Squamous cell carcinoma arising from lesions of porokeratosis palmaris et plantaris disseminata

ARTICLE

Porokeratosis palmaris et plantaris disseminata (PPPD) is a rare variant of porokeratosis [1], which occurs as an autosomal dominant condition or sporadically [2]. The lesions of PPPD begin on the palms and soles in the twenties, and the eruptions gradually spread to the entire trunk and extremities [3, 4]. Malignant epithelial tumors such as squamous cell carcinoma may develop from lesions of PPPD [1, 5, 6]. The treatment of PPPD with oral retinoids has been effective [7] and the possible effects of retinoids against malignant changes of lesions might be an additional benefit [8]. We here describe a rare case of PPPD where multiple squamous cell carcinoma arose after the cessation of oral administration of retinoids.

Case report

A 63-year-old Japanese man with numerous hyperkeratotic papules without itching or pain on the bilateral palms and soles consulted Ogaki Municipal Hospital on March 28, 1989. These papules were noted on the palms and soles, in 1954 (at the age of 28) and in 1969 (age 43), respectively. The number of these papules had gradually increased. His right middle finger was amputated because of probable squamous cell carcinoma in 1975, but precise information was not obtained. He had numerous hyperkeratotic papules of 1-1.5 mm in diameter not only on the palms and soles but also on the dorsa of the hands and feet, but no eruptions on the face, scalp, trunk and arms or thighs. No involvement was observed on any mucous membranes. He has no family history of such hyperkeratotic papules. He had been a teacher in primary school from 19 to 63 years of age and denies exposure to arsenic compounds, irradiation and treatment for syphilis. The histological findings of a skin biopsy specimen obtained from the left palm (Fig. 1A, B) taken in 1984 in Gifu Prefectural Gifu Hospital showed tightly packed columns of parakeratotic cells in the cornified layer (cornoid lamella), lost granular layer, and dyskeratotic keratinocytes in the epidermis below the cornoid lamella (Fig. 2). The histological findings were diagnosed as PPPD. From August 1985, he received treatment with etretinate (50-25 mg/day) orally and with ointment including 10% urea topically. The treatment with etretinate (10-20 mg/day) was continued discontinuously in Ogaki Municipal Hospital until July in 1998 and the total dose of etretinate amounted to approximately 21 g over the 14-year period (average: 0.07 mg/kg/day). Since the number and sizes of papules had not changed for a long time, the patient refused further oral treatment with etretinate, and the treatment was stopped in August, 1998. He noticed a tiny erosion on a hyperkeratotic papule on the left heel on May 25, 1999, although the number and sizes of other hyperkeratotic papules had not changed after the cessation of etretinate. Since the size of the erosion had increased on July 5, 1999 (Fig. 3), a biopsy was performed for an erosion with a 2-mm diameter. Histological findings showed atypical keratinocytes in the epidermis and upper dermis, with mononuclear cell infiltration seen in the upper dermis (Fig. 4). We performed additional biopsies from two small erosions and one hyperkeratotic papule on the left palm (Fig. 1C, D) and left sole each, and squamous cell carcinoma was demonstrated histologically in all four erosions but not in any hyperkeratotic papules. Human papilloma virus (HPV) DNAs (type 6, 11, 16, 18, 30, 31, 33, 35, 45, 51 and 52) were not detected by in situ hybridization using HPV spectrum DNA probe (Y1404) and alkaline phosphatase detection kit (DAKO A/S, Copenhagen, Denmark). Laboratory examinations on August 17, 1999 were within normal limits including negative results for syphilis. Computed tomography of the whole body showed no abnormal findings except for slight emphysema and fibrosis in bilateral lungs. The findings of scintigraphy with gallium did not indicate the presence of metastasis. The diagnosis of squamous cell carcinoma arising from lesions of porokeratosis palmaris et plantaris was made. Five erosions with histologically malignant changes were removed 1 cm from the margin of the erosions.

Discussion

The punctate keratodermas in soles and palms cause much confusion because of a varied nomenclature and differing usage of the terms [2]. The diagnosis of PPPD in the present case was made by histological findings, although the lesions were limited to the parts distal to the wrists and ankles and there was no family history of this disease.

The use of oral retinoids such as etretinate in PPPD has yielded conflicting results: whereas excellent results were obtained in some patients [7] and relapses follow several weeks or months after cessation of retinoid therapy [8], some cases with worsening of lesions were also reported in several patients treated with etretinate [9]. Exacerbation of the hyperkeratotic papules was not shown in the present case by the cessation of retinoid for at least 1 and a half years.

Malignant epithelial tumors such as squamous cell carcinoma have been reported to arise from PPPD [1, 5, 6]. The lesions of porokeratosis evolve from a clone of abnormal epithelial cells at the base of the cornoid lamella [10], and malignant changes develop from the areas of epidermal dysplasia. An increased oncogenic potential is suggested in lesional keratinocytes of PPPD by a high rate of abnormal DNA-ploidy [6, 11-13] and by certain pheotypic features indicative of malignant transformation such as p53 overexpression [14-16]. However, the precise mechanisms for malignant change from PPPD are still unknown. It has also been pointed out that retinoids may make cytological atypia disappear and have an inhibitory effect on cutaneous carcinogenesis in porokeratotic lesions [8]. In the present case, erosions which were proved as squamous cell carcinoma histologically were noticed more than 9 months after cessation of etretinate, suggesting that retinoids might have inhibitory effects on malignant changes from PPPD, although the total dosage of etretinate was low.

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