**5.3 Frozen section**

Given our inability to predict lymph node metastasis pre-operatively with accuracy, can intra-operative frozen section analysis help determine which patients should have a systematic PLND and PaLND? The literature on this is conflicting.

Correlations of 58% to 96% for grade with intra-operative frozen section analysis and final pathologic results have been reported. A similar variation is reported in the accuracy of intra-operative section analysis of depth of myometrial invasion (72% to 95%) as well as of cervical involvement (66% to 97%) (Frumovitz et al., 2004; Loubeyre et al., 2011).

Several retrospective studies, which used a combination of risk factors (grade and depth of myometrial invasion, histological subtype) to compare intra-operative frozen section analysis and final pathologic results, found that the correlation was not sufficient to dispense with surgical staging (Frumovitz et al., 2004; Denschlag et al., 2007; Papadia et al., 2009). According to Papadia et al., 78% of patients undergo appropriate surgery, while 16% are under-staged and 6% over-staged.

## **5.4 Adding tumor size**

In an attempt to increase the accuracy of frozen section analysis, several investigators have studied the benefit of factoring in tumor size as determined intraoperatively. In 1987 Schink et al. described that patients with clinical Stage 1 endometrial cancer had only a 4% risk of lymph node metastasis if their endometrial cancer was ≤2cm. The Mayo Clinic in Rochester, Minnesota, uses a thorough intra-operative frozen section to identify a sub-group of patients with endometrioid adenocarcinoma in whom the risk of lymph node metastasis is negligible and who therefore do not warrant lymphadenectomy. The characteristics are: Type I, Grades 1 and 2; myometrial invasion less than 50%; primary tumor diameter less than 2cm, (Mariani et al. 2008).

The concept of adding tumor size to improve the ability of frozen section to correctly identify low-risk patients was evaluated by Yanazume et al. (2011) in a retrospective study of 228 patients. They used tumor size of ≤3cm as their cut off. This study found that a Grade 1 or 2 endometrial cancer, with a tumor diameter of ≤3cm and ≤50% myometrial invasion, accurately predicts the absence of lymph node metastasis.

## **5.5 Conclusion**

The palpation of lymph nodes during a laparotomy should not be used to determine the need for a systematic PLND and PaLND. Frozen section analysis is useful to distinguish a benign from a malignant lesion, but it has limitations with regard to time involvement, inadequate sampling (only part of the tumor) and the technique of rapid freezing itself. However, despite these constraints, a detailed and thorough intra-operative frozen section that assesses subtype, grade, myometrial invasion and tumor size is preferable to the alternatives, namely, that of an unnecessary lymphadenectomy with its attendant complications in low risk patients, or not carrying out a systematic lymphadenectomy in patients at high risk of lymph node metastasis.
