Lymphovascular invasion in endometrial cancer: diagnostic problems

Lymphovascular invasion (LVI) is an independent prognostic parameter in endometrial cancer. This parameter is of particular importance, as it can be evaluated by routine microscopy without the cost of additional research methods. a significant disadvantage is the lack of universal criteria for qualitative and quantitative assessment of lvi. The presence of artifacts and other morphological “imitators” of vascular invasion complicates the detection of lvi. The article provides literature data on the importance of lvi as a prognostic factor in endometrial cancer, recommendations for qualitative and quantitative assessment of LVI.

1. Matias-Guiu X., Selinger C.I., Anderson L. et al. Data set for the reporting of endometrial cancer: recommendations from the international collaboration on cancer reporting (ICCR). Int J Gynecol Pathol 2022;41(Suppl 1):90–118. DOI: 10.1097/PGP.0000000000000901

2. Peters E.E.M., Nucci M.R., Gilks C.B. et al. Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma. Histopathology 2025;86:173–82. DOI: 10.1111/his.15272

3. Feng J., Zhang Y., Huang C. et al. Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study. Eur J Surg Oncol 2024;50(4):108261. DOI: 10.1016/j.ejso.2024.108261

4. Нечушкина В.М., Коломиец Л.А., Кравец О.А. и др. Рак тела матки и саркомы матки. Практические рекомендации RUSSCO. Часть 1.2. Злокачественные опухоли 2024;14(3s2):165–88. Nechushkina V.M., Kolomiets L.A., Kravets O.A. and others. Cancer of the uterine body and uterine sarcomas. RUSSCO’s Practical Recommendations. Part 1.2. Zlokachestvennye opukholi = Malignant Tumors 2024;14(3s2):165–88.

5. Berek J.S., Matias-Guiu X., Creutzberg C. et al. Endometrial cancer staging subcommittee, FIGO Women’s Cancer Committee. FIGO staging of endometrial cancer: 2023. DOI: https://doi.org/10.1002/ijgo.14923

6. Krizova A., Clarke B.A., Bernardini M.Q. et al. Histologic artifacts in abdominal, vaginal, laparoscopic, and robotic hysterectomy specimens: a blinded, retrospective review. Am J Surg Pathol 2011;35:115–26. DOI: 10.1097/PAS.0b013e31820273dc

7. Malpica A., Euscher E.D., Hecht J.L. et al. Endometrial Carcinoma, Grossing and Processing Issues: Recommendations of the International Society of Gynecologic Pathologists. Int J Gynecol Path 2018;38:9–24. DOI: 10.1097/PGP.0000000000000552

8. Yamazawa K., Seki K., Matsui H., Sekiya S. Significance of perivascular lymphocytic infiltrates in endometrial carcinoma. Cancer 2001;91:1777–84. DOI: 10.1002/1097-0142(20010501)91:9<1777::aidcncr1196>3.0.co;2-#

9. Wei S., Conner M.G., Zhang K. et al. Juxtatumoral stromal reactions in uterine endometrioid adenocarcinoma and their prognostic significance. Int J Gynecol Pathol 2010;29:562–7. DOI: 10.1097/PGP.0b013e3181e36321

10. Mannelqvist M., Stefansson I., Salvesen H.B., Akslen L.A. Importance of tumour cell invasion in blood and lymphatic vasculature among patients with endometrial carcinoma. Histopathology 2009;54:174–83. DOI: 10.1111/j.1365-2559.2008.03201.x

11. WWeber S.K., Sauerwald A., Polcher M. et al. Detection of lymphovascular invasion by D2–40 (podoplanin) immunoexpression in endometrial cancer. Int J Gynecol Cancer 2012;22:1442–8. DOI: 10.1097/IGC.0b013e318269139b

12. Visser N.C.M., Werner H.M.J., Krakstad C. et al. Type of vascular invasion in association with progress of endometrial cancer. APMIS 2017;125:1084–91. DOI: 10.1111/apm.12774

13. Alexander-Sefre F., Singh N., Ayhan A. et al. Detection of tumour lymphovascular space invasion using dual cytokeratin and CD31 immunohistochemistry. J Clin Pathol 2003;56:786–8. DOI: 10.1136/jcp.56.10.786

14. Alexander-Sefre F., Singh N., Ayhan A. et al. Clinical value of immunohistochemically detected lymphovascular invasion in endometrioid endometrial cancer. Gynecol Oncol 2004;92: 653–9. DOI: 10.1016/j.ygyno.2003.11.012

15. Kayraklioglu N., Katsakhyan L., Cohen P.A. et al. Perceptions of controversies and unresolved issues in the 2014 FIGO staging system for endometrial cancer: survey results from members

16. Bosse T., Peters E.E., Creutzberg C.L. et al. Substantial lymphvascular space invasion is a significant risk factor for recurrence in endometrial cancer-a pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer 2015;51(13):1742–50. DOI: 10.1016/j.ejca.2015.05.015

17. Fujimoto T., Nanjyo H., Fukuda J. et al. Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. Gynecol Oncol 2009;112:342–7. DOI: 10.1016/j.ygyno.2008.10.019

18. Han L., Chen Y., Zheng A. et al. Prognostic value of three-tiered scoring system for lymph-vascular space invasion in endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol 2024;184:198–205. DOI: 10.1016/j.ygyno.2024.01.046

19. Tortorella L., Restaino S., Zannoni G.F. et al. Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer. J Gynecol Oncol 2021;32(2):e11. DOI: 10.3802/jgo.2021.32.e11

20. Peters E.E.M., Leon-Castillo A., Hogdall E. et al. Substantial lymphovascular space invasion is an adverse prognostic factor in high-risk endometrial cancer. Int J Gynecol Pathol 2022;41: 227–34. DOI: 10.1097/PGP.0000000000000805

21. Peters E.E.M., Leon-Castillo A., Smit V. et al. Defining substantial lymphovascular space invasion in endometrial cancer. Int J Gynecol Pathol 2022;41:220–6. DOI: 10.1097/PGP.0000000000000806