Lymphovascular Space Invasion in Endometrial Cancer: Does it Matter Where and How Much to Sample? A Macroscopic Study...

Lymphovascular space invasion (LVSI) is a key prognostic factor in endometrial cancer, guiding adjuvant treatment decisions. This retrospective study analyzed 208 hysterectomy specimens with confirmed LVSI to determine optimal sampling strategies for detecting substantial LVSI. Samples/blocks from tumor infiltration fronts were reviewed microscopically, and LVSI foci were counted per slide and summed across all slides. Cutoffs of ≥5, ≥4, and ≥3 LVSI foci were evaluated. Only the ≥5 threshold significantly correlated with lymph node metastasis (P = .038) compared with <5 LVSI. Both patients with ≥5 LVSI foci either on a single slide or those reaching this threshold by summing across slides were associated with nodal metastasis (P = .023). However, significantly worse overall survival was observed only in patients with ≥5 foci on a single slide, not in those reaching the threshold by summing across multiple slides (P < .001). Focal LVSI (<5 foci) showed no significant overall survival compared with substantial LVSI. Increased sampling from the tumor infiltration front improved LVSI detection rates (P < .001), but gains in detecting substantial LVSI plateaued after 7 samples/blocks. Higher LVSI levels were associated with deep LVSI and cervical/endocervical LVSI (P < .001). Deep LVSI was linked to reduced overall survival compared with superficial LVSI (P < .001), whereas cervical/endocervical LVSI showed no significant association with overall survival (P = .273). Tumor grade, deep LVSI, and cervical involvement predicted nodal metastasis, whereas the microcystic, elongated, and fragmented pattern did not. These findings support using a threshold of ≥5 LVSI foci on at least 1 slide-as opposed to summing across slides-as a marker of worse overall survival. For optimal evaluation, at least 7 tumor infiltration front samples/blocks should be taken, including deep myometrium and cervical/endocervical canal, to ensure adequate assessment and identify patients at higher risk of nodal spread.