Prospective evaluation of uterine artery Doppler for prognosis in endometrial cancer: A tertiary single-center experience.

AIMS: Our research aims to shed light on the connection between histopathological differences that affect the prognosis of endometrial cancer and Doppler indices measured in the uterine arteries. METHODS: Seventy-four women with a confirmed diagnosis of endometrial cancer participated in this prospective study. The flow characteristics of the bilateral uterine arteries were evaluated and recorded using color Doppler sonography. After hysterectomy, a correlation analysis was performed between these factors and histological findings. RESULTS: Patients who complained of menometrorrhagia had significantly higher uterine artery peak systolic flow (p = 0.020) than those who had postmenopausal vaginal bleeding. Endometrioid adenocarcinoma was the most common type (71.4%). Doppler pulsatility index and resistance index in the uterine arteries didn't show statistically significant differences between histologic subtypes, tumor grade, myometrial invasion, lymphovascular invasion, lymph node involvement, malignant peritoneal cytology, genetic mutation, or extrauterine involvement. Those without cervical involvement had higher uterine artery Doppler peak systolic flow/end diastolic flow (p = 0.024). CONCLUSIONS: Endometrial cancer made uterine artery, myometrium and endometrium less resistant to blood flow. However, these blood flow indices have not been standardized enough to be utilized as diagnostic tests just yet. Standardization based on more advanced studies would make it possible to use ultrasonography for non-invasive diagnosis and would accelerate and facilitate clinical management.

Blood and tissue levels of persistent organic pollutants and genetic susceptibility in patients with breast cancer.

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR. However, the GSTT1 null polymorphism represented a significant risk for breast cancer when OR adjusted for age and smoking status. CYP1A1 polymorphism was a significant risk factor for breast cancer, regardless of whether the OR was adjusted. These results suggest that exposure to certain POPs, GSTT1 and CYP1A1 polymorphisms, age, and smoking status are risk factors for breast cancer. In addition, the blood concentrations of some POPs represent surrogates for breast tissue concentrations.

PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

OBJECTIVE: Our primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. STUDY DESIGN: Records of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: The median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72-124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). CONCLUSION: This retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

Prognosis-related novel immunostaining pattern for programmed cell death ligand 1 and prognostic value of tumour-infiltrating lymphocytes in triple-negative breast cancer.

This study aims to determine the prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) in triple- negative breast cancer (TNBC). PD-L1 expression and TIL percentage were determined in TNBCs that did not receive neoadjuvant therapy. The relationship between PD-L1 expression and the percentage of TILs with survival was investigated. The presence of intratumoural PD-L1-positive tumour-infiltrating immune cells (TIICs) in tumours with ≥ 1% PD-L1 expression was identified as a new PD-L1 evaluation parameter. The presence of intratumoural PD-L1-positive TIICs as a new parameter in PD-L1-positive cases increased overall survival. The percentage of TILs increased in both overall and distant metastasis-free survival (p = 0.040 and p = 0.006, respectively). As a result, it was found that the risk of death was increased 5.18-fold (p = 0.013) in patients without intratumoural PD-L1-positive TIICs. This risk of death was calculated to be 5.40-fold higher in patients with TIL percentage ≤ 10% than in those with > 40% (p = 0.024), and the risk of distant metastasis was calculated to be 11.95 times higher. In our study, we discovered that the percentage of TILs made a statistically significant difference in TNBC survival. The presence of intratumoural PD-L1-positive TIICs in PD-L1-positive cases significantly increased survival.

The usefulness of p16 and COX-2 expression on the prediction of progression to endometrial cancer.

OBJECTIVES: Endometrial cancer (EC) is the most commonly diagnosed gynecological cancer. Endometrial hyperplasia (EH) is a more common diagnosis than EC. Endometrial hyperplasia is found in approximately 1.5% of all women presenting with abnormal bleeding. Endometrial hyperplasia progresses to EC, and especially, cancer risk increases in cases with atypical hyperplasia. p16, one of the tumor suppressor proteins involved in the cell cycle, and COX-2, one of the key enzymes of prostaglandin synthesis, are important markers for the diagnosis of both EH and EC. There is lack of consensus in the classification, diagnosis and treatment of EH. The subject of changes in the cell cycle in the progression of endometrial pathologies may help to identify and prevent these affected pathways in the treatment stage. The aim of this study is to investigate the expression of p16 and COX-2 during the development of EC from EH. MATERIAL AND METHODS: We investigated COX-2 and P16 expressions in patients with proliferative endometrium, complex/simple endometrial hyperplasia and endometrioid adenocarcinoma. RESULTS: p16 expression increased in EH and EC (p<0.001). COX-2 expression was increased in endometrial cancer compared to other groups, but this increase was not found to be statistically significant. Although p16 and COX-2 expression were increased in patients with advanced grade/stage, lymphovascular invasion, and >50% of myometrial invasion, this increase was not statistically significant. CONCLUSIONS: More detailed studies are needed to investigate the prognostic significance of the COX-2 molecule. COX-2 might be a potential biomarker for the prognosis of endometrial cancer and a potential therapeutic target for EC treatment. Also, it might be used to prevent the progression of precursor lesions to invasive EC.

High-Grade Ductal Carcinoma In Situ of the Breast With Regressive Changes: Radiological and Clinicopathological Findings.

Objective: Tumour regression is defined as continuity of changes leading to the elimination of a neoplastic population and is reflected as periductal fibrosis and intraductal tumour attenuation. The aim of this study was to describe the radiological and clinicopathological characteristics of high-grade breast ductal carcinoma in situ (DCIS) with regressive changes (RC). Materials and Methods: Thirty-two cases of high-grade DCIS with RC on biopsy specimens followed by excision were included. The mammographic, ultrasonographic (US), and magnetic resonance imaging (MRI) findings of cases were retrospectively reviewed according to the breast imaging reporting and data system (BI-RADS) lexicon. Clinical and histopathological findings [comedonecrosis, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Ki-67 proliferation index] were recorded. The rate of upgrade to invasive cancer after surgical excision and lymph node involvement were evaluated. Results: The most common mammographic finding was microcalcifications alone (68.8%). The most frequently seen findings on US were microcalcifications only (21.9%), followed by microcalcifications and hypoechoic area (18.7%). On MRI, most lesions presented as clumped non-mass enhancement with segmental distribution. ER/PR negativity (53.1%, 65.6%), HER2 positivity (56.3%) and high Ki-67 (62.5%), which are known to be associated with more aggressive behavior, were found to be proportionally higher. The rate of upgrade to invasive cancer was 21.8%. Conclusion: DCIS with RC lesions present most often as microcalcifications alone on both mammography and US. MRI features are not distinguishable from those of other DCIS lesions. DCIS with RC lesions show biomarker status reflecting more aggressive behavior and high upgrade rate to invasive cancer.

Prediction of malignancy upgrade rate in high-risk breast lesions using an artificial intelligence model: a retrospective study

PURPOSE: High-risk breast lesions (HRLs) are associated with future risk of breast cancer. Considering the pathological subtypes, malignancy upgrade rate differs according to each subtype and depends on various factors such as clinical and radiological features and biopsy method. Using artificial intelligence and machine learning models in breast imaging, evaluations can be made in terms of risk estimation in different research areas. This study aimed to develop a machine learning model to distinguish HRL cases requiring surgical excision from lesions with a low risk of accompanying malignancy. METHODS: A total of 94 patients who were diagnosed with HRL by image-guided biopsy between January 2008 and March 2020 were included in the study. A structured database was created with clinical and radiological characteristics and histopathological results. A machine learning prediction model was created to make binary classifications of lesions as malignant or benign. Random forest, decision tree, K-nearest neighbors, logistic regression, support vector machine (SVM), and multilayer perceptron machine learning algorithms were used. Among these algorithms, SVM was the most successful. The estimations of malignancy for each case detected by artificial intelligence were combined and statistical analyses were performed. RESULTS: Considering all cases, the malignancy upgrade rate was 24.5%. A significant association was observed between malignancy upgrade rate and lesion size (P = 0.004), presence of mammography findings (P = 0.022), and breast imaging-reporting and data system category (P = 0.001). A statistically significant association was also found between the artificial intelligence prediction model and malignancy upgrade rate (P < 0.001). With the SVM model, an 84% accuracy and 0.786 area-underthe- curve score were obtained in classifying the data as benign or malignant. CONCLUSION: Our artificial intelligence model (SVM) can predict HRLs that can be followed up with a lower risk of accompanying malignancy. Unnecessary surgeries can be reduced, or second line vacuum excisions can be performed in HRLs, which are mostly benign, by evaluating on a case-by-case basis, in line with radiology-pathology compatibility and by using an artificial intelligence model.

Radiological and clinicopathological findings of breast cancer during the COVID-19 pandemic: a comparative study with the pre-pandemic era.

PURPOSE: The diagnosis and surgical treatment delays that occurred during the coronavirus disease-2019- (COVID-19) pandemic may have affected breast cancer presentation. This study aimed to determine whether there was a difference in the clinicopathological characteristics of breast cancers during the pandemic by comparing them with similar cases from the previous year. The study also aimed to determine the radiological findings of breast cancers during the pandemic. METHODS: A retrospective review was made of patients who underwent surgery for breast cancer between March 11, 2020, and December 11, 2020 (the pandemic group). These patients were compared with similar patients from the previous year (the pre-pandemic group). The postoperative histopathology results of both groups were compared, and the preoperative radiological findings of the pandemic group were defined. RESULTS: There were 71 patients in the pandemic group and 219 patients in the pre-pandemic group. The tumor size was significantly greater, lymph node involvement was more frequent, and waiting time for surgery was longer in the pandemic group (P < 0.001, P = 0.044, P = 0.001, respectively). There was no significant difference between the groups in respect of in situ/invasive tumor distribution, histological type and histological grade of tumor, the presence of lymphovascular/perineural invasion, multifocal/multicentric focus, and Breast Imaging Reporting and Data System Classification (P > 0.15). The radiologic findings of breast cancer during the pandemic typically showed characteristics of malignancy. CONCLUSION: Patients diagnosed with breast cancer during the COVID-19 pandemic had larger tumor sizes, more frequent lymph node involvement and longer waiting time for surgical treatment. Screening programs should be continued as soon as possible by taking necessary precautions.

Tuberculous mastitis: A masquerading face of granulomatous mastitis.

Introduction: Tuberculosis (TB) mastitis is a rare form of granulomatous mastitis. We aimed to evaluate the clinical characteristics and prognosis of patients diagnosed with TB mastitis. Materials and Methods: A descriptive study was carried out on patients who were reported to national tuberculosis control authorities as having TB mastitis between 2003 and 2021. Demographic, histopathological, and radiological data including mammography, ultrasonography (US), and magnetic resonance imaging (MRI) were reviewed. All were followed up to 24 months and prognosis was also evaluated. Result: This study identified 29 TB mastitis patients who had been diagnosed using excisional biopsies. The mean age was 33.5 ± 10.1, all were premenopausal women. The most common symptom was breast mass (n= 24, %82.8), nearly half of the patients also had ipsilateral axillary lymphadenopathy (n= 14, 48.3). One-fourth of the patients had bilateral involvement (n= 7, 24.1%), and half of the patients (n= 16, 55.2%) presented with multiple masses. One patient had co-existing pulmonary TB. Predisposing factors for TB were not identified in any of the patients. Nearly half of the patients received prior mastitis treatment. The most common radiological finding was mass in both mammography and US. All patients received anti-tuberculosis treatment of a standard regimen for six to 21 months, three patients had a relapse but were finally cured. Conclusions: TB mastitis should be suspected in young and premenopausal women presenting with a breast mass and axillary lymphadenopathy in an endemic region. Radiological findings could not identify the diagnosis. A multidisciplinary approach including bacteriology and histopathology should be performed. Anti-tuberculosis treatment can be implemented successfully.

Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205.

Breast cancer was ranked first in global cancer incidence in 2020, and HER2 overexpression in breast cancer accounts for 20-30% of breast cancer patients. Current therapeutic strategies increase the survival rate, but resistance to them occurs frequently, and there is an urgent need to develop novel treatments such as DNA vaccines which can induce a specific and long-lasting immune response against HER2 antigens. To enhance the immunogenicity of DNA vaccines, dendritic cells (DCs) can be targeted using multi-epitope proteins that provide accurate immune focusing. For this purpose, we generated a DNA vaccine encoding a fusion protein composed of 1) in silico discovered antigenic epitopes of human and rat HER2 proteins (MeHer2) and 2) a single-chain antibody fragment (ScFv) specific for the DC-restricted antigen-uptake receptor DEC205 (ScFvDEC). The xenogeneic multi-epitope DNA vaccine (pMeHer2) encodes three only T-cell epitopes, two only B-cell epitopes, and two T and B cell epitopes, and pScFvDEC-MeHer2 vaccine additionally encodes ScFvDEC introduced at the N terminus of the MeHer2. Then, mouse groups were immunized with pScFvDEC-MeHer2, pMeHer2, pScFvDEC, pEmpty, and PBS to determine the elicited immune response. pScFvDEC-MeHer2 vaccinated mice showed a strong IgG response (P < 0.0001) and pScFvDEC-MeHer2 induced a significant IgG2a increase (P < 0.01). The percentages of both IFN-γ secreting CD4 and CD8 T cells were higher in mice immunized with pScFvDEC-MeHer2 compared with the pMeHer2. pScFvDEC-MeHer2 and pMeHer2 secreted significantly higher levels of extracellular IFN-γ compared with to control groups (P < 0.0001). In addition, the IFN-γ level of the pScFvDEC-MeHer2 vaccine group was approximately two times higher than the pMeHer2 group (P < 0.0001). Overall, this study identified the pScFvDECMeHer2 construct as a potential DNA vaccine candidate, supporting further studies to be conducted on HER2+ animal models.

Controlled ovarian stimulation outcomes of fertility preservation procedures in newly diagnosed breast cancer patients: a retrospective study from a single-tertiary-IVF centre.

The aim of this study was to evaluate the effectiveness of controlled ovarian stimulation (COS) using the letrozole-supplemented stimulation protocol in breast cancer (BC) patients prior to their cancer treatment. Sixty-one BC patients (Stages 0-3) who were referred to a university IVF unit for fertility preservation (FP) and underwent embryo and/or oocyte cryopreservation between 2008 - 2020 were included in this retrospective study. Time intervals between breast surgery and initial fertility consultation (IFC)/completion of FP procedures were evaluated. COS outcomes were assessed and compared between the early follicular phase (EFP) and the random-start (RS) protocols. The patients' mean age was 33.3 ± 4.9 years. The mean time interval between breast surgery and IFC was 20.6 ± 11 (day, mean ± SD) and from IFC to completion of FP procedure was 14.7 ± 5.3. Overall, 9.1 ± 5.9 mature oocytes were obtained, with a peak serum oestradiol level of 388 ± 358 pg/mL. The number of oocytes obtained (11.5 ± 9.3 vs. 10.9 ± 6.9, p = .9) and maturation rates (84.3 ± 17.5% vs. 89.2 ± 11.7, p = .5) were not statistically different between the EPF and RS protocols. The study results support that oocyte or embryo freezing can be performed effectively in a limited time period with letrozole-supplemented COS protocols before the initiation of oncological treatments in breast cancer patients.Impact statementWhat is already known on this subject? Currently, embryo and oocyte freezing are considered the most established fertility preservation (FP) methods for newly diagnosed cancer patients.What do the results of this study add? This study reports the COS outcomes of newly diagnosed breast cancer patients for FP over a period of twelve years from a single IVF unit. The results support that a considerable number of oocytes can be harvested with letrozole-supplemented COS protocol, which appears to be an effective protocol for BC patients.What are the implications of these findings for clinical practice and/or further research? There is a need for additional studies evaluating long-term follow-up of patients with their pregnancy outcomes.

Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer.

BACKGROUND: Breast cancer is the most common malignancy in women and thought to be hereditary in 10% of patients. Recent next-generation sequencing studies have increased the detection of pathogenic or likely pathogenic (P/LP) variants in genes other than BRCA1/2 in patients with breast cancer. This study evaluated pathogenic variants, likely pathogenic variants, and variants of unknown significance in 18 hereditary cancer susceptibility genes in patients with BRCA1/2-negative breast cancer. PATIENTS AND METHODS: This retrospective study included 188 high-risk BRCA1/2-negative patients with breast cancer tested with a multigene cancer panel using next-generation sequencing. RESULTS: Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as P/LP in PALB2 (n = 6), CHEK2 (n = 5), MUTYH (n = 4), ATM (n = 3), TP53 (n = 2), BRIP1 (n = 1), and MSH2 (n = 1). Three novel P/LP variants were identified. An additional 28 variants were classified as variants of unknown significance and detected in 30 different patients (15.9%). CONCLUSION: This is one of the largest study from Turkey to investigate the mutation spectrum in non-BRCA hereditary breast cancer susceptibility genes. A multigene panel test increased the likelihood of identifying a molecular diagnosis in patients with BRCA 1/2-negative breast cancer at risk for a hereditary breast cancer syndrome. More studies are needed to enable the clinical interpretation of these P/LP variants in hereditary patients with breast cancer.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

The Impact of Carbon Dioxide Pneumoperitoneum on Ovarian Ischemia-Reperfusion Injury during Laparoscopic Surgery: A Preliminary Study.

STUDY OBJECTIVE: To investigate whether carbon dioxide pneumoperitoneum causes ischemia-reperfusion injury to the ovaries during laparoscopic surgery. DESIGN: A prospective controlled clinical study (Canadian Task Force classification II-1). SETTING: A tertiary academic center. PATIENTS: Premenopausal women who underwent hysterectomy with bilateral salpingo-oophorectomy (HSO) via open abdominal and laparoscopic approaches between 2014 and 2015. INTERVENTIONS: In both surgical approaches, unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue. Additionally, plasma samples were collected at the following time points: (1) before abdominal entry, (2) at the end of hysterectomy, and (3) before contralateral oophorectomy. Plasma samples were assessed for biochemical oxidative stress markers malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Ovarian tissue samples were assessed for MDA and further evaluated for ischemia-reperfusion injury using a histologic scoring method. MEASUREMENTS AND MAIN RESULTS: Twenty premenopausal women undergoing HSO via open abdominal surgery (n = 10) and laparoscopy (n = 10) were included. Baseline characteristics (age, body mass index, parity, and gravida) and operative data (operative time, estimated blood loss, and intraoperative complication) were similar between groups. Perioperative plasma MDA levels, histologic scores, and tissue oxidative stress markers did not show a significant difference in either group or between groups. However, plasma 8-OHdG levels were significantly different when the second sample in the abdominal HSO group was compared with the first sample in the abdominal HSO group and the third sample in the laparoscopic HSO group (p = .012 and .001, respectively). CONCLUSION: Carbon dioxide pneumoperitoneum does not cause ischemia-reperfusion injury in the human ovaries at clinically safe levels of intra-abdominal pressure.

Comparison of HER2 status determination methods in HER2 (2+) patients: Manual fluorescent in situ hybridization (FISH) vs. dual silver enhanced in situ hybridization (SISH).

HER2 amplification has been demonstrated in 15-25% of invasive breast carcinomas and can be assessed using immunohistochemical and in situ hybridization methods. Here, we compared the accuracy of dual SISH to manual FISH in HER2 (2+) breast carcinoma and evaluated the feasibility of dual SISH method in routine practice. Sixty HER2 (2+) consecutive tumor samples diagnosed between January 2009 and February 2013 were selected. Demographic, histological and immunohistochemical features and FISH results were recruited from patient records and compared to dual SISH results. Nine (15%) of the 60 tumor samples were excluded from statistical analysis due to lack of interpretable SISH signals. HER2 staining percentages by immunohistochemistry differed between 20 and 80%. HER2 amplification was shown in 7 (13.7%) and 8 (15.7%) patients by FISH and SISH, respectively. Very good agreement was observed between FISH and SISH methods (kappa value: 0.92). Significant correlation was found between HER2 staining percentage and FISH positivity, in contrast to SISH positivity (p=0.012 vs. p=0.069). Our results are consistent with previously reported literature, indicating SISH can be used to determine HER2 status. However, preanalytical and analytical problems may cause inadequate or uncountable signals, making interpretation impossible for the pathologist and highlighting the importance of standardization and quality control programs.

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

OBJECTIVE: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. MATERIAL AND METHOD: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. RESULTS: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". CONCLUSION: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

Do tumor-infiltrating lymphocytes really indicate favorable prognosis in epithelial ovarian cancer?

OBJECTIVE: The aim of this study is to evaluate the impact of lymphocyte infiltration on prognostic parameters, recurrence and survival in ovarian cancer. STUDY DESIGN: Sixty-two patients who were primarily operated for epithelial ovarian carcinoma between 1997 and 2008 were included. CD3, CD4, CD8, CD20 and FoxP3 expressions were evaluated immunohistochemically on sections obtained from paraffin-embedded tissues. RESULTS: Median follow up was 87 months. In whole cohort, CD3+ and CD8+ T lymphocyte infiltrations were significantly higher in patients with high-grade tumors, advanced stage tumors and the patients with omental metastasis (for CD3 p=0.0001, p=0.029, p=0.016; for CD8 p=0.044, p=0.002, p=0.046, respectively). DFS was significantly lower among patients with CD8+ T lymphocytes with regard to patients who did not have CD8+ T lymphocyte infiltration (p=0.028). In univariate analysis, presence of CD8 cytotoxic T lymphocyte infiltration (p=0.03), stage (0.0001), tumor grade (p=0.007), omental metastasis (p=0.0001) and lymph node metastasis (p=0.0001) were significant risk factors for recurrence. But in multivariate analysis, only stage [HR: 116.6 (95% CI: 13.09-1039.45) (p=0.0001)] was found as an independent risk factor for recurrence. CONCLUSION: CD3+ and CD8+ T lymphocyte infiltrations were related with advanced stage, high-grade tumor and the omental metastasis in ovarian cancer. DFS was significantly shorter in patients with CD8+ T lymphocyte infiltration. CD3+ and CD8+ T lymphocyte infiltrations were related with poor prognosis in ovarian cancer.

Ovarian serous cystadenoma with ectopic adrenal tissue in a 65-year-old patient: A case report.

INTRODUCTION: Ectopic adrenal tissue is a very rare entity in adult females, especially in the ovary, and is generally diagnosed incidentally during surgery. Although it can present at various sites during childhood, it becomes atrophic by adulthood due to normally functioning adrenal glands. Patients are predominantly asymptomatic; however, in some cases endocrine symptoms such as hypertension and fasciotruncal obesity due to hormonal activity can be seen or neoplastic transformation can appear. PRESENTATION OF CASE: A 65-year-old patient with progressive pelvic pain and postmenopausal vaginal bleeding was evaluated by transvaginal ultrasound, which revealed bilateral adnexal masses measuring 5cm in size and a normal uterus with an increased endometrial thickness of 7mm. Initially the endometrial sampling result was reported as benign. The patient underwent abdominal hysterectomy and bilateral salpingo-oophorectomy and the pathological diagnosis was again benign, with serous ovarian cystadenoma being found in both ovaries. The pathologist also reported incidental ectopic adrenal tissue on the wall of the left ovarian cystadenoma. DISCUSSION: Ectopic adrenal tissue is infrequent in female genital organs especially at older ages. Only a few cases of ovarian ectopic adrenal tissue have been reported. To the best of our knowledge the present case is the fourth report in the English literature, and is of additional importance given the patient's age. CONCLUSION: Ectopic adrenal tissues are generally asymptomatic and revealed incidentally during surgery; however some cases have demonstrated the risk of neoplastic transformation. Therefore, surgeons must be aware of this rare entity that bears the risk of malignancy, and should surgically remove all suspicious lesions.

The prediction of myometrial infiltration by three-dimensional ultrasonography in patients with endometrial carcinoma: a validation study from Ege University Hospital.

AIM: To predict the myometrial invasion with three-dimensional (3D) ultrasonography in a cohort of patients with endometrial carcinoma by a previously described technique. MATERIAL AND METHODS: The moyometrial infiltration was evaluated by 3D ultrasonography before surgery in 54 patients with endometrial carcinoma. After scanning the whole uterus by ultrasonography, three perpendicular planes were identified to find the shortest myometrial tumor-free distance to serosa (TDS) by examining the lateral, anterior, posterior, and fundal parts of the myometrium. Myometrial infiltration was also estimated by the subjective impression of the examiner. The reference standards consist of myometrial infiltration and TDS which are measured by an experienced pathologist. RESULTS: Forty-five patients (age range 45-86 years) were included for the final analysis. Myometrial invasion was ˂50% in 36 and ≥50% in 9 cases at histologic sections. The TDS which is measured with 3D ultrasonography was positively correlated with histologically measured TDS (r=0.474, p=0.001). The best cut-off value for ultrasonographically measured TDS was 9 mm with a sensitivity of 89%, specificity of 61%, positive predictive value of 36%, and negative predictive value of 96%. Subjective impression has a sensitivity of 100%, specificity of 88%, positive predictive value of 69%, and negative predictive value of 100%. Cervical involvement was correctly identified in all 6 cases by subjective impression. CONCLUSION: This validation study confirms the 3D ultrasonography as a valuable tool for the evaluation of myometrial infiltration in patients with endometrial carcinoma.

Ovarian sertoli-leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients.

AIM: Information on the clinical behavior of ovarian Sertoli-Leydig cell tumors (SLCTs) as well as its prognostic factors and optimal management is limited due to a substantially low incidence of the disease. Also, limited data is available regarding the role of chemotherapy in the management of SLCTs. The aim of the study is to evaluate clinicopathological features and outcome of patients with ovarian SLCTs. MATERIALS AND METHODS: Twenty-seven patients with SLCT treated at two centers were reviewed retrospectively during 21 years. RESULTS: The median age was 45 years (range, 16-81) and the mean follow-up time was 86 months (range, 16-181). Twenty-three patients had stage IA, three patients had IC, and one patient had stage II disease. Eleven tumors (41%) were well-differentiated and 16 (59%) tumors were intermediately differentiated. Nine patients underwent unilateral salpino-oophorectomy and one patient, with a history of infertility, underwent cystectomy for fertility preservation. Eight patients with intermediately differentiated types of SLCT received adjuvant systemic chemotherapy including the combination bleomycin, etoposide, and cisplatin (BEP). Recurrence occurred in one patient with intermediated differentiated type SLCT with heterologous elements. She received four cycles of BEP chemotherapy. Twelve months later, she underwent cytoreductive surgery and received six cycles of cisplatin plus carboplatin. She died 24 months after the initial diagnosis. CONCLUSION: SLCTs of the ovary are usually in early stage, unilateral, and benign. Fertility-sparing surgery is the preferred option in young women. In the adjuvant treatment setting, although information about chemotherapy is limited, BEP is a commonly used regimen. The degree of differentiation and the presence of heterologous elements relate to a poor prognosis.