Umbilical Paget\'s disease and prostatic carcinoma

British Journal of Dermatology (J995) 128, 448-450

Umbilical Paget's disease and prostatic carcinoma B.REMOND. S.ARACTINGI. F.BLANC. O.VEROLA,* D.VIGNON AND L.DUBERTRET Clinique des Maladies Cutanees and *iMboratoire D'Anatomie-l'athologique. Paris. France

Hopilal Saint-Louis.

1. Avenue Claude Vellefaiix.

Accepted for publication 16 October 1992

Summary

We report a case of umbilical Paget's disease occurring in a patient with a prostatic carcinoma. No other malignancy was found, and the patient was treated by surgical excision ofthe lesion. To our knowledge, the occurrence of extramammary Paget's disease ofthe umbilicus has not been reported previously. The clinical presentation, its association with prostatic carcinoma, and the possible pathogenesis are discussed.

Hxtramammary Paget's disease (EMPD) was first described by Crocker in 1879. It is characterized by the development of Paget cells in the epidermis at a site other than the nipples.' Involvement of a number of sites has been reported, particularly the genital, perianal and axillary regions.^"'* To our knowledge, the occurrence of umbilical EMPD has not been described previously. We report a patient presenting with umbilical Paget's disease associated with a prostatic adenocarcinoma.

Case report A 78-year-old Caucasian man presented with a history of an irritating, erythematous and weeping lesion ofthe umbilicus since 1987. Despite several topical treatments, the lesion gradually enlarged. The patient was first seen at L'Hopital Saint Louis in May 1991.4 years after the onset of the disease. Examination revealed a well-demarcated, erythematous. oval plaque on the umbilicus (Eig. 1). The plaque was 8 cm in diameter, and had an oozing surface. The clinical appearance was consistent with EMPD or Bowen's disease. Histology of a skin biopsy showed diffuse infiltration of the epidermis with large pale cells with prominent nuclei (Eig. 2). These cells were periodic-acid-Schiff (PAS) and alcian blue positive. Immunohistochemical studies showed that the cells stained with antibodies directed against carcino-embryonic antigen (CEA; Dako. Erance) {Eig. 3). epithelial membrane antigen fEMA: Dako. Erance) and cytokeratin KL-I (Immunotech, Erance). The cells were not labelled by antibodies directed against S-100 protein (Dako. Erance). HMB 4S (Dako, Erance), Correspondence: Dr S.Aractingi,

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prostate-specific antigen (Biogenex. Erance) or prostatic acid phosphatase (Biogenex, France). Neither pagetoid cells, nor prostatic carcinoma cells were observed in the dermis on standard or labelled sections. A review of his past medical history revealed that he had undergone a prostatectomy in 1990 because of prostatic hypertrophy. Pathological examination demonstrated the presence of a well-differentiated adenocarcinoma. and bilateral orchidectomy was therefore performed. Thorough clinical examination of the prostate revealed no abnormality. Abdominal and pelvic computer tomography scans with multiple prostatic views were unremarkable. Serum levels of prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) were within normal limits. Intravenous pyelography. colonoscopy and cystoscopy were also normal. The umbilical lesion was excised, and 1 year later the patient remained symptom-free.

Discussion EMPD is a rare disease which occurs in elderly patients, usually over (SO years old. There is a female predominance, probably as a consequence ofthe high incidence of vulvar involvement.' The significance of EMPD is not as well understood as Paget's disease ofthe breast.^ Clinically. Paget's disease appears as an erythematous. exudative dermatitis, usually with a well-detined margin.- ' Histologically. the characteristic finding is the presence in the epidermis of large (10-20 /im) cells with pale cytoplasm, large nuclei, and prominent nucleoli. PAS-positive granules are present within the cytoplasm of these cells. These Paget cells are also found in the suprabasal region of the appendages. Immunohisto-

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I'igure I. Erythematous plaque on the umbilicus.

noma is usually closely related to the site ofthe EMPD. so that perianal EMPD is associated with lower gastrointestinal tract malignancies, and genital EMPD with urogenital tract malignancies.-' ''•'' The pathogenesis of EMPD remains unknown, but there have been several hypotheses proposed, (i) The Paget cells could represent metastases from an underlying carcinoma to the epidermis.' (ii) Paget's disease could reflect multicentric malignant transformation of histogenetically similar cells which have migrated together during embryonic life. These cells would respond similarly to a neoplastic stimulus.- ''^ (iii) Paget cells could derive primarily from intraepidermal precursors of either apocrine or eccrine glands'—development of another carcinoma would therefore be a coincidence.

chemical studies of Paget cells have demonstrated expression of CEA. EMA and cytokeratin.^'' EMPD usually occurs in sites containing apocrine glands.'^ In a review of 197 cases. Chanda reported involvement ofthe vulva in 65% of cases, ofthe perianal region in 14%. and the male genitalia in 14% of cases.'' Involvement of other areas such as the axillae, eyelids, external auditory canal, oesophagus and urethra has also been reported.'"^ EMPD can occur alone, or may be associated with an internal or an adnexal cancer. Internal malignancy is found in 24-33% of EMPD cases, and adnexal cancers in 12-18%.- •• The site of the underlying internal carci-

Umbilical involvement by EMPD would appear to be exceedingly rare, as we are not aware of any other reported cases. However, the association of prostatic carcinoma with perinanal EMPD has been documented. Five cases of perianal EMPD with prostatic carcinoma have been reported.-'^ '- Oka et «/.'' reported a patient with EMPD ofthe scrotum associated with an underlying soft-tissue adenocarcinoma and a prostatic carcinoma. The other cases concerned patients with prostatic adenocarcinoma and EMPD of the penis, glans penis, urethra or inguinal region. Several authors^** have proposed that the pathogenetic mechanism for this association is related to the common embryonic origin of perineum and prostate, with identical response of similar cells to a unique neoplastic stimulus. Eurthermore. most

Figure 2. Pagel cells within the epidermis (hacniatoxyiin and eosin x4()()).

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f Kigure 3.fclxpressionof carcino-embryonic antigen by Paget cells (CEA x40()).

of the other internal tumours associated with perineal EMPD occur in epithelium derived from the cloacii. The cloaca, which is lined by endoderm. gives rise to the terminal part of the ileum. the whole of the large intestine, urachus. urinary bladder, the urethra, and vestibule ofthe vagina in the female, and the prostate and most ofthe urethra in the male.In our case, the absence of staining of the cells infiltrating the epidermis with prostate-specific and prostatic acid phosphatase antibodies makes it extremely unlikely that these cells represented metastasis from malignant prostatic cells to the umbilical skin. Both the umbilicus and prostate are derived from a similar embryonic origin, the cloaca. Therefore, although a chance association cannot be ruled out, concomitant umbilical EMPD and prostatic carcinoma could be the consequence of a common response to a unique mitogenic stimulus. In EMPD, the prognosis is related to the location and extent ofthe associated cancer. Wide surgical excision is the treatment of choice for EMPD,' "*'' This case emphasizes the need for a thorough search for an internal carcinoma when EMPD is diagnosed.

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