PERIANAL PAGETS-DISEASE - A HISTOLOGIC AND IMMUNOHISTOCHEMICAL STUDY OF 11 CASES WITH AND WITHOUT ASSOCIATED RECTAL ADENOCARCINOMA

Perianal Paget's disease is rare, and its relationship to an associate d internal regional cancer has been ill defined. We analyzed the histo logic and immunohistochemical features of perianal Pagets disease in 1 1 patients to determine the frequency and relationship of associated r egional internal carcinoma and to gain insight into its histogenesis. Of five patients with documented rectal adenocarcinoma, it was discove red synchronously with the Paget's disease in four and, subsequently, in one. Paget's cells of signet ring type predominated in four cases. Intraepithelial glands with intraluminal dirty necrosis were present i n four cases. The immunophenotype in four cases studied was cytokerati n (CK)7(+)/CK20(+)/gross cystic disease fluid protein(-) (GCDFP) in bo th the intraepithelial Paget's cells and the invasive rectal adenocarc inoma. Six patients did not have documented rectal carcinoma. The Page t's cells in four were CK7(+)/CK20(-)/GCDFP15(+). Three of these had p urely intraepithelial Paget's disease, and invasive or metastatic dise ase developed in none after wide local excision. Bilateral inguinal ly mph node metastases developed in the fourth patient, and the patient d ied 8 months after diagnosis of Paget's disease. In two patients, the Paget's cells were CK7(+)/CK20(+)/GCDFP15(-). Recurrent intraepithelia l perianal Paget's disease developed in one patient at 7 months; the p atient was alive without disease at 24 months, and the other patient h ad several intraepithelial recurrences of peri anal Paget's disease, a nd, subsequently, a large perianal tumor of uncertain cell type develo ped at 108 months, which led to the patient's death. We conclude that there are two types of perianal Paget's disease. One type has endoderm al differentiation with gastrointestinal-type glands containing intral uminal dirty necrosis, numerous signet ring cells, CK20 positivity, an d GCDFP15 negativity. Such cases are especially likely to be associate d with synchronous or metachronous rectal adenocarcinoma. The other ty pe is a primary cutaneous intraepithelial neoplasm in which the Paget' s cells display sweat gland differentiation, including GCDFP15 positiv ity; it generally lacks gastrointestinal-type glands, intraluminal dir ty necrosis, and CK20 positivity. The CK7 is a sensitive, albeit nonsp ecific, marker for Paget's cells.