S. Leenen

Immunologic factors involved in the malignant transformation of endometriosis to endometriosis-associated ovarian carcinoma

Endometriosis is a risk factor for low-grade serous, clear cell, and endometroid ovarian carcinoma. In both endometriosis and ovarian carcinoma, immunological factors are associated with clinical outcome. Chronic inflammation in endometriosis may be linked to tumorigenesis, but exact processes contributing to endometriosis-associated ovarian carcinoma remain unknown. This review aims to describe potential immunological factors involved in the malignant transformation of endometriosis into ovarian carcinoma. PubMed and Embase were searched from inception up to October 2020 for studies comparing immunological processes in endometriosis and endometriosis-associated ovarian carcinoma. Detailed analysis of immune components in the malignant transformation of endometriosis into endometriosis-associated ovarian carcinoma is lacking. Altered levels of chemokines and cytokines as IL-6, IL-8, IL-10, and TNF-α are reported and the function, number and polarization of NK cells, dendritic cells, and monocytes differ between endometriosis and associated ovarian carcinoma compared to healthy tissue. In addition, altered inflammasome and complement systems, indicate a role for the immune system in the carcinogenesis of endometriosis. Chronic inflammation in endometriosis may potentially drive inflammation-induced carcinogenesis in endometriosis-associated ovarian carcinoma. Exact immunological pathways and cellular processes remain unknown and require more thorough investigation.

The occurrence and histopathological recognition of atypical endometriosis in patients with ovarian endometriosis – a retrospective cohort study

- Atypical endometriosis (AE) is considered a potential precursor of endometriosis-associated ovarian carcinoma (EAOC). Despite this, AE identification currently lacks established clinical implications and is not routinely incorporated in histopathological examinations of endometriosis. This study aimed to determine the interobserver variability in AE diagnosis and to classify the features that may attribute to consistent AE identification and diagnosis. - Cases of ovarian endometriosis, collected between 1985 and 2017 at the Radboud University Medical Centre Nijmegen, were identified using the PALGA database. Pathology reports were reviewed for descriptions of atypical features and mentions of AE. Using a predefined set of criteria adapted from the literature, two independent pathologists re-evaluated the 266 most recent ovarian endometriomas for AE. After revision, the pathologist revised cases with AE to reach consensus when discrepancies occurred. - Among 266 cases of ovarian endometriosis, AE was reported in 31 (11.7 %) cases. The revising pathologists identified AE in 48 cases (18 %), a number that was reduced to 19 cases (7.1 %) after a consensus meeting between the pathologist. After consensus was reached, the diagnostic criteria, adapted from the literature, were adjusted. DISCUSSION/FUTURE DIRECTIONS: - High interobserver variability likely reflects AE's heterogeneous presentation, the uncertain role of inflammation-driven atypia and AE's undefined clinical significance. However, given AE's association with malignant transformation, consistent identification may be essential. Stricter criteria were developed for AE in order to encourage uniform identification. Furthermore, we encourage adequate documentation of AE in order to increase the insight in endometriosis behavior by linking endometriosis subtypes to clinical progression.