Extramammary Paget’s disease of the scrotum with Bowenoid features

ARTICLE

Extramammary Paget’s disease of the scrotum with Bowenoid features

Auteur(s) : Serafinella P. CANNAVÒ¹, Fabrizio GUARNERI¹, Patrizia NAPOLI²

¹ Department of Territorial Social Medicine, Section of Dermatology, University of Messina (Italy),
² “Piemonte” Hospital, Section of Pathologic Anatomy – Messina (Italy)
Fax + 39 090 2927691
< patrizia.cannavo@unime.it > 

A 76-year-old man, in good general health, presented to our department with a 15-year history of an erythematous, infiltrative lesion, asymptomatic and slow-growing, involving the scrotum.
Examination revealed an 11 x 5 cm brownish, rough patch with a verrucous surface covering much of the surface of the scrotum. No inguinofemoral lymphadenopathy was present. The lesion was removed surgically (figure 1A).
Microscopic examination of hematoxylin-eosin-stained sections showed intraepidermal nests of light-colored cells dispersed in a pagetoid pattern (figure 1B) among keratinocytes that, in some areas, demonstrated cytological pleomorphism and mitoses (figure 1C). An inflammatory reaction was evident in the papillary dermis. Sections stained with periodic acid-Schiff revealed focal cytoplasmic staining of the characteristic Paget cells. Immunohistochemical stains for CEA (figure 1D), EMA, and CK7 (figure 1E) were strongly positive. The atypical keratinocytes expressed CK19 (high-molecular-weight cytokeratin). Both the pagetoid cells and the atypical keratinocytes were negative for S100 and HMB45.
No relapse or metastasis was detected 2 years after surgery.

Discussion

First reported by Crocker more than a century ago [1], extramammary Paget’s disease (EMPD) is an uncommon intraepithelial neoplasm, which arises most commonly on the vulva and in the perianal region and less frequently on the male genitalia (14%) [2, 3]. Whereas mammary Paget’s disease is almost always associated with a neoplasm involving the apocrine glands or the mammary glands, an equally close link between EMPD and an underlying neoplasm has not been reported. Different variants of EMPD have been proposed: a primary limited cutaneous form, a primary cutaneous form with secondary contiguous or lymphatic metastases, a secondary form arising from an underlying neoplasm, and a form associated with a visceral malignancy (rectal, genitourinary, uterine, hepatic, pancreatic or adnexal carcinomas) [4].
Due to the clinical picture, which is generally characterized by an erythematous, desquamative, frequently pruritic (60%) patch, EMPD may be confused with other dermatoses, such as intertrigo, contact dermatitis, psoriasis, lichen simplex chronicus, and pagetoid basal cell carcinoma. For this reason the correct diagnosis is often achieved late and intervention occurs when the lesion is very extensive.
The therapeutic approach is still difficult nowadays, due to the high relapse rate, the wide extent of the lesions and the involvement of particular anatomical areas that make surgical excision difficult. When possible, however, this remains the treatment of first choice; alternative treatment comprises photodynamic therapy associated with Mohs micrographic surgery, laser ablation [5], topical 5-fluorouracil 1% [6], radiation therapy [7], and topical imiquimod 5% [4].
The hypothesis that Paget’s cells in mammary Paget’s disease and in many cases of EMPD are of apocrine gland derivation is today the most widely accredited and is supported by immunohistochemical studies that show strong CEA expression by Paget’s cells; other immunohistochemical stains include CK7 and CAM 5.2 (low molecular-weight cytokeratins) [8, 9]. It is believed that EMPD derives from the malignant transformation of a pluripotent basal stem cell, from which the squamous epithelium, pilary structures and glandular structures originate, and that, in the case of EMPD, it expresses apocrine gland differentiation [1]. This hypothesis moreover provides an explanation for the polymorphism of cases such as ours, characterized by an unusual verrucous clinical presentation and by histological features that in some areas are suggestive of Bowen’s disease [10]. n

References

1. Balducci L, Crawford D, Smith G, et al. Extramammary Paget’s disease: an annotated review. Cancer Invest 1988; 6: 293-303.

2. Park S, Grossfeld GD, Mcannish JW, Santucci R. Extramammary Paget’s disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy. J Urol 2001; 88: 297-8.

3. Kageyama N, Izumi AK. Bilateral scrotal extramammary Paget’s disease in a Chinese man. Int J Dermatol 1997; 36: 695-7.

4. 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: S229-35.

5. Becker-Wegerich PM, Fritsch C, Schulte KW, et al. Carbon dioxide laser treatment of extramammary Paget’s disease guided by photodynamic diagnosis. Br J Dermatol 1998; 138: 169-72.

6. Bewley AP, Bracka A, Staughton RCD, Bunker CB. Extramammary Paget’s disease of the scrotum: treatment with topical 5-fluorouracil and plastic surgery. Br J Dermatol 1994; 131: 445-6.

7. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experience with extramammary Paget’s disease. Br J Dermatol 2000; 142: 59-65.

8. Helm KF, Goellner JR, Peters MS. Immunohistochemical stains in extramammary Paget’s disease. Am J Dermatopathol 1992; 14: 402-7.

9. Mazoujian G, Pinkus GS, Haagensen DF. Extramammary Paget’s disease: evidence for an apocrine origin. Am J Surg Pathol 1984; 8: 43-50.

10. Quinn AM, Sienko A, Basrawala Z, Campbell SC. Extramammary Paget disease of the scrotum with features of Bowen disease. A case report and review of the literature. Arch Pathol Lab Med 2004; 128: 84-6.