23].