Case Report Dermatology 1992; 185:316-318
Department of Dermatology, University of Liege. Belgium
Key Words Squamous-cell carcinoma Genitalia PUVA Carcinogenesis
Genital Squamous-Cell Carcinoma after PUVA Therapy
Abstract Among our patients treated with very high doses of PUVA (more than 1,500 J/ cnr) for recalcitrant disseminated psoriasis, three developed squamous-cell carcinoma of the genitalia. The tumors were located on the scrotum in all patients; one of them displayed three times running a carcinoma of the dorsal aspect of the penis. All these genital tumors arose more than 2 years after PUVA cessa tion, in patients with previous arsenic and tar treatment.
Case Report 1 This 61-year-old patient had suffered from a disseminated and recalcitrant psoriasis since the age of 21. Topical treatments including corticosteroids and tars have been used for several years. Systemic cor ticosteroids and arsenic had also been part of his previous treatment. PUVA therapy was started in 1978. and the patient was completely cleared after a few weeks but relapsed rapidly. PUVA was reused, and it was impossible to stop it because of relapses after each attempt. In 1980 the patient developed a squamous-cell carcinoma of the neck. A second squamous-cell carcinoma arose on the dorsal aspect of the penis in 1982. At this time the total dose of UVA radiation reached 5.417 J/cm \ PUVA treatment was then stopped, and the patient received retinoids (etretinate) until 1990 with satisfying results, but this had to be stopped when the patient developed a chronic cirrhosis. He had a history of angor and severe hypertension excluding ciclosporin A treatment. Topical corticosteroids were the only possibility left. In 1991. that is 9 years after cessation of the PUVA. a squamous-cell carcinoma arose on the scrotum (fig. I).
Case Report 2 This 69-year-old patient had been suffering from disseminated guttate psoriasis since the age of 16. Previous treatments included arsenic.
tars, vitamin A and topical corticosteroids. PUVA therapy was begun in 1978. and complete clearing was obtained after 6 weeks. Relapse occurred within a few days leading to the need of a long-term photo chemotherapy until 1990 when a squamous-cell carcinoma appeared on the scrotum (fig. 2). The total amount of UVA radiation was 2,504 J/cnr. A treatment with methotrexate was started, but the patient developed a chronic hepatitis. At the present time, topical corticoste roids remain the only treatment.
Case Report 3 This 55-ycar-old patient had his first manifestation at the age of 17. Previous treatments included topical tars and corticosteroids, systemic corticosteroids and arsenic. Photochemotherapy was started in 1976. and complete clearing was obtained in 6 weeks. Each attempt to stop PUVA was followed by a relapse. Long-term PUVA therapy was then necessary. In 1988. a genital squamous-cell carcinoma arose on the scrotum, and PUVA was stopped. Systemic retinoids were adminis tered. but the patient developed a hepatic toxicity. Ciclosporin A was excluded because of a history of hypertension. Topical treatment is the only present possibility. In 1990. a genital squamous-cell carcinoma arose on the dorsal aspect of the penis (fig.3). In 1991.2 other squa mous-cell carcinomas appeared on the same location. Up to now. the patient has had a total of 4 genital squamous-cell carcinomas.
Michel dc la Brassinne. MD. PhD Department of Dermatology University of Liège Quai G.-Kurth 45. B—4020 Liège (Belgium)
© 1992 Karger A G. Basel 1018-8665/92/1854-0316 $ 2.75/0
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M. de la Brassinne B. Richert
Discussion Tar is a well-known carcinogen since the first description by Pott, in 1775. of squamous-cell carcinomas on the scro tum in chimney sweeps [1], In the general population, the risk of developing a genital tumor, especially on the scro tum, is linked with exposure to peculiar occupational agents (tars, metals) [2], The carcinogen effect of arsenic is demonstrated. The risk of developing a squamous-cell carcinoma in patients suffering from psoriasis is not significantly different from that of the general population [3], It has been shown that the risk of squamous-cell carcinomas of the whole in tegument after PU VA is dependent on the total UVA dose received [4-7). As in the study of Stern et al. [8] and a Swedish report of epidemiology [9], we have observed the arising of tumors among men following PUVA therapy and topical tar treatment. Stern et al. put forward that 'the risk of invasive squamous-cell carcinoma of the genitalia among men exposed to high-intensity PUVA is nearly 300 times that in the general population’ [8]. The genital skin being very thin, a more important part of UVA radiation could reach the germinative epidermal layer than in the other areas of the body. Moreover, since patients remain standing during PUVA, the male genitalia are exposed to the radiation (especially the lateral sides of the scrotum and the dorsal aspect of the penis) while the female genitalia are not. It seems to us particularly impor tant to shield the genitalia during PUVA therapy if this area is not affected with psoriasis and to prefer topical treat ment for the genitalia when they are involved. The present fashion demands a tan. Thousands of peo ple expose themselves daily to UVA and/or UVB radia tions for therapeutic or esthetic reasons. It would be useful to check if the frequency of carcinomas of the genitalia will rise during the years to come. Advice should be given to regular customers of tanning salons.
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Fig. 1. Patient l : squamous-cell carcinoma on the scrotum 9 years after cessation of PUVA. Fig. 2. Patient 2: squamous-cell carcinoma on the scrotum, after I2 years of PUVA therapy. Fig. 3. Patient 3: squamous-cell carcinoma on the dorsal aspect of the penis, after 12 years of PUVA therapy and 2 years after its cessa tion.
References
2
3
4
Poll P: Chirurgical observations relative lo the cataract. the polypus of the nose, the cancer of the scrotum, the different kinds of ruptures, and the mortifications of the toes and feet. London. Hawes. Clarke. Collins. 1775. Rough GC. Kelly JA. Meigs JW. Flannery JT: Scrotal carcinomas in Connecticut metalwork ers: Sequel of a study of sinonasal cancer. Am .1 Epidemiol 1982:116:76-85. Stern RS. Scot to J. Fears TR: Psoriasis and the susceptibility to non-melanoma skin cancer. .! Am Acad Dermatol 1985;12:67-73. Stern RS. Thibodeau I.A. Kleincrman RA: Risk of cutaneous carcinoma in patients treated with oral methoxalcn photochemother apy for psoriasis. N Engl J Med 1979:300: 809-813.
.318
5
6
7
Stern RS. I.aird N. Melski .1. Parrish JA . Fitz patrick TU. Bleich ML: Cutaneous squamous cell carcinoma in patients treated with PUVA. N Engl J Med 1984:310:1156-1161. Stern RS. Lange R: Non-melanoma skin can cer occurring in patients treated with PUVA five to ten years after the first treatment. J Invest Dermatol 1988:91:120-124. lie la Brassinne M. Legrain A. AI Rustom K. Dcpairon M. Dehavay J. Lesuisse M: Induc tion de dermatoses précancéreuses et cancé reuses par la photochimiothérapie à long terme. Nouv Dermatol 1986:5:62-63.
do la Brassinne/Richert
8
9
Stern RS. members of the photochemotherapy follow-up study: Genital tumors among men with psoriasis exposed to psoralens and ultra violet A radiation (PUVA) and ultraviolet B radiation. N Engl J Med 1990:322:1093-1097. Lindelöf B. Sigurgeirsson B. Tegncr E. I.arko O. Johannesson A. Berne B. Christensen OB. Andcrsson T. Törngrcn M. Mohn L. Nylandcr-Lundqvist E. Emtcstam L: PUVA and cancer: A large epidemiological study. Lancet 1991:338:91-93.
Genital Carcinoma after PUVA
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 8:50:56 AM
1
Department of Dermatology, University of Liege. Belgium
Key Words Squamous-cell carcinoma Genitalia PUVA Carcinogenesis
Genital Squamous-Cell Carcinoma after PUVA Therapy
Abstract Among our patients treated with very high doses of PUVA (more than 1,500 J/ cnr) for recalcitrant disseminated psoriasis, three developed squamous-cell carcinoma of the genitalia. The tumors were located on the scrotum in all patients; one of them displayed three times running a carcinoma of the dorsal aspect of the penis. All these genital tumors arose more than 2 years after PUVA cessa tion, in patients with previous arsenic and tar treatment.
Case Report 1 This 61-year-old patient had suffered from a disseminated and recalcitrant psoriasis since the age of 21. Topical treatments including corticosteroids and tars have been used for several years. Systemic cor ticosteroids and arsenic had also been part of his previous treatment. PUVA therapy was started in 1978. and the patient was completely cleared after a few weeks but relapsed rapidly. PUVA was reused, and it was impossible to stop it because of relapses after each attempt. In 1980 the patient developed a squamous-cell carcinoma of the neck. A second squamous-cell carcinoma arose on the dorsal aspect of the penis in 1982. At this time the total dose of UVA radiation reached 5.417 J/cm \ PUVA treatment was then stopped, and the patient received retinoids (etretinate) until 1990 with satisfying results, but this had to be stopped when the patient developed a chronic cirrhosis. He had a history of angor and severe hypertension excluding ciclosporin A treatment. Topical corticosteroids were the only possibility left. In 1991. that is 9 years after cessation of the PUVA. a squamous-cell carcinoma arose on the scrotum (fig. I).
Case Report 2 This 69-year-old patient had been suffering from disseminated guttate psoriasis since the age of 16. Previous treatments included arsenic.
tars, vitamin A and topical corticosteroids. PUVA therapy was begun in 1978. and complete clearing was obtained after 6 weeks. Relapse occurred within a few days leading to the need of a long-term photo chemotherapy until 1990 when a squamous-cell carcinoma appeared on the scrotum (fig. 2). The total amount of UVA radiation was 2,504 J/cnr. A treatment with methotrexate was started, but the patient developed a chronic hepatitis. At the present time, topical corticoste roids remain the only treatment.
Case Report 3 This 55-ycar-old patient had his first manifestation at the age of 17. Previous treatments included topical tars and corticosteroids, systemic corticosteroids and arsenic. Photochemotherapy was started in 1976. and complete clearing was obtained in 6 weeks. Each attempt to stop PUVA was followed by a relapse. Long-term PUVA therapy was then necessary. In 1988. a genital squamous-cell carcinoma arose on the scrotum, and PUVA was stopped. Systemic retinoids were adminis tered. but the patient developed a hepatic toxicity. Ciclosporin A was excluded because of a history of hypertension. Topical treatment is the only present possibility. In 1990. a genital squamous-cell carcinoma arose on the dorsal aspect of the penis (fig.3). In 1991.2 other squa mous-cell carcinomas appeared on the same location. Up to now. the patient has had a total of 4 genital squamous-cell carcinomas.
Michel dc la Brassinne. MD. PhD Department of Dermatology University of Liège Quai G.-Kurth 45. B—4020 Liège (Belgium)
© 1992 Karger A G. Basel 1018-8665/92/1854-0316 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 8:50:56 AM
M. de la Brassinne B. Richert
Discussion Tar is a well-known carcinogen since the first description by Pott, in 1775. of squamous-cell carcinomas on the scro tum in chimney sweeps [1], In the general population, the risk of developing a genital tumor, especially on the scro tum, is linked with exposure to peculiar occupational agents (tars, metals) [2], The carcinogen effect of arsenic is demonstrated. The risk of developing a squamous-cell carcinoma in patients suffering from psoriasis is not significantly different from that of the general population [3], It has been shown that the risk of squamous-cell carcinomas of the whole in tegument after PU VA is dependent on the total UVA dose received [4-7). As in the study of Stern et al. [8] and a Swedish report of epidemiology [9], we have observed the arising of tumors among men following PUVA therapy and topical tar treatment. Stern et al. put forward that 'the risk of invasive squamous-cell carcinoma of the genitalia among men exposed to high-intensity PUVA is nearly 300 times that in the general population’ [8]. The genital skin being very thin, a more important part of UVA radiation could reach the germinative epidermal layer than in the other areas of the body. Moreover, since patients remain standing during PUVA, the male genitalia are exposed to the radiation (especially the lateral sides of the scrotum and the dorsal aspect of the penis) while the female genitalia are not. It seems to us particularly impor tant to shield the genitalia during PUVA therapy if this area is not affected with psoriasis and to prefer topical treat ment for the genitalia when they are involved. The present fashion demands a tan. Thousands of peo ple expose themselves daily to UVA and/or UVB radia tions for therapeutic or esthetic reasons. It would be useful to check if the frequency of carcinomas of the genitalia will rise during the years to come. Advice should be given to regular customers of tanning salons.
3I7
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 8:50:56 AM
Fig. 1. Patient l : squamous-cell carcinoma on the scrotum 9 years after cessation of PUVA. Fig. 2. Patient 2: squamous-cell carcinoma on the scrotum, after I2 years of PUVA therapy. Fig. 3. Patient 3: squamous-cell carcinoma on the dorsal aspect of the penis, after 12 years of PUVA therapy and 2 years after its cessa tion.
References
2
3
4
Poll P: Chirurgical observations relative lo the cataract. the polypus of the nose, the cancer of the scrotum, the different kinds of ruptures, and the mortifications of the toes and feet. London. Hawes. Clarke. Collins. 1775. Rough GC. Kelly JA. Meigs JW. Flannery JT: Scrotal carcinomas in Connecticut metalwork ers: Sequel of a study of sinonasal cancer. Am .1 Epidemiol 1982:116:76-85. Stern RS. Scot to J. Fears TR: Psoriasis and the susceptibility to non-melanoma skin cancer. .! Am Acad Dermatol 1985;12:67-73. Stern RS. Thibodeau I.A. Kleincrman RA: Risk of cutaneous carcinoma in patients treated with oral methoxalcn photochemother apy for psoriasis. N Engl J Med 1979:300: 809-813.
.318
5
6
7
Stern RS. I.aird N. Melski .1. Parrish JA . Fitz patrick TU. Bleich ML: Cutaneous squamous cell carcinoma in patients treated with PUVA. N Engl J Med 1984:310:1156-1161. Stern RS. Lange R: Non-melanoma skin can cer occurring in patients treated with PUVA five to ten years after the first treatment. J Invest Dermatol 1988:91:120-124. lie la Brassinne M. Legrain A. AI Rustom K. Dcpairon M. Dehavay J. Lesuisse M: Induc tion de dermatoses précancéreuses et cancé reuses par la photochimiothérapie à long terme. Nouv Dermatol 1986:5:62-63.
do la Brassinne/Richert
8
9
Stern RS. members of the photochemotherapy follow-up study: Genital tumors among men with psoriasis exposed to psoralens and ultra violet A radiation (PUVA) and ultraviolet B radiation. N Engl J Med 1990:322:1093-1097. Lindelöf B. Sigurgeirsson B. Tegncr E. I.arko O. Johannesson A. Berne B. Christensen OB. Andcrsson T. Törngrcn M. Mohn L. Nylandcr-Lundqvist E. Emtcstam L: PUVA and cancer: A large epidemiological study. Lancet 1991:338:91-93.
Genital Carcinoma after PUVA
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 8:50:56 AM
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