History
Epidermodysplasia verruciformis usually begins in infancy or early childhood, with the development of various types of flat, wartlike lesions and confluent plaques on the skin, especially on dorsal hands, extremities, face, and neck. Patients may also develop tinea versicolor–like lesions on the trunk.
Epidermodysplasia verruciformis lesions may progress to form verrucous plaques and nodules, or they may transform into invasive squamous cell carcinomas, most commonly between the ages of 20 and 40 years.
The clinical course of epidermodysplasia verruciformis is protracted. As the disease progresses, some lesions disappear, while new lesions may appear on other areas of the body. The rate of appearance of new lesions varies considerably.
The diagnosis of epidermodysplasia verruciformis should be suspected in the clinical setting of numerous verrucous lesions or when lesions are resistant to appropriate therapy.
Epidermodysplasia verruciformis variants may be suspected when a patient has the typical clinical presentation in the setting of epidermodysplasia verruciformis–associated HPV but lacks nonmelanoma skin cancers at a young age or has late-onset disease.
Physical Examination
Pertinent physical findings are limited to the skin and rarely occur on the mucosa.
Primary skin lesions manifest as two types, although they generally are polymorphic. The first type is flat, wartlike lesions resembling verruca plana; they are flat-topped papules with scaly, hyperpigmented or hypopigmented, sometimes confluent patches or plaques. Flat macules and reddish brown plaques with slightly scaly surfaces and irregular borders are also noted, as shown in the image below. These lesions may resemble tinea versicolor. Papules on the knees, the elbows, and the trunk may coalesce into large plaques.
Epidermodysplasia verruciformis cutaneous lesions with flat macules that vary from flesh-colored to reddish brown or brown plaques, with slightly scaly surfaces and irregular borders present on the forehead of an 8-year-old boy, who is one of the 2 sons of the epidermodysplasia verruciformis patient shown in the next image.
The second type is verrucous or seborrheic keratosis–like lesions; they are commonly seen on sun-exposed skin, including dorsum of hands, as shown in the image below.
Verrucous or seborrheic keratosis–like lesions of epidermodysplasia verruciformis; they are commonly seen on sun-exposed skin. Lesions are present on dorsum of hands of a 34-year-old man who had 2 affected sons (previous image).
The wartlike lesions are mostly localized on sun-exposed areas, mainly distributed on the hands, the feet, and the face, sometimes in a linear arrangement, as demonstrated in the image below. The pigmented plaques preferentially involve the trunk, the neck, and the proximal extremities. The lesions may be found on the palms and the soles, in the axillae, and on the external genitalia. A 2018 report also uniquely described a case of AEV with lesions that were widespread in the bilateral inguinal folds with sparing of the vulva and anal mucosa. [43] The mucous membranes (conjunctiva and oral cavity) are rarely affected. The lesions are typically spread throughout the body, but limitation to one extremity has also been described in a few cases. [6]
A 41-year-old white woman with a 25-year history of numerous flat warts on her bilateral upper and lower extremities. Shave biopsy of a leg papule showed findings consistent with verruca plana.
Cutaneous lesions induced by EV-HPVs vary from flesh-colored warts (verruca vulgaris) to red, reddish-brown, and brown plaques.
Complications
Malignant transformation of skin lesions, particularly ocular squamous cell carcinoma and cutaneous squamous cell carcinoma, has been observed in more than half the patients followed for 20-30 years. Malignant tumors are typically found after age 30 years, usually during the fourth and fifth decades of life. [44, 45]
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Epidermodysplasia verruciformis cutaneous lesions with flat macules that vary from flesh-colored to reddish brown or brown plaques, with slightly scaly surfaces and irregular borders present on the forehead of an 8-year-old boy, who is one of the 2 sons of the epidermodysplasia verruciformis patient shown in the next image.
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Verrucous or seborrheic keratosis–like lesions of epidermodysplasia verruciformis; they are commonly seen on sun-exposed skin. Lesions are present on dorsum of hands of a 34-year-old man who had 2 affected sons (previous image).
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A 41-year-old white woman with a 25-year history of numerous flat warts on her bilateral upper and lower extremities. Shave biopsy of a leg papule showed findings consistent with verruca plana.
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Mild acanthosis, bridging of rete ridges, prominent granular layer, and rare koilocytotic keratinocytes, as is seen in lesions of verruca plana, are present in this lesion of epidermodysplasia verruciformis (hematoxylin and eosin; X150).
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Left: Photomicrograph of a precancerous, verrucous skin lesion from a patient with epidermodysplasia verruciformis depicts the characteristic microscopic features of specific cytopathic effect, that is, the presence of clear cells and an occasional enlarged, hyperchromatic, atypical nucleus (center of the field) in the epidermis. These changes are seen in human papillomavirus (HPV)-associated epithelial lesions (hematoxylin-eosin stain, original magnification X250). Right: Photomicrograph of the same skin lesion shows positive staining of keratinocytes infected with HPV type 8 (in situ hybridization, original magnification X250). Note the darker, spherical-to-ovoid shaped positive nuclear staining. These are sites of HPV DNA.
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Dense deposits of human papillomavirus (HPV) DNA are demonstrated by immunostaining the skin biopsy of a warty lesion of epidermodysplasia verruciformis. Note prominent vacuolation of the cytoplasm of the infected cells (koilocytosis), typical of lesions associated with HPV infection. The darker positive staining areas are sites of HPV DNA (in situ hybridization, original magnification X450).
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A photomicrograph shows an invasive well-differentiated squamous cell carcinoma, that arose in a warty lesion on sun-exposed skin of a middle-aged patient with epidermodysplasia verruciformis. Notice the atypical, neoplastic squamous cancer cells with irregular, hyperchromatic nuclei, and an occasional bizarre mitotic figure (shown near the 12-o'clock position in this field) invading into the dermis. A moderate host lymphocytic inflammatory response is present within the tumor (hematoxylin-eosin stain, original magnification X300). Squamous cell carcinoma is the most common type of skin cancer found in patients with epidermodysplasia verruciformis.
