Clinical significance of lympho vascular space involvement and lymph node micrometastases in early-stage cervical cancer: a retrospective case-control surgico-pathological study

OBJECTIVE: Several studies have shown that lympho vascular space involvement (LVSI) and lymph node micrometastases (LNmM) may be risk factors for recurrence in early-stage cervical cancer with no apparent lymph node metastases. We performed a retrospective case-control study to reassess whether the presence of lymph node micrometastases and LVSI is predictive of subsequent recurrence following surgical resection of early-stage cervical cancer. METHODS: In a series of 292 patients diagnosed with early cervical cancer and treated by the same surgical procedure (laparoscopic-vaginal radical hysterectomy) during the same time period, two paired series were selected. The first series consisted of 26 cases who recurred in a median time of 36.8 months and the second series were 26 cases matched for age, histological sub-type, surgico-pathological stage and maximal tumor diameter, who did not recur after a median follow-up of 122 months. Sections taken from the hysterectomy specimens were reassessed for LVSI. All the lymph node blocks which have initially been considered as uninvolved were submitted to serial sectioning. Immunohistochemical staining using anti-cytokeratins AE1 and AE3 was used for identifying LNmM. RESULTS: LVSI was twice more frequent and LNmM ten-fold more frequent in the group of patients who recurred: 20/26 (77%) versus 9/26 (35%) and 11/26 (42%) versus 1/26 (4%) respectively. The relative risk of recurrence is 2.64 (1.67-5.49, P < 0.01) in the presence of LVSI and 2.44 (1.58-3.78, P < 0.01) in the presence of LNmM. All the patients with LNmM were LVSI positive. At bivariate analysis, the true LNmM (deposits more than 200 um in size) was the only independent risk factor. CONCLUSIONS: LNmM is an important risk factor of tumor recurrence in patients with early cervical cancer with no apparent lymph node metastases. LNmM seems to occur only in LVSI positive tumors. These data may lead to improve management of early-stage cervical cancer to reduce the risk of recurrence in those cases.