Signet ring cell perianal paget disease: loss of MUC2 expression and loss of signet ring cell morphology associated with invasive disease.

Perianal Paget disease (PPD) is a rare and heterogeneous neoplasm in which underlying associated adenocarcinoma is a frequent comorbidity. Previous attempts have been made to define the cells of origin of this neoplasm and delineate the discriminating immunohistochemical (IHC) signature of primary versus secondary disease. We report a case of PPD in a 32-year-old male, that displays an unusual multiclonal immunostaining pattern with focal loss of MUC2 expression and simultaneous phenotypic loss of signet ring cell morphology associated with invasive disease. We postulate that our case captures the transition from PPD to invasive carcinoma. The loss of MUC2 positivity seen in this case could be relevant to biopsies of PPD in which no areas of invasion are initially found, and consequently a more thorough pathologic evaluation for invasive disease should be undertaken in cases with MUC2 negativity. Despite promising IHC staining patterns in individual case reports, PPD remains a heterogeneous entity. The specific IHC signature of primary versus secondary disease remains difficult to define due to the small number of cases reported in the literature and additional studies are needed. Therefore, in addition to a case's microscopic findings including IHC studies, distinguishing individual cases of primary from secondary PPD requires clinical correlation.