Extramammary Paget's disease H.F. HABERMAN, MD, FRCP[C]; J. GOODALL, MD, FRCPIiC]; MARCIA LLEWELLYN, MD
In a 74-year-old man extramammary Paget's disease of the scrotal and perianal areas masqueraded as tinea cruris and chronic dermatitis for 7 years before it was diagnosed. Topical therapy with 10/0 5-fluorouracil cream resulted in clinical improvement but not histologic clearing. Chez un homme de 74 ans une maladie de Paget, sans atteinte mammaire, localisee dans Ia region scrotale et p6rianale a et6 confondue pendant 7 ans avec une epidermophytie inguinale et avec une dermatite chronique avant d'etre diagnostiquee. Un traitement topique avec une creme de 5-fluorouracil a lob a entraine une amelioration clinique sans toutefois parvenir a une gu6rison histologique. An apparently chronic persistent dermatitis of the scrotal and perianal areas that does not respond to conventional therapy, as in the case described below, should undergo biopsy to exclude neoplastic conditions such as extramammary Paget's disease.
Case report A 74-year-old man was referred to us for investigation. He had first consulted his physician 7 years before because of an extremely pruritic rash that had started on his scrotum and slowly spread to the perianal area. Over the years physicians had given the diagnoses tinea cruris and chronic dermatitis. Treatment had included tolnaftate, Ozonol (active ingredients, zinc oxide and phenol) and various corticosteroid creams; none had resulted in significant improvement. Four years before referral he had been noted to have microscopic hematuria, but cystoscopy had demonstrated no abnormalities. An unexplained weight loss of 16 kg over 18 months preceded his referral. Results of physical examination were normal except for skin findings. A slightly elevated, sharply demarcated, erythematous plaque with areas of central clearing involved the posterior lower third of the scrotum, the area between the scrotum and the anus with some perianal spread, and both upper inner thighs adjacent to the scrotum for approximately 5 cm (Fig. 1). In addition there was a basal cell carcinoma of the right shoulder. A skin biopsy specimen confirmed the diagnosis of extramammary Paget's disease. Microscopy and culture of scrapings did not demonstrate fungi. Hemoglobin concentration, hematocrit, erythrocyte sedimentation rate, leukocyte Reprint requests to: Dr. H.P. Haberman, Photobiology and phototherapy Unit, Division of dermatology, Toronto Western Hospital, 399 Bathurst St., Toronto, Ont. M5T 2S8
count and differential, and creatinine clearance were normal, as were results of liver function tests. Urinalysis showed persistent microscopic hematuria but cystoscopy was refused. Sigmoidoscopy, roentgenography after a barium enema, and intravenous pyelography yielded no abnormalities. Because the patient refused any surgical approach to his problem, 1 % 5-fluorouracii cream was applied every morning to the affected area in addition to 1% hydrocortisone cream every evening. He suffered two episodes of erosions and acute dermatitis during therapy, but these settled and he was able to continue 5-fluorouracil therapy for 12 weeks. A biopsy specimen from a clinically "cleared" area taken after 9 weeks of 5-fluorouracil therapy showed "a relatively normal surface epithelium with only a few scattered individual Paget's cells in the peribasal area" (Fig. 2). A specimen from an area that was still erythematous showed "prominent replacement of epidermal cells by large clear Paget's cells. In some areas Paget's cells replaced almost the full thickness of squamous epithelium." A biopsy specimen from the first area taken before 5-fluorouracil therapy was begun showed the same histologic features as the second area after 9 weeks of therapy. The patient continued to receive 5fluorouracil therapy for 12 weeks. There was progressive but not complete clinical clearing; however, biopsy specimens of clinically cleared areas again showed a few scattered Paget's cells.
Discussion Extramammary Paget's disease has been described as occurring at the following sites: vulva,1'2 anus,3 pubic area, groin,4 scrotum,4'5 buttocks, thighs, axilla, external ear canal,6 eyelid,7 tongue and mucosa of the lower esophagus. Any chronic persistent dermatitis should undergo biopsy so that extramammary Paget's disease can be ruled out. The clinical differential diagnosis includes Bowen's disease, erythroplasia of Queyrat, superficial fungal infection, superficial basal cell carcinoma and various forms of chronic dermatitis such as seborrheic dermatitis and psoriasis. Special stains should be used to differentiate extramammary Paget's disease from superficial spreading malignant melanoma. Paget's disease of the nipple virtually always indicates an underlying intraductal carcinoma and, therefore, therapy is directed to the carcinoma. However, with extramammary Paget's disease the situation is not clear. This condition may be associated with underlying adenocarcinoma of the sweat glands or concurrent cancer of an internal organ, especially the rectum or
FIG. 2-Same patient after 9 weeks of 5-fluorouracil therapy. CMA JOURNAL/JANUARY 21, 1978/VOL. 118 161
the urethra. Usually therapy is directed to the underlying tumour if found. However, if no tumour is found, usually wide, full excision is performed to remove any intraglandular carcinoma of the skin, thus ensuring inclusion of the entire area of Paget's disease, which characteristically extends beyond the seemingly distinct clinical margin. Our patient refused surgical excision, so we offered him a trial of 5-fluorouracil therapy on the basis of its previous use in superficial basal cell carcinoma, actinic keratosis, erythroplasia of
Queyrat and resistant urethral warts, and one report that suggested it may be of value in extramammary Paget's disease.2 Although our patient improved clinically with this therapy, complete clearing was not evident histologically. It may be that topical 5-fluorouracil will prove to be of only adjuvant or symptomatic benefit. References 1. VOGEL EH, AYERS MA: Primary epidermal Paget's disease of the vulva. Obstet Gynecol 36: 284, 1970
2. FETHERSTON WC, FRIEDRICH EG JR: The origin and significance of vulvar Paget's disease.
Obstet Gynecol 39: 735, 1972
3. HELWIG EB, GRAHAM JH: Anogenital (extramammary) Paget's disease. A clinicopathological study. Cancer 16: 387, 1963 4. HAGAN KW, BRAREN V, VINER NA, et al: Extramammary Paget's disease in the scrotal and inguinal area. J Urol 114: 154, 1975 5. PERRI AJ, FELDMAN AE, KENDALL AR, et al: Paget's disease of the scrotum. Need for early biopsy. Urology 6: 94, 1975 6. FLIGIEL Z, KANEKO M: Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma. Case report. Cancer 36: 1072, 1975 7. KNAUER WJ JR. WHORTON CM: Extramammary Paget's disease originating in Moll's
gland of the lids. Trans Am Acad Ophthalmol Ofolaryngol 67: 829, 1963
Reaction allergique aux medicaments topiques LOUIS-PHILIPPE DUROCHER, MD, FRCP[C]
Les dermites de contact peuvent aggraver une eruption cutanee en cours de traitement et ii importe de los distinguer d'un echec de traitement. Une etude qui avait pour but de depister l'origine des reactions allergiques secondaires a l'application d'un medicament sur Ia poau a ete effectuee chez 87 malades ayant presente co type de dermite de contact. Seize epreuves percutanees representant autant de composants medicamenteux allergisants connus ont ete faites. Les huit composants chimiques suivants ont ete responsables de 86.50/0 des reactions observees: neomycine, ethylenediamine, mercure, benzocavne, iodochlorhydroxyquin, baume du Perou, nitrofurazone et cinchocaine. La neomycine, I'ethylenediamine ot lo mercure, a oux souls, ont provoqu6 plus do Ia moitie des reactions observeos. II est plus facile do diagnostiquer cette maladie si l'on connait Ia composition dos medicaments quo l'on prescrit et Ia frequenco des allergies provoquees par los ingr6dients qu'ils contiennont. It is important to differentiate worsening of a cutaneous eruption following topical therapy from lack of response to the medication. A study to determine the origin of contact dermatitis secondary to topical therapy was conducted among 87 patients with this kind of contact dermatitis. Sixteen Dermatologiste, h8pital Maisonneuve-Rosemont, Montreal, et charg6 de clinique, d.partement de n.decine, universit6 de Montreal Travail presente au congr.s de 1'Association canadienne de dermatologie, le 16 juin 1977 . Montreal Les demandes de tires . part doivent etre adressees au Dr L.P. Durocher, 5955, est rue Sherbrooke, Montreal, PQ HiN 1B7
patch tests with chemical compounds known to be allergenic were done. The following eight chemical compounds were responsible for 86.50/0 of the positive reactions observed: neomycin, ethylenediamine, mercury, benzocaine, iodochlorhydroxyquin, peruvian balsam, nitrofurazone and cinchocaine. More than half of the reactions were to neomycin, ethylenediamine and mercury. It is easier to diagnose this condition if one knows the composition of the topical medications one prescribes and the allergenic potency of their ingredients. Les dermites de contact sont des r.actions allergiques ecz.mateuses m.di.es par les lymphocytes thymod6pendants. Elles sont secondaires . 1'application d'un produit chimique sur la peau et originent principalement de biens de consommation courants, de produits uti1is.s dans l'industrie et de m6dicaments topiques. Les m.dicaments appliqu.s sur la peau et les muqueuses sont responsables de 15% . 20% des dermites de contact.13 Quand une 6ruption ecz.mateuse survient . la suite de l'application d'un m6dicament topique ii faut se rappeler que non seulement 1'ingr.dient actif peut en .tre Ia cause mais aussi le pr.servateur ou Ia base. Pour pr6ciser Ia nature du produit chimique . 1'origine d'une dermite de contact ii faut recourir aux .preuves percutan.es d'allergie; cependant, pour que ces .preuves puissent nous renseigner ii faut connaitre le m6dicament uti1is. et ses composantes. Or, si le nom commercial du m.dicament topique employ6 est souvent disponible, sa composition Vest rarement; on doit d.s lors recourir d'embl.e . des .preuves percutan.es uniformisdes utilisant les com-
162 CMA JOURNAL/JANUARY 21, 1978/VOL. 118
posants m.dicamenteux reconnus les plus souvent . l'origine des dermites de contact. La pr6sente &ude avait pour but de mettre en evidence les produits chimiques les plus souvent responsables des dermites de contact aux m.dicaments topiques. Methodes Les malades inclus dans 1'&ude ont pr6sent6 soit une dermite de contact, soit 1'aggravation d'une eruption cutan6e pr6existante, . la suite de 1'application d'un m.dicament topique. L'.valuation des malades a 6t. faite par un dermatologiste. La liste des 16 cornposants chimiques recherch.s apparaft au tableau I.
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1
V 5 4
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In a 74-year-old man extramammary Paget's disease of the scrotal and perianal areas masqueraded as tinea cruris and chronic dermatitis for 7 years before it was diagnosed. Topical therapy with 10/0 5-fluorouracil cream resulted in clinical improvement but not histologic clearing. Chez un homme de 74 ans une maladie de Paget, sans atteinte mammaire, localisee dans Ia region scrotale et p6rianale a et6 confondue pendant 7 ans avec une epidermophytie inguinale et avec une dermatite chronique avant d'etre diagnostiquee. Un traitement topique avec une creme de 5-fluorouracil a lob a entraine une amelioration clinique sans toutefois parvenir a une gu6rison histologique. An apparently chronic persistent dermatitis of the scrotal and perianal areas that does not respond to conventional therapy, as in the case described below, should undergo biopsy to exclude neoplastic conditions such as extramammary Paget's disease.
Case report A 74-year-old man was referred to us for investigation. He had first consulted his physician 7 years before because of an extremely pruritic rash that had started on his scrotum and slowly spread to the perianal area. Over the years physicians had given the diagnoses tinea cruris and chronic dermatitis. Treatment had included tolnaftate, Ozonol (active ingredients, zinc oxide and phenol) and various corticosteroid creams; none had resulted in significant improvement. Four years before referral he had been noted to have microscopic hematuria, but cystoscopy had demonstrated no abnormalities. An unexplained weight loss of 16 kg over 18 months preceded his referral. Results of physical examination were normal except for skin findings. A slightly elevated, sharply demarcated, erythematous plaque with areas of central clearing involved the posterior lower third of the scrotum, the area between the scrotum and the anus with some perianal spread, and both upper inner thighs adjacent to the scrotum for approximately 5 cm (Fig. 1). In addition there was a basal cell carcinoma of the right shoulder. A skin biopsy specimen confirmed the diagnosis of extramammary Paget's disease. Microscopy and culture of scrapings did not demonstrate fungi. Hemoglobin concentration, hematocrit, erythrocyte sedimentation rate, leukocyte Reprint requests to: Dr. H.P. Haberman, Photobiology and phototherapy Unit, Division of dermatology, Toronto Western Hospital, 399 Bathurst St., Toronto, Ont. M5T 2S8
count and differential, and creatinine clearance were normal, as were results of liver function tests. Urinalysis showed persistent microscopic hematuria but cystoscopy was refused. Sigmoidoscopy, roentgenography after a barium enema, and intravenous pyelography yielded no abnormalities. Because the patient refused any surgical approach to his problem, 1 % 5-fluorouracii cream was applied every morning to the affected area in addition to 1% hydrocortisone cream every evening. He suffered two episodes of erosions and acute dermatitis during therapy, but these settled and he was able to continue 5-fluorouracil therapy for 12 weeks. A biopsy specimen from a clinically "cleared" area taken after 9 weeks of 5-fluorouracil therapy showed "a relatively normal surface epithelium with only a few scattered individual Paget's cells in the peribasal area" (Fig. 2). A specimen from an area that was still erythematous showed "prominent replacement of epidermal cells by large clear Paget's cells. In some areas Paget's cells replaced almost the full thickness of squamous epithelium." A biopsy specimen from the first area taken before 5-fluorouracil therapy was begun showed the same histologic features as the second area after 9 weeks of therapy. The patient continued to receive 5fluorouracil therapy for 12 weeks. There was progressive but not complete clinical clearing; however, biopsy specimens of clinically cleared areas again showed a few scattered Paget's cells.
Discussion Extramammary Paget's disease has been described as occurring at the following sites: vulva,1'2 anus,3 pubic area, groin,4 scrotum,4'5 buttocks, thighs, axilla, external ear canal,6 eyelid,7 tongue and mucosa of the lower esophagus. Any chronic persistent dermatitis should undergo biopsy so that extramammary Paget's disease can be ruled out. The clinical differential diagnosis includes Bowen's disease, erythroplasia of Queyrat, superficial fungal infection, superficial basal cell carcinoma and various forms of chronic dermatitis such as seborrheic dermatitis and psoriasis. Special stains should be used to differentiate extramammary Paget's disease from superficial spreading malignant melanoma. Paget's disease of the nipple virtually always indicates an underlying intraductal carcinoma and, therefore, therapy is directed to the carcinoma. However, with extramammary Paget's disease the situation is not clear. This condition may be associated with underlying adenocarcinoma of the sweat glands or concurrent cancer of an internal organ, especially the rectum or
FIG. 2-Same patient after 9 weeks of 5-fluorouracil therapy. CMA JOURNAL/JANUARY 21, 1978/VOL. 118 161
the urethra. Usually therapy is directed to the underlying tumour if found. However, if no tumour is found, usually wide, full excision is performed to remove any intraglandular carcinoma of the skin, thus ensuring inclusion of the entire area of Paget's disease, which characteristically extends beyond the seemingly distinct clinical margin. Our patient refused surgical excision, so we offered him a trial of 5-fluorouracil therapy on the basis of its previous use in superficial basal cell carcinoma, actinic keratosis, erythroplasia of
Queyrat and resistant urethral warts, and one report that suggested it may be of value in extramammary Paget's disease.2 Although our patient improved clinically with this therapy, complete clearing was not evident histologically. It may be that topical 5-fluorouracil will prove to be of only adjuvant or symptomatic benefit. References 1. VOGEL EH, AYERS MA: Primary epidermal Paget's disease of the vulva. Obstet Gynecol 36: 284, 1970
2. FETHERSTON WC, FRIEDRICH EG JR: The origin and significance of vulvar Paget's disease.
Obstet Gynecol 39: 735, 1972
3. HELWIG EB, GRAHAM JH: Anogenital (extramammary) Paget's disease. A clinicopathological study. Cancer 16: 387, 1963 4. HAGAN KW, BRAREN V, VINER NA, et al: Extramammary Paget's disease in the scrotal and inguinal area. J Urol 114: 154, 1975 5. PERRI AJ, FELDMAN AE, KENDALL AR, et al: Paget's disease of the scrotum. Need for early biopsy. Urology 6: 94, 1975 6. FLIGIEL Z, KANEKO M: Extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma. Case report. Cancer 36: 1072, 1975 7. KNAUER WJ JR. WHORTON CM: Extramammary Paget's disease originating in Moll's
gland of the lids. Trans Am Acad Ophthalmol Ofolaryngol 67: 829, 1963
Reaction allergique aux medicaments topiques LOUIS-PHILIPPE DUROCHER, MD, FRCP[C]
Les dermites de contact peuvent aggraver une eruption cutanee en cours de traitement et ii importe de los distinguer d'un echec de traitement. Une etude qui avait pour but de depister l'origine des reactions allergiques secondaires a l'application d'un medicament sur Ia poau a ete effectuee chez 87 malades ayant presente co type de dermite de contact. Seize epreuves percutanees representant autant de composants medicamenteux allergisants connus ont ete faites. Les huit composants chimiques suivants ont ete responsables de 86.50/0 des reactions observees: neomycine, ethylenediamine, mercure, benzocavne, iodochlorhydroxyquin, baume du Perou, nitrofurazone et cinchocaine. La neomycine, I'ethylenediamine ot lo mercure, a oux souls, ont provoqu6 plus do Ia moitie des reactions observeos. II est plus facile do diagnostiquer cette maladie si l'on connait Ia composition dos medicaments quo l'on prescrit et Ia frequenco des allergies provoquees par los ingr6dients qu'ils contiennont. It is important to differentiate worsening of a cutaneous eruption following topical therapy from lack of response to the medication. A study to determine the origin of contact dermatitis secondary to topical therapy was conducted among 87 patients with this kind of contact dermatitis. Sixteen Dermatologiste, h8pital Maisonneuve-Rosemont, Montreal, et charg6 de clinique, d.partement de n.decine, universit6 de Montreal Travail presente au congr.s de 1'Association canadienne de dermatologie, le 16 juin 1977 . Montreal Les demandes de tires . part doivent etre adressees au Dr L.P. Durocher, 5955, est rue Sherbrooke, Montreal, PQ HiN 1B7
patch tests with chemical compounds known to be allergenic were done. The following eight chemical compounds were responsible for 86.50/0 of the positive reactions observed: neomycin, ethylenediamine, mercury, benzocaine, iodochlorhydroxyquin, peruvian balsam, nitrofurazone and cinchocaine. More than half of the reactions were to neomycin, ethylenediamine and mercury. It is easier to diagnose this condition if one knows the composition of the topical medications one prescribes and the allergenic potency of their ingredients. Les dermites de contact sont des r.actions allergiques ecz.mateuses m.di.es par les lymphocytes thymod6pendants. Elles sont secondaires . 1'application d'un produit chimique sur la peau et originent principalement de biens de consommation courants, de produits uti1is.s dans l'industrie et de m6dicaments topiques. Les m.dicaments appliqu.s sur la peau et les muqueuses sont responsables de 15% . 20% des dermites de contact.13 Quand une 6ruption ecz.mateuse survient . la suite de l'application d'un m6dicament topique ii faut se rappeler que non seulement 1'ingr.dient actif peut en .tre Ia cause mais aussi le pr.servateur ou Ia base. Pour pr6ciser Ia nature du produit chimique . 1'origine d'une dermite de contact ii faut recourir aux .preuves percutan.es d'allergie; cependant, pour que ces .preuves puissent nous renseigner ii faut connaitre le m6dicament uti1is. et ses composantes. Or, si le nom commercial du m.dicament topique employ6 est souvent disponible, sa composition Vest rarement; on doit d.s lors recourir d'embl.e . des .preuves percutan.es uniformisdes utilisant les com-
162 CMA JOURNAL/JANUARY 21, 1978/VOL. 118
posants m.dicamenteux reconnus les plus souvent . l'origine des dermites de contact. La pr6sente &ude avait pour but de mettre en evidence les produits chimiques les plus souvent responsables des dermites de contact aux m.dicaments topiques. Methodes Les malades inclus dans 1'&ude ont pr6sent6 soit une dermite de contact, soit 1'aggravation d'une eruption cutan6e pr6existante, . la suite de 1'application d'un m.dicament topique. L'.valuation des malades a 6t. faite par un dermatologiste. La liste des 16 cornposants chimiques recherch.s apparaft au tableau I.
T
w k.F*.uqn. .Ie 4.uv.s pr.u.
E.aw*in# j
1
V 5 4
a
