CHAPTER 2 38 Our study design is comparable to Reijnen et al. in which the diagnostic accuracy of pipelle endometrial sampling and the amount of endometrial tissue surface for benign, premalignant and malignant tissue was quantified.14 Reijnen et al. found a positive correlation between the amount of endometrial tissue surface and concordance of diagnosis for premalignant and malignant tissue, furthermore he defined a minimum cut-off of 35 mm2 to classify an endometrial sample as conclusive. Interestingly, whereas the amount of tissue seems to be important for classifying tissue as premalignant or malignant, in our study, no positive correlation was found when malignant tissue was classified into tumor grade and histology and we did not found a minimum cut-off for concordant grading (data not shown). An explanation for this contra-intuitive finding could be interobserver agreement, yet, both studies show a high intraclass correlation coefficient (ICC) (0.98 vs. 0.92 in our study).14 Another explanation could be sampling bias or a missed tumor component by the pathologist. In our study, three experienced expert gynecological pathologists (JB, HK, KV) performed an explorative analysis in 30 (46.9%) cases with low- vs. high-grade discrepancy. Sampling bias based on heterogeneous and mixed tumors, or only superficial tumor tissue sampling was present in a third of the cases. In two third of the cases the discrepancy was misjudged by the pathologist, by miscalculation of the percentage solid growth or missed tumor component (data not shown). So, incorrect classification by the pathologist seems to be present, and will remain in the current diagnostic context. This might partially be resolved by molecular profiling in high-grade EEC as demonstrated by Bosse et al., but will not solve the sampling bias.28 The concordance between pre- and postoperative low- and high-grade EC did not significantly differ between the three sampling methods, which is quite comparable to other studies.11, 29 Illustrating, that more tissue provided with D&C or accurate sampling by hysteroscopic biopsy will not automatically result in more concordant diagnoses. Accurate preoperative classification of tumor grade and histological subtype is crucial in EC, as this may be directive to the extent of the surgical approach. Consequently, postoperative upgrading will lead to omitted lymph node surgery and/or staging procedure and altered adjuvant therapy, whereas downgrading may result in unnecessarily surgical related complications both impacting clinical outcome.11 A significant increase of DSS has been found in patients that were postoperatively upgraded, compared to patients with concordant high-grade EC. Furthermore, patients that were downgraded had significant decreased DSS compared to concordant low-grade EC. Both of our findings are in line with Werner et al.13, and may be explained by the presence of tumor heterogeneity and/or minor mixed morphologic characteristics.30, 31
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