Epithelial Markers to Detect Occult Microinvasion in Serous Ovarian Tumors

Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis “serous borderline tumors with stromal microinvasion” seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of “eosinophilic metaplastic” cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that “eosinophilic metaplastic” cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of micro- invasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies. It is proposed that, in cases of atypical serous ovarian tumors, a panel of CAMS.2 with other antibodies such as epithelial membrane antigen (EMA) and/or polyclonal keratin (pKer) be applied on tissue sections with the highest degree of cytological and architectural atypia to detect microinvasion. Such a panel could increase the accuracy in the diagnosis of microinvasive lesions and as such contribute to a more objective and reproducible diagnosis, and thus treatment, of serous ovarian tumors.