Paget's disease of the anus: A clinicopathological study

Abstract

Paget's disease of the anus is a rare disorder of controversial origin and is frequently associated with malignancy. We studied eight patients and carried out immunohistochemical studies to determine whether particular functional profiles might be indicators of a malignant association. One patient presented with synchronous carcinoma and two developed carcinomas 3 and 10 years after excision of Paget's disease. Five patients underwent wide local excision and have not developed cancer (median follow-up 6 years, range 5-13 years). However, four patients developed recurrent Paget's disease. Immunohistochemical studies showed that in general Paget cells stained positively with CAM 5.2 (a cytokeratin marker), gross cystic disease fluid protein (a marker for apocrine cells), human milk fat globule glycoprotein (HMFG 1 and 2) and carcinoembryonic antigen but negatively for PR3A5 (a marker for colonic goblet cells). Three cases had a staining profile which was quite different from that usually observed and these were associated with malignancy. One showed an antigenic profile more typical of a large bowel carcinoma. Paget's disease of the anus appears to run one of two clinical courses: to develop malignancy; or to recur locally, often on repeated occasions. Wide local excision is the treatment of choice but long-term follow-up is necessary because of the cancer risk. An immunohistochemical staining pattern which is different from usual may indicate a higher malignant risk and/or identify some cases of Paget's disease as representing a downward 'pagetoid' extension from a anorectal adenocarcinoma rather than a true epidermotropic apocrine neoplasm of the perianal skin.

Long-term outcome of patients with perianal Paget's disease

“…For PPD patients without invasive malignancy, WLE has usually been considered an adequate treatment (3,5,17), but our present data show a high rate of recurrence. Four of eight patients treated by WLE developed local recurrences, one of which was invasive.…”

“…Recent studies suggest that certain molecular markers in Paget cells may have implications for clinical management and prognosis (17,18). The tumor suppressor gene p53 has been found to be the most commonly mutated gene in human malignancy (19,20).…”

Vulvar Paget Disease: One Century After First Reported

“…These cases, different from primary vulvar Paget disease, typically express cytokeratin 20 and, at the same time, immunohistochemical reactions for GCDFP15 are negative [57,[60][61][62][63][64][65][66][67][68][69][70][71][72].…”

Cytokeratins, CEA, and Mucin Histochemistry in the Diagnosis and Characterization of Extramammary Paget’s Disease

“…Diagnosis ofExtran the same antibody. Armitage et al 12 also found a few cases of EPD that were negative for CAM 5.2. While this antigen is expressed in most cases of EPD, a minority of cases may be negative, and these are not associated with specific clinical features.…”