AMOUNT OF PREOPERATIVE ENDOMETRIAL TISSUE 29 2 INTRODUCTION Endometrial cancer (EC) is the most common gynecological malignancy in industrialized developed countries with an increasing incidence.1-3 These carcinomas are histopathological classified as either endometrioid endometrial cancer (EEC) or non-endometrioid endometrial cancer (NEEC).4 Primary surgical treatment for EC consist of hysterectomy and bilateral salpingo-oophorectomy.5, 6 Additional lymph node surgery, i.e. sentinel lymph node mapping, lymph node dissection or algorithm-based approach for staging, is recommended in patients with increased risk of lymph node metastasis (LNM).7, 8 The recent ESGO-ESTRO-ESP guideline recommended a modified binary FIGO grading considering both grade 1 and 2 EC together as low-grade EC and grade 3 EC and NEEC as high-grade EC.9 Most patients are diagnosed with low-grade EC, and generally have a favorable prognosis with a 5-year survival rate of 85.6%.5 About 20.0% of the patients are diagnosed with high-grade EC, have an overall poor prognosis with a 5-year survival rate of 58.8% and are associated with increased risk of regional or distant metastases.5, 10 A meta-analysis has shown only moderate concordance of 67.0% between pre- and postoperative tumor grading.11 The lowest concordance was found for grade 2 EC (61.0%), and as these are generally classified as low-grade EC, disagreement in grading might impact treatment and outcome since performance of lymph node surgery is generally performed in high-grade EC only.9, 12, 13 Explanations for discordance on grade include 1) sampling errors leading to missed tumor components, 2) interobserver disagreement due to subjective interpretation of the defined criteria and 3) limited amount of tissue obtained by preoperative endometrial sampling, that might impair assessment of tumor characteristics. In 13-30% of the pipelle endometrial samples, insufficient material requires repeated biopsy for a reliable diagnosis, as in 7.3% of the failed samples women are subsequently diagnosed with EC.1417 Interestingly, Visser et al. showed that hysteroscopic biopsies had a higher concordance (89%) compared to samples obtained by dilatation and curettage (D&C) (70%), questioning whether in addition to the amount of tissue, the sampling method may also be relevant.11 In a previous study of our research group, we showed that the amount of endometrial tissue surface to classify an endometrial sample as conclusive with high diagnostic accuracy as malignant or non-malignant, was defined by a minimum cut-off level of 35 mm2.11, 14 However, this study was not designed to further specify the diagnosis on tumor grade and/ or histological subtype. Therefore, in the present study, we aim to evaluate the amount of preoperative endometrial tissue surface in relation to the degree of concordance with final low- and high-grade EC. Furthermore, we investigate whether discordancy in pre- and postoperative grading is influenced by the sampling method and whether discordancy impacts outcome.
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