DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues.

INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.

Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.

HISTOPATHOLOGICAL ANALYSIS OF NON-NEOPLASTIC OVARIAN LESIONS SEEN IN A TERTIARY HEALTH CENTRE IN NORTH WESTERN NIGERIA.

Introduction: Ovarian lesions may present as enlargements of the ovary and may occur at any age. Non-neoplastic enlargements develop almost exclusively during the childbearing years. They may be asymptomatic or, in rare cases, cause acute symptoms due to complications and account for the most prevalent cause of hospital admissions. They frequently form a pelvic mass and potentially mimic an ovarian neoplasm. Objective: To study the frequency and histopathological classification of non-neoplastic ovarian lesions in a tertiary institution in North-western Nigeria. Methodology: A retrospective study in which surgical biopsy specimens seen over a 9-year period were reviewed with respect to age and histopathological characteristics. Results: A total of 83 non-neoplastic lesions were histologically diagnosed during the period under review. They constitute 5.16 % and 40.9 % of both gynaecological and ovarian samples received respectively. Of which 33.7% were Corpus luteum, 13.3% were both Follicular cysts and simple cysts respectively. Luteoma of pregnancy and Infarction constitute 9.6% each respectively. Endometriosis and no pathology as part of TAH, 6.0% respectively. Ovarian ectopic gestation was 4.8% cases, Nonspecific inflammation (oophoritis) 2.4%, and 1.2% complex cyst. Majority of cases 45.8% occurred among women in the third decade and 26.5% in the fourth decade, cases within the fifth decade were 9.6% and the second decade constituted 8.4% cases. Conclusion: Ovarian non-neoplastic lesions are common in our environment; they potentially mimic ovarian neoplasms thereby posing a diagnostic challenge. Proper classifications are important for appropriate management.

Role of scrape cytology smear preparation in the diagnosis of ovarian masses-utility and pitfalls.

BACKGROUND: Scrape cytology technique is useful for rapid intraoperative diagnosis of ovarian mass lesions that acts as an adjunct to frozen section examination. Though ovaries can be accessed by laparoscopy and USG guided FNAC, there are controversial reports regarding the safety of these procedures. The present study has been designed to evaluate the role of scrape cytology in a variety of ovarian mass lesions. OBJECTIVES: To study the cyto-morphology of ovarian mass lesions and to evaluate the role of scrape cytology technique in correctly diagnosing the ovarian lesions taking histopathological diagnosis as gold standard. MATERIAL AND METHODS: This is a prospective observational study done on 61 ovarian mass lesions as received from the Obstetrics and Gynecology department of our Institution. RESULT: Out of 61 cases, 58 (95.08%) cases were correctly diagnosed with respect to categorization and typing. The age ranged from 14 to 65 years with the mean age being 38.1 years. On histopathology, out of 61 cases, 39 (63.93%) were epithelial along with sub categorization of benign, borderline, and malignant, 13 (22.9%) were germ cell tumors, 5(8.19%) were sex cord stromal tumors, 3 (4.91%) were hemorrhagic cysts and the remaining 1 (1.63%) was massive ovarian edema. Thus, on comparing with histopathology, the sensitivity and specificity of scrape cytology technique were 93.55% and 96.67%, and the diagnostic accuracy was 95.08%. CONCLUSION: Scrape cytology of ovarian lesions can give quick and reliable results. Also, proper training of cytopathologists chiefly regarding the sampling technique, gross presentation of ovarian lesions and interpretation of scrape cytology smears is needed. Further studies to provide standard guidelines and reporting criteria will prove to be helpful.

Comprehensive Review of Serous Tumors of Tubo-Ovarian Origin: Clinical Behavior, Pathological Correlation, Current Molecular Updates, and Imaging Manifestations.

Ovarian cancer is the eighth most common women's cancer worldwide, with the highest mortality rate of any gynecologic malignancy. On a global scale, the World Health Organization (WHO) reports that ovarian cancer has approximately 225,000 new cases every year with approximately 145,000 deaths. According to the National Institute of Health, Surveillance Epidemiology and End Results program (SEER) database, 5-year survival for women with ovarian cancer in the United States is 49.1%. High-grade serous ovarian carcinoma typically presents at an advanced stage and accounts for the majority of these cancer deaths. Given their prevalence and the lack of a reliable method for screening, early and reliable diagnosis of serous cancers is of paramount importance. Early differentiation of borderline, low and high-grade lesions can assist in surgical planning and support challenging intraoperative diagnoses. The objective of this article is to provide a review of the pathogenesis, diagnosis, and treatment of serous ovarian tumors, with a specific focus on the imaging characteristics that help to preoperatively differentiate borderline, low-grade, and high-grade serous ovarian lesions.

Surgical Resection of Bilateral Polycystic Ovaries Causing Ureteral Obstruction.

Ovarian cysts in adolescents are typically managed conservatively given the low rate of malignancy and the cysts typically regress over time. We present a case of a 14 year-old female with large bilateral adnexal cysts causing ureteral obstruction which was successfully treated with surgical resection and ensuring maximum preservation of ovarian tissue.

Laparoscopically assisted ovarian cystectomy with totally enclosed protective device for tumor isolation.

OBJECTIVE: To present a novel totally enclosed protective device for tumor isolation in laparoscopic ovarian cystectomy. METHODS: A retrospective study was conducted of 16 patients with unilateral ovarian teratoma in the Department of Obstetrics and Gynecology of the China-Japan Friendship Hospital. Laparoscopic surgery was performed with a totally enclosed protective device for tumor isolation, followed by a case series retrospective study. The indexes measured included size of cyst, rate of intraoperative rupture, duration of operation, amount of intraoperative blood loss, and postoperative length of stay in the hospital. An intact cyst resected in the device with no spillage seen indicated a successful surgery. RESULTS: A total of 16 operations were performed successfully. The mean diameter of the cysts was 7.2 ± 1.4 cm. Of them, 12 (75%) had an intraoperative cyst rupture without spillage. The mean duration of surgery was 1.3 ± 0.1 h and the mean amount of intraoperative blood loss was 12.5 ± 3.2 ml. All postoperative histology tests showed benign cysts. The mean length of stay after surgery was 2.4 ± 0.5 days. No peritonitis-related symptoms or complaints were reported. CONCLUSION: Laparoscopically assisted ovarian cystectomy with a totally enclosed protective device for tumor isolation was confirmed safe and feasible.

Quantification of ovarian lesion and fallopian tube vasculature using optical-resolution photoacoustic microscopy.

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies.

Magnetic resonance imaging findings of cystic ovarian tumors: major differential diagnoses in five types frequently encountered in daily clinical practice.

There are many types of ovarian tumors, and these different types often form cystic masses with a similar appearance, which can make their differentiation difficult. However, with the exclusion of rare ovarian tumors, the number of ovarian tumors encountered in daily practice is somewhat fixed. It goes without saying that magnetic resonance imaging (MRI) is useful for differentiating ovarian tumors. In this review, we summarize the differential diagnoses for each of the five types of MRI findings commonly encountered in daily practice. First, unilocular cystic masses without mural nodules/solid components include benign lesions such as serous cystadenoma, functional cysts, surface epithelial inclusion cysts, paratubal cysts, and endometriosis. Second, multilocular cystic ovarian lesions include mucinous tumors and ovarian metastases. It should be noted that mucinous tumors may be diagnosed as borderline or carcinoma, even if no solid component is observed. Third, cystic lesions with mural nodules that are unrelated to endometriosis include serous borderline tumor and serous carcinoma. Cystic lesions with solid components are more likely to be malignant, but some may be diagnosed as benign. Fourth, ovarian tumors deriving from endometriosis include seromucinous borderline tumors, endometrioid carcinoma, and clear cell carcinoma. These tumors sometimes need to be differentiated from serous tumors. Finally, cystic lesions with lipid contents include teratoma-related tumors. In mature cystic teratoma, mural nodules (called "Rokitansky protuberance" or "dermoid nipple") are sometimes seen, but they do not suggest malignancy. Some of these lesions can be diagnosed accurately by considering their characteristic imaging findings, their changes over time, MRI findings other than those of the primary lesion, and information from other modalities such as tumor markers. To ensure the optimal treatment for ovarian tumors, it is important to estimate the histological type as well as to diagnose whether a lesion is benign or malignant.

Sonographic features differentiating early-stage ovarian clear cell carcinoma from endometrioma with atypical features.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the most common endometriosis-associated ovarian cancer. Ovarian endometriosis may present with atypical or malignant sonographic features and interfere with clinical judgment about whether definitive surgical intervention is required. OBJECTIVE: To compare the characteristics of endometrioma with atypical features and OCCC. METHODS: This study enrolled patients with pathologic diagnoses of either endometrioma or OCCC. For patients with endometrioma, only those with atypical features, defined as the presence of at least one of the following sonographic characteristics: cyst diameter of 10 ± 1 cm, multi-cystic lesions, any solid component or papillary structure, and blood flow of any degree, were included. RESULTS: Sixty-three patients had endometriomas with atypical features, while 57 patients had OCCC. Patients with endometriomas were younger (39.33 ± 7.04 years vs. 53.11 ± 9.28 years, P < 0.01), had smaller cysts (7.81 ± 2.81 cm vs. 12.68 ± 4.60 cm, P < 0.01), and had smaller solid components (0.93 ± 1.74 cm vs. 4.82 ± 3.53 cm, P < 0.01). In contrast, OCCCs were associated with loss of ground-glass echogenicity (6.3% vs 68.4%, P < 0.01). In multivariate analysis, advanced age (> 47.5 years), large cysts (> 11.55 cm), large solid components (size > 1.37 cm), and loss of ground-glass echogenicity were independent factors suggestive of malignancy. CONCLUSION: Advanced age, larger cyst sizes, larger solid component sizes, and loss of ground-glass echogenicity are major factors differentiating endometriomas from malignancies. For women in menopausal transition who have finished childbearing who present with endometrioma with atypical features, removal of the adnexa intact could be considered.

Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, which limits early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared them to matched eutopic endometrium, unaffected endometrium and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell specific to the peritoneal lesions, with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesion microenvironments and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment that represents a comprehensive cell atlas of the disease in individuals undergoing hormonal treatment, providing essential information for future therapeutics and diagnostics.

[Neonatal bilateral ovarian cystadenoma: Conservative or surgical treatment?] / Cistoadenoma ovárico bilateral neonatal, ¿tratamiento conservador o quirúrgico?

INTRODUCTION: Bilateral complex ovarian cysts in newborns are rare and their reporting becomes imperative to in crease knowledge about the best therapeutic management. OBJECTIVE: To describe the clinical case of a newborn with a diagnosis of bilateral complex ovarian cysts and to discuss the conditions for conservative or surgical management according to the ultrasound characteristics of the cyst. CLINICAL CASE: At 35 weeks of gestational age, prenatal ultrasound identified the presence of cystic masses in both adnexa, so it was decided to interrupt the pregnancy by cesarean section at 37 weeks. After birth, bilateral ovarian cysts of 3.5 x 4.4 x 2.7 and 3.4 x 2.4 x 3.3 cm, right and left, respectively, were corro borated. The right cyst had a septum of 1.4 mm thick and thickened wall of 3 mm which was com patible with complex cysts. On the 4th day of extrauterine life, laparoscopic vacuum aspiration and deroofing with electrocautery of the upper wall of both cysts was performed, without complications. The diagnosis of ovarian serous cystadenoma was made by pathological anatomy. CONCLUSIONS: We describe a case with adequate prenatal diagnosis and laparoscopic surgical intervention of a bilateral ovarian cyst > 4 cm. Prenatal diagnosis is essential for choosing the best therapy management (con servative or surgical) depending on the echography characteristics of the cyst. Neonatal surgery is recommended for simple ovarian cysts >4 cm, complex cysts regardless of their size, and those that become complex cysts during conservative management.

Controlled aspiration of large paediatric ovarian cystic tumours.

AIM: Cystic ovarian masses in children may be physiological or neoplastic. It is mandatory that suspected neoplastic lesions are resected without tumour spillage. However, a large midline incision is cosmetically unappealing incision to young women. Here we describe our experience of using controlled drainage without spillage that allows a cosmetic pfannenstiel approach without compromising oncological principles. METHOD: All girls treated with large ovarian cystic masses since 2008 in our centre were identified and data was collected prospectively. A small pfannenstiel incision was performed followed by peritoneal washings; tissue glue was used to stick an Opsite™ dressing to the cyst surface and fluid drained so there was no leakage back into the patient. Once aspirated the cyst was delivered and an ovarian preserving cystectomy was performed where possible. RESULTS: Twenty-three girls (median age 14.5 years (8.1 to 16.5 years) were included. Pre-operative MRI scan showed a complex lesions with median volume of 1169 ml (range 252-7077 ml). At surgery 22/23 cysts were intact and removed without spillage. HISTOLOGY: mature teratoma (11), serous cyst (3), mucinous cyst adenocarcinoma (2), mucinous cystadenoma (5), Sertoli-Leydig tumour, sclerosing stromal tumour. One girl with pre-operative rupture of a mucinous adenocarcinoma subsequently died. Ovarian sparing cystectomy was performed in 17/23 girls. All other patients are well without evidence of recurrence. CONCLUSION: This is the largest series in children and adolescents using controlled drainage of cystic ovarian tumours. Though there were a range of diagnoses we have shown that these can be removed safely with a cosmetic pfannenstiel approach while following oncological principles.

Large Ovarian Follicle Cyst: Benign Mimic of Cystic Adult Granulosa Cell Tumor.

While most ovarian follicle cysts are <8 cm in greatest dimension, much larger follicle cysts (up to 18.5 cm) have been reported. To our knowledge, the FOXL2 mutation status of such cases has not been documented in the literature. Here, we report the features of a 14 cm ovarian cyst with no FOXL2 mutation detected by targeted next-generation sequencing. While adult granulosa cell tumor was the chief entity in our differential diagnosis, the absence of convincing nuclear grooves, lack of architectural variability, presence of a theca layer, and absence of FOXL2 mutation were consistent with a diagnosis of ovarian follicle cyst.

Asymptomatic autoamputation of ovary and fallopian tube in a 2 days newborn: a case report.

Automatic amputation of the ovary represents a rather uncommon condition. Especially asymptomatic autoamputation is an even more unusual laparoscopic finding. We hereby present a case of a 2-days´-old infant with a prenatal ultrasound (US) diagnosis of a cystic mass, laparoscopically proved as an amputated right adnexa. The female infant was asymptomatic and had normal laboratory exams, including hormone levels, according to her age. The infant was managed surgically, as the size of the cystic lesion, both prenatally and postnatally was indicative of surgical intervention. Careful monitoring is critical for the management of cystic lesions diagnosed prenatally. Although rare, the suspicion of an auto-amputated ovary has to be risen during diagnostic approach of infants with adnexal cysts, especially when these lesions are supposed to "wander" during imaging examinations, and also taking into account the size of the lesion in order for a final approach and management to be established.

Endometriosis-associated epithelial ovarian cancer is a more complicated disease than we suspected before.

OBJECTIVE: Endometriosis-associated epithelial ovarian cancer (EOC) often includes clear cell carcinoma and endometrioid-type carcinoma. Due to the low incidence of primary mucinous EOC and absence of association between endometriosis and primary mucinous EOC, we present an unusual endometriosis-associated mixed mucinous and endometrioid adenocarcinoma arising from the same ovary. CASE REPORT: A 54-year-old woman had an abdominal palpable mass for months. Medical and surgical history, as well as preoperative surveys was unremarkable, except of presence of a pelvic mass. She underwent an exploration laparotomy, and a 22-cm right ovarian tumor was found. Grossly, right ovarian tumor containing brownish cloudy cystic fluid 2450 ml and an apparent 4 × 4 × 2 cm-sized papillary growth. Microscopically, a confluent glandular and infiltrative pattern presented endometrioid adenocarcinoma, and cells with intracytoplasmic mucin and stratified elongated epithelial cells presented mucinous adenocarcinoma. Surgico-pathological stage was FIGO IIIA due to tumor invading to the peritoneum above the pelvis. Postoperatively, the dose-dense chemotherapy was applied with uneventful outcome. CONCLUSION: This is a rare case, composed with mixed mucinous and endometrioid adenocarcinoma of the same ovary, suggesting that careful pathological diagnosis of endometriosis-associated EOC is needed.

The Optimal Time of Ovarian Reserve Recovery After Laparoscopic Unilateral Ovarian Non-Endometriotic Cystectomy.

Background: Laparoscopic ovarian cystectomy is established as the standard surgical approach for the treatment of benign ovarian cysts. However, previous studies have shown that potential fertility can be directly impaired by laparoscopic ovarian cystectomy, diminished ovarian reserve (DOR), and even premature ovarian failure. Therefore, fertility-preserving interventions are required for benign gynecologic diseases. However, there are still little data on the time period required for recovery of ovarian reserve after the laparoscopic unilateral ovarian cystectomy, which is very important for the individualization of treatment protocols. This study aimed at investigating the time needed for the ovarian reserve to recover after laparoscopic unilateral ovarian non-endometriotic cystectomy. Materials and Methods: Sixty-seven patients with unilateral ovarian non-endometriotic cyst from Zhoupu and Punan Hospitals who underwent laparoscopic unilateral ovarian cystectomy were recruited as a postoperative observation group (POG). Also, 69 healthy age-matched women without ovarian cyst who did not undergo surgery were recruited as a referent group (RFG). Ovarian reserve with the serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2) levels, ovarian arterial resistance index (OARI), and antral follicle counts (AFCs) were measured on the third to fifth days of the same menstrual cycle. A postoperative 6-month follow-up of cases was performed. Results: Compared with RFG, AFC of cyst side in the POG group showed no difference in the first, third, and sixth postoperative month (F = 0.03, F = 0.02, F = 0.55, respectively; p = 0.873, p = 0.878, p = 0.460, respectively). The OARI of cyst side in the POG group revealed no differences in the first, third, and sixth postoperative month (F = 0.73, F = 3.57, F = 1.75, respectively; p = 0.395, p = 0.061, p = 0.701, respectively). In the first month, the postoperative AMH levels significantly declined, reaching 1.88 ng/ml [interquartile range (IQR): 1.61-2.16 ng/ml] in POG and 2.57 ng/ml (IQR: 2.32-2.83 ng/ml) in RFG (F = 13.43, p = 0.000). For the data of AMH levels stratified by age, the same trend was observed between less than 25 and more than 26 years old. At this same time interval, the postoperative rate of decline was significantly lower compared to the preoperative one in POG (32.75%). The same trend was observed between the POG and RFG groups (26.67%). Conclusions: The optimal time for recovery of ovarian reserve after laparoscopic unilateral ovarian cystectomy is estimated to be 6 months.