Immunohistochemistry Does Not Improve Reliability of Diagnosis of Lymphovascular Space Invasion in Endometrial Cancer

Background: Lymphovascular space invasion (LVSI) predicts nodal involvement, progression-free survival, and overall survival in patients with endometrial cancer. Despite its importance, the current approach to determining LVSI relies on slide review, which has substantial variability across pathologists. This variability is clinically important because it may alter the recommendation for treatment with radiation. Our study investigates whether immunohistochemical counterstaining to mark the border of the lymphovascular space increases diagnostic agreement among pathologists in diagnosing LVSI. Design: This is a single-center retrospective case series of 70 cases of endometrioid type endometrial adenocarcinoma diagnosed between May 1, 2005, and December 31, 2013. One representative block of each case was cut and stained with hematoxylin and eosin (H&E), reviewed, then stained with the endothelial marker CD31 and the lymphatic endothelium marker D2-40 and reviewed again. The slides were reviewed independently by six gynecologic pathologists. We quantified intra-rater reliability with Cohen's κ and inter-rater reliability with Krippendorff's α. We powered our study to detect a change in Krippendorff's α of 0.20. Results: Counterstaining had no significant effect on inter-rater reliability of LVSI diagnosis. Krippendorff's α was 0.503 [0.351-0.631] without counterstaining and 0.469 [0.319-0.589]. Brackets denote the 95% confidence interval. Counterstaining made pathologists revise their diagnoses with the average intra-rater reliability being 0.68 [0.58-0.78]. The most common change was from indeterminate LVSI to negative LVSI, which occurred in 87% (14 ± 6) slides. Pathologists reclassified positive LVSI to negative in 41% (4.5 ± 0.5) slides. Conclusions: In our study, counterstaining with CD-31 and D2-40 did not increase agreement among pathologists in determining LVSI but did decrease the number of slides pathologists identified as indeterminate LVSI. Our findings suggest that counterstaining decreases the number of indeterminate LVSI diagnoses but does not increase the reliability of LVSI assessment.