[Precursor lesions of endometrial carcinoma: diagnostic approach and molecular pathology]

For endometrial adenocarcinoma two precursor lesions are known: endometrioid adenocarcinoma which is the most frequent type 1 carcinoma develops from atypical endometrial hyperplasia whereas endometrial intraepithelial carcinoma (EIC) is the precursor of serous carcinoma and a subset of clear cell carcinoma both representing type 2 carcinomas. Atypical hyperplasia which shows progression rates into carcinoma of up to 40% is challenged by its poor interobserver reproducibility. A better reproducibility is obtained by the endometrial intraepithelial neoplasia (EIN) concept with fewer categories but it is not compatible with the World Health Organization (WHO) classification of endometrial hyperplasia. The EIN concept includes not only the vast majority of the WHO atypical hyperplasia but also approximately half of the complex hyperplasia without atypia. Rarely, atypical hyperplasia is associated with a secretory or mucinous cell type and two thirds of atypical hyperplasia resolve under long-term high dosage progestin therapy. Immunohistochemistry aids in the differential diagnosis of atypical hyperplasia and EIC. Atypical hyperplasia/EIN frequently show PTEN and/or Pax-2 negativity and low Ki-67 and differ from EIC which shows strong diffuse p53 staining and high Ki-67 staining index.