Section 9. Benign Epidermal Proliferations

Epidermal nevi are benign, well-circumscribed proliferations of the epidermis and papillary dermis appearing in the distribution of Blaschko’s lines.

Insight

When examining a lesion that appears linear, consider the swirled or undulating pattern of Blaschko’s lines; if present, this will immediately focus the differential diagnosis.

Synonyms Nevus verrucosus, nevus unius lateris, ichthyosis hystrix, and linear nevus sebaceus.

Epidemiology

Age 80% present in the first year of life. Most of them appear from birth to 18 years.

Gender M = F.

Prevalence 1 in 1000 infants.

Etiology Most cases sporadic, some cases familial. Mutations in gene for fibroblast growth factor receptor 3 (FGFR3) identified. Some exhibit a chromosomal break at 1q23.

Pathophysiology

Epidermal nevi arise from the pluripotent embryonic basal cell layer. There are likely many different candidate gene mutations that result in epidermal nevi, but only FGFR3, PTEN, and epidermal differentiation genes at 1q23 have been suggested thus far.

History

Epidermal nevi are present at or soon after birth. Solitary small lesions are common. Larger lesions can affect an entire limb or side of the body with associated adnexal tissue proliferations or hypertrophy.

Physical Examination

Skin Findings

Type At birth: macular/velvety. Later: warty/papillomatous plaques. Number Solitary or multiple.

Color At birth: white. Later: flesh-colored, light, or dark-brown. Rarely hypopigmented.

Size Few millimeters to several centimeters.

Distribution Typically unilateral, stopping abruptly at midline (Fig. 9-1A). Rarely can be bilateral.

Arrangement Linear following the lines of Blaschko (Fig. 9-1B).

Sites of Predilection Trunk or limb > head or neck. Flexural areas are more verrucous.

Differential Diagnosis

The diagnosis of an epidermal nevus is made based upon history and physical examination. The differential diagnosis includes linear and whorled hypermelanosis, nevus sebaceus, seborrheic keratosis, wart, psoriasis, lichen striatus, incontinentia pigmenti, hypomelanosis of Ito, or an inflammatory linear verrucous epidermal nevus (ILVEN).

Laboratory Examinations

Dermatopathology Skin biopsy shows epidermal hyperplasia, hyperkeratosis, acanthosis, papillomatosis, and parakeratosis. There may be increased melanin in the basal layer in places. There may be ballooning of the cells (epidermolytic hyperkeratosis) in places.

Course and Prognosis

Epidermal nevi are typically asymptomatic and grow proportionately with the child. May start macular and become more verrucous over time. Malignant degeneration of epidermal nevi is rare, and can occur after puberty. Case reports of basal cell carcinomas, squamous cell carcinomas, keratoacanthomas, and trichoblastomas have been reported to develop within epidermal nevi. Adults with epidermal nevi can have a keratin mutation in their germ line resulting in offspring with epidermolytic hyperkeratosis.

Management

Treatment of the skin lesions is not necessary. Symptomatic or cosmetically unwanted lesions can be treated with shave excision, dermabrasion, laser ablation, electrodesiccation, and cryotherapy. Recurrence is common especially if only the epidermis is removed, but deeper attempts remove epidermis and papillary dermis risks greater scarring. Test sites are recommended. Surgical removal is curative but is extensively scarring and risks possible keloid formation.

Inflammatory linear verrucous epidermal nevus (ILVEN) is a psoriasiform, pruritic, erythematous epidermal nevus appearing in a Blashko linear distribution.

Synonyms Dermatitis epidermal nevus.

Epidemiology

Age 75% present by age 5 years, 95% present by age 7 years.

Gender F > M, 4:1.

Prevalence Uncommon.

Etiology Unclear. May be a clonal dysregulation of keratinocytes. Rare familial cases.

Pathophysiology

Possible psoriasiform pathophysiology. Possible dysregulation of keratinocyte growth.

History

Initial presentation of ILVEN is of a barely palpable lesion or a confluence of smooth-topped papules. This progresses to a more psoriasiform erythematous and scaly lesion. It persists for years with episodes of inflammation. Other skin findings include an increased number of cutaneous lesions including café au lait spots, congenital hypopigmented macules, and congenital nevocellular nevi. Rarely, there may also be associated ipsilateral limb reductions, arthritis, skeletal defects, seizure disorders, mental retardation, and ocular abnormalities.

Physical Examination

Skin Findings

Type Scaling papules coalescing into plaques (Fig. 9-2).

Color Erythematous.

Size 2 to several cm in length.

Shape Linear.

Distribution Extremities > trunk.

Differential Diagnosis

The diagnosis of ILVEN is made on morphologic appearance of lesions, intense pruritus, and resistance to therapy. ILVEN can be confused with warts, psoriasis, lichen simplex chronicus, lichen striatus, lichen planus, incontinentia pigmenti, linear and whorled hypermelanosis, or hypomelanosis of Ito.

Laboratory Examinations

Dermatopathology Skin biopsy reveals hyperkeratosis, focal parakeratosis, acanthosis with elongation of the rete ridges, spongiosis, and a perivascular lymphocytic and histiocytic infiltrate.

Course and Prognosis

Most ILVEN lesions resolve by adulthood, but may last for years with episodes of intense pruritus that is refractory to treatment.

Management

Pruritus and inflammatory episodes may benefit from topical steroids but patients need to be cautioned about steroid overuse given the lesion may persist for years. The verrucous ILVEN appearance can be improved with emollients (such as hydrated petrolatum, Vaseline, mineral oil, moisturizers), keratolytics (hydroxy acid tretinoin, 5-fluorouracil creams) or topical calcipotriol. With noncompliance or discontinuation of therapy, lesions revert to their hyperkeratotic form. Curative attempts can be made with pulsed dye laser, dermabrasion, laser ablation, and surgical removal, but test patches are recommended to evaluate the scarring from these procedures.

Epidermal nevus syndrome likely encompasses a number of clinical entities, which have in common the presence of an epidermal nevus (or nevus sebaceus) with skin, skeletal, cardiovascular, and/or CNS abnormalities.

Synonyms Schimmelpenning syndrome, nevus sebaceus syndrome, Feuerstein and Mims syndrome, Solomon syndrome, Jadassohn syndrome.

Epidemiology

Age Birth to 40 years of age.

Gender M = F.

Incidence 33% of patients with epidermal nevi.

Genetics Believed to occur sporadically. Likely lethal disorder rescued by mosaicism.

Pathophysiology

Proposed mechanisms for the wide range of phenotypes seen include abnormal induction producing ectodermal and mesodermal malformations or abnormal neuroectoderm development.

History

A spectrum of epidermal nevi may be represented in this syndrome: verrucous epidermal nevus, nevus sebaceus, wooly hair nevus, Becker nevus, and nevus comedonicus. Other mucocutaneous lesions include hypo- or hyperpigmentation, café au lait macules, hemangiomas, aplasia cutic congenita, hair and dental abnormalities, and dermatomegaly (increase in skin thickness, warmth, and hairiness).

Associated systemic abnormalities may be seen in the CNS (hemimegalencephaly, seizures, hemiparesis, mental retardation), skeleton (bone deformities, cysts, atrophies, and hypertrophies), ocular, cardiac, and/or GU system.

Physical Examination

Skin Findings

Type Hypertrophic warty papules coalescing into plaques.

Color Orange, brown, or dark-brown.

Size and Shape 2- to 4-mm papules coalescing to larger plaques.

Distribution May be single linear lesion or more extensive Blashkoid lesion, unilateral (Fig. 9-3) or bilateral.

Sites of Predilection Trunk, extremities, head, neck.

Laboratory Examinations

Dermatopathology Skin biopsy shows findings consistent with an epidermal nevus.

Differential Diagnosis

Diagnosis should be suspected on presentation with extensive epidermal nevi or epidermal nevi associated with systemic abnormalities. Differential diagnosis includes Proteus syndrome, CHILD syndrome, Goltz syndrome, incontinentia pigmenti, and other disorders with Blashkoid skin findings.

Course and Prognosis

Rarely, malignant transformation of epidermal nevi may occur (basal cell carcinomas, squamous cell carcinomas, keratoacanthomas, and trichoblastomas). Transformation most common with nevus sebaceus. This syndrome may also be associated with various visceral malignancies: Wilms’ tumor, astrocytoma, adenocarcinoma, ameloblastoma, ganglioneuroblastoma, esophageal and stomach carcinoma, and squamous cell carcinoma.

Management

The treatment of skin lesions in the epidermal nevus syndrome is difficult given their extensive distribution. Symptomatic or cosmetically unwanted lesions can be treated with shave excision, dermabrasion, laser ablation, electrodesiccation, and cryotherapy. Recurrence is common especially if only the epidermis is removed, but deeper attempts remove epidermis and papillary dermis risks greater scarring. Test sites are recommended. Surgical removal is curative but is extensively scarring and risks possible keloid formation.

Pertinent medical history includes developmental history, specifically attainment of developmental milestones, history of seizures, and abnormalities of bones, eyes, and urinary tract. Mucocutaneous, neurologic, ophthalmologic, and orthopedic examinations must be performed. Regular follow-up should be instated. Periodic electroencephalograms and skeletal radiologic analysis may be important to the long-term care of the patient.