Section 10. Nevi

A young woman comes to the office because her husband has noted that the moles on her back are changing (Figure 162-1). A few have white halos around the brown pigmentation and some have lost their pigment completely, with a light area remaining. She has no symptoms but wants to make sure these are not skin cancers. Halo nevi are an uncommon variation of common nevi. These appear benign and the patient is reassured.

Most nevi are benign tumors caused by the aggregation of melanocytic cells in the skin. However, nevi can occur on the conjunctiva, sclera and other structures of the eye. There are also nonmelanocytic nevi that are produced by other cells as seen in Becker nevi and comedonal nevi. Although most nevi are acquired, many nevi are present at birth.

Moles.

• Acquired nevi are common lesions, forming during early childhood; few adults have none.
• Prevalence appears to be lower in dark-skinned individuals.
• Present in 1% of neonates increasing through childhood and peaking at puberty; new ones may continue to appear in adulthood. In a population study of children (N = 180, ages 1 to 15 years) in Barcelona, the mean number of nevi was 17.5.1
• Adults typically have 10 to 40 nevi scattered over the body. In a population study in Germany, 60.3% of 2823 adults (mean age: 49 years; 50% women) exhibited 11 to 50 common nevi and 5.2% had at least 1 atypical nevus.2
• The peak incidence of melanocytic nevi (MN) is in the fourth to fifth decades of life; the incidence decreases with each successive decade.3

• Benign tumors composed of nevus cells derived from melanocytes, pigment-producing cells that colonize the epidermis.
• MN represent proliferations of melanocytes that are in contact with each other, forming small collections of cells known as nests. Genetic mutations present in common nevi as well as in melanomas include BRAF, NRAS, and c-kit.4
• Sun (UV) exposure, skin-blistering events (e.g., sunburn), and genetics play a role in the formation of new nevi.3
• Nevi commonly darken and/or enlarge during pregnancy. Melanocytes have receptors for estrogens and androgens and melanogenesis is responsive to these hormones.3
• Three broad categories of MN are based on location of nevus cells2:
  • Junctional nevi—Composed of nevus cells located in the dermoepidermal junction; may change into compound nevi after childhood (except when located on the palms, soles, or genitalia) (Figure 162-2).
  • Compound nevi—A nevus in which a portion of nevus cells have migrated into the dermis (Figure 162-3).
  • Dermal nevi—Composed of nevus cells located within the dermis (usually found only in adults). These are usually raised and have little to no visible hyperpigmentation (Figures 162-4 and 162-5).
• Special categories of nevi:
  • Halo nevus—Compound or dermal nevus that develops a symmetric, sharply demarcated, depigmented border (Figure 162-1). Most commonly occurs on the trunk and develops during adolescence. Repigmentation may occur.
  • Blue nevus—A dermal nevus that contains large amounts of pigment so that the brown pigment absorbs the longer wavelengths of light and scatters blue light (Tyndall effect) (Figure 162-6). Blue nevi are not always blue and color varies from tan to blue, black, and gray. Types of blue nevi include amelanotic, desmoplastic, atypical, and malignant variants; genetic mutations seen in blue nevi are often different than those seen in common nevi and include the Gαq class of G-protein α subunits, Gnaq, and Gna11 proteins.4 The nodules are firm because of associated stromal sclerosis. Usually appears in childhood on the extremities, dorsum of the hands and face. A rare variant, the cellular blue nevus is large (>1 cm), frequently located on the buttocks, and may undergo malignant degeneration.
  • Nevus spilus—Hairless, oval, or irregularly shaped brown lesion with darker brown to black dots containing nevus cells (Figure 162-7). May appear at any age or be present at birth; unrelated to sun exposure.
  • Spitz nevus (formerly called benign juvenile melanoma because of its clinical and histologic similarity to melanoma)—Hairless, red, or reddish brown dome-shaped papules generally appearing suddenly in children, sometimes following trauma (Figures 162-8 and 162-9). The pink color is caused by increased vascularity. Most importantly, these should be fully excised with clear margins.
  • Nevus of Ota—Dark brown nevus that occurs most commonly around the eye and can involve the sclera (Figure 162-10).
• Both acquired and congenital MN hold some risk for the development of melanoma; the number of MN, especially more than 100, is an important independent risk factor for cutaneous melanoma.5

Nonmelanocytic Nevi

• Becker nevus—A brown patch often with hair located on the shoulder, back or submammary area, most often in adolescent men (Figures 162-11 and 162-12). The lesion may enlarge to cover an entire shoulder or upper arm. Although it is called a nevus, it does not actually have nevus cells and has no malignant potential. It is a type of hamartoma, an abnormal mixture of cells and tissues normally found in the area of the body where the growth occurs.
• Nevus depigmentosus is usually present at birth or starts in early childhood. There is a decrease number of melanosomes within a normal number of melanocytes. It typically has a serrated or jagged edge (Figure 162-13).
• Nevus anemicus—A congenital hypopigmented macule or patch that is stable in relative size and distribution. It occurs as a result of localized hypersensitivity to catecholamines and not a decrease in melanocytes. On diascopy (pressure with a glass slide) the skin is indistinguishable from the surrounding skin (Figure 162-14).
• Nevus comedonicus (comedonal nevus) is a rare congenital hamartoma characterized by an aggregation of comedones in one region of the skin (Figure 162-15).
• Epidermal nevi are congenital hamartomas of ectodermal origin classified on the basis of their main component: sebaceous, apocrine, eccrine, follicular, or keratinocytic. See Chapter 163, Congenital Nevi for a full discussion of this type of nevus.

Note nevus comedonicus and epidermal nevi tend to follow Blaschko lines, which come from embryologic development.

• In the Barcelona study of children, male gender, past history of sunburns, facial freckling, and family history of breast cancer were independent risk factors for having a higher number of nevi.1
• In one study among very light-skinned (and not darker skinned) children without red hair, children who develop tans have greater numbers of nevi.6
• Neonatal blue-light phototherapy is not related to nevus count.7

Clinical Features

Most benign MN are tan to brown, usually less than 6 mm, with round shape and sharp borders.

• Junctional nevi—Macular or slightly elevated mole of uniform brown to black pigmentation, smooth surface, and a round or oval border (Figure 162-2). Most are hairless and vary from 1 to 6 mm.
• Compound nevi—Slightly elevated, symmetric, uniformly flesh colored or brown with a round or oval border, often becoming more elevated with age (Figure 162-3). Hair may be present and a white halo may form.
• Dermal nevi (same as intradermal nevi)—Skin color or brown color that may fade with age; dome shaped is most common, but shapes vary, including polypoid, warty, and pedunculated. Often found on the face and may have telangiectasias (Figures 162-4 and 162-5). Size ranges from 1 to 10 mm.

Typical Distribution

• Most often above the waist on sun-exposed areas but may appear anywhere on the cutaneous surface; less commonly found on the scalp, breasts, or buttocks.
• Among the children in the Barcelona study, 61.1% had nevi on the face and neck, 17.2% on the buttocks, and 11.7% on the scalp; approximately one-third had congenital nevi (Chapter 163, Congenital Nevi).1
• In an Australian study of white children, MN of all sizes were highest on the outer forearms, followed by the outer upper arms, neck, and face.8 Boys had higher densities of MN of all sizes on the neck than girls, and girls had higher densities of MN of 2 mm or greater on the lower legs and thighs than boys. Habitually sun-exposed body sites had higher densities of small MN and highest prevalence of larger MN.

Imaging

• Dermoscopy can be a useful technique for diagnosing benign nevi. For MN, dermoscopic diagnosis relies on color; pattern (i.e., globular, reticular, starburst, and homogeneous blue pattern); pigment distribution (i.e., multifocal, central, eccentric, and uniform); and special sites (e.g., face, acral areas, nail, and mucosa), in conjunction with patient factors (e.g., history, pregnancy).9 (See Appendix C: Dermoscopy.)
• In the Barcelona study, the most frequent dominant dermoscopic pattern was the globular type with the homogeneous pattern predominating in the youngest children and the reticular pattern predominating in adolescents.1

Biopsy

Biopsy is necessary if you suspect melanoma or a Spitz nevus. A biopsy that cuts below the pigmented area is preferred if there is a reasonable suspicion for melanoma. This can be done with a scoop shave, a punch that gets the whole lesion, or an elliptical excision. If the patient wants a raised benign appearing nevus excised for cosmetic reasons, a shave excision may be adequate. Send all lesions (except skin tags) to the pathologist for examination, even when they appear benign, to avoid missing a melanoma.

Benign nevi may develop atypia or become melanoma. This should be suspected if a lesion has atypical features including asymmetry, border irregularity, color variability, diameter greater than 6 mm, and evolving (called the ABCDE approach [asymmetry, border irregularity, color irregularity, diameter >6 mm, evolution]). Any lesion that becomes symptomatic (e.g., itchy, painful, irritated, or bleeding), or develops a loss or increase in pigmentation, should be evaluated and biopsied if needed. Dermoscopy can be used to increase one's accuracy in distinguishing between benign and malignant lesions (see Appendix C, Dermoscopy).

• Melanomas are skin cancers that may develop from a preexisting nevus. The most important skill to develop is how to distinguish a benign nevus from a nevus that might be malignant melanoma. Because clinical appearance can be misleading, a biopsy is necessary when there is a reasonable suspicion for cancer (Chapter 172, Melanoma).
• Dysplastic or atypical nevi are variants that are relatively flat, thinly papular, and relatively broad. Often, the lesions exhibit target-like or fried egg-like morphology, with a central papular zone and a macular surrounding area with differing pigmentation (Chapter 165, Dysplastic Nevus).
• Seborrheic keratoses are benign growths that appear more with increasing age and are often hyperpigmented as seen with many nevi. These are more superficial and stuck-on in their appearance (Chapter 158, Seborrheic Keratosis).
• Labial melanotic macules are benign dark macules on the lip that are not nevi and not melanomas (Figure 162-16). They can be removed for cosmetic purposes.

Nevi are generally only removed for cosmetic reasons or because of concern over changes in the lesion suggestive of dysplasia or melanoma.

• A full excisional biopsy with a sutured closure is usually the best means to diagnose a lesion if concern exists regarding the possibility of melanoma. If the lesion is found to be benign, no further treatment is usually required.
• Punch excision can be used to excise smaller lesions.
• Scoop shave—Unfortunately, if a punch biopsy is used to sample a larger lesion it may miss a melanoma in another part of the lesion. A broad scoop shave is better than a punch biopsy when a full elliptical excision is not possible or desirable (e.g., a large flat pigmented lesion on the face).
• Nevi removed for cosmesis are often removed by shave excision.3

If a Spitz nevus is suspected, either biopsy it now or schedule the patient for a full excision. The histopathology is too close to a melanoma to just watch it.

• Becker nevi and comedonal nevi do not become melanoma because they lack melanocytes. Therefore, there is no reason to excise them. Generally, these are large and the risks of excision for cosmetic reasons outweigh the benefits.

• Sun protection to limit sunburn may help reduce the appearance of nevi. In a trial of 209 white children, children randomized to the sunscreen group, especially those with freckles, had significantly fewer new nevi on the trunk than did children in the control group at 3-year follow-up.10

• Degeneration of common nevi into melanoma is very rare.
• Patients with multiple or large MN appear to have an increased risk of melanoma.3
• Nevi may recur or persist following removal; in one study, dysplastic MN were the most likely to persist.11 In another study, of 61 benign nevi biopsy sites reexamined, two (3.3%) recurred.12

• Patients with multiple or sizable MN should be followed by an experienced clinician because they appear to have an increased lifetime risk of melanoma, with the risk increasing in rough proportion to the size and/or number of lesions.3

• Patients should be encouraged to use sunscreen to prevent skin cancer as well as to reduce the development of new nevi.
• Patients with multiple or sizable MN should be taught to look for and report asymmetry, border irregularity, new symptoms, and color and size changes.

Patient Resources

• VisualDxHealth. Good information with excellent photographs—http://www.visualdxhealth.com/adult/nevus.htm.
• MedlinePlus—http://www.nlm.nih.gov/medlineplus/moles.html.
• American Osteopathic College of Dermatology—http://www.aocd.org/skin/dermatologic_diseases/moles.html.
• American Academy of Dermatology—http://www.aad.org/for-the-public.

Provider Resources

• http://emedicine.medscape.com/article/1058445-overview.

A small congenital nevus (Figure 163-1) was noted on this 6-month-old child by his new family physician during a routine examination. The parents acknowledged that it was present from birth and asked if it needed to be cut out. They were reassured that nothing needs to be done about it at this time.

Congenital melanocytic nevi are benign pigmented lesions that have a wide variation in presentation and are composed of melanocytes, the pigment-forming cells in the skin (Figures 163-1, 163-2, 163-3, 163-4, 163-5, 163-6, and 163-7).

• Garment nevus, bathing trunk nevus, giant hairy nevus, giant pigmented nevus, pigmented hairy nevus, nevus pigmentosus, nevus pigmentosus et pilosus, and Tierfell nevus.1
• Tardive congenital nevus refers to a nevus with similar features to congenital nevi, but appears at age 1 to 2 years.

• Congenital melanocytic nevi develop in 1% to 6% of newborns and are present at birth or develop during the first year of life.1
• In an Italian prevalence study of more than 3000 children ages 12 to 17 years, congenital melanocytic nevi or congenital nevus-like nevi were found in 17.5%; most (92%) were small (<1.5 cm).2
• Congenital nevi are also seen in neurocutaneous melanosis, a rare syndrome characterized by the presence of congenital melanocytic nevi and melanotic neoplasms of the central nervous system.
• The development of melanoma within congenital nevi (Figure 163-8) is believed to occur at a higher rate than in normal skin. Estimates range from 4% to 10%, with smaller lesions having lowest risk.1
  • In a systematic review, 46 of 651 patients with congenital melanocytic nevi (0.7%), who were followed for 3.4 to 23.7 years, developed melanomas, representing a 465-fold increased relative risk of developing melanoma during childhood and adolescence.3 The mean age at diagnosis of melanoma was 15.5 years (median: 7 years).
  • Patients with giant congenital melanocytic nevi appear to be at highest risk where subsequent melanoma has been reported in 5% to 7% by age 60 years.4 In one study, 70% of patients with a large congenital melanocytic nevi diagnosed with melanoma were diagnosed within the first 10 years of life.5
  • In a prospective study of 230 medium-size congenital nevi (1.5 to 19.9 cm) in 227 patients from 1955 to 1996, no melanomas occurred. The average follow-up period being 6.7 years to an average age of 25.5 years.6
  • Other risk factors for melanoma include personal or family history of melanoma or other skin cancer, presence of multiple nevi, red hair, blue eyes, freckling, and history of radiation (see Chapter 172, Melanoma).1

• The etiology of congenital nevi is unknown.
• Congenital nevi result from a proliferation of benign melanocytes in the dermis, epidermis, or both. Melanocytes of the skin originate in the neuroectoderm and migrate vertically to the skin and other locations such as the central nervous system and eye.1 Defects in migration or maturation are hypothesized as causal.

Diagnosis is usually made based on clinical features and the history of the nevus being present at birth or develop during the first year of life.

Clinical Features1

• Variable mixtures of color including pink-red (primarily at birth), tan, brown, black, or multiple shades within a single lesion (Figures 163-1, 163-2, 163-3, 163-4, 163-5, 163-6, and 163-7); color usually remains constant over time but the nevus will grow as the person grows.
• Shapes are also highly variable, including oval, round, linear, and random; lesions have irregular but well-demarcated borders (Figures 163-1, 163-2, 163-3, 163-4, 163-5, 163-6, 163-7, and 163-8). The pigment may fade off into surrounding skin (Figures 163-3 and 163-4).
• Nevi may become raised over time (Figures 163-2 and 163-3) and the skin surface ranges from smooth to pebbly to hyperkeratotic (eczema-like appearance).
• Macular portion usually found at edges.
• Frequently exhibit hypertrichosis (Figure 163-5).
• Heavily pigmented large congenital melanocytic nevi over a limb may be associated with underdevelopment of the limb.1
• Lesions are classified by size in adulthood as:1
  • Small (<1.5 cm) (Figure 163-1).
  • Medium (1.5 cm to 19 cm) (Figures 163-2 and 163-3).
  • Large (>20 cm) (Figures 163-5, 163-6, and 163-7). Giant nevi are often surrounded by several smaller satellite nevi (Figures 163-5, 163-6, and 163-7).
  • Lesions on a child's head of less than 9 cm or body of greater than 6 cm are considered large based on likely eventual growth.1

Imaging

• Dermoscopy findings depend on the age and location. In one study, the globular pattern was most common in children younger than age 11 years and on the trunk.7 The majority of reticular lesions were located on the limbs and the variegated pattern was the most specific for congenital nevi.
• MRI of the central nervous system can be a useful diagnostic tool in patients suspected of having neurocutaneous melanosis; one author recommended a screening MRI for patients with giant congenital melanocytic nevi.8

Typical Distribution

• Congenital nevi can be found anywhere on the body.

Biopsy

• Although there are many histologic subtypes, distinguishing histologic features of congenital nevi include:1
  • Involvement by nevus cells of deep dermal appendages and neurovascular structures (e.g., hair follicles, sebaceous glands, arrector pili muscles, and within walls of blood vessels).
  • Infiltration of nevus cells between collagen bundles.

• Becker nevus—A brown macule, patch of hair, or both on the shoulder, back, or submammary area that develops in adolescence. The border is irregular and the lesion may enlarge to cover an entire shoulder or upper arm. It is a type of hamartoma and is not a melanocytic nevus (see Chapter 162, Nevus).
• Café-au-lait spots—Coffee-and-milk-colored patch that can be present at birth or develop during early childhood. Although a number of large café-au-lait spots are associated with neurofibromatosis, a few of them can occur in completely unaffected children. These light-brown patches have increased melanin but are not nevi (see Chapter 234, Neurofibromatosis).

The management of congenital nevi depends on size and location of the lesion (difficulty in monitoring), associated symptoms, the age of the patient, the effect on cosmesis, and the potential for malignant transformation.

• For small- and medium-size congenital melanocytic nevi, the risk of malignant transformation is small and prophylactic removal is not recommended. For cosmesis, treatments include surgical excision or laser treatment.
• Larger congenital nevi can be surgically removed but may require tissue expanders, tissue grafts, and tissue flaps to close large defects. Excisions can also be staged in multiple steps. Because the melanocytes may extend deep into underlying tissues (including muscle, bone, and central nervous system), removing the cutaneous component may not eliminate the risk of malignancy.
  • There is also concern that surgical intervention may adversely affect congenital melanocytic nevi cells.9
• Laser treatment of the lesions has been performed with a number of different types of lasers.10 Because of the lack of penetrance to deeper tissue levels, long-term recurrence or malignant transformation is also an issue with these techniques.
• Careful life long follow-up with photographs is an acceptable approach, especially now with the affordability of digital cameras.
• Garment or bathing trunk nevi (Figures 163-5, 163-6, and 163-7):
  • Approximately half of the melanomas that develop in bathing trunk nevi do so before age 5 years.11 These melanomas can be missed by observation because they can have nonepidermal origins.
  • Surgical excision is recommended by some experts to prevent melanoma.11 SOR C.
• Changes to watch for that call for a biopsy include:
  • Partial regression (depressed white areas).
  • Inflammation.
  • Rapid growth or color change.
  • Development of a firm nodule (Figure 163-8).

• All patients should be told about the importance of protection from UV light exposure. This is especially important in people with giant congenital nevi, because they at a significantly increased risk of melanoma.
• Patients (or their parents) should be taught to look for signs of melanoma (ABCDE) (asymmetry, border irregularity, color irregularity, diameter >6 mm, evolution).

• Patients with giant congenital nevi or multiple congenital nevi may benefit from consultation with a neurologist, pediatrician, or both, because of the risk of neurocutaneous melanosis and its neurologic manifestations or obstructive hydrocephalus.
• Bathing trunk nevi can also be associated with spina bifida, meningocele, and neurofibromatosis.11
• Because patients with all forms of congenital nevi, especially giant congenital melanocytic nevi, have an increased risk of developing melanoma, physicians should consider baseline photography and regular follow-up with an experienced clinician for these patients.

Patient Resources

• http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001831/.
• Giant congenital nevi—http://www.nlm.nih.gov/medlineplus/ency/article/001453.htm.
• Support group—http://www.nevus.org.

Provider Resources

• http://emedicine.medscape.com/article/1118659.
• http://www.dermatlas.org.

A 15-year-old boy is brought in by his mother with a concern about growth of his birthmark. It has become somewhat more raised and bumpy in the past year (Figure 164-1). The adolescent reports no symptoms and is not worried about the appearance. He is otherwise healthy with no neurologic symptoms. The joint decision of the family and the doctor was to not excise the epidermal nevus at this time. He may choose to have this removed by a plastic surgeon in the future.

• Epidermal nevi (EN) are congenital hamartomas of ectodermal origin classified on the basis of their main component: sebaceous, apocrine, eccrine, follicular, or keratinocytic.
• Nevus sebaceous (NS) is a hamartoma of the epidermis, hair follicles, and sebaceous and apocrine glands. A hamartoma is the disordered overgrowth of benign tissue in its area of origin.

• EN syndrome is also called Solomon syndrome and is a neurocutaneous disorder characterized by EN and an assortment of neurologic and visceral manifestations.
• NS is also called sebaceous nevus and nevus sebaceus of Jadassohn (Figure 164-2).
• An inflammatory linear verrucous epidermal nevus (ILVEN) (Figure 164-3) can be part of an epidermal nevus syndrome but some affected persons only have the cutaneous EN.

• EN are uncommon (approximately 1% to 3% of newborns and children), sporadic, and usually present at birth, although they can appear in early childhood (Figure 164-4).
• EN are associated with disorders of the eye, nervous, and musculoskeletal systems in 10% to 30% of patients; in one study, 7.9% of patients with EN had 1 of the 9 syndromes—an estimated 1 per 11,928 pediatric patients.1
• In another review of 131 cases of EN, most (60%) had noninflammatory EN, one third had NS, and 6% had ILVEN.2
• NS is usually present at birth or noted in early childhood (Figure 164-5).3 Most cases are sporadic but familial cases have been reported.2
• Linear NS is estimated to occur in 1 per 1000 live births.4
• Linear NS syndrome includes a range of abnormalities, including the central nervous system (CNS); patients with CNS involvement typically have cognitive impairment and seizures3; other organ systems, including the cardiovascular, skeletal, ophthalmologic, and urogenital systems, may be involved.

• EN histologically display hyperkeratosis and papillomatosis, similar microscopically to seborrheic keratosis (see Chapter 158, Seborrheic Keratosis).2 Also similar to seborrheic keratosis, some EN of keratinocyte differentiation (approximately one third) have been found to have a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.
• Nine EN syndromes have been reported and are described in the referenced article.5
• EN frequently have a linear pattern that follows Blaschko lines (Figures 164-1, 164-3, and 164-4), which are believed to represent epidermal migration during embryogenesis.
• EN tend to become thicker, verrucous (Figure 164-4), and hyperpigmented at puberty.2
• Similarly, NS demonstrates stages of evolution paralleling the histologic differentiation of normal sebaceous gland:6
  • Infancy and young children—Smooth to slightly papillated, waxy, hairless thickening (Figure 164-5).
  • Puberty—Epidermal hyperplasia resulting in verrucous irregularity of the surface covered with numerous closely aggregated yellow-to-brown papules (Figure 164-6).
  • Development of secondary appendageal tumors (Figures 164-7 and 164-8) occurs in 20% to 30% of patients, most are benign (most commonly basal cell epithelioma or trichoblastoma), but single (most commonly basal cell carcinoma) or multiple malignant tumors of both epidermal and adnexal origins may be seen and metastases have been reported.2 Rarely, these malignancies are seen in childhood.
• NS was shown to have a high prevalence of human papillomavirus DNA and authors postulate that human papillomavirus (HPV) infection of fetal epidermal stem cells could play a role in the pathogenesis.7

Making the Diagnosis

Clinical features of EN

• EN are linear, round, or oblong; well-circumscribed; elevated; and flat-topped (Figures 164-1 and 164-4).
• Color is yellow-tan to dark brown.
• Surface is uniform velvety or warty (Figures 164-4 and 164-5).
• ILVEN, a less common type of EN, is pruritic and erythematous (Figure 164-3).

Clinical features of NS

• NS has an oval to linear shape ranging from 0.5 × 1 cm to 7 × 9 cm.
• NS is usually a solitary, smooth, waxy, hairless thickening noted on the scalp at birth or in early childhood (Figures 164-2 and 164-6).
• Early NS may be pink, orange, yellow, or tan; later lesions can appear verrucous and nodular (Figure 164-5).

Typical Distribution

• EN occur most commonly on the head and neck followed by the trunk and proximal extremities; only 13% have widespread lesions (Figure 164-9). Lesions may spread beyond their original distribution with age.
• NS are commonly found on the scalp followed by forehead and retroauricular region (Figures 164-2 and 164-5, 164-6, 164-7, and 164-8) and rarely involves the neck, trunk, or other areas.

Biopsy

• Biopsy is the most definitive method for diagnosing these nevi. A biopsy is not needed if the clinical picture is clear and no operative intervention is planned. A shave biopsy should provide adequate tissue for diagnosis because the pathology is epidermal and in the upper dermis.
  • Histologic features of epidermolytic hyperkeratosis within an EN are associated with mutations in the keratin gene that may be transmitted to offspring; widespread cutaneous involvement may be seen.2

• Linear lichen planus (Figure 164-10)—Discrete, pruritic, violaceous papules are arranged in a linear fashion, usually extending along an entire limb.
• Syringoma (Figure 164-11)—Benign adnexal tumor derived from sweat gland ducts. Autosomal dominant transmission, soft, small, skin-colored to brown papules develop during childhood and adolescence, especially around the eyes, but may be found on the face, neck, and trunk.
• Lichen striatus—Discrete pink, tan, or skin-colored asymptomatic papules in a linear band that suddenly appear. The papules may be smooth, scaly, or flat topped. It is mostly seen in children. Although it is most commonly seen on an extremity, it can appear on the trunk (Figure 164-12). It can resemble a linear EN but lichen striatus will spontaneously regress within 1 year.
• Linear porokeratosis—Characterized by small, annular, hypertrophic verrucous plaques with a linear morphology usually limited to a single extremity. The annular morphology and dermatomal distribution should help distinguish this condition from EN and NS.

Medications

• There are no proven topical methods for treatment of these lesions. Topical retinoids may improve lesion appearance but recurrence is common.2

Procedures

• Destructive modalities for EN, such as electrodessication and cryotherapy, may temporarily improve the appearance of the lesion, but recurrence is frequent.2
• Carbon dioxide laser is an alternative option for EN; however, scarring and pigment changes are potential permanent complications, especially in patients with darker skin types.8 This treatment does not completely remove NS and there is recurrence risk.2
• Surgical excision is an option that may be complicated by scarring.
• Because of the potential for malignant transformation particularly following puberty, some authors recommend early complete plastic surgical excision for NS; SOR C reconstructive surgery may be needed.
• Excision of large lesions may require reconstructive surgery with a rotation flap to close.9

• There are reports of spontaneous improvement in patients with widespread involvement of EN.
• Malignant potential is low in EN.2
• Malignant potential in NS is uncertain. Reports range from 0% to 2.7%.2
  • Early reports suggested a high rate of developing basal cell carcinomas, whereas more recent studies identified trichoblastoma and syringocystadenoma papilliferum in NS, usually in adulthood.2
  • In a retrospective analysis of 757 cases of NS from 1996 to 2002 in children age 16 years or younger, investigators found no malignancies and question the need for prophylactic surgical removal.10
  • Squamous cell carcinoma has also been described in a NS.11

• Patients with NS should be examined for other associated findings. Consider a consultation with a neurologist and/or ophthalmologist.
  • In a study of 196 subjects with NS examined for clinical neurologic abnormalities, only 7% had abnormalities.12 Abnormal exams were more frequent in individuals with extensive nevi (21% vs. 5%) and a centrofacial location (21% vs. 2%). The patients depicted in this chapter had no neurologic abnormalities.

Patient Resources

• Nevus Outreach. Other Kinds of Nevi—http://www.nevus.org/other-kinds-of-nevi_id559.html.
• Genetics Home Reference. Epidermal Nevus—http://ghr.nlm.nih.gov/condition/epidermal-nevus.

Provider Resources

• Medscape. Nevus Sebaceous—http://emedicine.medscape.com/article/1058733-overview.
• Medscape. Epidermal Nevus Syndrome—http://emedicine.medscape.com/article/1117506-overview.

A 44-year-old man presents with concern over a mole on his back that his wife says is growing larger and more variable in color. The edges are irregular and the color almost appears to be “leaking” into the surrounding skin. He reports no symptoms related to this lesion. On physical exam, the nevus is 9 mm in diameter with asymmetry and variations in color and an irregular border (Figure 165-1). A full-body skin exam did not demonstrate any other suspicious lesions. Dermoscopy showed an irregular network with multiple asymmetrically placed dots off the network (Figure 165-2). A scoop saucerization was performed with a DermaBlade taking 2-mm margins of clinically normal skin (Figure 165-3). Although this could have been an early thin melanoma, the pathology showed a completely excised compound dysplastic nevus with no signs of malignancy. No further treatment was needed except yearly skin exams to monitor for melanoma.

Dysplastic nevi (DN)/atypical moles are acquired melanocytic lesions of the skin whose clinical and histologic definitions are controversial and still evolving. These lesions have some small potential for malignant transformation and patients with multiple DN have an increased risk for melanoma.1

The presence of multiple DN is a marker for increased melanoma risk just as red hair is, and, analogously, cutting off the red hair or cutting out all the DN does not change that risk of melanoma. The problem with DN is that any one lesion that is suspicious for melanoma must be biopsied to avoid missing melanoma, not to prevent melanoma from occurring in that nevus in the future.

Atypical nevus, atypical mole, Clark nevus, nevus with architectural disorder, and melanocytic atypia.1

• Two percent to 9% of the population has atypical moles (AMs).2,3 In a Swedish case-control study, 56% of cases (121 patients with melanoma) and 19% of 310 control subjects had nevi fulfilling the clinical criteria for DN.4 Among patients with melanoma, the rate of DN ranges from 34% to 59%.3 DN are uncommon in children; in a study of Swedish children (N = 524), none had DN.5 In another study of pathology reports from nevi removed from patients younger than 18 years old, 3 of 199 nevi submitted for histologic analysis met the histologic criteria for DN.6
• Individuals with fair skin types are at higher risk of DN.3
• The sudden eruption of benign and atypical melanocytic nevi has been reported and is associated with blistering skin conditions and a number of disease states, including immunosuppression. Subsets of patients with immunosuppression have increased numbers of nevi on the palms and soles.7
• The National Institute of Health Consensus Conference on the diagnosis and treatment of early melanoma defined a syndrome of familial atypical mole and melanoma (FAMM). The criteria of FAMM syndrome are:8
  • The occurrence of malignant melanoma in one or more first- or second-degree relatives.
  • The presence of numerous (often >50) melanocytic nevi, some of which are clinically atypical.
  • Many of the associated nevi show certain histologic features (see below under BIOPSY).

• Most DN are compound nevi (Figure 165-1) possessing a junctional and intradermal component (see Chapter 162, Nevus).1 The junctional component is highly cellular and consists of an irregular distribution of melanocytes arranged in nests and lentiginous patterns along the dermoepidermal junction. The dermal component, located at the center, consists of nests and strands of melanocytes with distinct sclerotic changes.1
• DN exhibit a host response consisting of irregular rete ridge elongation, subepidermal sclerosis, proliferation of dermal capillaries, and a perivascular, lymphohistiocytic inflammatory infiltrate.1
• Individuals with DN may have deficient DNA repair, and DN lesions are associated with overexpression of pheomelanin (pigment produced by melanocytes), which may lead to increased oxidative DNA damage and tumor progression.9

Clinical Features

• Variable mixtures of color including tan, brown, black, and red within a single lesion (Figures 165-4 and 165-5).
• Irregular, notched borders; pigment may fade off into surrounding skin (Figure 165-5).
• Flat or slightly raised (Figures 165-4, 165-5, and 165-6) with the macular portion at edge. Not verrucous or pendulous.
• Lesions frequently surrounded by a reddish hue from reactive hyperemia making them appear target-like.
• Usually larger than 6 mm; may be larger than 10 mm (Figures 165-1 and 165-4).
• Patients with FAMM syndrome may have more than 100 lesions, far greater than the average number of common moles (<50) in most individuals.

Typical Distribution

• Usually on sun-exposed areas, especially the back (Figure 165-5); may be found on sites where nevi are usually absent or rare such as the scalp, breasts, genital skin, buttocks, palm (Figure 165-6), and dorsa of feet.

Imaging

• Although eccentric peripheral hyperpigmented and multifocal hyper- or hypopigmented types are more commonly seen in melanoma, no digital dermatoscopic criteria have been identified that can clearly distinguish DN from in situ melanomas.10 However, dermoscopy increases diagnostic sensitivity and specificity of cutaneous melanoma from 60% to greater than 90%, especially using pattern recognition.3

Biopsy

• The importance of histology is to distinguish DN from melanoma. Although not universally accepted, the World Health Organization Melanoma Program proposed a list of characteristics/criteria with individual lesions requiring two major and two minor criteria to be classified as a DN:3
  • Major criteria are basilar proliferation of atypical nevomelanocytes and organization of this proliferation in a lentiginous or epithelioid cell pattern.
  • Minor criteria are: (a) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (b) neovascularization, (c) inflammatory response, and (d) fusion of rete ridges. These established criteria yielded 92% mean concordance overall by panel members.

• Melanocytic nevi—Most common moles are tan to brown, smaller than 6 mm, round in shape, and with sharp borders (see Chapter 162, Nevus).
• Melanoma—Skin cancer is often asymmetric, with irregular border and varied colors. It is usually larger than 6 mm in diameter (see Chapter 172, Melanoma).

Nonpharmacologic

• Obtain a family history of DN and melanoma for patients presenting with DN.
• Because of the low risk of any one DN developing malignant transformation, the prophylactic removal of all DN is not recommended. SOR C

Medications

• Of the medications tested, including topical 5-fluorouracil, systemic isotretinoin, topical tretinoin with or without hydrocortisone, and topical imiquimod, none completely destroy DN.3

Procedures

• Removal of at least one lesion is reasonable to histologically confirm the diagnosis and rule out melanoma. This should be accomplished with excisional biopsy and histologic confirmation of DN versus melanoma. DN is usually removed with conservative surgical margins (about 2 mm) to provide adequate tissue for the pathologist.3 SOR C
• Scoop saucerizations (deep shave biopsy with a DermaBlade or razor blade) including at least a 2-mm margin of clinically normal skin surrounding the pigmented lesion is a rapid and acceptable method of excision for pathology (Figure 165-7).

• Avoid direct sunlight.

• DNs appear to be dynamic throughout adulthood. In a study of the natural history of DN, investigators found that 51% of all evaluated nevi (297 of 593) showed clinical signs of change during an average follow-up of 89 months.11 New nevi were common in adulthood, continuing to form in more than 20% of patients older than age 50 years, and some nevi disappeared.
• The risk of a melanoma arising within a DN is estimated at 1:3000 per year.1 However, there is also an increased risk of melanoma arising elsewhere on the skin in patients with DN; the actual incidence rate is uncertain and ranges from 0.5% to 46%.3 There is also a substantially increased risk of melanoma associated with the number of atypical nevi (relative risk [RR] = 6.36; 95% confidence interval [CI]: 3.80, 10.33; for 5 versus 0).12
• In one case-control study, the estimated 10-year cumulative risk for developing melanoma in patients with AM syndrome was 10.7% (versus 0.62% in a control population).13

• Patents with DN should have regular skin examinations with biopsy performed of any suspicious lesions (Figure 165-7).3
• Consider total-body photographs for monitoring (Figures 165-8 and 165-9).3 In a study of 50 patients with 5 or more DN, the use of baseline digital photographs improved the diagnostic accuracy of skin self-examination on the back, chest, and abdomen, and improved detection of changing and new moles.14 Individual DN can be monitored more precisely with digital dermoscopic photos added to the skin photographs (Figure 165-9).
• MelaFind, a lesion imaging device using multispectral imaging analysis, may be helpful in differentiating DN from melanoma.15 It is a very expensive computerized device that is not affordable in a primary care office.
• Patients with numerous DN and who have a family history of melanoma are at a higher risk of developing melanoma and should be encouraged to have regular follow-up with a provider skilled in detecting melanoma.
• Patients with FAMM should also consider a baseline ophthalmologic examination because of a possible association between uveal melanoma and FAMM syndrome.3
• First-degree relatives of patients diagnosed with FAMM syndrome should be encouraged to be examined for DN and melanoma.

• Patients with DN should avoid excessive exposure to natural or artificial UV light and routinely use a broad-spectrum sunscreen with a sun protective factor of 30 or greater and/or sun-protective clothing.
• Patients should be taught self-examination to detect changes in existing moles and to recognize clinical features of melanomas. Patients should be taught to look for and report asymmetry, border irregularity, new symptoms (e.g., pain, pruritus, bleeding, or ulceration), and color and size changes.

Patient Resources

• http://www.nlm.nih.gov/medlineplus/moles.html.
• http://www.cancer.gov/cancertopics/wyntk/moles-and-dysplastic-nevi.
• http://www.ncbi.nlm.nih.gov/books/NBK7030/.

Provider Resources

• http://www.dermatlas.com.
• http://emedicine.medscape.com/article/1056283-overview.