Nevi and Malignant Melanoma

Nevus Cells

The nevus cell differs from melanocytes. The nevus cell is larger, lacks dendrites, has more abundant cytoplasm, and contains coarse granules. Nevus cells aggregate in groups (nests) or proliferate in a non-nested pattern in the basal region at the dermoepidermal junction. Nevus cells in the dermis are classified into types A (epithelioid), B (lymphocytoid), and C (neuroid). Through a process of maturation and downward migration, type A epidermal nevus cells develop into type B cells and then into type C dermal nevus cells.

Incidence and Evolution

Moles are so common that they appear on virtually every person. They are present in 1% of newborns and increase in incidence throughout infancy and childhood. The incidence peaks in the fourth to fifth decades. Nevi then diminish in number with advancing age.

Size and pigmentation may increase at puberty and during pregnancy. Nevi may occur anywhere on the cutaneous surface. There is a strong correlation between sun exposure and the number of nevi. Acquired nevi on the buttocks or female breast are unusual.

Nevi Versus Melanoma

Nevi exist in a variety of characteristic forms that must be recognized to distinguish them from malignant melanoma. Except for certain types, such as large congenital nevi and atypical moles, most nevi have a very low malignant potential.

Nevi vary in size, shape, surface characteristics, and color. The important fact to remember is that each individual nevus tends to remain uniform in color and shape. Although various shades of brown and black may be present in a single lesion, the colors are distributed over the surface in a uniform pattern.

Melanomas consist of malignant pigment cells that grow and extend with little constraint through the epidermis and into the dermis. Such unrestricted growth produces a lesion with a haphazard or disorganized appearance, which varies in shape, color, and surface characteristics. The characteristics of uniformity cannot always be relied on to differentiate benign from malignant lesions because very early melanomas may appear quite uniform, having a round or oval shape with a uniform brown color.

Examination With a Hand Lens and Dermoscope

Careful inspection of suspicious lesions with a powerful hand lens and dermoscope will reveal a number of features that cannot be appreciated with the naked eye. Dermoscopy is discussed at the end of the chapter.

Classification

Common moles are subdivided into three types – junction, compound, and dermal – based on the location of the nevus cells in the skin ( Fig. 22.1 ). The three types represent sequential developmental stages in the life history of a mole. During childhood, nevi begin as flat junction nevi in which the nevus cells are located at the dermoepidermal junction. They evolve into compound nevi when some of the cells migrate into the dermis. Migration of all of the nevus cells into the dermis results in a dermal nevus. Dermal nevi usually form only in adults, but this evolution does not consistently occur. Nevi with cells confined to the dermoepidermal junction area tend to be flat, whereas those with cells confined to the dermis are usually elevated.

Junction Nevi

Junction nevi are flat (macular) or slightly elevated, and they are light brown to brown-black with uniform pigmentation that may be slightly irregular ( Fig. 22.2 ). The surface is smooth and flat to slightly elevated, and the border is round or oval and symmetric. Most lesions are hairless. Junction nevi vary in size from 0.1 to 0.6 cm; some are larger. Junction nevi may change into compound nevi after childhood, but they remain as junction nevi on palms, soles, and genitalia. Junction nevi are rare at birth and generally develop after the age of 2 years. Degeneration into melanoma is very rare.

Compound Nevi

Compound nevi are slightly elevated and skin-colored or brown. They are elevated and smooth or warty and become more elevated with increasing age ( Fig. 22.3 ). They are uniformly round, oval, and symmetric. Hair may be present. If a white halo appears at the periphery of the lesion, it is referred to as a halo nevus.

Dermal Nevi

Dermal nevi are brown or black, but may become lighter or skin-colored with age. Lesions vary in size from a few millimeters to a centimeter. The variety of shapes reflects the evolutionary process in which moles extend downward with age and nevus cells degenerate and become replaced with fat and fibrous tissue.

Dome-shaped lesions are the most common ( Figs. 22.4 to 22.6 ). They generally appear on the face and are symmetric, with a smooth surface. They may be white or translucent, with telangiectatic vessels on the surface mimicking basal cell carcinoma. The structure may be warty ( Fig. 22.7 ) or polypoid ( Fig. 22.8 ). Pedunculated lesions with a narrow stalk are located on the trunk, neck, axillae, and groin. They may appear as a soft, flabby, wrinkled sack ( Fig. 22.9 ). Solitary cutaneous mucinosis, spiradenoma, eccrine poroma, and palisaded encapsulated neuroma can mimic dermal nevi ( Figs. 22.10 to 22.13 ).

Elevated nevi are exposed and are prone to trauma from clothing and other stimuli, often causing them to bleed and inflame, making some patients suspect malignancy. A white border may appear, creating a halo nevus. Degeneration to melanoma is very rare, but dermal nevi may resemble nodular melanoma (NM); therefore knowledge of duration and a history of recent change is important.

Suspicious Lesions

Any pigmented lesion suspected of being malignant should be biopsied or referred for a second opinion. Suspicious lesions should be completely removed by excisional biopsy down to and including subcutaneous tissue.

Nevi

Patients frequently request removal of nevi for cosmetic purposes. It is good practice to biopsy all pigmented lesions; therefore total removal by electrocautery should be avoided. Nevi are removed either by shave excision or by simple excision and closure with sutures. Most common nevi are small and shave excision is adequate.

Recurrent Previously Excised Nevi (Pseudomelanoma)

Weeks to months after incomplete removal of a nevus, brown macular pigmentation may appear in the scar ( Fig. 22.14 ). Some nevus cells remain with shave excision and partial repigmentation is possible. Residual pigmentation may be removed with electrocautery or cryosurgery. An unusual histologic picture resembling melanoma (pseudomelanoma) may follow partial removal of nevi. If the repigmented area is excised, the pathologist should be notified that the submitted tissue was acquired from a previously treated area. Histologically, the melanocytes appear atypical but are confined to the epidermis, and there is no lateral spread of individual melanocytes as is seen in melanoma.

Nevi With Small Dark Spots

A small percentage of small dark spots within melanocytic nevi (MNs) are due to melanoma. These roundish areas of brown or black hyperpigmentation measure 3 mm or less in diameter and are located peripherally. Biopsy specimens of nevi with small dark dots should be sectioned to ensure histologic examination of this focus of hyperpigmentation.

Congenital Melanocytic Nevi

It is estimated that between 1% and 6% of the population have a congenital melanocytic nevus (CMN). Congenital melanocytic nevi (birthmarks) are present at birth and vary in size from a few millimeters to several centimeters, covering wide areas of the trunk, extremity, or face. Some lesions first become apparent during infancy. Not all pigmented lesions present at birth are CMNs; café-au-lait macules and neurofibromas may also be present at birth. Congenital nevi may contain hair; if present, it is usually coarse. Such nevi are uniformly pigmented, with various shades of brown or black predominating, but red or pink may be a minor or sometimes predominant color. Most are flat at birth but become thicker during childhood, and the surface becomes verrucous and sometimes nodular. Scalp CMN may lighten with time. Table 22.1 summarizes clinical considerations for CMN.

Classification

The diameter of CMNs serves as the major criterion for determining risks of adverse outcomes such as melanoma. Other factors such as diameter, satellite nevus count, anatomic localization, color heterogeneity, surface rugosity, hypertrichosis, and dermal or subcutaneous nodules should be considered when examining CMNs.

Small Congenital Melanocytic Nevi

The incidence of malignant degeneration in small congenital nevi (<1.5 cm in diameter) is extremely low and prophylactic removal is not recommended ( Fig. 22.15 ). Melanomas arising within a small CMN occur superficially and may be detected visually at an early stage. In most cases, prophylactic excision is performed after puberty, since melanoma does not tend to occur within the early childhood years. Multiple factors must be considered in the management of small CMN (see Table 22.1 ).

Medium-Sized Congenital Melanocytic Nevi

The risk of the occurrence of malignant melanoma in medium-sized (1.5 to 19.9 cm in diameter) CMN is the subject of controversy ( Figs. 22.16 and 22.17 ). Management is determined on a case-by-case basis. Banal-appearing medium-sized CMN may be observed for changes and should not be prophylactically removed. Individual medium-sized CMN should be monitored for change with photographs. Changing or suspicious areas within the nevus should be biopsied or the entire CMN should be surgically removed (see Table 22.1 ).

Large Congenital Melanocytic Nevi (LCMN)

LCMN may undergo malignant transformation (see Table 22.1 ; Figs. 22.18 and 22.19 ). The incidence ranges from 1.8% to 7.1%. Approximately half of the melanomas occur by 3 to 5 years of age. Many of the melanomas arise within the deeper tissues and therefore are detected at advanced stages. Melanoma occurs less often in the head and neck location and has not been detected within satellite nevi. Management of large CMN requires a multidisciplinary approach to care (see Table 22.1 ).

Dermoscopy of Congenital Melanocytic Nevi

The most commonly observed dermoscopic features are globules (79.7%), reticular networks (70.3%), hypertrichosis (68.9%), milia-like cysts (52.7%), and perifollicular hypopigmentation (32.4%).

Neurocutaneous Melanosis (NCM)

Proliferation of melanocytes in the leptomeninges and CNS may occur in patients with CMN. Patients at greatest risk for NCM are those with large CMN >40 cm, multiple satellite nevi, and more than two medium-sized CMN. MRI with gadolinium is the best test to detect NCM (see Table 22.1 ). The median age of presentation is 2 years of age. Patients may have developmental disabilities and seizures. Death occurs in up to 34% of patients with symptomatic NCM. Patients with NCM must be followed closely by a neurologist and have serial MRI examinations (see Table 22.1 ).

Management of Congenital Melanocytic Nevi

Risk assessment and treatment options are considered for each patient. Medical and psychosocial concerns need to be discussed. Management goals are to decrease the risk for developing melanoma by surgical removal and to produce good cosmetic results. Removal of a small CMN, with a low risk for developing melanoma, may result in a disfiguring scar and would not be acceptable. Removal of a large, thick CMN that leaves a large, dense scar may be acceptable. Timing of surgery is a consideration. The best surgical scars result from surgery performed early in life; however, it may be best to delay surgery until after age 2 when the full extent of the nevus is evident. Very large lesions may require multiple procedures. CMNs should be removed down to the fascial layer.

Prophylactic Treatment

Prophylactic removal is considered for thick lesions in which it is difficult to detect melanoma. Dense nevi with a wrinkled (rugous) surface have the greatest risk. Growths that appear in covered areas (e.g., scalp, medial buttocks, perianal, genital areas) that are difficult to examine and follow are considered for early excision.

Speckled Lentiginous Nevus

Speckled lentiginous nevus (nevus spilus) is a common hairless, oval or irregularly shaped brown lesion that is dotted with darker brown-to-black spots. They may appear at any age. Lesions can appear at birth or in early infancy as lightly colored café-au-lait macules. Pigmented macules and papules then develop over a period of months to years. Lesions may be very large. It has been suggested that speckled lentiginous nevus is a subtype of CMN. The brown area is usually flat, and the black dots may be slightly elevated and contain typical nevus cells ( Fig. 22.20 ). The spots range from 1 to 3 mm in diameter and may be lentigines, junctional, compound, or intradermal nevi. The background hyperpigmentation histologically has the features of a lentigo or café-au-lait macule. There is considerable variation in size, ranging from 1 to 20 cm. The anatomic position or time of onset is not related to sun exposure. Transformation into melanoma is rare. The risk of transformation may be similar to that for classic congenital nevi of similar size. Examine lesions periodically and educate the patient regarding the clinical signs of melanoma. Routine excision is not necessary. Biopsy suspicious areas. Speckled lentiginous nevus is flat and necessitates excision and closure if the patient desires removal. Lasers have been used to treat both the background hyperpigmentation and the speckles of speckled lentiginous nevi.

Becker Nevus

Becker nevus is not a nevocellular nevus because it lacks nevus cells. The lesion is a developmental anomaly consisting of either a brown macule ( Fig. 22.21 ) or a patch of hair ( Fig. 22.22 ), or both ( Fig. 22.23 ). Nonhairy lesions may later develop hair. The lesions appear in adolescent men on the shoulder, submammary area, and upper and lower back; they rarely appear on the lower limbs. Becker nevus varies in size and may enlarge to cover the entire upper arm or shoulder. The border is irregular and sharply demarcated.

Becker nevus syndrome is the presence of an epithelial nevus showing hyperpigmentation, increased hairiness, and hamartomatous augmentation of smooth muscle fibers as well as other developmental defects such as ipsilateral hypoplasia of the breast and skeletal anomalies, including scoliosis, spina bifida occulta, or ipsilateral hypoplasia of a limb. The Becker nevus syndrome usually occurs sporadically.

Dermoscopic features of Becker nevus include network, focal hypopigmentation, skin furrow hypopigmentation, hair follicles, perifollicular hypopigmentation, and vessels.

Becker nevus is usually too large to remove by excision. The hair may be shaved or permanently removed. Laser removal of hair and pigmentation is reported.

Halo Nevi

A compound or dermal nevus that develops a white border is called a halo nevus. The incidence in the population is estimated to be 1%. Halo nevi are found most commonly in children. The average age of onset is 15 years. Halo nevi typically persist for a decade or longer. The depigmented halo is symmetric and round or oval with a sharply demarcated border ( Fig. 22.24 ). There are no melanocytes in the halo area. Halo nevi have the dermoscopic features of benign MNs, with globular and/or homogeneous patterns that are typically observed in children and young adults. Halo nevi structural patterns remain unchanged over time. Patients with Turner syndrome (short stature, gonadal dysgenesis, webbed neck, cubitus valgus, and lymphedema at birth) have a halo nevus prevalence of 18%.

Histologic Characteristics

T lymphocytes at the site of depigmentation suggest that these cells participate in the halo phenomenon. Most halo nevi are located on the trunk; they never occur on palms and soles. They may occur as an isolated phenomenon, or several nevi may spontaneously develop halos. Halos may repigment with time, or the nevus may disappear. Repigmentation often takes place over months or years; however, it does not always occur. Repigmentation does not follow removal of the nevus. The incidence of vitiligo may be increased in patients with halo nevi. A halo may rarely develop around malignant melanoma, but in such instances it is usually not symmetric.

Removal of a halo nevus is unnecessary unless the nevus has atypical features. Parental concern over this impressive change is often the reason for a conservative excision. In such cases, the mole part of a halo nevus may be removed by shave, excision, or laser.

Spitz Nevus

Spitz nevus (Spitz tumor, spindle and epithelioid cell nevus) is most common in children but does appear in adults. The most frequent sites include the head and neck regions (37%) and lower extremities (28%). They are hairless, red or reddish-brown, dome-shaped papules or nodules with a smooth ( Fig. 22.25 ) or warty surface; they vary in size from 0.3 to 1.5 cm. The color is caused by increased vascularity, and bleeding sometimes follows trauma. Spitz nevi are usually solitary but may be multiple. They appear suddenly and, contrary to slowly evolving common moles, patients can sometimes date their onset. Banal-appearing, stable Spitz nevi may be monitored clinically. Atypical Spitz nevi (growing, bleeding, change in color, unusual dermoscopic findings) should be completely removed for microscopic examination. Histologic differentiation from melanoma is sometimes difficult. Histopathologic features that suggest more aggressiveness relate to mitotic activity, mitoses near the base, and inflammation.

Dermoscopy of Spitz nevus shows: (1) a starburst pattern, characterized by a prominent, black to blue diffuse pigmentation and pseudopods regularly distributed at the periphery in a radiate pattern; and (2) a globular pattern, typified by a discrete, brown to gray-blue pigmentation and a peripheral rim of large brown globules, often extending throughout the entire lesion.