Quadruple extra-mammary Paget's disease.

Extra-mammary Paget's disease may occur simultaneously in the genital area and, unilaterally or bilaterally, in the axillary region (1). Such cases have been reported as double or triple extra-mammary Paget's disease. We describe here a patient with quadruple extra-mammary Paget's disease, who developed the erythematous eruption in the genital, bilateral axillary and umbilical regions. A 73-year-old Japanese man presented with a 20-year history of an erythematous eruption in the genital area. His medical history and family histories were unremarkable. On physical examination, there was a centrally eroded, scaly erythematous lesion, 5 cm in diameter, on his left groin, spreading to the scrotum (Fig. 1 a). In addition, ill-defined, irregularly shaped, erythematous lesions were present on both axillae (Fig. 1 b, c) and umbilicus (Fig. 1 d). No lesions were seen in the other apocrine-bearing regions, including breasts, perianal area, or external auditory canals. Superficial lymph nodes were not palpable in the axillary regions. Results of complete blood counts and blood chemistry examinations, including carcinoembryonic antigen (CEA), were normal. There was no evidence of internal malignancy on clinical and X-ray examinations. Biopsy specimens taken from the 4 lesions showed the presence of large pale cells with prominent nuclei infiltrating diffusely or focally in the epidermis. A diagnosis of multiple extra-mammary Paget's disease was made, and all of the lesions were surgically removed, with a 2-cm free margin from the lesional border. The excisional specimens were investigated histologically and immunohistochemically with anti-CEA, anti-epithelial membrane antigen (EMA) and anti-cytokeratin (CK) antibodies. The genital lesion exhibited a moderate acanthosis of the epidermis filled with Paget's cell nests (Fig. 2 a). In both the axillary lesions and the umbilical one, Paget's cells were located in the thin epidermis (Figs 2 b–d). The tumour cells in all the lesions were positive histochemically for periodic acid-Schiff stain and immunohistochemically for CEA and EMA. In CK stainings, there was no immunoreactivity with 34βB4(CK1), DE-K10(CK10) or Ks13.1(CK13) antibodies in any of the lesions. Epithelial CKs recognized by 35βH11(CK8), RCK102(CK5,8) and RCK108(CK19) were expressed by the tumour cells of all 4 lesions, suggesting the same origin or differentiation of the neoplastic cells. In addition, since this CK staining pattern was the same as found in 5 patients with genital Paget's disease, the tumour cells in this case had no peculiar phenotypic feature. DISCUSSION Extra-mammary Paget's disease develops in apocrine-bearing areas other than the breasts, i.e. genital, peri-anal and axillary lesions …