SOX3 duplication in a boy with 46,XX ovotesticular disorder of sex development and his 46,XX sister with atypical genitalia: Probable germline mosaicism.

Ovotesticular disorders of sex development (OT-DSD) are characterized by ovarian follicles and seminiferous tubules in the same individual, with a wide range of atypical genitalia. We report on two sibs with atypical genitalia and SRY-negative 46,XX DSD, OT-DSD was confirmed only in the boy, while the girl had bilateral ovaries. Chromosome microarray analysis (CMA) showed a 737-kb duplication at Xq27.1 including the entire SOX3 gene in both sibs, which was confirmed by quantitative real time PCR. Also, X chromosome inactivation assay showed random inactivation in both sibs. Whole exome sequencing revealed no pathogenic or likely pathogenic variant. CMA of the parents showed normal results for both, suggesting that germline mosaicism could be the reason of recurrence of this duplication in the siblings. Our results support a pathogenic role of SOX3 overexpression in 46,XX subjects leading to variable DSD phenotypes.

Adult Granulosa Cell Tumour With Heterologous Adipocytic Differentiation: Report of a Unique Case.

Adult granulosa cell tumor is the most common malignant ovarian sex cord-stromal tumor and heterologous elements, in the form of hepatocytes or mucinous epithelium, have rarely been described in these neoplasms. Here, we report an adult granulosa cell tumor in a 61-year-old woman with classic and luteinized elements and exhibiting a previously unreported feature in the form of foci of mature adipocytes. In reporting this case, we review heterologous adipocytic elements and other heterologous elements in ovarian sex cord-stromal tumors and speculate on the pathogenesis of the adipocytic differentiation.

Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer.

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II - versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II - versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

Endometriosis-Associated Ovarian Cancer: Population Characteristics and Prognosis.

OBJECTIVE: The aim of this study was to analyze and compare the clinicopathologic features and prognosis of clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (EOC) associated or not with endometriosis. METHODS: This was a reconstituted cohort study from a single-institution Brazilian cancer center approved under review board no. 68150617.7.0000.5404 with 50 patients with CCOC and EOC diagnosed between 1995 and 2016, followed up until 2017. Clinicopathologic characteristics and survival outcomes were analyzed. RESULT(S): There were 23 women (46%) with CCOC and 27 with EOC (54%); 80% of those women had histologic confirmation of endometriosis; 42% were nulliparous, and 42% were premenopausal; and cancer antigen 125 was elevated in both International Federation of Gynecology and Obstetrics stages I-II disease (mean, 614.7 Ui/mL; range, 3-6030 Ui/mL) or International Federation of Gynecology and Obstetrics stages III-IV disease (mean, 2361.2 Ui/mL; range, 8-12771 Ui/mL). Women with EOC were 7 years younger than those with CCOC. When associated with endometriosis, CCOCs were more likely diagnosed at earlier stages. Endometrioid ovarian carcinoma and CCOC at initial stage and EOC at advanced stage share similar good prognosis. Univariate analysis showed that CCOC not associated with endometriosis has worse overall survival (OS). However, multivariate analysis showed that only abnormally elevated levels of cancer antigen 125 and advanced stage at diagnosis were significantly associated with reduced progression-free survival. Tumor stage remains the only prognostic factor for OS. CONCLUSIONS: The presence of coexisting endometriosis did not change the prognosis of EOC but was associated with better OS in patients with CCOC. Patients with CCOC and EOC at initial stages and EOC at advanced stages have a good prognosis; however, CCOC at advanced stages had a sooner recurrence and shorter OS.

BRCA1, Ki67, and ß-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma.

OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and ß-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and ß-catenin expression was assessed using tissue microarray-based immunohistochemistry. RESULTS: Women with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and ß-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and ß-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS). CONCLUSIONS: Ki67 expression was significantly higher in HGSOC. BRCA1 and ß-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and ß-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.

CAISMOV24, a new human low-grade serous ovarian carcinoma cell line.

BACKGROUND: The spontaneous immortalization of primary malignant cells is frequently assigned to their genetic instability during in vitro culturing. In this study, the new epithelial ovarian cancer cell line CAISMOV24 was described and compared with its original low-grade serous ovarian carcinoma. METHODS: The in vitro culture was established with cells isolated from ascites of a 60-year-old female patient with recurrent ovarian cancer. The CAISMOV24 line was assessed for cell growth, production of soluble biomarkers, expression of surface molecules and screened for typical mutations found in serous ovarian carcinoma. Additionally, comparative genomic hybridization was employed to compare genomic alterations between the CAISMOV24 cell line and its primary malignant cells. RESULTS: CAISMOV24 has been in continuous culture for more than 30 months and more than 100 in vitro passages. The cell surface molecules EpCAM, PVR and CD73 are overexpressed on CAISMOV24 cells compared to the primary malignant cells. CAISMOV24 continues to produce CA125 and HE4 in vitro. Although the cell line had developed alongside the accumulation of genomic alterations (28 CNV in primary cells and 37 CNV in CAISMOV24), most of them were related to CNVs already present in primary malignant cells. CAISMOV24 cell line harbored KRAS mutation with wild type TP53, therefore it is characterized as low-grade serous carcinoma. CONCLUSION: Our results corroborate with the idea that genomic alterations, depicted by CNVs, can be used for subtyping epithelial ovarian carcinomas. Additionally, CAISMOV24 cell line was characterized as a low-grade serous ovarian carcinoma, which still resembles its primary malignant cells.

Analysis of Conservative Surgical Treatment and Prognosis of Microinvasive Squamous Cell Carcinoma of the Cervix Stage IA1: Results of Follow-Up to 20 Years.

OBJECTIVE: The aim of this study was to evaluate the prognosis and recurrence of microinvasive squamous cervical (MIC) cancer stage IA1 in women treated conservatively or by hysterectomy, and followed-up to 20 years. METHODS: It was studied in a cohort of 139 women with MIC, 41 definitively managed by conization and 98 by hysterectomy from January 1994 to December 2003 and followed-up until 2013. The definitive treatment, age, conization technique (loop electrosurgical excision procedure or cold knife conization), cone margin, residual disease in hysterectomy specimen, and the association with recurrence (intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse, and microinvasive or worse) were analyzed. RESULTS: There were 2.5 times more conservative treatment in younger women than older (>40 years), and high proportion of residual disease in hysterectomy specimens (67% of intraepithelial cervical neoplasia grade 3 or worse), more common if positive cone margin (74% vs 35%, P < 0.002). There were 2.3% (3/133) recurrences detected as microinvasive or worse, and 6% (8/133) recurrences detected as intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse: 7.3% (3/41) in the conization group and 5.4% (5/92) in the hysterectomy group (P = 0.701). Almost all recurrences (88%, 7/8) were diagnosed until 36 months after treatment, and they were not associated with conization technique. There were no differences in risk of recurrence and overall disease-free survival time related to type of treatment. CONCLUSIONS: This study demonstrates the good prognosis of MIC, regardless the treatment. When fertility is not a concern, hysterectomy should be considered as definitive treatment to avoid the risk of residual disease. Regular follow-up for a long period should be maintained.

p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical Intraepithelial Neoplasia Progression.

OBJECTIVE: The aim of this study was to evaluate p16, cytokeratin 7 (CK7), and Ki-67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking for differences among cases that progress to high-grade squamous intraepithelial lesion, maintain LSIL, or regress. MATERIALS AND METHODS: Sixty-six LSIL biopsies were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9% LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion. Immunostaining for these markers were performed in the first biopsy. A qualitative evaluation method was used, as well as histomorphometry, using ImageJ software. Pearson χ, Mann-Whitney, Kruskal-Wallis, and Fisher tests were used to compare the groups (P ≤ .05). A cutoff point was assessed through receiver operating characteristic curve positive cell ratio, for each marker, as progression predictors. RESULTS: The mean age of patients with and without progression was 33 and 27 years (P = .006), respectively. The qualitative evaluation indicated a tendency of progression, but without statistical significance. However, through histomorphometry, the receiver operating characteristic curve analysis showed cutoff points of 0.396, 0.345, and 0.026 for p16, CK7, and Ki-67 ratios, respectively, as predictors of progression (P = .003, .03, and .002, respectively). In a logistic regression analysis, p16, CK7, and Ki-67 positive cell ratio showed a significant correlation with progression (P = .036, .012, and .006, respectively). CONCLUSIONS: p16, CK7, and Ki-67 may represent useful biomarkers that can identify LSIL lesions that need particular attention.

Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

AIM: To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. RESULTS: Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CONCLUSION: CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.

Performance of the Risk of Malignancy Index for Discriminating Malignant Tumors in Women With Adnexal Masses.

OBJECTIVES: We examined the performance of 4 risk of malignancy index (RMI) variants in a medium-resource gynecologic cancer center. METHODS: A total of 158 women referred for adnexal masses were evaluated before surgery by the 4 RMI variants. Physicians with varied experience in ultrasound assessment of adnexal masses performed ultrasound examinations. We compared the performance of the 4 RMI variants using receiver operating characteristic curve analyses followed by calculation of sensitivity, specificity, and positive and negative likelihood ratios using the pathologic diagnosis of the masses as the reference standard. RESULTS: Among the 158 women with adnexal masses included in this study, 51 (32%) had malignant tumors; 26 (51%) of them were stage I. All RMI variants performed similarly (accuracy range, 74%-83%), regardless of menopausal status. Considering all women included, the positive likelihood ratios of the 4 RMI variants ranged from 3.52 to 4.41. In subset analyses, all RMI variants had decreased sensitivity for stage I malignant tumors and for those of nonepithelial histologic types. CONCLUSIONS: The 4 RMI variants performed acceptably in a medium-resource setting where ultrasound examiners were physicians with varied experience. This finding indicates a good tradeoff between performance and feasibility, since ultrasound RMI protocols are of low complexity.

Microinvasive adenocarcinoma of the cervix in a young woman vaccinated against human papillomavirus: the screening must be continued.

OBJECTIVE: This report describes a case that illustrates the limitations of the vaccination screening process for human papillomavirus (HPV) infection. CASE: We report an unexpected microinvasive adenocarcinoma of the cervix arising in a young woman vaccinated against HPV as part of a clinical trial 6 years previously and followed up annually by cytology. In January 2012, at age 23 years, the patient received a cytological result of atypical squamous cells, cannot exclude high-grade cervical squamous intraepithelial lesion, and colposcopy showed slight abnormalities. Biopsy revealed an adenocarcinoma in situ. Conization of the cervix was performed, and the diagnosis was microinvasive adenocarcinoma. Polymerase chain reaction and immunohistochemical study of conization material showed positivity for HPV-18 L1, p16, and Ki-67. Retrospective analysis of the clinical trial information revealed that 7 HPV tests had been performed, and all were positive for HPV-18, including the sample collected before the first vaccination. CONCLUSIONS: HPV-18 was present in the cervix before vaccination. Persistent detection of HPV-18 should be considered an important factor in treatment planning. This case demonstrates the need to vaccinate women before their first sexual contact and highlights the need for keeping adequate screening even in vaccinated individuals.

Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses.

BACKGROUND: This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound. METHODS: This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae. RESULTS: Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI. CONCLUSION: Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.

Prognosis determination of endocervical adenocarcinomas morphologically reclassified as HPV associated or HPV independent.

OBJECTIVE: To evaluate the prognosis of endocervical adenocarcinomas after reclassification according to the morphologic type based on the 2020 World Health Organization Classification. METHODS: A retrospective longitudinal study with cases admitted at the University of Campinas, Brazil, from 2013 to 2020. The sample included 140 cases morphologically reclassified: 100 cases as adenocarcinoma HPV-associated (HPVA), 17 as HPV-independent (HPVI), and 23 non-HPVA/HPVI. Clinic and pathologic variables were evaluated. Analyses were performed by χ2 , Fisher exact, and Mann-Whitney U tests, Kaplan-Meier curves, Log-rank test, and Cox regression. RESULTS: Compared with the HPVA group, advanced stage (FIGO Stage II+) was more frequent in the HPVI group (P = 0.009), which also showed older patients (P = 0.032), and a higher proportion of deaths (P = 0.006). The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005). At the multivariate analysis, the risk of death was 6.7 (95% confidence interval 1.9-23.0) times higher in patients diagnosed in advanced stages. CONCLUSION: HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS. The morphology-based approach of the new WHO classification appears to be prognostically valuable and applicable in lower- and middle-income settings.

Metastatic mucinous carcinomas in the ovary: a practical approach to diagnosis related to gross aspects and to immunohistochemical evaluation.

Ovarian mucinous carcinomas are uncommon, and the differential diagnosis is metastatic carcinoma mainly from the gastrointestinal tract. The aim was to verify the importance of immunohistochemical reactions and the algorithm described in literature on the basis of laterality and tumor size. Twenty-five cases identified as metastatic mucinous adenocarcinomas were reviewed, along with clinical records; a tissue microarray was created, and immunohistochemical reactions for CK7, CK20, Ca125, hormonal receptors, WT1, DPC4, ß-catenin, and Cdx2 were determined. The median age was 51, and only 9 patients had a history of cancer. Sixteen patients (64%) had bilateral tumors, with sizes ranging from 5 to 36 cm (average, 20.5 cm); 9 (36%) had unilateral tumors varying from 5.5 to 38 cm (average, 21.8 cm). Algorithm agreement was 76%; most unilateral tumors were >13 cm. Common positive markers were Dpc4 (88%), Cdx2 (68%), CK20 (60%), and CK7 (44%). The useful markers were CK7, CK20, and Cdx2, although there were cases with overlapping results. The most common primary tumor was of colorectal origin (14 cases). The mean survival age was 32.6 mo. Although the proposed algorithm and immunohistochemical reactions are useful tools for diagnosis, some mucinous tumors cannot be definitively classified as primary or metastatic without further clinical evaluation, emphasizing the limits of this challenging diagnosis.

Conservative treatment of microinvasive squamous cell carcinoma of the cervix stage IA1: Defining conization height to an optimal oncological outcome.

OBJECTIVE: This paper searches an ideal cone height for stage definition and safe treatment of cervical microinvasive squamous carcinoma stage IA1 (MIC IA1), avoiding excessive cervix resection, favoring a future pregnancy. METHODS: A retrospective study was performed involving 562 women with MIC IA1, from 1985 to 2013, evaluating cone margin involvement, depth of stromal invasion, lymph vascular invasion, conization height, and residual uterine disease (RD). High-grade squamous lesions or worse detection was considered recurrence. Univariate and multivariate regression analyses were performed, including age, conization technique (CKC, cold-knife, or ETZ, excision of transformation zone), and pathological results. Conization height to provide negative margins and the risk of residual disease were analyzed. RESULTS: Conization was indicated by biopsy CIN2/3 in 293 cases. Definitive treatments were hysterectomy (69.8%), CKC (20.5%), and ETZ (9.7%). Recurrence rate was 5.5%, more frequent in older women (p = 0.030), and less frequent in the hysterectomy group (p = 0.023). Age ≥40 years, ETZ and conization height are independent risk factors for margin involvement. For ages <40 years, 10 mm cone height was associated with 68.6% Negative Predictive Value (NPV) for positive margins, while for 15 mm and 25 mm, the NPV was 75.8% and 96.2%, respectively. With negative margins, the NPV for RD varied from 85.7-92.3% for up to 24 mm cone height and 100% from 25 mm. CONCLUSION: Conization 10 mm height for women <40 years provided adequate staging for almost 70%, with 10% of RD and few recurrences. A personalized cone height and staging associated with conservative treatment are recommended.

Preoperative Differentiation of Benign and Malignant Non-epithelial Ovarian Tumors: Clinical Features and Tumor Markers.

OBJECTIVE: To evaluate the role of clinical features and preoperative measurement of cancer antigen 125 (CA125), human epididymis protein (HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. METHODS: One hundred and nineteen consecutive women with germ cell, sex cord-stromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. RESULTS: Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, among malignant, four were immature teratomas. The most common tumors in the sex cord-stromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign and malignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. CONCLUSION: Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant cases were diagnosed at initial stages with good prognosis. The measurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

OBJETIVO: Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. MéTODOS: Cento e dezenove mulheres consecutivas com tumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. RESULTADOS: Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estroma malignos foram tratadas com cirurgia preservadora de fertilidade. Cinco (71,4%) mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. CONCLUSãO: Os tumores de ovário não epiteliais foram benignos na maioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico pré-operatório desses tumores.

Three-Dimensional Cell Culture Based on Magnetic Fields to Assemble Low-Grade Ovarian Carcinoma Cell Aggregates Containing Lymphocytes.

There is a limited number of established ovarian cancer cell lines matching the low-grade serous histotype available for research purposes. Three-dimensional (3D) culture systems provide in vitro models with better tissue-like characteristics than two-dimensional (2D) systems. The goal in the study was to characterize the growth of a given low-grade serous ovarian carcinoma cell line in a 3D culture system conducted in a magnetic field. Moreover, the culture system was evaluated in respect to the assembly of malignant cell aggregates containing lymphocytes. CAISMOV24 cell line alone or mixed with human peripheral blood mononuclear cells (PBMC) were cultured using a commercially available 3D culture system designed for 24 well plates. Resulting cell aggregates revealed the intrinsic capacity of CAISMOV24 cells to assemble structures morphologically defined as papillary, and reflected molecular characteristics usually found in ovarian carcinomas. The contents of lymphocytes into co-cultured cell aggregates were significantly higher (p < 0.05) when NanoShuttle-conjugated PBMC were employed compared with non-conjugated PBMC. Moreover, lymphocyte subsets NK, T-CD4, T-CD8 and T-regulatory were successfully retrieved from co-cultured cell aggregates at 72h. Thus, the culture system allowed CAISMOV24 cell line to develop papillary-like cell aggregates containing lymphocytes.

HPV in situ hybridization signal patterns as a marker for cervical intraepithelial neoplasia progression.

OBJECTIVE: HPV-DNA integration is one factor for malignant transformation and can be identified using in situ hybridization (ISH), where a diffuse signal represents episomal HPV and punctate, integrated. The aim is to verify if a punctate pattern could be a marker of CIN1 that progresses. METHODS: 74 CIN1 biopsies were studied. In the follow up, a second biopsy was performed and 65% showed CIN1 or no lesion (group without progression) and 35% CIN2/3 (with progression). ISH was carried out with HR-HPV GenPoint in the first biopsy looking for the positive distribution in epithelium regions (basal, intermediate, superficial) and reaction pattern (diffuse and punctate). The Mann-Whitney and Fisher tests were used to compare the groups (p

Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis.

BACKGROUND: Disorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation. CASE: We present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor. SUMMARY AND CONCLUSION: To our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.

Clinical Features and Management of Women with Borderline Ovarian Tumors in a Single Center in Brazil.

OBJECTIVE: The aim of the present study was to describe and analyze data of 57 women with borderline ovarian tumors (BOTs) regarding histological characteristics, clinical features and treatment management at the Department of Obstetrics and Gynecology of the Universidade Estadual de Campinas (Unicamp, in the Portuguese acronym). METHODS: The present retrospective study analyzed data obtained from clinical and histopathological reports of women with BOTs treated in a single cancer center between 2010 and 2018. RESULTS: A total of 57 women were included, with a mean age of 48.42 years old (15.43-80.77), of which 30 (52.63%) were postmenopausal, and 18 (31.58%) were < 40 years old. All of the women underwent surgery. A total of 37 women (64.91%) were submitted to complete surgical staging for BOT, and none (0/57) were submitted to pelvic or paraortic lymphadenectomy. Chemotherapy was administered for two patients who recurred. The final histological diagnoses were: serous in 20 (35.09%) cases, mucinous in 26 (45.61%), seromucinous in 10 (17.54%), and endometrioid in 1 (1.75%) case. Intraoperative analyses of frozen sections were obtained in 42 (73.68%) women, of which 28 (66.67%) matched with the final diagnosis. The mean follow-up was of 42.79 months (range: 2.03-104.87 months). Regarding the current status of the women, 45 (78.95%) are alive without disease, 2 (3.51%) are alive with disease, 9 (15.79%) had their last follow-up visit > 1 year before the performance of the present study but are alive, and 1 patient (1.75%) died of another cause. CONCLUSION: Women in the present study were treated according to the current guidelines and only two patients recurred.

OBJETIVO: O objetivo do presente estudo foi descrever uma série de 57 mulheres com tumores borderline de ovário (TBO) em relação às características histológicas, clínicas, e ao manejo do tratamento realizado no Departamento de Obstetrícia e Ginecologia da Universidade Estadual de Campinas (Unicamp). MéTODOS: O presente estudo retrospectivo analisou dados obtidos dos registros clínicos e histopatológicos de mulheres com TBO tratadas em um único centro oncológico de 2010 a 2018. RESULTADOS: Um total de 57 mulheres foram incluídas, com uma média de idade de 48,42 anos (15,43­80,77), das quais 30 (52,63%) eram menopausadas, e 18 (31,58%) tinham < 40 anos. Todas as mulheres foram operadas. Um total de 37 mulheres (64,91%) foram submetidas a cirurgia de estadiamento completo para TBO, e nenhuma foi submetida a linfadenectomia pélvica ou paraórtica. O tratamento com quimioterapia foi administrado em duas pacientes que recidivaram. Os diagnósticos histológicos finais foram: seroso em 20 mulheres (35,09%), mucinoso em 26 (45,61%), seromucinoso em 10 (17,54%) e endometrióide em 1 (1,75%). A avaliação histológica intraoperatória foi realizada em 42 (73,68%) das mulheres, das quais 28 (66,67%) foram compatíveis com os diagnósticos finais. O tempo médio de seguimento foi de 42,79 meses (variando de 2,03 a 104,87 meses). Em relação ao status atual das mulheres, 45 (78.95%) estão vivas sem doença, 2 (3,51%) estão vivas com doença, 9 (15.79%) tiveram a última consulta de seguimento há > 1 ano antes da realização do presente estudo, mas estão vivas, e 1 paciente faleceu por outra causa. CONCLUSãO: As mulheres do presente estudo foram tratadas de acordo com as recomendações atuais e apenas duas mulheres apresentaram recorrência.