Nodal endosalpingiosis in ovarian serous tumors of low malignant potential with lymph node involvement: A case for a precursor lesion

Lymph node involvement (LNI) in ovarian serous tumors of low malignant potential (OSLMP) upstages 22% of patients. The origin of LNI has been a subject of debate in the literature. The purpose of this study was to investigate the role of nodal endosalpingiosis in the pathogenesis of this entity. We first examined the frequency of nodal endosalpingiosis in 30 OSLMP cases, 30 cervical adenocarcinoma cases, and 30 endometrial endometrioid adenocarcinoma cases. The rate of nodal endosalpingiosis was significantly higher in OSLMP cases (33%) compared with both cervical (0%, P < 0.0001) and endometrial tumor cases (3%, P = 0.0015). We then compared the frequency of nodal endosalpingiosis in 36 cases of OSLMP with LNI and 36 cases of OSLMP without LNI. The rate of nodal endosalpingiosis was significantly higher in OSLMP with LNI (66%) than in OSLMP without LNI (14%, P < 0.0001). We further investigated the cohort cases of OSLMP with LNI by recording the presence of nodal endosalpingiosis and LNI in each individual lymph node in every case. This analysis revealed that nodal endosalpingiosis and LNI appear together in the same lymph nodes at a much higher rate than would be expected by random chance alone (OR = 71.2, P < 0.0001). Lastly, in OSLMP cases with LNI, we recorded the types of LNI patterns. We found that the intraglandular pattern was present in a higher percentage of cases with nodal endosalpingiosis (50%) than in cases without nodal endosalpingiosis (8%, P = 0.0253). Overall, the intraglandular pattern of LNI appeared in 36% of OSLMP cases with LNI. In this study, we show that nodal endosalpingiosis not only occurs more commonly in OSLMP compared with other Mullerian malignancies, but also in OSLMP with LNI compared with OSLMP without LNI. For the first time, we demonstrate a statistically significant association between endosalpingiosis and the intraglandular pattern of LNI, and we propose that in up to a third of patients with OSLMP and LNI, nodal foci of serous tumor of low malignant potential may derive independently, from nodal endosalpingiosis. This result contributes to the understanding of the pathogenesis of extraovarian disease in cases of OSLMP and has important implications for patient management and follow-up.