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 external genitalia. We present the clinical and pathologic features of 5 cases of 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, including periodic acid-Schiff, mucicarmine, Alcian blue, carcinoembryonic antigen, S100 protein, pan-keratin, gross cystic disease fluid protein-15 (GCDFP-15), lysozyme, CD15 (Leu-M1), cytokeratin 7 (CK7), and cytokeratin 20 (CK20).

RESULTS

Three (60%) of 5 patients had concurrent rectal adenocarcinomas. All cases reacted positively for pankeratin, although the intensity and distribution of staining varied. Both cases not associated with an underlying carcinoma showed strong GCDFP-15 and CK7 expression and an absence of CK20 expression. The 3 cases associated with an underlying malignancy demonstrated 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 underlying malignancies and resultant poor clinical outcomes highlight the importance of an aggressive search for a second malignancy. In some cases, perianal Paget's disease merely represents a cutaneous manifestation of an underlying rectal adenocarcinoma and demonstrates a CK7+/CK20+/GCDFP-15-/lysozyme-/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 excellent prognosis if adequately resected. Immunohistochemical studies, particularly CK20 and GCDFP-15, are useful adjuncts in distinguishing primary and secondary perianal Paget's disease.