The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor, its clinical course, and the prognosis of the disease. On the basis of a prospective study of 366 patients with endometrial carcinoma, the author postulates that there are two different pathogenetic types of endometrial carcinoma. The first pathogenetic type of the disease arises in women with obesity, hyperlipidemia, and signs of hyperestrogenism: anovulatory uterine bleeding, infertility, late onset of the menopause, and hyperplasia of the stroma of the ovaries and endometrium. The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined. The frequency of the first pathogenetic type in the studied group of women was 65%, whereas the frequency of the second type was 35%. The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors (82.3% G1 and G2), superficial invasion of the myometrium (69.4%), high sensitivity to progestogens (80.2%), and favorable prognosis (85.6% 5-year survival rate). In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult, poorly differentiated tumors arise (62.5% G3), a tendency to deep invasion of tumor into the myometrium is observed (65.7%); high frequency of metastatic spread into the pelvic lymph nodes (27.8%); decrease of sensitivity to progestogens (42.5%); and doubtful prognosis (58.8% 5-year survival rate) are noted.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.Copyright © 2021. Published by Elsevier Inc.

Endometrial intraepithelial carcinoma (EIC) is a recently described lesion characterized by replacement of endometrial surface epithelium or glands by malignant cells resembling high-grade invasive endometrial carcinoma. EIC has been identified in a high proportion of uteri containing serous carcinoma, but its association with other endometrial tumors is unknown. To determine the strength and specificity of the association of EIC with tumors displaying serous differentiation, the appearance of the endometrium in 38 uteri with serous carcinoma, 113 with endometrioid carcinoma, and 34 with malignant mixed mesodermal tumor (MMMT) were compared. EIC was present in 34 (98%) uteri with serous carcinoma compared with 7 (6%) uteri removed for endometrioid carcinoma (P =.0001). Hyperplasia without atypia was found in only 2 (5%) of 38 serous carcinomas compared with 38 (34%) of 113 endometrioid carcinomas. Similarly, atypical hyperplasia was not found in any uterus with serous carcinoma, but was present in 14 (12%) uteri with endometrioid carcinoma (P =.02). The endometrium was inactive or atrophic in 29 (76%) patients with serous carcinoma compared with 33 (29%) with endometrioid carcinoma (P =.0001). EIC was found in five (56%) of nine MMMTs with a serous epithelial component (serous-MMMT) compared with one (4%) of 25 MMMTs woth an endometrioid epithelial component (endometrioid-MMMT). As with endometrioid and serous carcinomas, hyperplasia with and without atypia was more common with endometrioid-MMMTs as compared with serous-MMMTs. Hyperplasia was found in 25 (100%) and atypical hyperplasia in 8 (32%) of 25 endometrioid-MMMTs, but in none of the nine serous-MMMTs. This study shows that EIC is frequently and specifically associated with uterine tumors displaying serous differentiation. The findings suggest that EIC represents a form of intraepithelial tumor growth characteristic of serous carcinoma and serous MMMT and that EIC is the likely precursor of these neoplasms. In addition, the findings provide further evidence supporting the view that MMMTs represent variants of carcinoma not sarcoma.

The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice.To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology.The 4th and 5th editions of the World Health Organization Classification of Tumours.The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice.© 2022 College of American Pathologists.

To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) or aromatase inhibitor (letrozole) in women with endometrial carcinoma or atypical endometrial hyperplasia who wished to preserve fertility.Patients at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital between January 2013 and December 2020 were retrospectively reviewed. A total of 179 patients who were unsuitable to undergo treatment with high-dose oral progestin, including those with progestin allergies, body mass index ≥30 kg/m, liver and/or renal dysfunction, hypercoagulable state, and thrombosis were included. Patient data were retrieved from medical records and a prospectively maintained database that represented the standard protocol was followed for all patients. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed. Logistic regression models were constructed to determine the associations between complete remission, recurrence, and fertility.Overall, 169 patients (94.4%) achieved complete remission; 58 (96.7%) had atypical endometrial hyperplasia and 111 (93.3%) had endometrial carcinoma. The complete remission rates for the GnRHa plus LNG-IUD and GnRHa plus letrozole groups were 93.5% and 95.8%, respectively. The median time to complete remission was 6 (range 3-18) months: 4 (range 3-10) months for atypical endometrial hyperplasia and 8 (range 3-18) months for endometrial carcinoma. After a median follow-up of 27.5 (range 3-92) months, 41 (24.3%) women developed recurrence, with a median recurrence time of 17 (range 6-77) months. Of the patients with complete remission, 134 patients desired to conceive and 42 (32.3%) became pregnant, 24 (17.9%) were successfully delivered, 5 (3.7%) were still pregnant, while 13 miscarried.GnRHa combined treatment provides favorable oncological and reproductive outcomes. Larger multi-institutional studies are required to confirm these preliminary findings.© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.

1  背景        在我国，乳腺癌发病居女性癌症发病第1位，每年乳腺癌新发病例约7.95万［1-2］。在诊断年龄上，美国乳腺癌患者的中位诊断年龄为64岁，在我国为48岁，早于美国10～15岁，近60%的患者确诊时为绝经前期。乳腺癌首选手术治疗，术后内分泌治疗为激素受体阳性乳腺癌重要的辅助治疗手段［3］。2019年版我国指南与规范中，乳腺癌术后内分泌治疗指征为雌激素受体（estrogen receptor，ER）和（或）孕激素受体（progesterone receptor，PR）阳性 ［4］。浏览更多请关注本刊微信公众号及当期杂志。