DIVERGENT CLINICAL COURSE OF EPIDERMODYSPLASIA-VERRUCIFORMIS IN SIBLINGS

In 1960, when he was 5 years old, Patient 1 was first noted to have pl ane wart-like lesions on the dorsum of his hands and on the back of hi s neck. He was seen at age 14 when he presented with pityriasis versic olor-like lesions on his trunk and persistent warts on his hands and n eck. A biopsy confirmed the clinical diagnosis of epidermodysplasia ve rruciformis (EV); however, he was lost to follow-up until age 30 when he presented with hundreds of plane wart-like lesions on his face, nec k, and hands, as well as reddish scaly plaques on his trunk, arms, and forearms. One of the plaques on his right forearm was confirmed to be Bowen's disease on biopsy. He received treatment with etretinate 1 mg /kg per day for 8 months. He did not develop any new lesions while on the drug; however, he was lost to follow-up again for another 8 years until he was 38 (Fig. 1), when he presented with an invasive squamous cell carcinoma (SCC) on the dorsum of his right hand. Patient 1 is the eldest of six siblings (two men, and four women). His brother, who is 5 years younger, is Patient 2. No other members of the family are aff ected so far. Our patients are a product of a consanguineous marriage of first cousins. Patient 2 was first documented with symptoms of his disease at approximately age 6. He was seen on one occasion when he wa s 9 years old with pityriasis versicolor-like lesions on his trunk, He was not seen again until age 25, when he presented with several verru cous tumors on his right upper and lower and left lower eyelids, dorsu m of nose, and right retroauricular zone; he also had hundreds of redd ish, scaly, pityriasis versicolor-like lesions on his trunk, arms, and forearms and warts on his wrists and dorsum of his hands. Biopsies sh owed invasive SCCs of his nose, right eyelids, and retroauricular zone , as well as Bowen's disease of the lower left eyelid and suprasternal area. He was treated surgically and alo given etretinate 1 mg/kg per day for 8 months during which no new lesions were detected. At age 27, he had a recurrence of nasal SCC. He was treated surgically and with methotrexate but, as tumor progression was noted and not having anythi ng better to offer our patient, it was then decided to treat him with radiotherapy. One year later he presented with a second recurrence of SCC and since then has never been without midfacial aggressive tumor a ctivity; he was treated again, first surgically and then using chemoth erapy with methotrexate and 5-fluorouracil. Two years later, at age 32 , he developed a third recurrence of his midfacial SCC affecting his g labellar zone, left malar area, and upper lip. The first two tumors re sponded well to surgery; the third one (upper lip) recurred so he rece ived radiotherapy once again. He then received interferon alpha 2b 5 m illion units, three times a week for 12 months; during this time he de veloped SCC in his right ear, upper lip (both treated surgically and w ith radiotherapy), neck, and wrist (treated surgically). He is now 35 years old. In order to identify human papillomaviruses (HPVs) of Patie nt 2, three biopsies were taken. Specimen A was from an in situ SCC fr om his right wrist, specimen B was a pityriasis versicolor-like plaque also from his right wrist, and specimen C was a wart from the dorsum of his right hand. Sections from these paraffin blocks were processed for histologic diagnosis and afterwards 10 sections (10-mu m thick) we re processed for polymerase chain reaction (PCR) analysis. Paraffin se ctions from block A (in situ SCC) did not contain amplifiable sequence s because the internal control, i.e. HLA-DR, did not work, presumably because the DNA was severely degraded. The DNA from block C (wart) con tained amplifiable HLA-DR sequences but no HPV sequences. Therefore, a ll results will describe the HPV sequences found in block B (pityriasi s versicolor-like plaque). Block B contained sequences that, at modera te stringency hybridized to HPV types 2, 3, 10, and 11. HPV 2 is assoc iated with verruca vulgaris. HPV 3 and 10 are associated with verruca plana acid these types share 34% homology with each other. HPV 3 and 1 0 are also found in patients with the autosomally recessive disease ep idermodysplasia verruciformis. HPV 11 is associated with condiloma acu minatum. Direct sequencing was performed in order to clarify which typ e was in the tissue. The homology showed substantial homology with HPV 2 (65/66 nucleotides).