Deniz Ates

Lymphovascular Space Invasion in Endometrial Cancer: Does it Matter Where and How Much to Sample? A Macroscopic Study of 208 Hysterectomies

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.

Stromal or intraepithelial tumor-infiltrating lymphocytes: which one has more prognostic significance in cervical cancer?

To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated. Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively). sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.