Section 10: Nevi and Melanoma

Patient Story

A teenager is brought to the office by her mother who has noted that the moles on her daughter’s back are changing (Figure 143-1). A few have white halos around the brown pigmentation and some have lost their pigment completely, with a light area remaining. The teenager 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 and her mother are reassured.

Introduction

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.

Synonyms

Moles.

Epidemiology

• 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 percent of neonates, increasing through childhood, and peaking at puberty; new ones may continue to appear in adulthood. In a convenience sample of children in Colorado, non-Hispanic white children had the highest number of nevi compared to other racial/ethnic groups. Beginning at age 6 years, non-Hispanic white boys had significantly more nevi than non-Hispanic white girls (median, 21 versus 17), Hispanic white children (median 11), black children (median 7), and Asian/Pacific Islander children (median 6).¹ This number is similar to a study of children (N = 180, ages 1 to 15 years) in Barcelona where the mean number of nevi was 17.5.²

• In the Colorado study previously cited, non-Hispanic white children developed an average of 4 to 6 new nevi per year from 3 to 8 years of age. Development of new nevi leveled off in chronically exposed body sites at 7 years of age and at a higher level for boys than girls.¹

• Adults typically have 10 to 40 nevi scattered over the body.

• The peak incidence of melanocytic nevi (MN) is in the fourth to fifth decades of life; the incidence decreases with each successive decade.³

Etiology and Pathophysiology

• 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

• Three broad categories of MN are based on location of nevus cells:⁵

  • 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 143-2).

  • Compound nevi—A nevus in which a portion of nevus cells have migrated into the dermis (Figure 143-3).

  • 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 143-4 and 143-5).

• Special categories of nevi:

  • Halo nevus—Compound or dermal nevus that develops a symmetric, sharply demarcated, depigmented border (Figure 143-1). 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 143-6). Blue nevi are not always blue and color varies from tan to blue, black, and gray. 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 143-7). 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 143-8 and 143-9). 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 143-10).

• 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.⁶

Nonmelanocytic Nevi

• Becker nevus—A brown patch often with hair located on the shoulder, back or submammary area, most often in adolescent boys (Figures 143-11 and 143-12). 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 143-13).

• 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 143-14).

• Nevus comedonicus (comedonal nevus) is a rare congenital hamartoma characterized by an aggregation of comedones in one region of the skin (Figure 143-15).

• Epidermal nevi are congenital hamartomas of ectodermal origin classified on the basis of their main component: sebaceous, apocrine, eccrine, follicular, or keratinocytic. See Chapter 144, Congenital Nevi for a full discussion of this type of nevus.

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

Risk Factors

• 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.²

• In one study among very light-skinned (and not darker skinned) children without red hair, children who develop tans have greater numbers of nevi.⁷

• Engaging in outdoor sports increases the number of nevi.⁸

• Although neonatal blue-light phototherapy (NBLP) was not related to nevus count at age 9 years in one study,⁹ investigators of a twin study (N = 59 sets) in which one of the pair received NBLP found a higher prevalence of both cutaneous and uveal melanocytic lesions in exposed twins.¹⁰

Diagnosis

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 143-2). Most are hairless and vary from 1 to 6 mm.

• Compound nevi—Slightly elevated, symmetric, flesh colored or brown with a round or oval border, often becoming more elevated with age (Figure 143-3). 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 (Figures 143-4 and 143-5) with the size ranging from 2 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 children in the Barcelona study, 61.1 percent had nevi on the face and neck, 17.2 percent on the buttocks, and 11.7 percent on the scalp; approximately 1/3 had congenital nevi (Chapter 144, Congenital Nevi).²

• 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.¹¹ 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).¹²

• Authors of a review of dermoscopy in the pediatric population reported that acquired MNs in children show peripheral globules and nevo-melanocytic junctional nests at the perimeter.¹³ Lesions tend to grow in a symmetric, centrifugal fashion with peripheral globules becoming sparser and eventually disappearing as the lesions mature; mature MNs manifest a reticular or homogeneous pattern. Investigators in one study found change in 16.2 percent of 2497 benign melanocytic lesions with minor suspicion of melanoma undergoing short term dermoscopy.¹⁴ Change was more often seen in younger (0 to 18 years and 19 to 35 years) and older patients.

• In the Barcelona study, the most frequent dominant dermoscopic pattern in children was the globular type (Figure 143-16) with the homogeneous pattern predominating in the youngest children and the reticular pattern predominating in adolescents.²

Biopsy

Biopsy is necessary if you suspect melanoma or a Spitz nevus (Figure 143-9). 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.

• Immunostaining is performed by the pathologist as a valuable adjunct to histopathologic evaluation in differentiating benign from malignant melanocytic tumors.¹⁵

Differential Diagnosis

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.

• Melanomas are skin cancers that can develop from a preexisting nevus. Distinguishing a benign nevus from a nevus that might be malignant melanoma is an important skill to develop. However, because clinical appearance can be misleading, a biopsy is necessary when there is a reasonable suspicion for cancer (Chapter 147, 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 146, Dysplastic Nevus).

• Labial melanotic macules are benign dark macules on the lip that are not nevi and not melanomas (Figure 143-17). They can be removed for cosmetic purposes.

Management

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.

Prevention

• 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.¹⁶

• In another study, a partially tailored mailed intervention on child sun protection behaviors was effective in increasing parental reported use of sunscreen, protective clothing and hats, shade-seeking, and midday sun avoidance, and resulted in fewer reported sunburns and fewer nevi ≥2 mm at 1 year.¹⁷

Prognosis

• 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.¹⁸ In another study, of 61 benign nevi biopsy sites reexamined, two (3.3%) recurred.¹⁹

Follow-Up

• 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

• As noted in the section on imaging, MN in children often undergo change. Change may be more common for scalp nevi; in a follow-up study of 44 scalp nevi in children (30% of total population), most (77%) showed clinical signs of change during mean follow-up of 2.8 years; about half (53%) became more atypical and the other half (47%) became less atypical since the initial examination.²⁰ Scalp MN may require closer monitoring.

Patient Education

• Patients and their parents 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 and their parents should be taught to look for and report asymmetry, border irregularity, new symptoms, and color and size changes.

Patient Story

A small congenital nevus (Figure 144-1) was noted on this 6-month-old child by his new family physician during a routine exam. The parents acknowledged that it was present from birth and asked if it needed to be removed. They were reassured that nothing needs to be done about it and unless there were suspicious changes in the future it could remain there for the remainder of their child’s life.

Introduction

Congenital melanocytic nevi (CMN) are benign pigmented lesions that have a wide variation in size and presentation and are composed of melanocytes, the pigment-forming cells in the skin.

Synonyms

• Garment nevus, bathing trunk nevus (Figure 144-2), giant hairy nevus, giant pigmented nevus, pigmented hairy nevus, nevus pigmentosus, nevus pigmentosus et pilosus (pigmented nevus with hair).¹

• Tardive congenital nevus refers to a nevus with similar features to congenital nevi, but appears at age 1 to 3 years.

Epidemiology

• CMN develop in 1 to 6 percent of newborns and are present at birth or occasionally develop during the first year of life.¹ In a recent case series in California (N = 594), 2.4 percent of the infants had CMN.²

• In an Italian prevalence study of over 3000 children aged 12–17 years, congenital melanocytic nevi or congenital nevus-like nevi were found in 17.5 percent; most (92%) were small (<1.5 cm).³

• 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 CMN (Figure 144-8) is believed to occur at a higher rate than in normal skin. Estimates range from 4 to 10 percent with smaller lesions having lowest risk.¹

  • In a systematic review, 46 of 651 patients with CMN (0.7%) followed for 3.4 to 23.7 years developed melanomas, representing a 465-fold increased relative risk of developing melanoma during childhood and adolescence.⁴ The mean age at diagnosis of melanoma was 15.5 years (median 7 years).

  • Patients with giant CMN (larger than 20 cm; Figures 144-2 to 144-5) appear to be at highest risk where subsequent melanoma has been reported in 5 to 7 percent by age 60 years.⁵ In one study, 70 percent of patients who had a large CMN diagnosed with melanoma were diagnosed within the first 10 years of life.⁶

  • However, in a prospective study of 230 medium-sized congenital nevi (1.5 to 19.9 cm; (Figures 144-6 to 144-7) in 227 patients from 1955 to 1996, no melanomas occurred. The average follow-up period was 6.7 years to an average age of 25.5 years.⁷

  • 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 147, Melanoma).¹

Etiology and Pathophysiology

• The etiology of CMN 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.

Making the Diagnosis

Diagnosis is usually made based on clinical features.

Clinical Features¹

• Variable mixtures of color including pink-red (primarily at birth), tan, brown, black, or multiple shades within a single lesion; color usual remains constant over time but the nevus will grow as the child grows.

• Shapes are also highly variable including oval, round, linear, and random; lesions have irregular but well demarcated borders. The pigment may fade off into surrounding skin.

• Nevi may become raised over time or a portion may become raised (Figure 144-8). The skin surface ranges from smooth to pebbly (Figure 144-9) to hyperkeratotic.

• Macular portion usually found at edges.

• Frequently exhibit hypertrichosis (Figures 144-10 and 144-11).

• 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 144-1).

  • Medium (1.5 cm-19.9 cm; Figures 144-6 and 144-10).

  • Large (>20 cm; Figures 144-2 through 144-5). Giant nevi are often surrounded by several smaller satellite nevi (Figures 144-2 through 144-5 and 144-11).

  • Lesions on a child’s head of >9 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 (Figure 144-12) was most common in children under age 11 years and on the trunk.⁸ The majority of reticular lesions were located on the limbs and the variegated pattern was the most specific for congenital nevi. In one Japanese follow-up study of children with acral CMN (N=24 lesions), changes in dermoscopic features were observed in 4 lesions on patients younger than age 14 years.⁹

• Magnetic resonance imaging (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.¹⁰

Typical Distribution

• Congenital nevi may be found anywhere on the body.

Biopsy

• Although there are many histological subtypes, distinguishing histologic features of CMN 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.

Differential Diagnosis

• Acral nevi—Congenital nevi that appear on the palms and soles are one type of acral nevus (Figure 144-13). Other acral nevi may be acquired. If acral nevi appear benign we do not need to be biopsied. The most benign easily recognizable benign pattern of an acral nevus shows pigment running in the valleys of the Hill in Valley pattern seen on the skin in these areas.

• Becker nevus—A brown macule, patch of hair, or both on the shoulder, back, or submammary area that most often 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 143, Nevus). A Becker’s nevus can appear at birth and enlarge during adolescence (Figure 144-14).

• 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 206, Neurofibromatosis).

• Dermal Melanocytosis (Mongolian Spot)—Blue-gray hyperpigmented patch present at birth with less well-defined borders than a congenital nevus. They are seen most often on the buttocks and back and can be quite large (see Chapter 168, Hyperpigmentation).

• Nevus depigmentosus—A benign nonmelanocytic nevus with hypopigmentation that may have jagged edges resembling a continent. These are often congenital but can also be acquired (Figure 144-15).

• Nevus spilus (speckled nevus)—Hairless, oval or irregularly shaped brown lesion with darker brown to black dots containing nevus cells. These may appear at birth or any age (Figure 144-16; see Chapter 143, Benign Nevus).

• Changes that can occur to a congenital nevus may include the development of a halo (Figure 144-17) or pigment incontinence (Figure 144-18). It is best to biopsy any suspicious changes.

Management

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

• For small and medium-sized CMN, the risk of malignant transformation is small and prophylactic removal is not recommended. For cosmesis, treatments include dermabrasion, curettage, laser therapy, and surgical excision.

• Larger CMN can be surgically removed but may require tissue expanders, tissue grafts, and tissue flaps to close large defects. 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 CMN cells.¹¹

• Laser treatment of the lesions has been performed with a number of different types of lasers.¹² Because of the lack of penetrance to deeper tissue levels, long-term recurrence or malignant transformation is also an issue with these techniques.

  • In a case series of patients with CMN (N-52) at a mean of 8 years follow-up, most (87%) were satisfied with their treatment and about three quarters had minimal visible pigmentation after treatment completion.¹³ Treatment failure occurred in 5 patients and recurrence developed in 5; a few patients had hypertrophic scarring or hyperpigmentation and 1 patient developed an intracranial melanoma.

• Careful life-long follow-up with photographs is an acceptable approach, especially with the affordability of digital cameras.

• Garment or bathing trunk nevi (Figures 144-2 through 144-5).

  • About half of the melanomas that develop in bathing trunk nevi do so before age 5 years.¹⁴ These melanomas can be missed by observation because they can have non-epidermal origins.

• Surgical excision is recommended by some experts to prevent melanoma.¹⁴ 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 144-19).

Follow-Up

• Patients with giant CMN or multiple CMN 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.¹⁴

• Because patients with all forms of CMN, especially giant CMN, have an increased risk of developing melanoma, physicians should consider baseline photography and regular follow-up with an experienced clinician for these patients.

Patient Education

• All patients should be told about the importance of protection from ultraviolet light exposure. This is especially important in people with giant CMN, 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 >5 mm, evolution).

Patient Story

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 145-1). 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.

Introduction

• 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.

Synonyms

• 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 sebaceous of Jadassohn (Figure 145-2).

• An inflammatory linear verrucous epidermal nevus (ILVEN; Figure 145-3) can be part of an epidermal nevus syndrome but some affected persons only have the cutaneous EN.

Epidemiology

• EN are uncommon (approximately 1 to 3 percent of newborns and children), sporadic, and usually present at birth, although they can appear in early childhood.

• EN are associated with disorders of the eye, nervous, and musculoskeletal systems in 10 to 30 percent of patients; in one study, 7.9 percent of patients with EN had one of the nine syndromes—an estimated one per 11,928 pediatric patients.¹

• In another review of 131 cases of EN, most (60%) had noninflammatory EN, 1/3 had NS, and 6 percent had inflammatory linear verrucous EN.²

• NS are usually present at birth or noted in early childhood.³ Most cases are sporadic but familial cases have been reported.

• Linear NS is estimated to occur in 1 per 1000 live births.⁴

• Linear NS syndrome includes a range of abnormalities including in the central nervous system (CNS). Patients with CNS involvement typically have cognitive impairment and seizures.⁴ The cardiovascular, skeletal, ophthalmologic, and urogenital systems may also be involved.

Etiology and Pathophysiology

• EN histologically displays hyperkeratosis and papillomatosis, similar microscopically to seborrheic keratosis.³ Also similar to seborrheic keratosis, some ENs of keratinocyte differentiation (about one third) have been found to have a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.³

• Nine EN syndromes have been reported and are described in the referenced article.⁵

• ENs frequently have a linear pattern that follows Blaschko lines (Figures 145-1, 145-3, and 145-4), which are believed to represent epidermal migration during embryogenesis.

• EN tend to become thicker, verrucous (Figure 145-4), and hyperpigmented at puberty.³

• Similarly, NS demonstrate stages of evolution paralleling the histologic differentiation of normal sebaceous glands:⁶

  • Infancy and young children—Smooth to slightly papillated, waxy, hairless thickening (Figure 145-5).

  • Puberty—Epidermal hyperplasia resulting in verrucous irregularity of the surface covered with numerous closely aggregated yellow-to-brown papules (Figure 145-6).

  • Development of secondary appendageal tumors (Figures 145-7) occurs in 20 to 30 percent 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. Rarely, these malignancies are seen in childhood.

• NS were shown to have a high prevalence of human papillomavirus DNA and authors postulate that HPV infection of fetal epidermal stem cells could play a role in the pathogenesis.⁷

Making the Diagnosis

Clinical Features of Epidermal Nevi

• EN are linear, round or oblong, well circumscribed, elevated, and flat-topped (Figures 145-8 and 145-9).

• Color is yellow-tan to dark brown.

• Surface is uniform velvety or warty (Figures 145-8 and 145-9).

• ILVEN, a less common type of EN, is pruritic and erythematous (Figure 145-3).

Clinical Features of Nevus Sebaceous

• NS has an oval to linear shape ranging from 0.5 × 1 cm to 7 × 9 cm.

• NS is usually solitary, smooth, waxy, hairless thickening noted on the scalp at birth or in early childhood (Figures 145-6, 145-6, and 145-10).

• Early NS may be pink, orange, yellow or tan; later lesions can appear verrucous and nodular (Figure 145-10).

Typical Distribution

• EN occur most commonly on the head and neck followed by the trunk and proximal extremities; only 13 percent have wide spread lesions (Figure 145-11). Lesions may spread beyond their original distribution with age. Inflammatory verrucous EN is found on the limbs.

• NS are commonly found on the scalp followed by forehead and retroauricular region (Figures 145-10 and 145-5) 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.³

Differential Diagnosis

• 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. While it is most commonly seen on an extremity, it can appear on the trunk (Figure 145-12). It can resemble a linear EN but lichen striatus will spontaneously regress within one year.

• Syringoma (Figure 145-13)—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.

Management

Medications

• There are no proven topical methods for treatment of these lesions. Topical retinoids may improve lesion appearance but recurrence is common.³

Procedures

• Destructive modalities for EN such as electrodessication or cryotherapy may temporally improve the appearance of the lesion, but recurrence is frequent.³

• 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.

• Surgical excision is an option, but may be complicated by scarring.

• Because of the potential for malignant transformation particularly following puberty, many authors recommend early complete plastic surgical excision for NS (Figure 145-14); reconstructive surgery may be needed. SOR C

• Excision of large lesions may require reconstructive surgery with a rotation flap to close.⁹

Prognosis

• There are reports of spontaneous improvement in patients with widespread involvement of EN.

• Malignant potential is low in EN.³

• Malignant potential in NS is uncertain. Reports range from 0 to 2.7 percent.³

  • Early reports suggested a high rate of developing basal cell carcinomas while more recent studies identified trichoblastoma and syringocystadenoma papilliferum in NS, usually in adulthood.

  • In a retrospective analysis of 757 cases of NS from 1996 to 2002 in children ≤ age 16 years, investigators found no malignancies and question the need for prophylactic surgical removal.¹⁰ In a study using data pooled from six large retrospective studies of giant NS (N = 2520), the cumulative incidence of malignant tumors was 0.5 percent.¹¹

  • Squamous cell carcinoma has also been described in a NS.¹²

Follow-up

• 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 percent had abnormalities.¹³ Abnormal exams were more frequent in individuals with extensive nevi (21% versus 5%) and a centrofacial location (21% versus 2%). The patients in Figures 145-1 through 145-3 had no neurological abnormalities.

Patient Story

A teenage boy presents with concern over a mole on his back that his mother says is growing larger and more variable in color. His mother, who is present with him, reports that his father had a melanoma that was caught early and successfully treated. 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, variations in color and an irregular border (Figure 146-1). 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 146-2). A scoop saucerization was performed with a DermaBlade taking 2-mm margins of clinically normal skin (Figure 146-3). 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.

Introduction

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

Synonyms

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

Epidemiology

• DN are uncommon in children; in a study of Swedish children (N = 524), none had DN.² In another study of pathology reports from nevi removed from patients younger than 18 years, 3 of 199 nevi submitted for histologic analysis met the histologic criteria for DN.³

• Two percent to 9 percent of the population has atypical moles (AMs).^4,5 Among patients with melanoma, the rate of DN ranges from 34 to 59 percent.⁴

• Individuals with fair skin types are at higher risk of DN.⁴

• 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.⁶

• 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 are⁷:

  • 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 the following section “Biopsy”).

Etiology and Pathophysiology

• Most DN are compound nevi (Figure 146-1) possessing a junctional and intradermal component (see Chapter 143, Benign Nevi).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.⁸

Diagnosis

Clinical Features

• Variable mixtures of color including tan, brown, black, and red within a single lesion (Figures 146-4 and 146-5).

• Irregular, notched borders; pigment may fade off into surrounding skin.

• Flat or slightly raised (Figures 146-4 to 146-6) 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 146-1 and 146-4).

• 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 (Figures 146-1 and 146-6); may be found on sites where nevi are usually absent or rare such as the scalp, breasts, genital skin, buttocks, palm, 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.⁹ However, dermoscopy increases diagnostic sensitivity and specificity of cutaneous melanoma from 60 to greater than 90 percent, especially using pattern recognition.⁴

• Investigators in one study found change in 16.2 percent of 2497 benign melanocytic lesions with minor suspicion of melanoma undergoing short-term dermoscopy.¹⁰ Change was more often seen in younger (0 to 18 years and 19 to 35 years) and older patients.

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:⁴

  • 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 percent mean concordance overall by panel members.

Differential Diagnosis

• Melanocytic nevi—Most common moles are tan to brown, smaller than 6 mm, round in shape, and with sharp borders (see Chapter 143, Benign Nevi).

• Melanoma—Skin cancer is often asymmetric, with irregular border and varied colors. It is usually larger than 6 mm in diameter (see Chapter 147, Melanoma).

Management

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.⁴

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 146-7).

Prevention

• Avoid direct sunlight.

• Sun protection to limit sunburn may also help reduce the appearance of nevi. In one trial (N = 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.¹¹

Prognosis

• 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 percent.⁴ 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 percent (versus 0.62% in a control population).¹³

• DNs appear to be dynamic throughout adulthood. In a study of the natural history of DN, investigators found that 51 percent of all evaluated nevi (297 of 593) showed clinical signs of change during an average follow-up of 89 months.¹⁴ New nevi were common in adulthood, continuing to form in more than 20 percent of patients older than age 50 years, and some nevi disappeared. Less is known about DN in children but change is common in other nevi (see Chapter 143, Benign Nevi).

Follow-Up

• Patents with DN should have regular skin examinations with biopsy performed of any suspicious lesions (Figure 146-7).⁴

• Consider total-body photographs for monitoring (Figures 146-8 and 146-9).⁴ 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.¹⁵ Individual DN can be monitored more precisely with digital dermoscopic photos added to the skin photographs (Figure 146-9).

• 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.⁴

• First-degree relatives of patients diagnosed with FAMM syndrome should be encouraged to be examined for DN and melanoma.

In a cohort study of 115 patients with dysplastic nevi an average follow-up of 17.4 years (range: 0.0 to 29.9) was achieved.¹⁶ During these long-term follow-up periods, no patient developed melanoma at the site of an incompletely or narrowly removed histological dysplastic nevus. The authors concluded that this provides evidence that routine re-excision of mildly or moderately dysplastic nevi may not be necessary.¹⁶

Patient Education

• 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 and their parents 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 Story

A 13-year-old red-haired female with a family history of melanoma in her father and multiple moles presents for a routine physical and is found to have a thin 8 mm pink papule on the right neck that has appeared in the last 6 months and occasionally bleeds when it rubs on a shirt (Figure 147-1). A narrow margin excisional biopsy was performed which revealed invasive melanoma 0.7 mm in depth with 2 mitoses per high power field. She was referred to pediatric surgery where she underwent wide local excision and sentinel lymph node biopsy of the neck, which revealed micrometastasis in one node. After PET scan showed no distant metastasis, she underwent lymph node dissection and was enrolled in a clinical trial through a major referral hospital in the region. Her prognosis is guarded, but similar to adults with the same cancer stage.

Epidemiology

• Although extremely rare, malignant melanoma is the most common skin cancer in children and represents 1 percent of all new cases of melanoma.¹

• Between 1973 and 2009, 1230 children in the US were diagnosed with melanoma at a rate of 6 per million overall. Children aged 0 to 9 had the lowest rate at 1.1 per million while children aged 15 to 19 were diagnosed at the highest rate of 18 cases per million.¹

• Melanoma incidence is on the rise in adults and children with the incidence increasing in children by 2 percent per year and 4 to 8 percent per year in adults.¹

• In the US, the death rate is decreasing among persons younger than 65.²

• The lifetime risk of developing melanoma is 1 in 55 for men and 1 in 36 for women.³

Risk Factors

Risk factors can be broadly thought of as genetic risks, environmental risks, and phenotypic risks—arising from a combination of genetic and environmental risks. For example, a fair skinned child (genetic risk) who gets a sunburn (environmental) is much more likely to develop freckles (phenotypic) and melanoma. Childhood sun exposure is a significant risk factor for developing melanoma as an adult.⁴

Environmental Risks

• Exposure to sunlight.

• History of sunburn doubles the risk of melanoma and is worse at a young age.

• Artificial tanning.

• History of immunosuppression.

• Higher socioeconomic status (likely associated with more frequent opportunity for sunburns).

Genetic Risks

• Fair skin, blue or green eyes, red or blonde hair.

• In children, female sex is higher risk, in adulthood, male sex is higher risk.

• Melanoma in a first-degree relative.

• History of xeroderma pigmentosa or familial atypical mole melanoma syndrome.

• Personal history of a BRCA2 mutation confers a high risk of uveal melanoma.⁵

Phenotypic Risks

• Many nevi.

• Congenital nevi (Figure 147-2).

• Multiple dysplastic nevi.

• Increased age.

• Personal history of skin cancer.

Diagnosis

Clinical Features

Melanoma in children may deviate significantly from the traditional ABCDE criteria used to assess risk of melanoma.⁶ The traditional ABCDE guidelines are listed below followed by newly proposed guidelines to increase the sensitivity of detecting melanoma in children.

Traditional Abcde Guidelines

ABCDE guidelines for diagnosing melanoma (Figure 147-3).⁷

A = Asymmetry. Most early melanomas are asymmetrical—A line through the middle will not create matching halves. Benign nevi are usually round and symmetrical (Figure 147-4).

B = Border. The borders of early melanomas are often uneven and may have scalloped or notched edges. Benign nevi have smoother, more even borders (Figure 147-4).

C = Color variation. Benign nevi are usually a single shade of brown. Melanomas are often in varied shades of brown, tan, or black, but may also exhibit red, white, or blue (Figures 147-4 and 147-5).

D = Diameter greater than or equal to 6 mm. Melanomas tend to grow larger than most nevi. Note that melanomas in children or adults can present less than 6 mm in diameter (Figure 147-5).

E = Evolving could be in size, shape, symptoms (itching, tenderness), surface (especially bleeding), and shades of color.

Modified ABCD criteria in children were developed and proposed by Cordoro, et al. in a recent large cohort study.⁶ The criteria were developed from the data presented in Figure 147-6 that compared conventional ABCDE criteria with other presenting features of melanoma in children.

In children, particularly those younger than 13, new ABCD detection criteria are needed as many childhood melanomas present as pink or skin colored uniform bumps. The modified ABCD detection criteria are listed below:

A = Amelanotic lesions are more common in children than adults (Figures 147-1, 147-6, and 147-7).

B = Bleeding, Bump. Suspect any new bleeding papule or macule.

C = Color uniformity may be present in childhood melanoma rather than the color variation that is traditionally associated with melanoma (Figure 147-8).

D = De Novo, any diameter. Any lesion arising out of the blue is suspicious in children.

Conventional subtypes of adult melanomas—superficial spreading, nodular, lentigo maligna melanoma, and acral lentiginous melanoma—are not as relevant in diagnosing childhood melanoma. In contrast, most childhood melanoma—especially in children under 10—is more clinically and histologically ambiguous and defies these classifications.⁶ Any subtype may be classified as amelanotic when pigment is absent to a degree that the lesion is pink in color. In adults, this is rare, representing less than 5 percent of all melanoma. In children, however, up to 70 percent of melanoma may be amelanotic (Table 147-1).⁶

• Other rare melanoma variants include (1) nevoid melanomas, (2) malignant blue nevus, (3) Desmoplastic/Spindled/Neurotropic Melanoma, (4) Clear Cell Sarcoma (in fact a melanoma), (5) Animal-Type Melanoma, (6) Ocular Melanoma (7) and mucosal (lentiginous) melanoma.⁸

Typical Distribution

In children, the most common sites of melanoma are the trunk and lower limbs in females and the head and neck in males.¹

Dermoscopy

Dermoscopy is a useful tool in pigmented lesions in adults and in children, though it is less well characterized in children. Dermoscopy is painless, adds information, and can assist in the decision to biopsy.⁹ In a prospective study of 401 lesions evaluated for melanoma by experts in dermoscopy, the sensitivity of 66.6 percent with ABCDE criteria improved to 80 percent, and specificity rose from 79.3 to 89.1 percent (Figure 147-9).⁹

In a study of dermoscopy done by 60 physicians (35 general practitioners, 10 dermatologists, and 16 dermatology trainees) on unaided photos of 40 lesions using the ABCD rule, the Menzies method, a 7-point checklist, and pattern analysis, the sensitivity rose over the unaided eye.¹⁰ In children, melanoma will deviate from the benign dermoscopic patterns and have at least one melanoma specific criteria, most commonly atypical vascular structure and crystalline structure (Figure 147-1).¹¹

Accepted dermoscopic local features of melanoma include:

• Atypical network (includes branched-streaks).

• Streaks—Pseudopods and radial streaming.

• Atypical dots and globules.

• Negative pigment network.

• Blotch (off center).

• Blue-white veil/peppering over macular areas (regression).

• Blue-white veil over raised areas.

• Vascular structures.

• Peripheral tan/brown structureless areas.

• Crystalline structures

Figure 147-8 demonstrates a number of these features.

Biopsy

In children, melanoma diagnosis is often delayed because of the rarity of the diagnosis and a natural tendency to avoid biopsy. Still, a full thickness skin biopsy remains the gold standard for diagnosing melanoma. Complete excisional biopsy with close margins (2 mm) is ideal for histologic diagnosis and tumor staging. Although there is evidence that an incisional biopsy of a portion of a melanoma does not worsen the prognosis, this should only be the rare case when a lesion is too large to excise in the office. When the clinical impression differs markedly from the pathology report, discuss the case with the reading pathologist and share clinical photos if you haven’t done so already. You may need to have the pathologist prepare “deeper sections” or “step sections”—meaning more slices from the same “loaf of bread.” Additionally, if the diagnosis of melanoma was expected and the result of an incisional biopsy does not meet the expectation, go forward with a complete excision or refer to a surgeon who can.

The National Comprehensive Cancer Network (NCCN) Melanoma Guidelines on the Principles of Biopsy state:¹²

• Excisional biopsy (elliptical, punch [when whole lesion is small], or saucerization) with 1- to 3-mm margins is preferred. Avoid wider margins to permit accurate subsequent lymphatic mapping.

• The orientation of the biopsy should be planned with definitive wide excision in mind.

• Full-thickness incisional or punch biopsy of clinically thickest portion of the lesion is acceptable in certain anatomic areas (e.g., palm/sole, digit, face, and ear) or for very large lesions.

• Shave biopsy (not saucerization or deep shave) may compromise pathologic diagnosis and complete assessment of Breslow thickness, but is acceptable when the index of suspicion is low.¹³

Despite strong opinions about biopsy technique, there is evidence that a scoop shave biopsy leads to an accurate diagnosis and staging 97 percent of the time.¹³ Still, a shallow shave biopsy may miss important staging information and may cause “upstaging” and unnecessary lymph node biopsy.

Differential Diagnosis

Nevi of all types may mimic melanoma. In children, because of the high percentage of melanomas that are melanocytic, broaden the differential to include many inflammatory and vascular papules. Nevi of all types can mimic melanoma. Congenital nevi can be especially large and asymmetrical. Therefore, it is important to ask the patient if the pigmented area has been there from birth and consider how it has changed over time.

• Atypical nevi, also called dysplastic nevi, often mimic melanoma (Figure 147-10). When an atypical nevus is suspicious for melanoma, perform a full thickness biopsy or a broad scoop shave for histology. Only the less suspicious dysplastic nevi should be followed with photography or serial exams.

• Epidermal nevi are warty in appearance and may fall along embryonic cleavage lines. These are benign and not precancerous but may grow rapidly especially during puberty (Figure 147-11).

• Pyogenic granulomas are benign vascular neoplasms that grow rapidly and are often friable. They are frequently associated with pregnancy, but can occur without a clear cause and mimic an amelanotic nodular melanoma (Figures 147-12 and 147-13).

• Pseudolymphoma presents as a pink papule or plaque without significant scaling that persists for weeks to months and may be associated with a history of an insect or spider bite (Figure 147-14).

• Dermatofibromas are fibrotic nodules that occur most frequently on the legs and arms. They can be any color from skin color to black and often have a brown halo surrounding them. A pinch test will produce a dimpling of the skin in most cases.

• Warts in children may mimic melanocytic lesions including Spitz nevi and melanoma (Figures 147-15 and 147-16).

• Benign adnexal tumors such as pilomatricomas may appear similar to a nodular melanoma and can occur on the head and neck (Figure 147-17).

Management

• Cutaneous melanoma is surgically treated with complete full skin depth excision using margins determined by the Breslow depth. This depth is a measure of tumor thickness from the granular layer of the epidermis to the point of deepest invasion using an ocular micrometer.

• Current recommendations for excision margins range from 5 mm for in situ lesions to 1 to 2 cm for invasive lesions. A recent study showed significant benefit with a 9 mm margin on Mohs excision of melanoma in situ compared with 6 mm margins at a referral center.¹⁴

• Sentinel lymph node biopsies are recommended for tumors of greater than or equal to 1 mm in depth (Figure 147-18) and should be considered for thinner lesions with ulceration or more than 1 mitosis per mm². Even in patients with thin melanoma with mitoses above 1 per mm² sentinel lymph node biopsy should be considered according to the most recent guidelines.¹⁵ In these guidelines, mitoses per mm² has replaced Clark’s levels to distinguish T1a from T1b tumors.¹⁵

• Melanoma staging takes into account tumor thickness and metastasis and prognosis worsens statistically with each increasing stage from 0 to IV. A patient with an in situ melanoma and no nodal metastasis is considered stage 0. Thicker tumors that remain localized to the skin may be staged as high as stage IIC and subcategories are based on tumor thickness and presence of ulceration. Any lymph node metastasis is considered stage III or higher and any distant metastasis beyond lymph nodes is categorized as stage IV.¹⁶

• Patients with advanced melanoma should be referred to medical oncology and may receive combination therapy with multiple chemotherapeutic agents and immunotherapy. Many trials are ongoing and three new drugs including interferon 2-alpha, vemurafenib, and ipilimumab have been approved for use in advanced melanoma. Treatment regimens in children are similar to regimens in adults.

• Recently two new chemotherapeutic agents have been FDA approved for the treatment of metastatic melanoma. One, vemurafenib is a monoclonal antibody targeting the BRAF mutation expressed on many melanomas. Ipilimumaub prevents dampening of the immune system by blocking a regulatory molecule CTLA-4. Both of these medications used in combination with dacarbazine have shown a small but significant increase in progression free survival in adults and are in ongoing trials in children.¹⁷

Follow-Up

The need for follow-up is largely determined by the stage of the disease. Updates to the staging criteria are published by the American Joint Committee. As previously mentioned, the prognosis is worsened by increasing depth, mitotic rate, ulceration, positive lymph nodes, and metastases.

The follow-up for stage 0 and 1 cutaneous melanoma includes regular skin examinations by a physician trained in skin screening. Total body photography is available in limited areas, but may be of benefit in monitoring patients with multiple nevi. The rate of subsequent cutaneous melanomas among persons with a history of melanoma was found to be more than 10 times the rate of a first cutaneous melanoma and the highest incidence of recurrence was in the first 3 to 5 years after initial diagnosis.^18,19

Patient Education

Advise patients to avoid future sun exposure and monitor their skin for new and changing moles. Advise avoidance of artificial tanning. Recommend a complete skin examination yearly by a physician trained to detect early melanoma. A large portion of adult melanoma is caused from childhood exposure.⁴