Endometrial Cancer Following Levonorgestrel-Releasing Intrauterine System Insertion in Young Women with Atypical Hyperplasia: Two Case Reports and Literature Review

Levonorgestrel-releasing intrauterine system (LNG-IUS) insertion is the first-line treatment for atypical hyperplasia (AH) in young women who wish to retain their fertility. However, the procedure is not always effective, and may allow AH to progress to endometrioid endometrial cancer (EEC). Two young women with AH who wished to preserve their fertility developed EEC following 52-mg LNG-IUS in insertion at our institution. One was a 34-year-old woman diagnosed with endometrial cancer 2 years after LNG-IUS insertion. The second was a 30-year-old woman diagnosed 17 months after LNG-IUS insertion. Proactive molecular risk classification for endometrial cancer (ProMisE) classification revealed that the first and second patients had p53-abnormal (p53abn) EEC and mismatch repair deficient (MMR-d) EEC, respectively. MMR-d and p 53abn were frequently observed in both AH and EEC specimens. Studies suggest that MMR-d and p53abn are predictors of the occurrence adverse effects after fertility-preserving treatment for EEC. AH is a precursor of EEC. Therefore, p53 and mismatch repair (MMR) mutation may be used to identify women with AH who will not likely benefit from progestin therapy. Molecular assays in women with AH will likely be useful for identifying novel predictive biomarkers of progestin resistance and to improve the safety of conservative treatment. Combined assessment of progesterone receptor (PR) with these predictive molecular markers may improve the predictive ability.