Endometrial hyperplasia as a risk factor of endometrial cancer

Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.

Clear cell endometrial carcinoma precursors: presentation of two cases and diagnostic issues

Background The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature. Case presentation Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC. Conclusions In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.

MOLECULAR CHARACTERISTICS AND PROGNOSTIC MARKERS IN ENDOMETRIAL INTRAEPITHELIAL NEOPLASIA (CRITICAL REVIEW)

Endometrial carcinoma represents the most common gynaecologic malignancy, which frequently arises from malignant progression of endometrial intraepithelial neoplasia (EIN). Nowadays, there are no defined prognostic markers for the prognosis of the malignant progression of EIN and it still represents the subject of various investigations. Different studies indicate, that sex hormone receptors, DNA damage and apoptosis proteins, as well as epithelial-mesenchymal transformation markers play an important role in the progression of EIN. However, most of the published studies are full of contradictory results, which indicates that additional studies are necessary. In current review, we will discuss the current knowledge about the mentioned markers in terms of the prognosis of EIN.

Possible Role of PTEN expression in discriminating Benign Endometrial hyperplasia from Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia in a series of Egyptian Patients

Background: Endometrial hyperplasia represents a heterogeneous group of lesions in response to the unopposed growth-promoting action of estrogen. WHO classified endometrial hyperplastic lesions into Benign Hyperplasia (BH) and atypical hyperplasia/ endometrial intraepithelial neoplasia AH/EIN. Phosphatase and tensin homolog (PTEN) is one of the earliest and most common genetic abnormalities detected in endometrioid adenocarcinoma (type I) and even in its precursors. This study aimed at histological evaluation of hyperplastic endometrial lesions according to WHO 2014 and investigating the role of PTEN expression in highlighting the precancerous group (AH/EIN). Patient and Method: This study included a series of 70 Egyptian patients suffered from hyperplastic endometrial lesions. They were previously diagnosed according to WHO1994 schema simple endometrial hyperplasia without atypia (n=18), simple endometrial hyperplasia with atypia (n=2), complex hyperplasia without atypia (n=25), complex hyperplasia with atypia (n=5) and hyperplastic endometrial polyps (n=20). Results: Cases were histologically re-evaluated according to WHO 2014 classification; BH (62 cases) and eight cases of AH/EIN. A significant difference in PTEN expression (regarding percentage and intensity of staining) in relation to histopathological diagnosis was detected (P-value 0.02 and <0.05, respectively). The sensitivity and specificity of the absence of diffuse PTEN protein expression (>50%) to detect AH/EIN were 100% and 77.4%, respectively. Conclusion: Diffuse, dim or loss of immunohistochemical expression of PTEN protein is significantly correlated with the new WHO classification segregation of AH/EIN as precancerous lesions. However, further studies are recommended to confirm this association.