A 39-year-old man presents to the clinic with a pigmented growth on his left upper back. The patient reports that the lesion has been present since childhood and claims that it grew and became darker when he was 14 years old. It has been stable and asymptomatic since then, but the patient dislikes its appearance. On examination, the lesion is a brown, linear, verrucous plaque. The surrounding skin tissue is unaffected. A biopsy of the plaque reveals hyperkeratosis, acanthosis, and papillomatosis.
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Epidermal nevi are congenital hamartomatous proliferations of the epithelium. A hamartoma is a disordered overgrowth of benign tissue in its area of origin. Epidermal nevi are classified based on the predominant epidermal cell involved: keratinocytic (verrucous [wart-like] epidermal nevus), sebaceous (nevus sebaceous), pilosebaceous (nevus comedonicus), eccrine gland (eccrine nevus), or apocrine gland (apocrine nevus).1
Epidermal nevi are uncommon, occurring in approximately 1 in 1000 live births, and equally affect males and females. They are typically seen at birth or develop in early childhood. Most cases are sporadic, occurring as an isolated finding and remaining quiescent after adolescence. However, a group of rare epidermal nevus syndromes have been associated with additional neurocutaneous abnormalities, most often affecting the brain, eyes, and skeletal system. Epidermal nevus syndrome is often termed Solomon syndrome.1
Epidermal nevi originate from pluripotent stem cells in the basal layer of the embryonic epidermis. The etiology of most epidermal nevi is thought to be due to the mosaicism of FGFR3 and PIK3CA mutations during embryologic development. These mosaics are only present in the cells of the nevus. However, if mutations occur very early in development, they lead to more extensive epidermal nevi and affect other organ systems.2
Ten different histologic patterns of epidermal nevus have been described. The most common type is linear epidermal nevus, also known as keratinocytic, or verrucous epidermal nevus. Histologically, it displays hyperkeratosis, papillomatosis, and acanthosis and appears similar to seborrheic keratosis.3 Linear epidermal nevi are typically found on the torso or limbs as linear, round, or oblong patches with pigmentation varying in color from yellow-tan to brown. They can be flat-topped, velvety, or verrucous. With age – particularly around puberty – nevi can become thicker, darker, and more verrucous. Linear epidermal nevi often follow relaxed skin tension lines or develop in a linear configuration known as the lines of Blaschko, which are thought to follow the paths that cells travel during fetal skin development. The differential diagnosis of linear epidermal nevus includes other linear dermatoses such as lichen planus, lichen striatus, linear porokeratosis, linear Darier disease, and linear psoriasis.3 Although the malignant potential of epidermal nevus is low, there have been rare cases of squamous cell carcinoma and basal cell carcinoma arising within epidermal nevi that warrant complete excision. This malignant transformation is most common in middle-aged or elderly individuals.4
Nevus sebaceous usually presents as a solitary, smooth, and waxy plaque with yellow-orange discoloration and surrounding alopecia. These nevi are found most frequently on the scalp at birth and can sometimes involve the neck, trunk, and proximal extremities. Like most epidermal nevi, they may also become more verrucous with age. Though rare, tumors may arise within nevus sebaceous. The most common benign tumors are syringocystadenoma and trichoblastoma. Malignant tumors are less common but include apocrine carcinoma, squamous cell carcinoma, and eccrine poromas. Differential diagnosis includes aplasia cutis, congenital nevi, and seborrheic keratosis.4
Nevus comedonicus lesions are hamartomas of the pilosebaceous unit. Clinically, they resemble comedones and are characterized by dilated follicular pores that contain keratinaceous plugs instead of hair shafts. They are usually asymptomatic and commonly affect the face and neck area. Differential diagnosis includes acne vulgaris, milia, acne neonatorum, nevus sebaceous, and linear Darier disease. The non-inflammatory variant is asymptomatic while the inflammatory variant might require surgical or medical intervention to alleviate significant pain.5
Eccrine nevus shows an increased number of eccrine glands on histology without any other abnormalities. These nevi are distributed on the trunk, arms, or legs and are often associated with hyperhidrosis. The morphology varies from tan to skin-colored papules. Therapy is focused on symptomatically treating the hyperhidrosis with surgery, iontophoresis, or sympathectomy, or with agents such as aluminum chloride solution, anticholinergics, or botulinum toxin.6
Apocrine nevi are hamartomatous proliferations of the apocrine glands. They can present as nodules on the axilla or upper chest and also as a solitary nodule on the scalp. Histology of apocrine nevus shows apocrine glands that extend from the epidermis to the subcutaneous fat.3
Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare variant presenting with pruritus, erythema, and scaling, often on the buttocks and lower extremities. Psoriasiform papules form linear plaques that follow the lines of Blaschko. Histopathology shows a dermal infiltrate of inflammatory cells as well as psoriasiform epidermal hyperplasia with alternating columns of orthokeratosis and parakeratosis.7 ILVEN appears similar to linear psoriasis clinically, but it is more resistant to therapy; glucocorticoids, cryotherapy, laser therapy, and surgical excision have shown variable success.8
In most cases, the diagnosis of epidermal nevi can be made clinically. However, skin biopsy with histopathologic confirmation provides the most definitive diagnosis. Children with small isolated epidermal nevi and normal physical examination are not at risk for complications. However, patients with extensive epidermal nevi or systemic abnormalities require further workup for epidermal nevus syndrome. Diagnosis in these patients requires a thorough developmental history, careful physical examination (especially neurologic and skeletal assessments), and individualized imaging based on the suspected system involved.9
Most epidermal nevi occur sporadically due to a postzygotic gene mutation and are present in only some of the cells in the body (mosaic). However, patients with the epidermolytic histologic variant of epidermal nevus may have gonadal mosaicism for the KRT1 or KRT10 (keratin 1 and 10) genes. Patients with this variant carry the genetic mutation for epidermolytic hyperkeratosis and are at risk of passing this gene on to children. Genetic counseling may be warranted for these patients.4
Treatment of epidermal nevus is challenging. There are no proven topical methods for treatment, and destructive modalities often only lead to temporary improvements. Topical retinoids, electrodessication, cryotherapy, and laser therapy may be marginally beneficial. Surgical modalities with full-thickness excision have better success in providing definitive treatment. However, significant scarring can complicate the excision of larger lesions, and recurrence is still possible.10
The patient in the case described above elected to have the nevus removed for cosmetic reasons. A full-thickness excision was performed and he healed well.
Gail Tan, BS, is a medical student; Ariella Noorily, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston, Texas.
- Brandling-Bennett HA, Morel KD. Epidermal nevi. Pediatr Clin North Am. 2010;57(5):1177-1198.
- Hafner C, Lopez-Knowles E, Luis NM, et al. Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proceed Natl Acad Sci U S A. 2007;104(33):13450-13454.
- Thomas VD, Valencia D, et al. Benign epithelial tumors, hamartomas, and hyperplasias. In Goldsmith AL, ed. Fitzpatrick’s Dermatology in General Medicine. 8th edition. New York, NY: McGraw-Hill; 2012.
- Jaqueti G, Requena L, Sánchez Yus E. Trichoblastoma is the most common neoplasm developed in nevus sebaceus of Jadassohn: a clinicopathologic study of a series of 155 cases. Am J Dermatopathol. 2000;22(2):108-118.
- Tchernev G, Ananiev J, Semkova K, Dourmishev LA, Schönlebe J, Wollina U. Nevus comedonicus: an updated review. Dermatol Ther (Heidelb). 2013;3(1):33-40.
- Kawaoka JC, Gray J, Schappell D, Robinson-Bostom L. Eccrine nevus. J Am Acad Dermatol. 2004;51(2):301-304.
- Meibodi NT, Nahidi Y, Javidi Z. Epidermolytic hyperkeratosis in inflammatory linear verrucous epidermal nevus. Indian J Dermatol. 2011;56(3):309-312.
- Abdullah L, Abbas O. Answer: Can you identify this condition? Canadian Fam Physician. 2012;58(3):286.
- Solomon LM, Fretzin DF, Dewald RL. The epidermal nevus syndrome. Arch Dermatol. 1968;97(3):273-285.
- Lee BJ, Mancini AJ, Renucci J, Paller AS, Bauer BS. Full-thickness surgical excision for the treatment of inflammatory linear verrucous epidermal nevus. Ann Plastic Surg. 2001;47(3):285-292.