Perianal Paget's disease - Distinguishing primary and secondary lesions using immunohistochemical studies including gross cystic disease fluid protein-15 and cytokeratin 20 expression

Background.-Extramammary Paget's disease most commonly occurs on the female external genitalia and rarely occurs in the perianal region and male exter nal genitalia. We present the clinical and pathologic features of 5 cases o f perianal Paget's disease and review the literature. Methods.-Clinical and pathologic data were recorded for 5 cases of perianal Paget's disease. Cases were studied retrospectively with special stains, i ncluding periodic acid-Schiff, mucicarmine, Alcian blue, carcinoembryonic a ntigen, S100 protein, pan-keratin, gross cystic disease fluid protein-15 (G CDFP-15), lysozyme, CD15 (Leu-M1), cytokeratin 7 (CK7), and cytokeratin 20 (CK20). Results.-Three (60%) of 5 patients had concurrent rectal adenocarcinomas. A ll cases reacted positively for pankeratin, although the intensity and dist ribution of staining varied. Both cases not associated with an underlying c arcinoma showed strong GCDFP-15 and CK7 expression and an absence of CK20 e xpression. The 3 cases associated with an underlying malignancy demonstrate d CK7 and CK20 expression and an absence of GCDFP-15 expression. All cases were negative for lysozyme and CD15 (Leu-M1). Conclusions.-The 5 cases reported herein demonstrate that perianal Paget's disease is a heterogeneous entity. The high frequency of associated underly ing malignancies and resultant poor clinical outcomes highlight the importa nce of an aggressive search for a second malignancy. In some cases, periana l Paget's disease merely represents a cutaneous manifestation of an underly ing rectal adenocarcinoma and demonstrates a CK7(+)/CK20(+)/GCDFP-15(-)/lys ozyme/Leu-M1(-) immunophenotype and signet ring Paget's cells. Other cases represent primary adenocarcinomas of the skin, which are associated with a CK7(+)/CK20(-)/GCDFP-15(+)/lysozyme(-)/Leu-M1(-) immunophenotype and an exc ellent prognosis if adequately resected. Immunohistochemical studies, parti cularly CK20 and GCDFP-15, are useful adjuncts in distinguishing primary an d secondary perianal Paget's disease.