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November 2015

Acantholytic Dyskeratotic Epidermal Nevus

Author Affiliations
  • 1University of Wisconsin School of Medicine and Public Health, Madison
  • 2Department of Dermatology, University of Wisconsin, Madison
  • 3Dermatopathologist, Dermpath Diagnostics, Brookfield, Wisconsin
  • 4Department of Dermatology, Lucile Packard Children’s Hospital at the Stanford University School of Medicine, Palo Alto, California
JAMA Dermatol. 2015;151(11):1259-1260. doi:10.1001/jamadermatol.2015.1663

Acantholytic dyskeratotic epidermal nevus (ADEN) is histologically similar to Darier disease (DD), and distinguishing the 2 entities may be challenging. We describe the case of an 18-month-old boy with congenital epidermal nevi, histological acantholytic dyskeratosis, and the presence of sarcoendoplasmic reticulum calcium transport ATPase 2 (SERCA2) protein by immunohistochemical (IHC) staining (Abcam PLC). We concluded that the best diagnosis was ADEN.

Report of a Case

An 18-month-old otherwise healthy Hispanic boy was referred for evaluation of congenital linear verrucous lesions on the upper and lower extremities. The lesions followed the lines of Blaschko. His mother observed that the plantar lesions were painful with ambulation. He had been treated with topical retinoids and steroids since age 3 months without improvement. The patient’s birth and family history were unremarkable.

Physical examination revealed hyperpigmented verrucous papules coalescing into plaques in a Blaschkoid distribution on the bilateral lower extremities, left groin, scrotum, and buttocks (Figure 1). Linear plaques were present on the scalp, left palm, left medial foot, and from the right heel to the right dorsal foot. Neither mucosal lesions nor nail abnormalities were present.

Figure 1.
Child With Acantholytic Dyskeratotic Epidermal Nevus (ADEN)
Child With Acantholytic Dyskeratotic Epidermal Nevus (ADEN)

Typical cutaneous findings in ADEN include verrucous papules and plaques, often following the lines of Blaschko. This patient had linear involvement of the left lower extremity.

A shave biopsy of lesional skin from the thigh showed papillomatous epidermal hyperplasia with zones of acantholytic dyskeratosis; IHC staining revealed SERCA2 protein in the lesional skin (Figure 2). In the context of the patient’s congenital presentation and lack of other clinical features or family history of DD, the patient was diagnosed with ADEN. He was subsequently observed for 7 years and continued to be without signs of Darier disease.

Figure 2.
Immunohistochemical Staining of Lesional Skin Using SERCA2
Immunohistochemical Staining of Lesional Skin Using SERCA2

This photomicrograph demonstrates that lesional skin tested positive under sarcoendoplasmic reticulum calcium transport ATPase 2 (SERCA2) immunohistochemical stain (1:100 dilution; Abcam PLC), favoring a diagnosis of ADEN over Darier disease in our patient (original magnification ×400).


Epidermal nevi are congenital malformations of the epidermis characterized clinically by verrucoid plaques on the skin often following lines of Blaschko and histologically by papillomatosis, acanthosis, and hyperkeratosis. Ten subtypes have been described. ADEN is a subtype distinguished by its “Darier-like” pattern of acantholysis and dyskeratosis.1

Distinguishing between ADEN and DD relies on clinical-pathologic correlation. Both demonstrate histologic loss of adhesion between suprabasal keratinocytes (acantholysis), abnormal keratinization (dyskeratosis) in the form of corps ronds and grains, hyperkeratosis, and parakeratosis. Both present clinically with hyperkeratotic papules and warty plaques but differ in their age of onset and associated abnormalities. ADEN is often congenital, while DD typically manifests in the second or third decade of life. Typically, DD has associated nail abnormalities, mucous membrane involvement, palmoplantar pits, and punctate keratoses, while ADEN does not.2

Genetic testing is available, as is immunohistochemical staining of tissue for SERCA2 protein expression. The genetic difference between the 2 disorders remains controversial. Darier disease is caused by mutations in ATP2A2, which encodes the SERCA2 pump. Mutations of SERCA2 have been discovered in at least 2 patients with ADEN, leading some clinicians to classify ADEN as segmental DD resulting from postzygotic mosaicism.3 Others maintain that congenital or early childhood onset and linear distribution suggest ADEN and not segmental DD.4 There is 1 reported case of ADEN where lack of ATP2A2 mutation was confirmed by DNA analysis.5

In our patient, IHC staining identified SERCA2 protein in lesional skin. However, the IHC staining does not substantiate normal function of the protein. Genetic testing was not economically feasible for this family but may be appropriate when a patient desires genetic counseling, prenatal diagnosis, or identification of at-risk family members. The Genetic Testing Registry lists several laboratories that will perform sequence analysis of the ATP2A2 gene.6 With 96% specificity, the lack of ATP2A2 gene mutation nearly excludes a diagnosis of DD. Our case supports the premise that ADEN has clinical and prognostic features distinct from DD despite their overlapping histopathologic findings. Although IHC staining of SERCA2 can be helpful, further study of genotype-phenotype correlations may allow better distinction of these 2 clinical entities.

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Article Information

Corresponding Author: Molly A. Hinshaw, MD, Department of Dermatology, University of Wisconsin, 1 S Park St, Madison, WI 53715 (mhinshaw@dermatology.wisc.edu).

Published Online: July 1, 2015. doi:10.1001/jamadermatol.2015.1663.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We are indebted to James Fitzpatrick, MD, Department of Dermatology, University of Colorado Health Sciences Center, who performed immunohistochemical staining on this specimen. Dr Fitzpatrick received no compensation for his contribution.

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