Congenital melanocytic nevi are benign melanocytic proliferations that are present at birth or, according to some authors, arise within the first few weeks of life. These nevi are one of the most common cutaneous lesions in a newborn. The terms “tardive” congenital melanocytic nevus has been used to represent nevi with clinical and histologic features of congenital melanocytic nevi that were not clinically apparent at birth but were detected within the first 2–3 years of life. Prevalence of congenital melanocytic nevi ranges from 0.2 to 2.7 % for lesions less than 1.5 cm in greatest diameter to 0.005 % for lesions greater than 10 cm in greatest diameter [1–4]. Most congenital melanocytic nevi occur sporadically but there may be familial clustering. These melanocytic lesions may pose considerable clinical dilemma given their frequency, wide variation in presentation, and potential for medical significance. The medical significance of these newborn skin lesions is that over a lifetime they can be a marker for increased risk of malignancy, may be associated with rare syndromes, or themselves can transform into melanoma. Furthermore, while small lesions are most often inconsequential, large nevi can carry a devastating psychosocial burden and increased risks of melanoma, since the relative risk for melanoma arising within a congenital nevus is directly related to the size of the lesion.

Several developmental abnormalities are associated with congenital nevi, especially with giant congenital nevi. These associations include scoliosis, spina bifida, atrophy, asymmetry, clubfoot, or cranial bone hypertrophy [5, 6]. In addition, patients with large congenital melanocytic nevi are at increased risk to develop neurocutaneous melanocytosis, in which collections of melanocytes are present in the leptomeninges. Neurocutaneous melanocytosis is a rare congenital disorder characterized by the presence of giant or multiple melanocytic nevi associated with benign or malignant melanotic tumors of the central nervous system. Neurocutaneous melanosis can occur in both patients with large nevi or with multiple small- or medium-sized congenital nevi. Patients with large congenital nevi located on the posterior axis have greater risk for neurocutaneous melanocytosis, particularly those patients with large congenital nevi and multiple satellite nevi [7]. Malignant transformation can also occur in neurocutaneous melanosis and result in primary melanoma of the central nervous system. Even without malignant transformation, neurocutaneous melanosis can carry significant morbidity and mortality, often from seizures, hydrocephalus, and other signs of irritation of the central nervous system.

Congenital nevi can be also associated with café au lait spots , mucosal nevi , fascicular schwannoma , lipoma, lymphangioma , capillary hemangioma , fibroepithelial polyp, ectopic mongolian spot, atopic dermatitis, vitiligo, neurilemmomas, perinevic leukoderma, and cartilaginous hamartomas [6, 8, 9]. Extracutaneous associations include limb hypertrophy, electroencephalography abnormalities, and cryptorchidism.

Congenital nevi change of appearance with age. At birth, the lesions may appear to be lightly pigmented macules that in some cases mimic café au lait spots. They are usually small and oval, but also round, linear, curvilinear, geographic pattern [14, 15]. Multiple lesions can be found, coalescing on one anatomic area, discontinuous in a geographic area, or randomly scattered. The lesions may change during the first few years of life and vary greatly from patient to patient. A common change is the presence of flat or elevated small, dark brown macules or papules within the parent lesion; this change may remain static into adult life. Once fully developed, the typical clinical features are those of a pigmented, brown plaque with regular, smooth, and well-demarcated borders. Formation of terminal hairs within the plaque and verrucous changes may be seen in older nevi, and some studies have even suggested that congenital nevi may lighten with age [16]. Congenital nevi located on the scalp have a peculiar tendency to gradually lighten and regress over time. As such, medium-sized to large congenital nevi on the scalp may undergo complete or almost complete clinical resolution [17, 18].

Congenital nevi can involve almost any location including the mouth, palms and soles, and nails. When located in the mouth and nails , the lesions adopt a macular appearance. On the other hand, when located on the scalp, the lesion commonly displays a central area of coloration that is a different shade or color than the periphery.

Several methods have been used to classify congenital melanocytic nevi. The most common classification defines melanocytic nevi on the basis of their size (small, medium, and large/giant) [19]; small congenital nevi are <1.5 cm, medium are 1.5–19.0 cm, and large are those >20 cm (as defined by the largest dimension diameter achieved in adulthood). The distinction between large and giant congenital nevi has been much debated [20]. The term “giant” congenital nevus is sometimes used for nevi covering large segments of the body; however, some authors have defined giant congenital nevi as those with >20 cm or body surface area [21–23]. In this chapter we will use the above described classification [19]

Small and medium congenital nevi : These nevi are often tan to brown in color and oval shaped with well-defined borders. Lesions may develop a mammillated surface and hypertrichosis over time. The risk of melanoma development in these nevi is thought to be less than 1 % over a lifetime and when it happens is usually seen after puberty [9, 16, 24–26]. Melanomas arising in small and medium congenital nevi tend to develop at the dermal-epidermal junction and at the peripheral edge of the congenital nevus; such changes make a clinical morphologic change readily recognized by patients and clinicians [27].

Giant congenital melanocytic nevi : These nevi are always present at birth; however, some congenital nevi are better visualized within the first years of life and are referred to as “tardive” nevi. Giant congenital melanocytic nevi can occupy large areas of the skin surface and most often occur on the trunk, followed by the extremities and the head and neck [28]. The clinical presentation often changes with age; a hairless, light brown, flat lesion at birth may evolve over months and years to develop areas of hyperpigmentation and color variegation, hypertrichosis, erosion or ulceration, a verrucous texture, and nodularity usually representing “neurotization” changes (see histology below). The majority of patients with giant congenital melanocytic nevi have also solitary or multiple satellite nevi associated with them and dispersed over the extremities, trunk, or head and neck.

The absolute risk of melanoma development in giant congenital nevi is approximately 2–5 % over one’s lifetime, considering prospective and retrospective cohort studies with significant follow-up [26]. About half of these melanomas occur in the first 5 years of life and tend to arise deep in the dermis or subcutaneous tissues, making early detection difficult [29, 30]. The number of satellite nevi does not portend a higher risk for developing cutaneous melanoma but having >20 satellite lesions increases the risk for neurocutaneous melanocytosis and melanoma of the central nervous system. Other malignancies such as liposarcomas, rhabdomyosarcomas, and malignant peripheral nerve sheath tumors have been associated with giant congenital nevi [31].

Congenital melanocytic nevi may be junctional, compound, or intradermal in type, depending on the phase at which they are removed. Congenital nevi have variable appearance, and in some cases, the histology is identical to their conventional acquired variant as some of the clues present in congenital nevi can also be noted in some examples of acquired melanocytic nevi. Of interest, there are some congenital nevi that do not show histologic features that indicate their congenital origin, and some small congenital nevi can be histologically indistinguishable from common acquired melanocytic nevi [2, 39, 40]. It has also been proven that congenital melanocytic nevi in infants have the pattern of distribution of melanocytes and the depth of the melanocytic proliferation established very early in life.

Junctional congenital nevi are rare and more commonly seen in small lesions in neonates. Some cases of junctional congenital nevi may display prominent melanocytic hyperplasia in the epidermis and adnexal epithelium. These junctional nevi are more commonly seen after birth and clinically present as small macular brown lesions. Congenital nevi are more commonly compound or intradermal. At low power, congenital melanocytic nevi are usually symmetric with a wedge-shaped or platelike dermal component. When a junctional component is present, it is usually well circumscribed with nests of melanocytes positioned at the side and base of rete ridges and relatively uniform in size and shape. The melanocytes are typically small to medium sized and monomorphous in appearance. One of the most common atypical features and possible pitfalls seen in congenital nevi is the presence of a lentiginous melanocytic proliferation, which may or may not be associated with variation in the size and shape of the melanocytic nests and cytologic atypia. The junctional component of congenital nevi, especially in patients younger than 10 years of age and in certain anatomic locations (e.g., scalp), may show large nests of melanocytes that vary in size and shape and that are not uniformly distributed. Single melanocytes may predominate over nests in some areas, and the melanocytes may be large and show mild degree of pleomorphism. Cases in which these findings are present may be misinterpreted as melanoma. However, such changes in congenital nevi are located in the center of the lesion, while most melanomas developing in the epidermis over a congenital nevus do extend beyond the dermal component.

In compound congenital nevi, in addition to a junctional component, there are melanocytes in the dermis which tend to be aggregated in nests. Melanocytes are typically larger in the superficial portion of the dermis. They are uniform, with minimal cytoplasm, and show maturation from the superficial to the deep aspect of the lesion with nests and individual melanocytes gradually diminishing in size with descent into the dermis. With increasing depth, the melanocytes often demonstrate less crowding and greater splaying of the collagen. Occasional mitotic figures may be noted in congenital nevi and when seen they are located in the superficial portion of the lesion.

Congenital melanocytic nevi usually reach the lower aspect of the dermis with a characteristic perivascular, perineural, and periadnexal distribution; however, aggregates of melanocytes can be seen located far away from the main dermal lesion giving a patchy pattern. In some examples melanocytes can be predominantly located around eccrine ducts in nests or single melanocytes (usually around the external end of the duct or in the intradermal portion).

The dermal component may reach the subcutaneous fat, and in such cases, melanocytes often extend along fibrous septa of the subcutaneous fat and, in some instances, may infiltrate the fat lobules, similar to diffuse neurofibromas. The presence of scattered single melanocytes infiltrating the subcutaneous fat is a clue to the congenital nature of the lesion. In some giant congenital nevi, the melanocytes can reach the fascia and skeletal muscle.

In those predominantly intradermal congenital nevi , there is often a grenz zone separating the dermal melanocytes from the overlying epidermis, although it is frequent to see slightly prominent junctional melanocytes with a lentiginous pattern. There may be superficial pigmented dermal melanocytes, but there is typical diminution or absence of pigment in deeper portions of the lesion. Congenital nevi characteristically show melanocytes that appear to splay the dermal collagen in aligned rows between collagen fibers. Spindled melanocytes and neuroid elements can be seen at the base of the lesion. The scalp is a common anatomic site in which these neuroid elements resemble the histologic pattern of a neurofibroma.

Some congenital nevi display pigmented melanocytes aligned in the junction of the follicular infundibula and within the sebaceous lobules, follicular sheath, epithelium of eccrine glands, and arrector pili muscle. In general, it is considered that the identification of melanocytes within the sebaceous glands, nerves, and blood vessels in the deep reticular dermis is highly specific for a diagnosis of congenital onset. Also the presence of large number of hair follicles within the lesion usually indicates a congenital origin. There may be intraepidermal pagetoid spread of melanocytes, especially in patients during their first year of life . These pagetoid cells often display no or slight cytologic atypia and are usually confined to the center of the lesion (along with a nested junctional component) and are restricted to the lower half of the epidermis, in contrast to melanoma in which the pagetoid growth is observed as lateral spread beyond the nested areas [41–43].

Diagnosing a congenital nevus is not a challenging process especially when all histologic features are present, such as circumscription, uniform melanocytic nests within the epidermis that are equidistant from each other, nests and individual melanocytes that mature with their descent, wrapping of melanocytes around vessels and adnexal structures, and splaying of melanocytes among collagen bundles. However, these histopathologic findings are not always clear-cut. There are some possible pitfalls, namely, intraepidermal lentiginous melanocytic proliferation, pagetoid spread of melanocytes, and proliferative nodules.

The most important differential diagnosis in congenital nevi is to rule out the development of melanoma. When melanomas originate in small- and medium-sized congenital nevi, they usually appear after puberty and often develop at the periphery of the preexisting nevus. Most of these melanomas have an intraepidermal origin (clear in situ component) and are usually of the conventional type (superficial spreading) [36]. As explained above, pagetoid change can occur in congenital nevi, particularly in neonates and young children, but in contrast to melanoma, those isolated cells tend to involve the lower half of the epidermis and display a limited degree of atypia.

Histologically, melanomas that are observed in giant congenital nevi are morphologically different to the melanomas seen in small- and medium-sized congenital nevi as the majority of such melanomas are intradermal without an obvious intraepidermal component . Melanomas in giant congenital nevi present as cohesive nodules that are distinctly different and clearly delimited from the surrounding nevus. These nodules tend to demonstrate marked cellularity, are composed of epithelioid melanocytes, and often have prominent nuclear pleomorphism and atypical mitotic figures. The malignant melanocytes can also be spindled or small and round in shape. Furthermore, these dermal nodules of melanoma show a pushing border against the surrounding melanocytes of the congenital nevus; in contrast, the benign proliferative nodules tend to be smaller, and the cells blend with the surrounding melanocytes.

Nevoid melanoma may resemble a compound or intradermal melanocytic nevus with features of congenital nevi. There are certain architectural features that should raise suspicion of a nevoid melanoma including asymmetry and prominent cellular density. At high power, the melanocytes of a nevoid melanoma show high degree of cytologic atypia with subtle pleomorphism, nuclear hyperchromasia, prominent nucleoli, dusty pigmentation of the cytoplasm, and absence of dermal maturation. Also, mitotic figures (some of atypical shape) in the deep aspects of the lesion favor the diagnosis of nevoid melanoma.

The distinction between congenital nevi and acquired nevi is very important for obvious reasons. However, as explained above, the histologic clues described in congenital nevi can also be shared with some acquired nevi. A good number of acquired nevi that appear in infancy have histologic features that are encountered in congenital nevi, and some examples of congenital nevi do not show any histological clues that indicate their congenital origin. Important information to rely on includes detection at birth; presence of melanocytes in the lower two thirds of the dermis and subcutaneous tissue; arrangement of melanocytes as isolated elements or single lines among the collagen bundles in the reticular dermis; the involvement of sebaceous glands, arrector pili muscles, eccrine glands, and lymphatic vessels; and the presence of melanocytes around perivascular, perifollicular, and/or around the eccrine gland distribution.

An important distinction is between congenital and dysplastic nevi. Congenital nevi can have a pattern reminiscent of dysplastic nevi (in compound and junctional nevi), and thus the distinction can be a challenging one. In addition, one study showed that up to 8.3 % of compound dysplastic nevi can show features of congenital nevi [44]. Congenital nevi can show junctional nests that are confluent and irregular with bridging between the rete ridges, lentiginous hyperplasia, extension of junctional component beyond the dermal component (shoulder phenomenon), and variable cytologic atypia. Importantly, it should be kept in mind that none of these features is by itself diagnostic of dysplasia or congenital nevi with dysplastic features, and it should always be interpreted in the clinical context. Classifying a nevus as congenital with dysplastic features or as a true dysplastic nevus with features of a congenital nevus can in some cases be arbitrary.

Congenital blue nevus is rare; the scalp and face are common locations. These lesions are large in size and may behave in an aggressive fashion with involvement of the underlying skull and dura mater or may remain superficial [52, 53]. Some cases may evolve into melanoma. Histologically, congenital blue nevus may acquire the appearance of common blue nevus or cellular blue nevus (see Chap. 3). In the spindle and epithelioid cell nevus type, the deep reticular dermis is infiltrated by epithelioid and spindle cells often mixed with small banal melanocytes or neuroid elements (combined nevus).

Congenital Spitz nevus is extremely rare with only a few sporadic cases reported [54, 55]. Histologically, congenital Spitz nevi display the same histologic features as the acquired type including the presence of large epithelioid or spindle-shaped melanocytes with abundant cytoplasm, well circumscribed, a variable number of multinucleate melanocytes, downward maturation of melanocytes, scatter of individual and nests of melanocytes above the dermoepidermal junction for compound cases , and melanocytes present far down the epithelial structures of adnexa [56–58]. Some cases may show histologic features that would classify them as congenital melanocytic nevi, such as angiocentricity, adnexocentricity, splaying of melanocytes between collagen bundles, and nests varying in size and shape.

Proliferative nodules are composed by a nodular population of melanocytes in the reticular dermis which on low power show clear-cut borders that contrast with the adjacent melanocytic nevus. Most proliferative nodules are small in size but some cases may reach several centimeters in diameter. The cellular density of melanocytes in the proliferative nodule differs with that of the adjacent nevus. At higher magnification, proliferative nodules show gradual intermixing between the large melanocytes of the nodule and the small benign appearing melanocytes of the rest of the nevus, i.e., melanocytes in proliferative nodules merge and blend with the surrounding melanocytes. Proliferative nodules can display atypical changes including melanocytes with prominent nucleoli, higher cellularity than the surrounding nevus , and focal areas of hemorrhage and ulceration. Furthermore, some of these cases can show chromosomal aberrations. These atypical proliferative nodules can show a high proliferative rate with ki-67 along with expression with bcl-2 and p53. However, they reportedly behave in a benign fashion.