Verrucous epidermal nevus with epidermolytic hyperkeratosis: Histopathological-dermoscopic correlation

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Verrucous epidermal nevi (VEN) are non-inflammatory hamartomatous growths composed of keratinocytes.^[1] They present as velvety, skin-colored to dark brown papules and plaques, appearing along the Blaschko lines.^[2] Epidermolytic hyperkeratotic epidermal nevus (EN) is a rare variant showing cutaneous mosaicism.^[3] Epidermolytic EN may present at birth, though it may appear as late as adulthood.^[4] This variant is classically caused by mutations in the KRT1 and KRT10 genes.^[3] While VEN may have a mutation in the FGFR3 gene, the same gene which is responsible for the development of seborrheic keratosis (SK).^[2] Dermoscopy of epidermolytic EN shows features similar to those of any other EN, but it can resemble that of SK because of their morphologic similarity. We present a case of epidermolytic VEN with SK-like dermoscopic features.

A 6-year-old girl presented with a few verrucous plaques in the groin area (extending from the right labia majus to the right inner thigh) in a blaschkoid pattern. Her mother confirmed the presence of lesions since birth and ablation of lesions with electric cautery in the past, which left smooth brownish plaques over the treated area [Figure 1a]. Now she observed a few new verrucous plaques regrowing over these smooth plaques. Lesions were completely asymptomatic. Systemic examination revealed no abnormality. No family history could be elicited. Dermoscopy done in the DermLite DL3 dermoscope (3rd Gen Inc., USA) showed milia-like cysts, brown ring-like patterns, exophytic papillary structures, and cerebriform pattern. [Figure 1b-d] Based on clinical and dermoscopic examination, differential diagnoses of VEN, Blaschkoid verruca vulgaris, and ILVEN were considered. SK was not kept as a differential diagnosis despite a similar dermoscopy picture, since it is a disease of middle to old age. Skin punch biopsy for histopathology showed hyperkeratosis, acanthosis, and papillomatosis [Figure 2a]. An occasional keratinous cyst was also noticed [Figure 2b]. Focal epidermolytic hyperkeratosis was noticeable in the form of perinuclear vacuolization of keratinocytes of the upper epidermis, granular cell degeneration with coarse keratohyaline granules [Figure 2c-f]. Based on the characteristic clinical and histopathological features, a diagnosis of verrucous epidermal nevus with epidermolytic hyperkeratosis was reached.

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Figure 1: (a) Multiple, hyperpigmented smooth plaques in the groin area extending from the right labium majus to the right inner thigh in a Blaschko-linear pattern; the morphology of the typical verrucous nevus changed after electric cautery ablation done earlier (blue stars). A few recent-onset verrucous papules are observed over the upper linear hyperpigmented plaque; two new growths can also be seen arranged linearly on the thigh (black arrows). Dermoscopic and histopathological examinations were done on these new lesions. (b) Cerebriform pattern (purple arrows) and cloudy milia-like cyst (blue stars) DermLite DL4 (10x polarised mode). (c) Starry milia-like cysts (blue stars), cloudy milia-like cyst (black arrows), brown ring-like structures (yellow arrows) DermLite DL4 (10x polarised mode). (d) Exophytic papillary structures (black arrows), cloudy milia-like cyst (yellow arrows) DermLite DL4 (10x polarised mode).

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Figure 2: Histopathology images (H&E staining, 10× view): (a) Hyperkeratosis, acanthosis, and papillomatosis. Hyperpigmented basal keratinocytes in the lower layer are also seen. (b) A large keratinous cyst (big yellow arrow), coarse keratohyaline granules (yellow arrows), epidermolytic keratinocytes with cytoplasmic vacuolization can also be appreciated (black arrows). (c) epidermolytic hyperkeratosis shown in perinuclear vacuolization of keratinocytes without nuclear atypia (black arrows), granular layer degeneration with coarse keratohyaline granules (yellow arrows). One can appreciate the crowding of basal keratnocytes around the dermal papilla (below the black arrows); this feature corresponds to a brown ring-like pattern upon dermoscopy. (d) Epidermolytic cells (black arrows), granular cell degeneration with coarse keratohyaline granules (yellow arrows). (e) Numerous cells with epidermolytic change (perinuclear vacuolization without nuclear atypia) (black arrows), granular cells with coarse keratohyaline granules (yellow arrows). A heavily pigmented basal cell layer can also be seen (blue stars). (f) Pigmented basal keratinocytes crowding around the dermal papilla (blue stars). Few epidermolytic cells (black arrows) and granular cells with coarse keratohyaline granules (yellow arrows) can also be appreciated.

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The classical histopathological picture of EN is hyperkeratosis, acanthosis, and papillomatosis.^[5] In 1970, Ackerman characterized EH as a minor pathological reaction pattern of the skin.^[5] EH upon histology comprises compact hyperkeratosis, perinuclear vacuolization of keratinocytes without nuclear atypia (psuedokoilocytes) in the upper epidermal layers, and coarse keratohyalin granules.^[3] Cases of EN with EH have been scarce in the literature. Das et al. summarised previous reports of a systematised VEN with EH and a case of ILVEN showing EH.^[5] Ansari et al. cited a previous report of a 27 year old woman who developed EN during pregnancy owing to hormonal and immunological alterations.^[4] VEN with Systemic involvement is called ‘epidermal nevus syndrome’ though the epidermolytic variety is not associated with extracutaneous abnormalities, as keratin genes are expressed only in the epithelia.^[3] Systematized VEN can involve one half of the body (Nevus unius lateris) or present bilaterally (Ichthyosis hystrix).^[3] According to Das et al. previous reports of rare dermatomal distributions of EN included V1 dermatome and zosteriform involvement of ear lobe.^[5] Clinically, EN can have ILVEN, wart, and SK as its differential diagnoses. Absence of erythema and inflammation of the lesions ruled out ILVEN.^[5] Others are ruled out by clinically observing the typical Blaschkoid distribution, though the Blaschkoid variety of Verruca and SK has also been reported. In our case, the age of the patient also goes against SK, as it occurs in middle to old age. Dermoscopy can be used to differentiate these lesions. Regularly distributed red dots in the yellow to light- brown background are seen in warts, while SK shows milia-like cysts, cerebriform pattern, velvety papules, comedo-like openings, and network-like structures.^[4] The dermoscopy of epidermolytic EN shows large brown circles.^[4] Ansari et al. are the first to describe dermoscopic features of epidermolytic EN, where they found large and small brown circles only, while no SK like findings were observed.^[4] In their report they referred to the first description of these brown circles where these were linked to the histological arrangement of pigmented keratinocytes around dermal papillae.^[4] In contrast, our patient’s dermoscopy resembled that of SK: starry and cloudy milia-like cysts that depict keratinous cysts, a cerebriform pattern denoting hyperkeratosis and acanthosis, in addition to the common brown ring-like patterns that correspond to pigmented basal keratinocytes crowding around dermal papilla and exophytic papillary structures representing papillomatosis. Treatment includes full-thickness surgical excision, electrofulguration, dermabrasion, and cryosurgery, but they all can cause scarring.^[1] A continuous-wave carbon dioxide laser can be used for extensive VEN.^[3] Oral and topical retinoids have also been shown to improve EHK.^[3] Due to relapse post-electric cautery, our patient was prescribed a topical retinoid and asked to follow up in six weeks.

Individuals with epidermolytic epidermal nevus may carry a risk of transmitting epidermolytic ichthyosis to offspring because of possible gonadal mosaicism. Arrangements should be made to counsel the patient at a suitable age.^[1]