The Grading of Lympho- Vascular Space Invasion in Endometrial Carcinoma

abstract & commentary

Synopsis: The grading of lymphovascular space invasion was found to be an important histologic prognostic variable.

Source: Hachisuga T, et al. Cancer 1999;86:2090-2097.

Hachisuga and colleagues conducted a study to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI) in endometrial cancer. They evaluated LVSI along with other pathologic variables in 303 Japanese women. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0.0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. Hachisuga et al conclude that the grading of LVSI was also found to be an important histologic prognostic variable. The severe degree of LVSI was also found to be a good indicator of lymph node metastasis. They recommend the evaluation of the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Comment by David M. Gershenson, MD

Several previous studies have found that LVSI is an independent prognostic factor in endometrial cancer. Reportedly, the incidence of LVSI is approximately 5% in patients with surgical stage I and II endometrial cancer and 25-35% in all patients with this malignancy. In this study, LVSI was found in 127 of the 303 patients (42%) with all stages of endometrial cancer and in 76 patients (32%) with surgical stages I and II endometrial cancer. The high incidence of LVSI in this study is most likely related to the fact that Hachisuga et al were focused on this variable. Their finding simply illustrates the principle that "the harder you look, the more you will find." In their multivariate analysis, Hachisuga et al found that LVSI was the most significant prognostic factor—more significant than grade and myometrial invasion. Cell type was also significant, as we already know. The major strength of this study is the quantification of the degree of LVSI. As with most histologic variables, however, reproducibility will be an issue. The obvious implication for evaluation of LVSI is the predictability of lymph node metastasis. In this study, 16 of 18 patients (89%) with lymph node metastases showed a severe degree of LVSI. In many centers, intraoperative assessment of histologic grade and depth of myometrial invasion determine whether lymph node sampling or lymphadenectomy is performed. Whether it is feasible to estimate LVSI based on frozen section analysis will require further study.

Prognostic factors for endometrial cancer include all the following except:

a. depth of myometrial invasion

b. histologic type

c. histologic grade

d. lymphovascular space involvement

e. uterine size