Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion with potential for progression to endometrial adenocarcinoma. It is associated with estrogen-driven clonal hyperplasia that can be seen as glandular crowding on histopathology. The pathogenesis of EIN is multifactorial and includes: inactivation of the PTEN tumor suppressor gene, inactivation of PAX2 gene, KRAS mutations and microsatellite instability.
EIN is a diagnostic challenge for the gynecologic oncologist due to its prognosis and invasive potential. It is a premalignant lesion and, as such, it warrants close follow-up and treatment. Distinguishing between atypical and nonatypical hyperplasia is crucial to identify patients that may benefit from pharmacologic intervention. Furthermore, recognizing the presence of EIN in patients with abnormal uterine bleeding may decrease the number of unnecessary D&Cs and hysterectomies performed for this indication.
Several classification systems exist for endometrial hyperplasia. However, the new WHO2014 schema offers a clear differentiation between benign (benign endometrial hyperplasia), premalignant (endometrial intraepithelial adenocarcinoma and EIN) and malignant (endometrial carcinoma) and it is based on histopathological criteria that correlate with clinical outcome. It is also tailored to improve diagnostic reproducibility.
The aim of this study is to evaluate the diagnostic accuracy and sensitivity of the EIN schema for diagnosing endometrial hyperplasia on biopsy/curettage specimens in an unselected patient population. To achieve this objective, 62 archival biopsy and curettage materials that were previously diagnosed as either atypical or complex nonatypical hyperplasia were reviewed in a random sample of patients. The EIN schema was applied by a group of pathologists and interobserver diagnostic reproducibility was assessed. The sensitivity of the EIN schema was compared to the sensitivity and negative predictive value of the classic morphological diagnosis for endometrial hyperplasia.
In addition, the occurrence of concurrent endometrial cancer in patients with a preoperative diagnosis of EIN was investigated. In 275 patients who underwent hysterectomy after a preoperative diagnosis of EIN, the majority of the lesions were categorized as benign or EIN and only 103 were found to have invasive endometrial cancer on final pathology. The results indicate that the EIN schema is a valid tool for identifying patients with EIN who are at risk of developing endometrial cancer and warrants careful clinical follow-up. Furthermore, the use of this classification system could decrease the number of D&Cs and hysterectomies that are unnecessarily performed in premenopausal women due to abnormal uterine bleeding. This is important because it would lead to a reduction in overtreatment cases and increase the quality of life of women. In addition, this approach would reduce the cost of unnecessary hysterectomies and chemotherapies. It is therefore recommended that the EIN schema be incorporated into the 2016 RCOG and ACOG guidelines.
