[Clinical Characterization of Patients with Ovarian Mass Combined with Dysplasia of Secondary Sexual Characteristics].

Objective To investigate the clinical characteristics of preadolescent and adolescent female patients with ovarian mass combined with dysplasia of secondary sexual characteristics. Methods This study retrospectively analyzed 18 cases of ovarian mass combined with dysplasia of secondary sexual characteristics aged 0-19 years admitted to Peking Union Medical College Hospital from January 2012 to November 2019.By analyzing the clinical manifestations,surgical methods,postoperative pathology,therapies and prognosis of the cases,we summarized the diagnosis and treatment ideas. Results Among the 18 cases,7(7/18,38.9%)developed secondary sex signs before puberty,including 5 cases showing precocity(including 2 cases of juvenile granulosa cell tumor,1 case of gonadoblastoma,1 case of ovarian follicular cyst,and 1 case of 46,XY simple gonadal dysplasia combined with dysgerminoma)and 2 cases presenting masculine manifestations(1 case of steroid cell tumor and 1 case of sclerosing stromal tumor).The rest 11(11/18,61.1%)cases showed abnormal development of secondary sexual characteristics during puberty,including 8 cases with masculine manifestations or abnormal menstruation after menarche(7 cases with sex cord stromal cell tumor and 1 case with cystic granulosa cell tumor),2 cases with primary amenorrhea(1 case with androgen insensitivity syndrome combined with testicular sertoli cell tumor and 1 case with endometriosis cyst combined with reproductive tract malformation),and 1 case diagnosed as 46,XX gonadal dysplasia with serous cystadenoma and no secondary sexual development during puberty. Conclusions Sex hormone levels should be actively tested in the case of prepubertal secondary sexual characteristics appearing early,pubertal secondary sexual characteristics being abnormal(underdevelopment),and/or menstrual abnormalities.Imaging examination should be performed to exclude ovarian organic lesions,and chromosome karyotype analysis should be performed if necessary.The diagnosis of ovarian mass in preadolescent and adolescent females with related symptoms should first be alerted to cord stromal cell tumor.It is recommended to rule out the possibility of combined reproductive tract malformation in the adolescent patients with primary amenorrhea.Chromosome examination should be conducted to rule out the possibility of gonadal dysplasia in the adolescent patients with primary amenorrhea and/or no development of secondary sexual characteristics.

Prolonged conservative treatment in patients with recurrent endometrial cancer after primary fertility-sparing therapy: 15-year experience.

OBJECTIVE: To evaluate the efficacy and prognosis of repeated treatment on patients with recurrent endometrial cancer (EC) after complete remission for primary fertility-preserving therapy. MATERIALS AND METHODS: We performed a retrospective study of patients with presumed stage IA endometrial cancer who had recurrence after achieving complete remission by fertility-preserving management at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2003 to April 2018. For each patient, medical records and pathology reports were reviewed. The demographic features, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed. RESULTS: Of the 41 recurrent patients with a median disease-free interval period of 16 months (range, 5-55 months), 23 were diagnosed at recurrence as EC, and 18 were diagnosed as atypical hyperplasia (AH) or endometrial intraepithelial neoplasia (EIN). 26 patients received repeated fertility-preserving treatment, and 23 patients were evaluable for efficacy. The complete response (CR) rate of repeated treatment (19/23, 82.6%) was lower than that of primary fertility-preserving treatment (161/170, 94.7%) with borderline significance (P = 0.053). The CR rate of AH/EIN patients was higher than that of EC patients with no statistical difference (92.9% vs 66.7%, P = 0.260). Among 19 patients achieved CR, 3 got pregnant and delivered successfully, while 3 had a second relapse. Four cases failed to response to the repeated treatment and underwent definitive surgery. 15 patients referred to definitive surgery directly after recurrence and one of them had a pelvic recurrence after 120 months. All patients are alive without evidence of disease at last follow-up. CONCLUSIONS: For patients with recurrent EC after primary fertility-preserving treatment, repeated fertility-preserving treatment can still achieve a promising response and patients have possibilities of completing childbirth.

[Experimental study on vagina reconstruction with tissue-engineering biological material.].

OBJECTIVE: To investigate the effect of vagina reconstruction using tissue-engineering biological material (acellular dermal matrix) in an animal model. METHODS: Vagina excision and vagina reconstruction with tissue-engineering biological material were performed in 12 Chinese experimental miniature pigs. The control group was matched with two of normal vagina specimens resected. At week 1, 2, 4, 6, 8, 12 after surgery, the animals were sacrificed, respectively, and the neovaginas were prepared for immunohistochemical and Van Gieson (VG) staining to evaluate the status of various layer growth of vagina. Epithelial broad spectrum of monoclonal antibodies of AE1/AE3 and alpha-actin were used to test the existence of epithelial and smooth muscle tissue by immunohistochemical staining. The ultrastructure of neovagina was studied by transmission electron microscope at week 1 and 12 after surgery. Contractile function of isolated smooth muscle of neovagina was evaluated by chemical and electronic stimulation after 12 weeks' reconstruction. RESULTS: (1) Epithelization of 2/3 neovaginal mucosa was observed within 1 week. Only 1 - 2 layer epitheliums were observed under the light microscopy and epithelial cells with characteristics of loose and disarrangement were shown with the electron microscopy. Within 4 - 6 weeks, epithelization in mucosa of neovaginal canal was intensified to 4 - 5 layers. After 12 weeks, the differences between the neovagina and the native vagina were harldy noted either in the gross or microscopically. (2) After 4 weeks, a few smooth muscle cells were observed with VG and immunohistochemical staining, and homogeneous muscle bundle was formed. (3) After 12 weeks, similar contractile responses between neovagina and native vagina were observed when KCl and electrical stimulation with different frequency and voltage were given [(2.96 +/- 0.29) g vs. (3.14 +/- 0.30) g, (3.43 +/- 0.34) g vs. (4.65 +/- 0.73) g, (4.92 +/- 0.38) g vs. (4.89 +/- 0.44) g]. CONCLUSION: The tissue-engineering biological material might be an ideal graft used in the reconstruction of vagina.

Genomic Comparison of Endometrioid Endometrial Carcinoma and Its Precancerous Lesions in Chinese Patients by High-Depth Next Generation Sequencing.

Endometrial intraepithelial neoplasia (EIN), also known as endometrial atypical hyperplasia (EAH) is believed to be the precursor lesion of endometrioid endometrial carcinoma (EEC). Many genetic factors play important roles in the process of carcinogenesis, however, the key genetic alterations from dysplasia to endometrial cancer remains poorly understood. Germline mutations in Lynch syndrome genes are associated with hereditary endometrial carcinoma. The role of other cancer susceptibility genes is unclear. The aim of this study was to investigate the genomic alterations of premalignant endometrial lesion and EEC, and to determine the prevalence of cancer predisposition gene mutations in an unselected endometrial carcinoma patient cohort. Here, we applied a comprehensive cancer gene panel (363 cancer-related genes) to capture the exomes of cancer-related genes. Samples were collected from 79 patients with EEC and 36 patients with EIN. Our results demonstrate that EIN harbors most of the driver events reported in EEC and for the first time we reported a high frequency of the amplification of VEGFB gene in endometrial cancer. Moreover, we identified four novel candidate cancer-associated genes (CTCF, ARHGAP35, NF1, and KDR) which may be crucial in the carcinogenesis of EEC. In addition, we identified 2 patients who had a deleterious germline mutation in Lynch syndrome genes (MLH1 and MLH2), and another 8 patients harbored germline mutations of 6 non-Lynch syndrome genes (MUTYH, GALNT12, POLE, MPL, ATM, and ERCC4) which may be associated with endometrial cancer. Larger series will have to be investigated to assess the risks and the proportion of endometrial cancers attributable to other genes.

Expression of Annexin-1 in patients with endometriosis.

BACKGROUND: Annexin-1 was identified as an endometriosis-related protein by comparative proteomics in previous study. As an endogenous anti-inflammatory mediator, Annexin-1 has been shown to regulate the immune response, cell proliferation and apoptosis. To investigate whether Annexin-1 is involved in the pathogenesis of endometriosis, we examined the expression of Annexin-1 in eutopic endometrium of women with or without endometriosis, and detected its expression in peritoneal fluids of those with endometriosis. METHODS: Eutopic endometrium samples from twenty-five women with endometriosis and those from sixteen age-matched women without endometriosis were collected. Peritoneal fluids were obtained from ten patients with endometriosis. The expression of Annexin-1 protein in eutopic endometrium was detected by immunohistochemistry and Western blotting, and mRNA detected by real-time PCR. Annexin-1 protein in the peritoneal fluids was detected by Western blotting. RESULTS: Annexin-1 mRNA and protein were overexpressed in eutopic endometrium of endometriosis without significant differences between the proliferative and secretory phase. Immunohistochemistry showed that Annexin-1 protein was expressed mainly in endometrial glandular cells throughout the menstrual cycle. Annexin-1 protein was detected in the peritoneal fluids of all the ten patients with endometriosis. CONCLUSIONS: Annexin-1 is overexpressed in eutopic endometrium and presents in the peritoneal fluids of patients with endometriosis, and may play a role in the pathogenesis of endometriosis.

[Clinical and pathological analysis of rare nonepithelial vulvar tumors].

OBJECTIVE: To study the clinical presentation and pathological features of rare nonepithelial vulvar tumors. METHODS: The clinical data of 42 patients with nonepithelial vulvar tumors who were operated on during 1986 to 2007 in Peking Union Medical College Hospital were analyzed. RESULTS: The average age of 42 patients was 44.1 years. There were 32 cases (76%) with a vulvar mass. Twenty one of these 42 patients (50%) complained of associated symptoms of itch and pain. Surgical treatment was the chief treatment of nonepithelial vulvar tumors, which included local excision (40, 95%), simple vulvectomy (1, 2%) and radical vulvectomy (1, 2%). Among the pathological diagnoses after operation, the most common benign histological subtypes were hidradenoma and haemangioma, while the most common malignant histological subtypes were leiomyosarcoma and aggressive angiomyxoma. CONCLUSIONS: Most of the nonepithelial vulvar tumors are mesenchymal tumors. The clinical presentation has no special characteristics. Diagnosis of nonepithelial vulvar tumors can be made based on histological inspection. Surgical treatment is the treatment of choice.

Duplicated uterus and hemivaginal or hemicervical atresia with ipsilateral renal agenesis: an institutional clinical series of 52 cases.

OBJECTIVES: To retrospectively review cases of unilateral vaginal or cervical atresia with ipsilateral renal agenesis at our institution and to analyze the clinical presentation, diagnostic pitfalls, management, and embryological implications for the vaginal origin that arise from this syndrome. STUDY DESIGN: A retrospective observational study that included 52 patients diagnosed with this syndrome between 1998 and 2008 at Peking Union Medical College Hospital. RESULTS: The median age at diagnosis was 21.5 years, and the median time between the first onset of symptoms and diagnosis was 12 months. The most common presenting complaints were dysmenorrhea, purulent discharge and irregular spotting, despite the wide spectrum of symptoms at referral. Patients with and without a communication between the two hemivaginas or hemiuteri had different clinical characteristics. Of the patients, 59.6% had an obstruction on the right side. Of patients who had received a check-up prior to referral, 92.9% (n=28) had been misdiagnosed, and 53.9% had received inappropriate surgery as therapy. The pathology of the resected septum showed squamous epithelium in 13 samples, while 5 samples had epithelium with paramesonephric characteristics. CONCLUSION: Knowledge of the origins and clinical presentation of this syndrome is the foundation for correct and timely diagnosis and treatment. Moreover, this unique anomaly may offer essential clues for determining the embryological origins of the vagina and cervix.

Symptomatic urinary problems in female genital tract anomalies.

Most of urological abnormalities in urogenital anomalies are asymptomatic and need no special treatment; however, a few patients have critical urinary complaints and surgical corrections are required for them. Unfortunately, these coexisting urinary problems are often neglected and failed to be treated. So, it is necessary to delineate the diagnosis and treatment of similar anomalies. Eight typical patients who had urogenital anomalies with urinary discomfort in our institution were excerpted and reported. In this series, the urinary symptoms ranged from cyclical hematuria and urinary incontinence to infection symptom. The involved urological anatomies were generally categorized into three types: abnormal communication of urogenital tracts, malformation of bladder or ectopic ureter, and anomalies of urethral orifice. Surgical corrections were helpful for most cases. For patients with genitalia anomalies, the coexisting urological defects should be highlighted by our gynecologists, especially when they are symptomatic and require surgical correction.

Venous malformations of the female lower genital tract.

OBJECTIVES: Vascular malformations are rarely located in the female lower genital tract. We present the specific clinicopathologic features of venous malformation in the lower genital tract and highlight the surgical management of these lesions. STUDY DESIGN: Between the years 1998 and 2008, 8 of 646 female patients were retrospectively defined as venous malformation in the lower genital tract according to the classification of the International Society for the Study of Vascular Anomalies (ISSVA). Clinical and pathologic information was analyzed according to the medical records and archived pathological sections. RESULTS: Venous malformations were located in the vagina in three women, and in two of these cases extended to the cervix, and were found at the vulva in five patients. The age of the patients ranged from 15 to 85. The clinical presentations were abnormal vaginal bleeding or vaginal mass in cases with cervicovaginal lesions, and non-specific vulvar nodules in women with vulvar lesions. The abnormalities were found shortly after birth and increased in size gradually thereafter, or become significantly enlarged during or following pregnancy. Postmenopausal episodes could occur, although rarely. Doppler ultrasound, MRI and angiography were available to help define the type of vascular anomalies. The therapeutic approach consisted of interventional embolization and surgical excision. In rare cases of refractory and diffuse cervicovaginal lesions, hysterectomy might be ultimately inevitable. CONCLUSION: Venous malformations in the lower female genital tract are rarely reported. Their clinical presentations mimic other genital tract neoplasms, including malignancies. Surgical excision is the curative procedure and is helpful to reach a definite pathological diagnosis.