eMedicine Specialties > Dermatology > Pediatric Diseases

Epidermal Nevus Syndrome: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Contributor Information and Disclosures

Updated: Jul 2, 2009

Differential Diagnoses

Acrokeratosis Verruciformis of Hopf
Lichen Simplex Chronicus
CHILD Syndrome
Lichen Striatus
Epidermodysplasia Verruciformis
Nevus Comedonicus
Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Nevus Sebaceus
Erythrokeratodermia Variabilis
Porokeratosis
Keratosis Follicularis (Darier Disease)
Proteus Syndrome
Lichen Nitidus
Lichen Planus

Other Problems to Be Considered

The ichthyosiform nevus of CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome) resembles inflammatory linear verrucous epidermal nevus, but CHILD syndrome has yellowish waxy scaling and histologic features of a verruciform xanthoma. Linear psoriasis with papules in a linear configuration may represent a Koebner reaction. Linear psoriasis is distinct from inflammatory linear verrucous epidermal nevus because linear psoriasis develops either later in life in patients with plaque-type psoriasis or as congenital plaque-type psoriasis with subsequent linear distribution along the lines of Blaschko. Inflammatory linear verrucous epidermal nevus and psoriasis each have a different protein analysis and a different pattern of epidermal keratin 16 and keratin 10 expression.

Other linear eruptions may clinically resemble inflammatory linear verrucous epidermal nevus and linear epidermal nevus; however, their histologic findings usually distinguish them. Lichen striatus (LS) tends to occur in children rather than in adults. LS consists of discrete erythematous, scaly, flat-topped asymptomatic papules on 1 of the extremities. LS has a sudden onset and spontaneous regression within 1 year.
 
Linear lichen planus typically occurs in children, in whom the characteristic discrete pruritic polygonal violaceous papules are arranged in a linear fashion, usually extending along an entire limb. Linear porokeratosis is a childhood disorder characterized by small, ringlike, hypertrophic verrucous plaques with a linear morphology usually limited to a single extremity. At times, linear lichen simplex chronicus, linear Darier disease, linear lichen nitidus, and linear human papillomavirus–induced warts may require differentiation from linear epidermal nevus and inflammatory linear verrucous epidermal nevus.

Linear epidermal nevus in the genital area may be mistaken for genital warts.12

Trichoblastomas with Merkel cell proliferation in nevi sebacea in Schimmelpenning-Feuerstein-Mims syndrome may facilitate histological differentiation between trichoblastomas and basal cell carcinomas.13 The detection of multiple Merkel cells within the epidermal layer by cytokeratin 20 staining was considered to be an important clue.

Workup

Imaging Studies

  • MRIs can be used to evaluate intracranial involvement. MRIs may show cerebral atrophy, dilated ventricles, hemimegalencephaly, pachygyria, or enlarged white matter.
  • Multiple abnormalities are found on neuroimaging studies in patients with Jadassohn nevus phacomatosis. Findings include hemimegalencephaly (usually ipsilateral to the major skin lesions and contralateral to neurologic deficits), cortical atrophy, pachygyria, cortical heterotopias, agenesis of the corpus callosum, and Dandy-Walker syndrome.

Other Tests

  • EEG findings are abnormal in approximately 90% of patients. In almost all patients who had focal paroxysmal electroencephalographic abnormalities, the epileptiform focus was ipsilateral to the major skin lesions.

Histologic Findings

Histologic examination of the 4 types of epidermal nevi is variable.

Typically, the histologic examination of linear epidermal nevus reveals marked hyperkeratosis, papillomatosis, and acanthosis with rete ridge elongation in a psoriasiform pattern. Changes of epidermolytic hyperkeratosis, acantholytic dyskeratosis, and those resembling verruca vulgaris and comedo formation may also be observed.

Histologic examination of inflammatory linear verrucous epidermal nevus reveals a similar psoriasiform hyperplasia of the epidermis, alternating parakeratosis without a granular layer, and orthokeratosis with a thickened granular layer. Occasionally, changes of epidermolytic hyperkeratosis, acantholytic dyskeratosis, and those resembling verruca vulgaris and comedo formation may be noted.

In nevus comedonicus, rudimentary hair follicles are dilated to form epidermal invaginations, which are filled with keratin in concentric lamellae. The follicular walls are composed of several layers of keratinocytes, which occasionally show changes of epidermolytic hyperkeratosis. Scattered hair shafts and small sebaceous lobes may be evident in early specimens; in older specimens, the shafts and lobes, as well as arrector pili muscles, are absent. The interfollicular epidermis is often papillomatous and hyperkeratotic, and ossification may be observed in the dermis.

Linear sebaceous nevus combines epidermal, follicular, sebaceous, and apocrine gland abnormalities. It reflects the normal sebaceous elements seen in infancy, childhood, and adolescence. Thus, in early life, the lesions are well developed because of maternal hormonal expression, whereas, in childhood, they are underdeveloped and reduced in size and number. At this stage, incomplete and undifferentiated hair structures may be a key to diagnosis, with prominent keratin-filled infundibula and malformed hair germs.

At puberty, this neoplasm tends to blossom with large, maturing sebaceous glands and papillomatous hyperplasia. In adulthood, benign appendageal tumors as well as malignant ones may develop. Syringocystadenoma papilliferum, chondroid syringoma, and nodular hidradenoma are most common in infancy. Basal cell carcinoma, squamous cell carcinoma, or keratoacanthoma are most common in adulthood. Rarely, tumors, such as apocrine carcinoma and porocarcinoma, may appear with more metastatic potential.

One series of 155 cases of linear sebaceous nevus with clinicopathologic correlation could not identify any cases of authentic basal cell carcinoma or other malignancies, whereas several examples of primitive follicular induction and trichoblastomas were evident.14 Other cutaneous hamartomas, hyperplasias, and neoplasms in that series included sebomatricoma, apocrine gland cyst, poroma, and different histopathologic variants of what are often considered to be warts (eg, classic warts, tricholemmoma, desmoplastic tricholemmoma).

Neuropathologic findings may also be evident. Nervous system changes may also occur in patients with linear epidermal nevus syndrome. Disorganization of cortical neuronal migration and organization, polymicrogyria, heterotopia, white matter gliosis, increased neuronal size, and/or excessive neuron and astrocyte proliferation may be observed.

More on Epidermal Nevus Syndrome

Overview: Epidermal Nevus Syndrome
Differential Diagnoses & Workup: Epidermal Nevus Syndrome
Treatment & Medication: Epidermal Nevus Syndrome
Follow-up: Epidermal Nevus Syndrome
Multimedia: Epidermal Nevus Syndrome
References
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Further Reading

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Keywords

epidermal nevus syndrome, epidermal nevus, epidermal nevi, EN, Solomon syndrome, linear sebaceous epidermal nevus syndrome, LSN, inflammatory linear verrucous epidermal nevus syndrome, ILVEN, Schimmelpenning syndrome, Schimmelpenning-Feuerstein-Mims syndrome, nevus comedonicus syndrome, NC, proteus syndrome, congential hemidysplasia with ichthyosiform nevus and limb defects, CHILD syndrome, Jadassohn nevus syndrome, nevus unius lateralis syndrome, ENS, linear epidermal nevus, LEN

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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