Anton, Cristina

Baracat, Edmund Chada

Carvalho, Filomena Marino

Carvalho, Jesus Paula

Luiz, Arthur Vicentini da Costa

Clinics

English

PubMed

ANTON, Cristina

LUIZ, Arthur Vicentini da Costa

CARVALHO, Filomena Marino

BARACAT, Edmund Chada

CARVALHO, Jesus Paula

Universidade de São Paulo

Clinical treatment of vulvar Paget's disease: a case report

Cristina Anton

Arthur Vicentini da Costa Luiz

Filomena Marino Carvalho

Edmund Chada Baracat

Jesus Paula Carvalho

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CASE REPORTClinical treatment of vulvar Paget’s disease: a casereportCristina Anton,I Arthur Vicentini da Costa Luiz,I Filomena Marino Carvalho,II Edmund Chada Baracat,III JesusPaula CarvalhoIIObstetrics and Gynecology – Faculdade de Medicina da Universidade de Sa˜o Paulo Sa˜o Paulo/SP, Brazil. IIPathology – Faculdade de Medicina daUniversidade de Sa˜o Paulo, Sa˜o Paulo/SP, Brazil. IIIGynecology – Hospital das Clı´nicas da Faculdade de Medicina da Universidade de Sa˜o Paulo, Sa˜o Paulo/SP, Brazil.Email: carvalhojp@uol.com.brTel.: 55 11 3255 5592INTRODUCTIONVulvar Paget’s disease is very rare malignancy originatingin vulvar apocrine-gland-bearing skin cells or as a manifes-tation of adjacent primary anal, rectal or bladder adeno-carcinoma.1 It is also called extramammary Paget’s diseaseand affects both sexes, in the vulvar, perineal or scrotalareas. Vulvar Paget’s disease is most commonly seen inpostmenopausal Caucasian females and appears clinicallyas red, eczematous and pruriginous – and sometimespainful – lesions. In most cases it is an intraepidermaladenocarcinoma in which tumor cells involve the epidermisand sometimes the underlying skin appendage, but some-times there is focal dermal invasion.2Probably because of its multicentric nature, Paget’sdisease has a chronic and relapsing course. Surgery hasbeen the treatment of choice, but disease frequently extendsfar from the visible lesion and surgical margins arefrequently positive. The Paget’s cells are larger thankeratinocytes, have clear chromatin, a prominent nucleolusand gray–blue cytoplasm and they may appear vacuolatedwith hematoxylin and eosin staining.3 All these character-istics are consistent with their glandular nature.Many patients undergo multiple surgical procedures,including wide local excision, simple vulvectomy or radicalvulvectomy. However, the margins of primary surgicalspecimens are positive in more than half of the patients.3Consequently, the recurrence rate is about 47%.4The disappointing results of surgical treatment and thehigh morbidity and side-effects of extensive vulvar resectionhave encouraged many authors to try innovative clinicaltreatment for vulvar Paget’s disease.CASE REPORTAn 84-year-old female patient sought treatment with thecomplaint of itching in the pubic area. She presented with alarge hyper-pigmented to pink plaque extending throughthe pubic area and left great labia (Figure 1A). Biopsyresulted in a diagnosis of Paget’s disease based onhematoxylin–eosin staining and the immunohistochemicalprofile (negative Melan-A and positive cytokeratin 7)(Figure 2).The treatment proposed was surgery with wide localresection and margin control by frozen section examination.The patient refused any kind of surgical treatment. As analternative treatment, we proposed topical imiquimod 5%cream, to be applied every other day, on the affected areafor at least 16 weeks.In the first two weeks of treatment she reported localburning, small erosion areas, two episodes of fever (38 C˚)and flu-like symptoms, which lasted until the fourth week.By the end of 16 weeks, there was clinical reduction of thelesion. The patient agreed to be subjected to multiple controlbiopsies. Pathological examination showed that the tissueremained positive for Paget’s disease. We decided tocontinue with another course of imiquimod 5% creamtreatment for a further nine weeks. At the end of 25 weeks oftreatment we performed other multiple biopsies, whichshowed no residual disease (Figure 1B).DISCUSSIONFor a long time, the standard treatment for vulvar Paget’sdisease has been surgery with intraoperative margincontrol, but results have been very disappointing. Positivemargins and recurrence rates are greater than 50%.Otherwise, wide local resection brings major functionalanogenital–vulvar defects.Alternative non-surgical or combined treatments havebeen proposed, including radiotherapy, topical chemother-apy with intralesional interferon alfa-2b, CO2 laser ablation,photodynamic therapy with topical aminolevulinic acid,topical fluorouracil (5-FU), and imiquimod 5% cream.5Radiotherapy has been used both as a definitive treatmentas well as in the postoperative setting to prevent localrecurrence, mainly in the management of anogenital Paget’sdisease. Moreno-Arias et al.6 reported a dosage of radio-therapy in the range 40–50 Gy resulting in low recurrencerates, but others have observed recurrences in patientstreated with slightly lower radiotherapy total doses.5Tanaka et al.7 reported 14 cases of extramammary Paget’sdisease, four of which involved women with disease in thevulvar, groin or perianal areas. Treatment included surgery,radiation therapy, photodynamic therapy, CO2 laser ther-apy and, in one case, imiquimod cream application. All fourcases of female genital Paget’s disease recurred or persisted.Copyright  2011 CLINICS – This is an Open Access article distributed underthe terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided theoriginal work is properly cited.CLINICS 2011;66(6):1109-1111 DOI:10.1590/S1807-593220110006000331109Imiquimod 5% cream appears to be a promising option forclinical treatment of vulvar Paget’s disease. The case thatwas treated with imiquimod cream 5%, reported by Tanakaet al.,7 was a very extensive vulvo-perineal lesion thatshowed more than 50% local regression after only 5 weeksof treatment. The residual lesion was subjected to otherkinds of treatment.Wang et al.8 reported a six-week course of nightlytreatment with imiquimod 5% cream for a recurrent caseof vulvar Paget’s disease. The patient reported marked localirritation, erosions, and tenderness, but did not report flu-like symptoms, nausea or diarrhea. Two weeks aftercompletion of therapy, the patient did not have symptomsof itching or burning and there was no clinical evidence ofresidual Paget’s disease. A post-treatment skin-biopsyspecimen showed no atypia in the epidermis.Hatch and Davis9 reported two women with vulvarPaget’s disease who achieved biopsy-confirmed resolutionof their disease after topical application of imiquimod 5%cream.Geisler and Manahan10 reported the case of an 80-year-old woman with recurrent Paget’s disease of the vulva. Shehad undergone multiple resections for the disease over a 12-year period. After a course of topical imiquimod, a post-treatment biopsy proved histological regression of thedisease. Bertozzi et al.11 reported on a 71-year-old patientwith recurrent disease treated successfully with imiquimodcream. Within eight weeks, complete clinical remission wasachieved.Sendagorta et al.12 reported on three patients diagnosedwith vulvar Paget’s disease who were each treated with adaily application of imiquimod 5% cream for three weeks,followed by a further three weeks of application every otherday. Complete clinical and histological remission of thedisease was achieved in the three patients. Mild irritationand tenderness were observed as the only side-effects.Tonguc et al.13 reported on the case of a 65-year-oldwoman initially treated by means of a wide vulvar excision:she had experienced two recurrences of the disease. Ourpatient also refused any kind of surgical treatment withimiquimod cream 5%.Our patient, however, had refused any kind of surgicaltreatment, so she was convinced to try local treatment with5% imiquimod cream instead. At the end of a total of 25weeks of treatment (16 weeks followed by 9 weeks),multiple vulvar biopsies showed no residual disease. Ourexcellent results are in accord with the literature reportsand suggest that imiquimod cream appears to be aneffective and safe therapeutic agent for vulvar Paget’sdisease.Figure 1 - Extramammary Paget’s disease. (A) Before treatment. Large hyperpigmented to pink plaque extending through the pubicarea and left great labia. (B) After 25 weeks of treatment. Some biopsy scars are visible but there is no residual Paget’s disease.Vulvar Paget’s disease: clinical treatmentAnton C et al.CLINICS 2011;66(6):1109-11111110Until now, most patients treated with imiquimod creamhave been those with recurrent disease. Our patient,however, experienced initial treatment with imiquimodcream. These promising results warrant further studies todetermine the real efficacy and safety of imiquimod 5%cream for the treatment of extramammary Paget’s disease.REFERENCES1. Niikura H, Yoshida H, Ito K, Takano T, Watanabe H, Aiba S, et al.Paget’s disease of the vulva: clinicopathologic study of type 1 casestreated at a single institution. Int J Gynecol Cancer. 2006;16:1212–5, doi:10.1111/j.1525-1438.2006.00602.x.2. Shaco-Levy R, Bean SM, Vollmer RT, Papalas JA, Bentley RC, Selim MA,et al. Paget disease of the vulva: a histologic study of 56 cases correlatingpathologic features and disease course. Int J Gynecol Pathol. 2010;29:69–78, doi: 10.1097/PGP.0b013e3181b1cc5e.3. Parker LP, Parker JR, Bodurka-Bevers D, Deavers M, Bevers MW, Shen-Gunther J, et al. Paget’s disease of the vulva: pathology, pattern ofinvolvement, and prognosis. Gynecol Oncol. 2000;77:183–9, doi: 10.1006/gyno.2000.5741.4. Shaco-Levy R, Bean SM, Vollmer RT, Jewell E, Jones EL, Valdes CL, et al.Paget disease of the vulva: a study of 56 cases. Eur J Obstet GynecolReprod Biol. 2010;149:86–91, doi: 10.1016/j.ejogrb.2009.11.003.5. Yanagi T, Kato N, Yamane N, Osawa R. Radiotherapy for extramammaryPaget’s disease: histopathological findings after radiotherapy. Clin ExpDermatol. 2007;32:506–08, doi: 10.1111/j.1365-2230.2007.02425.x.6. Moreno-Arias GA, Conill C, Castells-Mas A, Arenas M, Grimalt R.Radiotherapy for genital extramammary Paget’s disease in situ.Dermatol Surg. 2001;27:587–90, doi: 10.1046/j.1524-4725.2001.00304.x.7. Tanaka VD, Sanches JA, Torezan L, Niwa AB, Festa Neto C. Mammaryand extramammary Paget’s disease: a study of 14 cases and theassociated therapeutic difficulties. Clinics. 2009;64:599–606, doi: 10.1590/S1807-59322009000600018.8. Wang LC, Blanchard A, Judge DE, Lorincz AA, Medenica MM, Busbey S.Successful treatment of recurrent extramammary Paget’s disease of thevulva with topical imiquimod 5% cream. J Am Acad Dermatol.2003;49:769–72, doi: 10.1067/S0190-9622(03)02107-8.9. Hatch KD, Davis JR. Complete resolution of Paget disease of the vulvawith imiquimod cream. J Low Genit Tract Dis. 2008;12:90–4, doi: 10.1097/LGT.0b013e31815a58a5.10. Geisler JP, Manahan KJ. Imiquimod in vulvar Paget’s disease: a casereport. J Reprod Med. 2008;53:811–2.11. Bertozzi S, Londero AP, Fruscalzo A, Marchesoni D, Lelle´ RJ. [Pagetdisease of the vulva: resolution after local treatment with imiquimod–report of a case and review of the literature]. Gynakol GeburtshilflicheRundsch. 2009;49:326–30, doi: 10.1159/000301110.12. Sendagorta E, Herranz P, Feito M, Ramı´rez P, Florista´n U, Feltes R, et al.Successful treatment of three cases of primary extramammary Paget’sdisease of the vulva with Imiquimod–proposal of a therapeutic schedule.J Eur Acad Dermatol Venereol. 2010;24:490–2, doi: 10.1111/j.1468-3083.2009.03451.x.13. Tonguc E, Gu¨ngor T, Var T, Ozat M, Sahin I, Sirvan L. Treatment ofrecurrent vulvar Paget disease with imiquimod cream: a case report andreview of the literature. Arch Gynecol Obstet. 2011;283:97–101, doi: 10.1007/s00404-010-1653-4.Figure 2 - Histological presentation of the vulvar skin showing pleomorphic large cells, isolated or in groups, among normalkeratinocytes (left). These cells stained for cytokeratin 7 (middle) and were negative for Melan-A (right), allowing the diagnosis ofextramammary Pagets disease.CLINICS 2011;66(6):1109-1111 Vulvar Paget’s disease: clinical treatmentAnton C et al.1111

[Paget disease of the vulva: resolution after local treatment with imiquimod– report of a case and review of the literature]. Gynakol Geburtshilfliche Rundsch.

Complete resolution of Paget disease of the vulva with imiquimod cream.

Imiquimod in vulvar Paget’s disease: a case report.

Mammary and extramammary Paget’s disease: a study of 14 cases and the associated therapeutic difficulties.

Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

Paget disease of the vulva: a study of 56 cases.

Paget’s disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution.

Paget’s disease of the vulva: pathology, pattern of involvement, and prognosis.

Radiotherapy for extramammary Paget’s disease: histopathological findings after radiotherapy. Clin Exp Dermatol.

Radiotherapy for genital extramammary Paget’s disease in situ. Dermatol Surg.

Successful treatment of recurrent extramammary Paget’s disease of the vulva with topical imiquimod 5% cream.

Successful treatment of three cases of primary extramammary Paget’s disease of the vulva with Imiquimod–proposal of a therapeutic schedule.

Treatment of recurrent vulvar Paget disease with imiquimod cream: a case report and review of the literature.

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Clinical treatment of vulvar Paget's disease: a case report

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