Epidermodysplasia verruciformis: 14 members of a pedigree with an intriguing squamous cell carcinoma transformation
Authors: Sehgal Virendra N. , Luthra Amit , Bajaj Promila 
Published: March 2003

A 38‐year‐old farmer was apparently well until 5 years of age. At this age, the patient's mother found mildly itchy, raised eruptions over the scalp during combing of the scalp hair. Since then, the eruptions have progressed insidiously to involve the face and other parts of the body, with a preponderance over the face, upper back, and chest, including the palms. The soles, oral cavity, and genital tract were unaffected. The lesions were persistent in nature and showed no remission or exacerbation. Mild to moderate pruritus/discomfort was experienced following sunlight exposure. A prominent, raised eruption appeared on the right side of the forehead 9 years ago, 25 years after the initial eruptions, which in due course ulcerated. It was progressive in nature and acquired a large size. Two years later, it was diagnosed as squamous cell carcinoma, for which liquid nitrogen cryosurgery was performed. There was a recurrence of the lesion at the site of surgery, which was excised 4 months later. Subsequently, there was a sudden flare up at the same site. It was badly infected with maggot infestation. The relentless course of the disease was evident by the appearance of two similar lesions, one on the right half of the nose and the other on the left preauricular region.

A short while ago, fatigue and loss of weight were also recorded. Bladder and bowel functions were normal and there was no loss of appetite, hoarseness of voice, or breathlessness.

Four of the patient's six children (three sons and one daughter) were reported to have similar lesions all over the body. In addition, nine other relatives were also affected. Accordingly, a total of 14 (12 males and two females) family members were found to be affected from amongst 41 individuals (26 males and 15 females) spread across several generations (Fig. 1). There was a second‐degree consanguinity of marriage, with the patient's grandmother and wife's father being brother and sister.

Epidermodysplasia verruciformis: pedigree

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Skin surface examination was marked by multiple, discrete, flat‐topped, scaly, brownish‐black papules of diverse morphology, from hypopigmented macules to verrucous lesions, with a few coalescing to form plaques. The scales were brown, dry, and adherent (Fig. 2a). The lesions were conspicuous by their presence over the face, neck, and front and back of the chest. The extremities were also affected. Nevertheless, the soles and genitalia were spared. The oral mucosae, hair, and nails were normal. Koebner's phenomenon was explicit, whereas Auspitz's sign was not demonstrable. In addition, a perceptible nodulo‐ulcerative lesion (size, 3 in × 2 in) with indurated, raised, averted margins was encountered on the right side of the forehead. The ulcer was tender and had a fetid discharge. Necrotic slough was prominent over its base. Similar lesions were located on the left preauricular region and right half of the nose.

(a) Epidermodysplasia verruciformis: classic lesions. (b,c) Hyperkeratosis, acanthosis, and mild papillomatosis. Extensive vacuolization confined to the upper stratum Malpighian and granular cell layer. Vacuolated cells were fairly large, with their nuclei in the center with variable pyknosis. The granular cell layer was uniformly thickened with the stratum corneum showing a basket‐weave appearance (hematoxylin and eosin, × 40, × 200)

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Hematoxylin and eosin‐stained sections prepared from biopsies taken from representative lesions of epidermodysplasia verruciformis and squamous cell carcinoma revealed their diagnostic features. Epidermodysplasia verruciformis showed features of hyperkeratosis and acanthosis with hardly any papillomatosis. Marginal elongation of the rete ridges was present. Extensive vacuolization was a remarkable feature, and was largely confined to the upper stratum Malpighian and the granular cell layer. Some of the vacuolated cells were fairly large; their nuclei were located in the center and had variable pyknosis. The granular cell layer was uniformly thickened, whereas the stratum corneum had a loosely felted (basket‐weave) appearance. The dermis was apparently normal (Fig. 2b,c).

The other microsection(s) from squamous cell carcinoma were conspicuous by the presence of hyperkeratosis, acanthosis, and irregular masses of epidermal cells, proliferating downwards and invading the dermis. Varying proportions of differentiated squamous cells formed their bulk. These cells were atypical, characterized by variations in size and shape, hyperplasia and hyperchromasia of the nuclei, absence of prickles, characterization of individual cells, and the presence of both mitotic and atypical mitotic figures (Fig. 3b).

(a) Squamous cell carcinoma. (b) Irregular masses of epidermal cells. Varying proportions of differentiated cells characterized by a variation in size and shape, hyperchromasia of the nuclei, absence of prickles, and typical and atypical mitotic figures (hematoxylin and eosin, × 200)

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