Treatment of primary extramammary Paget's disease of the perineum with topical imiquimod 5% cream

ARTICLE

Auteur(s) : Joana Dias Coelho¹, Esmeralda Vale², Isabel Viana², Orlando Martins¹

¹Clínica Dermatologia do Areeiro, Av^a Afonso Costa, 20-22 Gal/Dt^a 1900-036 Lisboa, Portugal
²Centro de Dermatologia Médico-Cirúrgica de Lisboa, Lisbon, Portugal

Extramammary Paget's disease (EMPD) is an uncommon cutaneous malignant neoplasia that usually occurs in the genitalia, perineum and axilla. It mainly affects elderly women and presents clinically as erythematous plaques that may be crusted, eczematous, papillomatous, scaling or ulcerated [1]. Pruritus is the most common symptom [2]. The clinical aspect of EMPD is often non-specific, and, therefore, significant delays in diagnosis and treatment are common. Surgical excision is considered the treatment of choice despite the high recurrence rates reported. Wide local excisions often lead to permanent mutilation and functional impairment [3].

The pathogenesis of EMPD remains controversial. In the majority of cases it represents an in situ malignancy; it can also be a manifestation of an epidermotropic metastasis from a regional malignant neoplasm (rectal or genitourinary) [1]. An evaluation of EMPD patients for malignancy is necessary [1, 2].

We report a 63-year-old Caucasian female with a 4-year history of erythematous pruritic confluent plaques in the perineum, from the anal margin to the major labia, with moderate maceration, which had been treated with multiple topical treatments (clotrimazole cream 1%, zinc oxide and fusidic acid cream) without any improvement (figure 1A).

Microscopic evaluation of two skin biopsy samples revealed an acanthotic epidermis with numerous large cells with abundant pale staining cytoplasm and large pleomorphic nuclei, isolated or in clusters, in the basal and parabasal regions of the epidermis (some cells scattered throughout all layers of the epidermis). The cells were positive for cytokeratin 7, pankeratin, Cam 5.2 and Ber-EP4 (figure 1C-F). The patient was given the diagnosis of EMPD. The physical examination was unremarkable. An investigation for an underlying malignancy (computed tomography scans of the chest, abdomen and pelvis, chest x-ray film, cystoscopy, urynalysis, upper endoscopy, coloscopy and mammography) was negative.

Cryosurgery treatment was performed and only partial clinical improvement was obtained (figures 1B, C). The patient was started on imiquimod 5% cream nightly (about 12.5 mg per application), five days a week, but, because of severe inflammation and erosions, treatment was withdrawn for seven days. After this period she was able to tolerate the application of imiquimod, at first three times a week and after one month, five days a week (for a total of 16 weeks). The patient confirmed clearance of the lesions after 3 months of treatment and no symptoms were present during the last month of therapy (figure 1D). Two skin biopsies were obtained after the treatment and only mild chronic inflammation and dermal fibrosis were observed (figure 1E). In the 6-month follow-up, no evidence of recurrence was present. Depigmentation was noted in the treated area.

Current recommended treatments for EMPD are surgical excision, Mohs’ micrographic surgical technique or laser ablation [1, 4]. Some reports about the efficacy of imiquimod in the treatment of EMPD have been recently published [1-5], although there is no consensus about posology and treatment duration. EMPD is an unpredictable malignancy with a high recurrence rate after surgical excision [3], and surgical intervention frequently leads to functional, sexual and psychological problems. Imiquimod is a biological response modifier that binds to the Toll-like receptor 7 on the cell surface of dendritic cells, macrophages, and monocytes, stimulating both innate and acquired immune function [1, 2]. It is a very promising treatment option for the treatment of EMPD, particularly in cases of extensive or multifocal tumors, or when these tumors are located in peculiar anatomical sites, that are difficult for any surgical approach [1-5].

We highlight the good result obtained in the single case reported. However, due to the limited numbers of patients treated, long-term follow-up is essential and randomized controlled trials are needed before imiquimod can be recommended as the first-choice treatment.

Acknowledgements

References

2 Zampogna JC, Flowers FP, Roth WI, Hassenein AM. Treatment of primary limited cutaneous extramammary Paget's disease with topical imiquimod monotherapy: two case reports. J Am Acad Dermatol 2002; 47: S229-S235.

3 Wang LC, Blanchard A, Judge DE, Lorincz AA, Medenica MM, Busbey S. Successful treatment of recurrent extramammary Paget's disease of the vulva with topical imiquimod 5% cream. J Am Acad Dermatol 2003; 49: 769-72.

4 Berman B, Spencer J, Villa A, Poochareon V, Elgart G. Successful treatment of extramammary Paget's disease of the scrotum with imiquimod 5% cream. Clin Exp Dermatol 2003; 1: 36-8.

5 Sendagorta E, Herranz P, Feito M, Ramírez P, Floristán U, Feltes R, et al. Successful treatment of three cases of primary extramammary Paget's disease of the vulva with Imiquimod - proposal of a therapeutic schedule. J Eur Acad Dermatol Venereol 2010; 24: 490-2.

6 Sellheyer K, Krahl D. Ber-EP4 enhances the differential diagnostic accuracy of cytokeratin 7 in pagetoid cutaneous neoplasms. J Cutan Pathol 2008; 35: 366-72.