There are numerous types of melanocytic nevi, including the benign congenital melanocytic nevi, the blue nevi, and the common acquired melanocytic nevi. Atypical and dysplastic nevi are discussed with melanoma in the section on malignant growths. Evaluation of melanocytic nevi is one of the dermatologist’s most common and important tasks. Every patient who enters a derma- tologist’s office should be offered the opportunity to have a full-body skin examination, specifically evaluat- ing melanocytic nevi for any signs of malignant transformation and or de novo melanoma production. The importance of evaluating melanocytic nevi is to screen for melanoma. Melanoma is a life-threatening skin cancer that, if discovered early, can be cured. Different types of melanocytic nevi have varying rates of malignant transformation, and it is critical for the clinician to be aware of those nevi that are likely to be encountered on a daily basis.
Clinical Findings: Melanocytic nevi can be classified both clinically and histopathologically. The common acquired melanocytic nevus is a clinical diagnosis, and if the lesion is biopsied, it may show some evidence of atypia or dysplasia of melanocytes. It is for this reason that a universally accepted classification of melanocytic nevi has yet to be adopted.
Benign melanocytic nevi are extremely common. Virtually all humans have some form of these growths on their body. Common acquired melanocytic nevi are universally found and can have varying morphologies. They affect males and females equally. They are uncommon at birth but increase in number over the first 4 decades of life, after which the number typically stabilizes. As one ages, the nevi tend to slowly involute. They can be macular or papular in appearance. Most are uniform and symmetric in size and color. They can be flesh colored or slightly brown in coloration. They tend to grow proportionally as a child grows or as an adult gains weight. They also can become slightly larger and darker during pregnancy.
There is a risk for malignant degeneration into mela- noma, and changes in color, size, symmetry, or border should be assessed. Nevi that become symptomatic, especially pruritic, and nevi that spontaneously bleed should be evaluated and biopsied appropriately.
Blue nevi are unique benign melanocytic tumors that have a characteristic clinical and histological pattern. These nevi tend to be small, to be located on the dorsal aspect of the hands or feet, and to have a bluish to blue-gray coloration due to their location within the dermis. The blue color is believed to result from the Tyndall effect. This is a process by which various wavelengths of light are absorbed preferentially, and the reflected light or color that is seen depends on the material and depth of the substance being illuminated. Blue nevi share similar histological characteristics with the nevus of Ota, nevus of Ito, and Mongolian spots. However, the clinical appearance is so different that these lesions are not considered in the differential diagnosis of a blue nevus.
Blue nevi can occur at any age, and they appear equally often in men and in women. They typically manifest as small (2-5 mm), oval or round macules or papules. They are well circumscribed with nice, distinct borders. They are commonly located on the dorsal aspect of the hands and feet but have been reported to occur anywhere, including the mucous membranes. They are frequently biopsied because of their unusual coloration. They are small and usually can be removed easily with a punch biopsy that is 1 mm larger than the lesion. Patients often give a history of having been stabbed with a pencil during childhood and believe that the lesion is a graphite tattoo. This occasionally is the case, but most of these lesions are actually blue nevi. Malignant transformation of blue nevi is extremely rare.
Multiple blue nevi can be seen in the Carney complex, also known as the NAME or LAMB syndrome. This complex of clinical findings includes multiple blue nevi, lentigines, ephelides, myxomas, atrial myxomas,testicular tumors, pituitary tumors, psammomatous melanotic schwannomas, and adrenal tumors. This is a rare syndrome that has been determined to be caused by a genetic defect in the gene PRKAR1A. This is a tumor suppressor gene that encodes a protein kinase A subunit.
Congenital melanocytic nevi can be divided clinically into distinct subtypes based on size (small, medium, and giant). Small congenital nevi are the most common type; they are defined as those nevi smaller than 2 cm in greatest diameter. These nevi occur with equal frequency in males and females and have no race predilection. Some authors estimate their prevalence at about 1% of the population. These nevi are typically described as well-defined macules, papules, or plaques. They are hyperpigmented compared with the normal surrounding skin. They are almost always uniform in color and symmetric. Over time, some 50% develop terminal hair growth within the nevi. The risk of malignant trans- formation in these small congenital nevi is low and approaches that of the common acquired melanocytic nevi. Melanoma can arise in these nevi at any point in the patient’s life but usually after puberty.
Medium-sized congenital melanocytic nevi are defined as those that have a diameter between 2 and 20 cm. They have the same risk of malignant transformation as small congenital nevi. They occur equally in males and females and can be seen in about 1% of the population. They can occur anywhere on the body.
Giant or large congenital melanocytic nevi, also known as “bathing trunk” nevi, are important clinically in many ways. First, they have an increased risk of malignant transformation. This transformation can be difficult to discern clinically until the lesions are quite large. Most melanomas develop in a dermal or subcutaneous location, which make them difficult to assess clinically. Melanomas typically occur before puberty, and they have been reported to occur in as many as 15% of giant congenital nevi. The risk of malignant transformation is higher in axial nevi than in acral nevi. For this reason, these lesions are treated more aggressively, and patients with large congenital melanocytic nevi need lifelong, frequent routine follow-up. These nevi occur equally in men and women and in any racial group. They affect the truncal region more often than any other region of the body.
The significant finding of neurocutaneous melanosis occurs at a higher rate in patients with large congenital nevi of the trunk. These nevi almost always occur over the majority of the trunk, and they can have any number of satellite melanocytic nevi. Patients with large truncal congenital melanocytic nevi should undergo magnetic resonance imaging (MRI) of the nervous system to evaluate for neurocutaneous melanosis. Patients with neurocutaneous melanosis are at a high risk (almost 50%) for development of leptomeningeal melanoma, which is almost always fatal. A multidisciplinary approach to care for these patients is required, including the patient’s pediatrician, dermatologist, neurologist, and neurosurgeon.
Histology: In common acquired melanocytic nevi, the melanocytes are arranged symmetrically in a lateral fashion. They are arranged in nests. The nested mela- nocytes do not have the typical dendritic appearance of normal melanocytes found within the stratum basalis. They are round and uniform in shape and show increasing maturation with depth in the dermis. Maturation of nevi cells implies a decrease in the ratio of nuclear to cytoplasmic volume and an overall decrease in the size of the melanocytes. The melanocytes are still uniform in size and shape at various depths within the dermis; they are not symmetric vertically. Many forms are seen histologically. Based on the location of the melanocyte nests, they can be classified as junctional, intraepidermal, dermal, or compound nevi. A junctional nevus has its nests arranged along the basement membrane zone, whereas a compound nevus has epidermal and dermal nests.
Blue nevi are located entirely within the dermis. These nevi are made of melanocytes that resemble dendrites. The dendritic processes contain melanin pigment, and this pigment is responsible for the coloration of the lesion. Collagen is interwoven between the dermally located melanocytes. Melanophages are almost always seen in and around the lesion. A grenz zone is sometimes appreciated above the melanocytic lesion. Numerous histological subtypes of blue nevi have been described, including the dendritic blue nevus (common blue nevus), amelanotic blue nevus, cellular blue nevus, and epithelioid blue nevus.
Small, medium, and large congenital nevi all show the same histological characteristics, and they cannot be distinguished on pathological evaluation. The major criteria used to separate congenital nevi from other types of nevi are size and location. The nests are found deep within the dermis and can also be found within the subcutaneous tissue, fascia, and underlying muscle. Infiltration of muscle is unusual and is more likely to be seen in large congenital nevi. The nests of nevus cells accumulate around adnexal structures and are frequently seen juxtaposed to hair follicles, sebaceous glands, and eccrine glands. The melanocytes can penetrate the arrector pili muscles. The nevus cells show proper maturation and are uniform in appearance.
Pathogenesis: There are many conflicting theories as to the pathogenesis of common acquired melanocytic nevi and blue nevi. Some think that there is an abnormal migration of melanocytes embryologically, whereas others believe that stem cells are located within the dermis or epidermis and melanocytes migrate upward or downward to form the nevi. Perhaps a combination of these processes occurs, but no definitive pathogenic mechanism has been universally accepted.
Congenital melanocytic nevi are thought to be caused by an embryological malfunction of melanocyte migration. The precise mechanism that causes the disrupted or abnormal migration of melanocytes into the involved areas has not been determined. Migration in these cases is believed to be controlled by a complex but abnormal growth and regulatory signaling pathway.
Treatment: Common acquired melanocytic nevi do not need to be treated. They can be removed by various means for cosmetic purposes. Shave removal and punch biopsy removal are two highly successful techniques. Elliptical excision should be reserved for larger lesions in areas where the scar can be camouflaged. Only highly skilled physicians should consider removing pigmented lesions with laser therapy, because there is no tissue left for histological evaluation.
Blue nevi are easily removed by punch biopsy or elliptical excision. They are often removed for cosmetic reasons, and a small excision gives an excellent cosmetic result.
Removal of small and medium congenital nevi should be done with surgical excision. This removes the entire lesion and allows for pathological evaluation. Most of these small and medium congenital melanocytic nevi can be observed over time and removed if there are changes. Serial photographs are invaluable in monitoring these nevi for changes. Some of these lesions occur in cosmetically sensitive areas, such as the face, and patients should be referred to a plastic surgeon for evaluation. The social and psychological well-being of the child can be enhanced by having a disfiguring congenital nevus removed.
Large congenital nevi present the biggest treatment difficulty because of the high rate of malignant transformation. If possible, serial excisions to remove large nevi are the best option. Tissue expanders are often used to help decrease the need for skin grafting. The goal should be 100% removal, although in some cases this is not feasible. If the nevi cover 10% to 30% or more of body surface area, they become almost impossible to remove. In these cases, as in all the others, the importance of lifelong surveillance needs to be taught to the parents, the afflicted individuals, and the participating physicians. The goal in these cases is to biopsy and remove any changing areas of the nevi in an effort to prevent metastasis if a melanoma were to develop.