The Pattern of Myometrial Invasion as a Predictor of Lymph Node Metastasis or Extrauterine Disease in Low-grade Endometrial Carcinoma

Abstract

The purpose of this study was to examine predictors of lymph node metastases (LN+) or extrauterine disease (ED) in low grade (FIGO grades 1 or 2) endometrioid carcinoma (LGEC) in a multi institutional setting. For LGEC with and without LNM or ED, each of the 9 participating institutions evaluated patients age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic elongated and fragmented glands (MELF) and single cell/cell cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement and numbers of pelvic (PLN) and para-aortic (PALN) LNs sampled.302 cases were reviewed: LN+ or ED +, 96; LN-/ED-, 208. Patients' ages ranged from 23-91 yrs (median 61). Table 1 summarizes the histopathologic variables that were noted for the LN+ or ED+ group: tumor size ≥2cm, 93/96 (97%), MI >50%, 54/96 (56%), MELF, 67/96 (70%), SCI, 33/96 (34%), LVI, 79/96 (82%), >20% solid, 65/96 (68%), papillary architecture present, 68/96 (72%), LUS involved, 64/96 (67%) and CX involved, 31/96 (32%). For the LN-/ED- group, the results were as follows: tumor size ≥2cm, 152/208 (73%), MI >50%, 56/208 (27%), MELF, 79/208 (38%), single cell invasion, 19/208 (9%) , LVI, 56/208 (27%), >20% solid, 160/208 (77%), papillary architecture present, 122/208 (59%), LUS involved, 77/208 (37%), CX involved, 31/208 (15%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (p=0.9 and 0.1, respectively). Following multivariate analysis, depth of myometrial invasion, cervical stromal involvement, lymphovascular space invasion, and the single cell pattern of invasion emerged as significant predictors of advanced stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement and LV as significant predictors of LN+ or ED. The association of SCI pattern with advanced stage LGEC is a novel finding.

Influence of Prognostic Factors on Lymph Node Involvement in Endometrial Cancer

“…Similar results regarding tumor size and tumor stage were shown by others. 13,27 Furthermore, we could show a significant association between histology and lymph node involvement, with higher rates of lymph node metastasis in patients with nonendometrioid tumors. This pattern is well-known and has already been shown in several studies.…”

How to approach the many faces of endometrioid carcinoma

“…9 Another study confirmed that the MELF pattern of invasion was not an independent predictor of lymph node metastases. 10 However, other investigators have found an association between this pattern, lymphovascular invasion, as well as lymph node metastases. [11][12][13][14] In our experience, papillary ECa of intermediate grade, with or without MELF pattern, tends to be associated with vascular/lymphatic invasion and lymph node metastasis.…”

Unusual Patterns of Endometrial Carcinoma Including MELF and its Relation to Epithelial Mesenchymal Transition

“…Euscher and colleagues identified MELF in 70% of Grades 1 and 2 endometrioid adenocarcinomas with extrauterine spread or lymph node metastasis, in contrast to only 38% of tumors confined to the uterus (Po0.0001). However, the statistical significance was lost in a multivariate analysis of predictors of advanced stage disease(45). So we are left with intriguing but inconclusive results with respect to the biologic significance MELF or the fibromyxoid response.…”