子宫内膜增生与子宫内膜上皮内瘤变的临床病理分析

目的 探讨WHO1994有关子宫内膜增生(endometrial hyperplasia,EH)和子宫内膜上皮内瘤变(endometrial intraepithelial neoplasia,EIN)的形态学特点以及分类的优点.方法 观察474例刮宫标本HE切片中的EH性病变(包括子宫内膜单纯性增生、复杂性增生及两者伴有的不典型增生),根据新标准找出EIN,总结分析EH分类与EIN分类的关系,同时对部分EIN患者进行随访.结果 379例子宫内膜单纯性增生中EIN 11例(2.9%),16例伴有不典型增生的单纯性增生中EIN 1例(6.25%),48例子宫内膜复杂性增生中EIN 6例(12.5%),31例伴有不典型增生的复杂性增生中EIN 28例(90.3%).共随访到EIN患者13例,因恶变摘除子宫者3例(23.07%).结论 EIN为单克隆增生(肿瘤增生)性病变,恶变潜能较高,完全不同于良性的EH,具有其特殊的形态学特点和生物学行为,EIN的分类方法在诊断标准上和对恶变潜能的预判方面优于WHO 1994年分类,明确EIN的病理学诊断特点对今后的诊断及治疗都有极其重要的意义.     

Nucleolar organiser regions in endometrial hyperplasia and neoplasia

Nucleolar organiser regions (NORs) were counted in the nuclei of both epithelial and stromal cells in cases of endometrial hyperplasia and carcinoma. The scores for each case were expressed as a ratio. No significant difference was found between the ratios for cystic hyperplasia and hyperplasia with architectural atypia, confirming the view that these are morphological variants of the same benign hyperplastic process. The ratios for hyperplasia with cytological atypia and adenocarcinoma differed significantly from the benign hyperplasias. This adds support to the view that hyperplasia with cytological atypia should be considered a neoplastic condition.     

子宫内膜增生性病变分类的新观点

长期以来,为了对子宫内膜增生性病变给予恰当治疗和判定预后,曾提出了多种病理分类.其中以1994年由WHO根据增生腺体结构的复杂性及细胞的不典型性而提出的4种病变分类法(简称WHO-94分类法)最具代表性[1],在2003年WHO乳腺及女性生殖器官肿瘤病理学和遗传学分类中同时也提到了由Mutter等倡导的以"子宫内膜上皮内瘤变(EIN)"为标志的,将子宫内膜增生病变分为良性子宫内膜增生、EIN及子宫内膜癌的新分类法[2],虽迄今仍未被普遍采用,但近几年来,不少的国内外学者支持和赞同这种新的分类法[3-8].在EIN分类法的运用过程中,有些要点应该强调,有些概念必须澄清.     

Demystifying endometrial hyperplasia

The endometrial hyperplasias form a spectrum of proliferative lesions, not all of which conform to conventional definition of hyperplasia. For whilst most hyperplastic lesions are composed of cells normally occurring in the late proliferative phase endometrium, there are those few which consist of genuine atypical cells. Lesions of this type, so-called “atypical endometrial hyperplasias”, tend to merge imperceptibly with well differentiated endometrioid adenocarcinomas, giving rise to major challenges: First and foremost, what are the very essential criteria that should be met before diagnosing such a lesion? And what are the very least that should be insisted upon for diagnosing malignancy once an atypical endometrial hyperplasia has been established? What is its true nature and how should ideally be classified? Other less conflicting, but equally interesting, aspects of endometrial hyperplasia which are covered in this account include the conventional hyperplasias, i.e. those lacking cytological atypia, and the overall incidence, risk factors and treatment of the disease. It is worth noting that “pure” stromal cell proliferations are, in itself, not necessarily neoplastic, for many take the form of endometrial stromal hyperplasia.     

Oxidative stress in endometrial hyperplasia

OBJECTIVE: Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. DESIGN: Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). RESULTS: Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. CONCLUSION: Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.     

Recent advances in endometrial neoplasia.

Electron microscopy, Feulgen nuclear DNA-content analysis and in vitro historadioautography with tritiated thymidine significantly objectivate the presently imprecise light microscopic criteria used for distinguishing between adenomatous hyperplasia and carcinoma in situ of the endometrium. Moreover, the changes observed in hyperplastic endometrium seem to be mediated by chronic estrogenic stimulation in the absence of progesterone. The hyperestrogenic morphologic alterations, such as cilia, surface microvilli, primary lysosomal activity and RNA-synthesis are strikingly decreased in early as well as advanced endometrial neoplasia. Failure to express estrogen-dependent cellular specializations in endometrial malignancy seems to be related to the neoplastic dedifferentiation, rather than to the presence or absence of estrogenic stimulation. The results support the concept that carcinoma in situ rather than adenomatous hyperplasia is the immediate precursor of invasive carcinoma of the endometrium. To date, the available evidence is too meager for a definite establishment of a relationship of adenomatous hyperplasia to the development of preinvasive endometrial carcinoma.     

Expression of cyclin D1 in endometrial hyperplasia and endometrial carcinoma

This study investigates the role of cyclin D1 in 30 uterine surgical resection and endometrial biopsy specimens from 30 patients with simple hyperplasia (10 cases), complex hyperplasia (6 cases) and endometrial carcinoma (14 cases). Cyclin D1 immunohistochemistry was performed on 2-4 mm thick paraffin sections using labelled streptavidin biotin kit. Cyclin D1 expression was present in 2/6 (33%) cases of complex hyperplasia, 7/14 (50%) cases of endometrial carcinoma and none in simple hyperplasia. Difference in cyclin D1 immunopositivity in simple hyperplasia and endometrial carcinoma was statistically significant (p = 0.018) but the difference in cyclin D1 immunopositivity between complex hyperplasia and endometrial carcinoma was not statistically significant. Our study suggests that cyclin D1 over-expression may be an early event in endometrial carcinogensis. Since there was no difference in extent and intensity of cyclin D1 expression between complex hyperplasia and endometrial carcinoma, it appears that deregulation is maximal in complex hyperplasia.     

Morphological and immunohistochemical characteristics in endometrial hyperplasia

The development of different types of endometrial hyperplasia is associated with the changes in the proliferation/apoptosis ratio, with the former being predominant in the presence of increased neoangiogenesis and altered endometrial cell receptor status.