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To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes.The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT).Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates.PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

Introduction: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes. Methods: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B. In addition, sFRP-1, -2, -3, -4, -5 mRNA levels were determined by quantitative reverse transcription-PCR in primary keratinocytes and FaDu cells expressing HPV16-E6, -E7, or -E6E7. Results: Our data indicated that the Wnt/beta-catenin signaling is activated in HPV (+) cervicovaginal cells that can already be detected in cells with no obvious changes in cellular morphology (HPV [+]/cyto [−]). These cells also had significantly higher sFRP4 levels when compared to HPV-negative samples. In primary keratinocytes, sFRP4 was found to be absent and sFRP1 and sFRP2 to be repressed in the presence of HPV16-E6 and E7. Interestingly, sFRP4 is expressed in FaDu cells and can be upregulated in the presence of E6E7. Curiously, SFRP4 expression correlated with an increase in the level of autophagic markers in HPV (+)/cyto (−) smears. Conclusion: In conclusion, the activation of the Wnt/beta-catenin signaling pathway and upregulation of sFRP4, paralleled by an activation of the autophagic pathway may represent predisposing cellular factors early after HPV infection which need to be further determined in larger study.

OBJECTIVE To explore the relationship of lymph node ratio (LNR) and other lymph node parameters with disease-free (DFS) and overall (OS) survival among women with endometrial cancer. METHODS Retrospective analysis of data of women diagnosed with endometrial cancer at Hacettepe University Hospitals, Ankara, Turkey, between 2003 and 2013. Women who had their surgical procedure, pathology review, and follow-up at Hacettepe University Hospitals were included in the study. Receiver operator characteristic (ROC) curve analysis was used to determine the threshold LNR associated with survival. RESULTS Overall, 376 women were included in the study. A higher number of excised metastatic lymph nodes was associated with decreased survival. ROC curve analysis determined a threshold LNR of 0.03. Women with LNR higher than 0.03 had decreased DFS (P

To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT).Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated.Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively).sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.

Ovarian mucinous tumors are one of the common epithelial tumors in the ovary, but their recurrence is extremely rare. In a 37-year-old female patient who had had five operations in 7 years due to recurrent mucinous neoplasms, a mass extending to the umbilicus was recently detected during a routine examination. With this finding the patient underwent cystectomy, total abdominal hysterectomy, and left salpingo-oophorectomy. Two of the five operations were performed during cesarean delivery. In the recent surgical procedure, two cysts were removed. A 20 cm cyst in the pelvic region was diagnosed as a mucinous cystadenoma. The other cyst located in the myometrium was a mucinous cystadenoma with focal borderline change and arose in the previous cesarean scar. The authors present what is believed to be the first case of recurrent mucinous neoplasm arising within a cesarean scar. A review of the literature concerning the topic is also presented.

Objective: The aim of this research was to determine the association between uterine weight and surgical outcomes of vaginal hysterectomies (VHs). Materials and Methods: This retrospective...

Introduction. High-grade endometrial stromal sarcomas (HGESS) are rare malignant mesenchymal tumors of the uterus with aggressive poor clinical outcome, which frequently exhibit YWHAE::NUTM2 and ZC3H7B::BCOR fusions. In this study, we aimed to investigate HGESSs with YWHAE and BCOR translocations through our archive materials, and to identify morphological, immunohistochemical and molecular features of these tumors. We also assessed the diagnostic value of BCOR immunohistochemistry (IHC) in HGESSs, low-grade endometrial stromal sarcomas (LGESS) and uterine leiomyosarcomas. Methods. One hundred fifty-one uterine sarcomas diagnosed between 2000-2019 were reevaluated, and tumors of 39 patients with specific features were included in the study. Fluorescence in situ hybridization (FISH) studies using YWHAE and BCOR break-apart probes and BCOR IHC were performed. BCOR IHC was also performed in 20 leiomyosarcomas and 19 LGESSs. Results. In six HGESSs, translocations involving YWHAE or BCOR were detected. Five tumors showed high-grade morphology and revealed YWHAE translocation. One HGESS with myxoid morphology revealed BCOR translocation. In immunohistochemistry, three (3/4) YWHAE translocated HGESSs showed BCOR expression. However, the BCOR translocated HGESS was BCOR negative. The study showed that all LGESSs were immunohistochemically negative with BCOR. Although 15% (3/20) leiomyosarcomas reveal focal weak-moderate BCOR expression. Conclusion. BCOR IHC is a useful marker to distinguish LGESS from HGESS. A small percentage of uterine leiomyosarcomas reveal BCOR expression; however, it is not as diffuse and strong as in HGESSs. Strong and diffuse BCOR IHC expression is highly suggestive for HGESS. The diagnosis of HGESS should be supported by molecular studies such as FISH.

Aim The aim of the study was to evaluate the results of the laparotomies due to gynecological pathologies in breast cancer patients and to assess the distribution of gynecological pathologies and the clinical and laboratory findings contributing to the diagnosis. Methods This study was conducted between years 2002 and 2011 at Hacettepe University Hospital. We obtained information about 86 consecutive breast cancer patients, including age, time of diagnosis and pathology of breast cancer, hormone receptor status, history of endocrine therapy, presenting symptoms, ultrasonography findings, CA 125 levels, endometrial biopsy results, type of gynecological surgery and pathology results. Data were analyzed with the use of SPSS software. Results Twenty-one (24.4%) out of 86 patients had endometrial pathology, and 24 (27.9%) had adnexal pathology. Fourteen patients (16.2%) had malignant pathology, and of them, 11 had ovarian cancer 3 had endometrial cancer. There were five abnormal cytological findings: 2 ASCUS, 1 LSIL, 1 ASC-H and 1 adenocarcinoma. The patient with the cytology report of adenocarcinoma had the final diagnosis of endometrial cancer. Of the patients, 67 (77.9%) used tamoxifen, whereas 19 (22.1%) did not. Thirty-three patients (38.4%) with gynecological pathologies were detected incidentally during routine follow-up of breast cancer. Conclusion This study supports the increase of the gynecological pathology incidence in breast cancer patients and the recommendation of close gynecological follow-up in these patients. Asymptomatic patients might also develop genital cancer. The ultrasonographic appearance of the adnexal masses or endometrial thickness and any abnormal vaginal bleeding or high CA 125 levels are important parameters for evaluating breast cancer patients.

Introduction Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast actions. We hypothesized that the localization and expression patterns of LIF and IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first trimester placentas may provide an understanding of the proliferative processes in HMs. Methods The study population included curettage material of women diagnosed as complete or partial HM as a result of histopathological and immunohistochemical examination (complete HM group, n = 8; partial HM group, n = 8) and women undergoing dilatation&curettage for unwanted pregnancies (control group, n = 8). Expression of LIF and IGF-1 among placental cell groups was evaluated immunohistochemically and given a score depending on immunostaining intensity. Results In normal chorionic villi strong expression of LIF and IGF-1 was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of complete HMs. In complete mole decidua there was a significant decrease in glandular and endothelial IGF-1 expression along with a decrease in decidual cell LIF expression compared to normal first trimester decidua. LIF expression in extravillous trophoblasts was stronger in complete molar placentas compared to normal placentas. Discussion LIF and IGF-1 are important regulators of trophoblast proliferation and invasion. Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs.

Objective The objective of this study was to investigate the clinicopathological features and factors associated with recurrence in patients with uterine smooth muscle tumor of uncertain malignant potential (STUMP). Methods Forty-six cases diagnosed between 2000 and 2014 from 2 tertiary centers underwent blind slide review. Initial diagnosis included smooth muscle tumors with equivocal diagnosis, STUMPs, and cases that were named as leiomyosarcomas (LMS) or low-grade LMS despite not fulfilling the Stanford criteria. Results In total, 21 patients with a final diagnosis of STUMP were available. Fifteen (68.1%) of 22 patients with an initial diagnosis of STUMP, 4 (22.2%) of 18 cases with an equivocal smooth muscle tumor diagnosis, and 2 (33.3%) of 6 cases with an initial diagnosis of LMS were interpreted as STUMP after slide review. The mean age at diagnosis was 43 years (range, 20–64 years). The mean follow-up time was 65.9 months (range, 10–154 months). Four patients (19.0%) developed recurrent disease. Recurrent tumors were LMS in 3 patients (75%). One patient (4.8%) with recurrence succumbed to disease. There was no difference in patients9 age (P = 1.0) or type of initial surgery (uterus conserving versus hysterectomy) (P = 0.57) between patients who recurred and did not recur. Conclusions Uterine STUMPs can harbor significant uncertainty regarding the original diagnosis and clinical outcomes. Recurred cases may have an aggressive clinical course associated with multiple relapses and death. Uterine mesenchymal tumors other than ordinary myomas and overt sarcomas deserve a second opinion in centers with experience because the real diagnosis may vary significantly.

Prolactin was first identified as a lactation hormone, but subsequent studies revealed its complex effects in the maintenance of homeostasis (Riddle and Dykshorn 1933). Pituitary lactotroph cells a...

Başlıca bulguları over kaynaklı kitle, asit ve CA 125 yüksekliği olduğu için over kanseri ön tanısı ile cerrahiye alınan 78 yaşındaki olgunun kesin tanısı ancak patoloji raporunun malign mezotelyoma olarak raporlanması üzerine konulabilmiştir. Öyküsünden yıllar önce yaşadığı yer nedeniyle asbeste maruz kaldığı düşünülen hastada kesin tanı ameliyat öncesi konulamamıştır. Over kanseri ile klinik tablo açısından benzerlikler gösterse de tedavileri ve sonuçları açısından aralarında farklılık bulunan bu malign peritoneal mezotelyoma olgusu ayırıcı tanıya yardımcı olması açısından sunulmuştur., A patient who had ovarian mass, ascites and elevated CA 125 levels was treated with presumptive diagnosis of ovarian cancer. After pathological examination, she was finally diagnosed as malign peritoneal mesothelioma. Although exposure to asbestos was considered, the diagnosis was not revealed before surgery. Despite similarity of clinical features, ovarian cancer and malign peritoneal mesothelioma have different treatment options and long-term outcomes. The aim of this case report is to describe the process of differential diagnosis between malign peritoneal mesothelioma and ovarian cancer.

Sclerosing stromal tumors of the ovary are very rare. We report the case of a 29-year-old pregnant woman who presented with a history of preterm labor and gestational hypertension. A huge mass measuring 30 cm in greatest dimension was recognized on the right ovary during cesarean section. Signet ring cell infiltration was seen during intraoperative frozen section consultation. She underwent a right salpingo-oophorectomy, and the permanent diagnosis was sclerosing stromal tumor infiltrated by signet ring cells. Pregnancy-related changes were seen in tumor morphology. Signet ring cells were immunoreactive with antibodies MUC5ac, MUC2, and EMA. Thus, stromal cells were immunoreactive with antibodies inhibin and calretinin. Endoscopic biopsy of the stomach showed a signet ring cell carcinoma, from which the metastasis had originated. This is the first reported case in the literature, and is notable for its challenging differential diagnosis, which included a pregnancy luteoma and primary signet ring stromal tumor of the ovary.

Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p = 0,001 and p = 0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p = 0,001, p = 0,001, p = 0,001 and p = 0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p = 0,001 and p = 0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRI, 7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.

To compare the performance of collagenated bone graft substances with different collagen ratios after sinus floor augmentation.The cross-sectional study was conducted at Hacettepe University, Ankara, Turkey, from September 2011 to September 2013. Sinus floor augmentation was done with two different equinederived xenografts in patients before dental implant application. Of the two randomised groups, one was treated with 100% collagenated bone mix (Group A), and the other half with 90% collagenated bone mix + 10% collagen gel (Group B).Six months after sinus augmentation, prior to dental implant surgery, a specimen was taken from the implant socket with trephine drill for histopathological evaluation of new bone, connective tissue and residual graft material at each augmented site. SPSS 19 was used for data analysis.Of the 19 patients, 12(63%) were females and 7(37%) were males. The overall mean age was 51.68±11,96 years (range: 24-69 years). A total of 30 sinus floor augmentations were done. New bone formation was significantly better in Group A(15 sinus floor augmentation) than in Group B (the other 15 sinus floor augmentation) (p0.05), but there was no significant difference in connective tissue formation and residual graft materials between the groups (p0.05).Collagenated bone mix was found to be a suitable graft material for sinus floor augmentation, but increased collagen ratio did not improve new bone formation over the 6-month healing process.

Ovarian cancer has a high mortality rate. Serous carcinoma is the most common subtype and can be detected by distant or lymph node metastasis in advanced stages. Apelin, an adipokine associated with obesity, and its receptor, APJ, participate in lymphatic invasion. Angiogenesis also can affect lymph node involvement in serous ovarian carcinomas. We investigated apelin/APJ receptor immunoreactivity in stages III and IV ovarian cancer with or without lymph node involvement and correlated the results with body mass index (BMI) to determine whether the potential relation of the two affects the outcome of the cancer. We investigated 30 patients diagnosed between 2014 and 2016 with high grade serous ovarian cancer. Tumor:stroma ratio, indirect immunoperoxidase method, H-score and MATLAB analysis were performed. In obese and pre-obese patients, tumor apelin immunoreactivity was stronger than for patients with normal BMI. Tumor:stroma ratio was correlated with survival and lymph node involvement. Strong apelin and moderate APJ immunoreactivity was detected in both lymph node negative and positive patients. BMI was related to both survival outcome and apelin immunoreactivity. BMI, adipokines such as apelin, and the stromal compartment play critical roles in advanced stage serous carcinomas. © 2019, © 2019 The Biological Stain Commission.

Aim To investigate the expression of Wilms' tumor 1 (WT1) protein in endometrial adenocarcinoma (EC) and endometrial intra-epithelial neoplasia (EIN). Methods WT1 protein expression was determined on immunohistochemistry in 30 EC patients and in 20 EIN patients. WT1 protein expression in proliferative (n = 7), secretory (n = 9) and atrophic endometrium (n = 9) and benign endometrial polyps (n = 28) was used as the control group. Cellular and vascular WT1 staining was scored semiquantitatively. Results Cellular WT1 staining was 67% and vascular positivity was 73% in the EC group. In the EIN group the cellular staining was 100% and vascular staining was 85%. Although all EIN samples were positive for cellular WT1 staining, median cellular staining score was similar to that of EC (median, 2; range, 1–3; IQR, 1.75 vs 2, 0–3, 0.75, respectively). Increasing EC grade and stage were not associated with cellular or vascular WT1 staining score. Conclusion WT1 is expressed in EIN.

Metastatic involvement of the ovaries is not rare. The most common tumor types metastasizing to the ovaries, from non-gynecological organs, are breast, colorectal, gastric, and appendix tumors. Lymphogenous, hematogenous, and transcoelomic pathways have all been proposed among potential pathways. Early diagnosis and treatment have an important potential to improve the patient outcome. Krukenberg tumors typically appear as complex semisolid masses with varying amounts of solid and cystic components. Ovarian metastases from the colon primaries are predominantly cystic in nature. Secondary lymphomatous involvement of ovary is mostly bilateral and solid with heterogeneous signal intensity on MRI. Metastatic breast cancer to the ovaries is typically bilateral and tends to be of small size. Among all the other imaging characteristics, bilateral involvement of secondary tumors of the ovary appears to be most potentially helpful finding in differentiating from primary ones.

ObjectiveThe aim of this study was to compare Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination in patients with endometrial cancer (EC).MethodsA total of 904 patients with EC underwent surgical treatment between 2004 and 2016 at Hacettepe University Hospital, and clinicopathological data of patients were retrieved from the computerized database of the Hacettepe University. Patients who did not undergo lymphadenectomy and who had nonendometrioid histology, stage-IV disease, and synchronous epithelial ovarian and EC were excluded. All slides of the cases were reviewed by the same gynecologic pathology subspecialist.ResultsThe study group consisted of 307 consecutive patients with a mean age of 59.4 years (range, 26–86 years). Lymph node metastasis was detected in 28 subjects (9.1%). Primary tumor diameter, depth of myometrial invasion, lymphovascular space invasion, and cervical stromal and glandular involvement were associated with lymph node metastasis. Patients with low-risk histological features based on Mayo risk stratification system in our study group had a 0% rate of lymph node positivity. However, of the 28 patients with lymph node metastasis, 3 (10.7%) had low-risk features based on Milwaukee model. The sensitivity, specificity, false negative rate (FNR) and false positive rate of Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination among women with endometrioid EC were 100%, 27.3%, 0%, and 72.7%; and 89.3%, 61.3%, 10.7%, and 38.7%, respectively.ConclusionsAlthough Milwaukee risk stratification model had a lower false positive rate and can decrease the number of lymphadenectomies, FNR of this new model was found as 10.7% in the present study. Furthermore, we found that Mayo model had a lower FNR and higher sensitivity. Therefore, Mayo model still looks more beneficial to predict lymph node metastasis in patients with endometrioid EC and Milwaukee risk stratification model still requires external validation.

PURPOSE To evaluate the radioprotective efficacy of amifostine on irradiated mature rat retina. METHODS A total of 108 Wistar albino rats were categorized into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late changes in retinal cell layers (n = 20). Each group was further subcategorized into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A and RT + A arms 30 minutes before irradiation. Control and A groups were sham-irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours after irradiation. Electron microscope was used 2 weeks after irradiation for evaluation and scoring of early morphologic changes in retina. Late effects were assessed and scored accordingly by using both the electron and the light microscope on Week 10. RESULTS At acute phase, although no notable change was seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT arm (P = 0.029). Comparative analyses between the groups in 3 different time points displayed a higher apoptotic rate in RT group than the RT + A group (P = 0.008). Similarly, comparisons between groups for late effects on the basis of electron microscopic findings revealed lower scores in the RT + A than the RT arm (P < 0.001). CONCLUSION This study suggested a potential radioprotective role for amifostine on mature rat retina by reducing radiation-induced apoptosis in retinal cells. These results form a basis for such preclinical investigations and call for future clinical studies.

Background Odontogenic keratocysts have been reported with high recurrence rates in the literature so various treatment modalities from simple enucleation to resection have been performed to achieve the cure. The purpose of this retrospective study was to investigate the recurrence rate of odontogenic keratocysts (OKCs) treated by enucleation and peripheral ostectomy. Material and Methods An electronic search of the database of the Hacettepe University, Faculty of Medicine, Department of Pathology, was undertaken to identify patients histologically diagnosed with OKCs treated at Department of Oral and Maxillofacial Surgery between 2001 and 2015. Results In total, 81 patients were studied. The mean age at the time of diagnosis was 42 years, and the male:female ratio was 1:0.7. OKCs were located primarily in the posterior mandibular region (41%). Twenty-seven patients were re-examined to determine the recurrence rate. The mean follow-up period was 5 years (range, 1–12 years). The recurrence rate was 14.8%. The relationship between location of the lesion and recurrence was not statistically significant (p = 0.559). There was also no statistically significant relation between the recurrence rate and treatment option of teeth involved in the lesion (p = 0.579). Conclusions The authors conclude that treatment of OKCs by enucleation with peripheral ostectomy is associated with minimal morbidity and is preferred over other aggressive treatment modalities. Meticulous radiographic examination and careful surgical resection may decrease the recurrence rate of OKCs. Key words:Odontogenic keratocyst, recurrence rate, enucleation, enucleation plus peripheral ostectomy.

Background/aim: Human papillomaviruses have been established as a risk factor for invasive carcinoma of the uterine cervix. HPV E6/E7 oncogene expression has recently emerged as a promising biomarker to determine the risk for progression to high-grade cervical lesions. The aim of this study was to evaluate HPV mRNA and DNA detection in samples with abnormal cytology. Materials and methods: Cervical specimens were obtained at the Department of Obstetrics and Gynecology via cervical brushes during January-October 2011. Liquid-based cytology slides were evaluated according to the 2001 Bethesda System. Cytology specimens from a total of 81 women with abnormal cytology were included. Real-time PCR and NASBA assays were performed to detect HPV DNA and E6/E7 mRNA, respectively. Results: HPV DNA was identified in 73 samples (90.1%). HPV E6/E7 mRNA expression was observed in 45 samples (55.6%). A statistically significant difference was observed among cytological diagnosis groups. In 25 patients, a biopsy was performed during the follow-up. HPV DNA was detected in all of these patients. HPV E6/E7 expression was present only in CIN I-III diagnosed patients. Conclusion: The E6/E7 mRNA test is a robust indicator of cytological atypia and correlates better with progressive lesions than DNA assays.

To evaluate the accuracy of intraoperative frozen section in the evaluation of patients with adnexal mass and to define the clinicopathological factors associated with misdiagnosis during frozen section evaluation. The clinicopathological data of patients who underwent exploratory laparotomy for adnexal mass were reviewed. Results of the intraoperative frozen section and permanent histology reports were compared. Univariate and multivariate analyses were performed to reveal factors associated with misdiagnosis. The study group consisted of 748 patients. Of these patients, 509 (68.0 %) had benign, 43 (5.7 %) had borderline, 196 (26.2 %) had malignant histological diagnosis at permanent section. The overall agreement between intraoperative frozen section and permanent pathology was 96.8 %. Twenty four out of 745 cases (3.8 %) were misdiagnosed by frozen section. Univariate analysis showed that borderline histology (p

e17107 Background: Endometrial cancer(EC) is a heterogeneous disease with diverse histological features and biological behaviour. Microsatellite instability (MSI) which occurs in cancerous tissue secondary to mismatch repair (MMR) defect of hereditary or somatic origin is a well-known feature further diversifying genetic tumor landscape. In this study, we aim to investigate the relationship between MSI and prognosis in patients with early stage EC. Methods: The patients diagnosed with EC between 2004 and 2017 were retrospectively analysed in the study. The demographic characteristics, disease stage, menopausal status, and clinical and laboratory values were noted. MLH1, MSH2, MSH6 and PMS2 antibodies were used to detect microsatellite status within the tumor tissue samples. Results: The mean age of the 93 patients and menopause was 60.6 ± 9.8 and 49.68 ± 4.5 years , respectively. The median follow-up period was 28 (1-110) months. At the time of diagnosis, number of the patients with stage IA, IB, II, III, and IV were 5, 64, 8, 14, and 2, respectively. Forty three patients were grad 1, 23 patients grad 2, and 27 patients were grade 3. In terms of microsatellite status, 59 patients (63.4%) were microsatellite stable (MSS) and 34 patients (36.6%) were microsatellite instable(MSI). There was no significant association between MSI and tumor stage or grade (X2 = 1.97 p = 0.74 and X2= 3.2, p = 0.19, respectively). There was a significant relationship between peritumoral lymphocyte infiltration rate (pTIL) and MSI. PTIL ratio was higher in tumoral tissues with MSI, whereas pTIL was low in MSS tumor tissues (X2= 28.6, p < 0.0001). Patients with MSI tended to have poorer survival than patients with MSS irrespective of disease stage; mOS rates were 76 and 91 months, respectively (p = 0.086). However, patients with early stage disease and MSI had significantly poorer survial in comparison to patients with similar disease stage and MSS: Overall survival rates for patients with MSI and MSS were 75.8 and 94.7 months, respectively (Log-rank p = 0.048). Conclusions: There is a limited number of studies assessing the association between MSI and clinical outcomes in EC. Our study hints at the presence of potential relationship between MSI and pognosis in patients with MSI. Similar to previous studies performed with various types of tumors we found that EC with MSI attract more immune cells to tumor microenvironments. Interestingly, patients with MSI tended to have poorer prognosis despite augmented immune-cell inftration.

PubMed ID: 28832077, 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. © 2017, Federation of Turkish Pathology Societies. All rights reserved., Idaho Humanities Council, IHC, We thank Sitogen and BD for providing the IHC markers for the study and we thank ?zlem Kalaycl for her technical assistance.

Erdogan, Kivilcim Eren/0000-0002-4951-8703; kilic bagir, Emine/0000-0002-1447-1060; Celik, Betul/0000-0001-9731-9939; Tatli Dogan, Hayriye/0000-0003-4318-2775; Cakir, Asli/0000-0003-0128-6947 WOS: 000414649400006 PubMed: 28272675 Objective: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. Material and Method: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. Results: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells/Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. Conclusion: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Objective To compare the performance of collagenated bone graft substances with different collagen ratios after sinus floor augmentation. Methods The cross-sectional study was conducted at Hacettepe University, Ankara, Turkey, from September 2011 to September 2013. Sinus floor augmentation was done with two different equinederived xenografts in patients before dental implant application. Of the two randomised groups, one was treated with 100% collagenated bone mix (Group A), and the other half with 90% collagenated bone mix + 10% collagen gel (Group B).Six months after sinus augmentation, prior to dental implant surgery, a specimen was taken from the implant socket with trephine drill for histopathological evaluation of new bone, connective tissue and residual graft material at each augmented site. SPSS 19 was used for data analysis. Results Of the 19 patients, 12(63%) were females and 7(37%) were males. The overall mean age was 51.68±11,96 years (range: 24-69 years). A total of 30 sinus floor augmentations were done. New bone formation was significantly better in Group A(15 sinus floor augmentation) than in Group B (the other 15 sinus floor augmentation) (p 0.05). Conclusions Collagenated bone mix was found to be a suitable graft material for sinus floor augmentation, but increased collagen ratio did not improve new bone formation over the 6-month healing process.

Mucinous adenocarcinoma of the cervix has 5 subtypes: endocervical, intestinal, signet-ring cell, minimal deviation, and villoglandular. There are only rare reports of primary signet-ring cell carcinoma of the cervix in the literature. Herein we report a 53-year-old woman with cervical adenocarcinoma with signet-ring cell morphology. Thorough systemic examination did not reveal another primary focus. DNA extraction from paraffin-embedded tissue revealed the presence of human papilloma virus (HPV) type 18, which supports the cervical origin of the tumor. Signet-ring cell morphology can be observed in both benign and malignant lesions of the uterine cervix. Most of the malignant lesions are metastatic. Histological features and immunohistochemical profiles are discussed, and a review of signet-ring cell morphology in the uterine cervix is included.

We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER., PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, kappa statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The kappa values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.

Epithelium cadherin (E-cad) is important for cell-to-cell adhesion of epithelial cells. Impairment of E-cad may have a role in the development and spreading of different malignancies and associated with poor differentiation, increased invasiveness, and poor prognostic factors in nongynecological carcinomas. However, prognostic significance of E-cad expression has not been investigated properly in cervical squamous cell carcinoma (SCC). The objective of this study was to investigate the association between reduced E-cad expression and clinicopathologic variables of cervical carcinoma. Specimens from 53 consecutive patients with stage IB-IIA SCC were evaluated immunohistochemically for E-cad expression, and the results were compared to grade, lymphvascular space invasion (LVSI), deep stromal involvement (DSI), parametrial involvement, lymph node metastasis, recurrences, and survival. Patients were divided into two groups arbitrarily: E-cad expression less than 10% (group 1) and E-cad expression more than 10% (group 2). There was no significant relationship between E-cad expression and DSI, LVSI, lymphatic metastasis. However, there was significant relationship between reduced E-cad expression and parametrial involvement (P= 0.024). Kaplan-Meier survival analysis revealed that reduced E-cad expression is significantly associated with reduced overall survival (OS) and disease-free survival (DFS). Furthermore, Cox regression analysis revealed that reduced E-cad expression is significantly associated with OS (P= 0.004, RR = 6.08, 95% CI: 1.75-21.1) and recurrences (P= 0.027, RR = 1.75, 95% CI: 1.06-2.88). We conclude that loss of E-cad expression is significantly associated with reduced OS and DFS in patients with SCC. Therefore, it might be used as an indicator of aggressive clinical behavior and tailoring aggressive adjuvant therapy in early-stage SCC. Further studies with larger number of patients are needed to evaluate the clinical significance of reduced E-cad expression in SCC.

ObjectiveThis study aims to assess the diagnostic performance of a novel intraoperative ex vivo ultrasonography technique in determining deep myometrial invasion (MI) in patients with apparently low-risk endometrial cancer (EC).MethodsThis prospective study included patients with type I EC who underwent staging laparotomy at Hacettepe University Hospital from December 2011 to September 2014. After hysterectomy, a radiologist with special training in gynecology examined the uterus ex vivo using a 12-MHz superficial linear probe. The specimen was sent for intraoperative frozen section (FS) analysis. The results were compared with permanent section reports.ResultsIn total, 45 female patients were eligible for analysis. Intraoperative ex vivo high-resolution sonography (IEVHS) correctly assessed depth of MI in 39 of 45 cases (86.6%) and overestimated it in 5 cases (11.1%). Only 1 case with deep infiltration was underestimated by IEVHS as invasion of less than one half of the myometrium. Frozen section correctly identified depth of MI in 41 of 46 cases (91.1%), overestimated it in 1 case (2.2%), and underestimated it in 3 cases (6.6%). The sensitivity, specificity, positive predictive value, and negative predictive value of IEVHS and FS for assessment of deep MI were 87.5%, 86.4%, 58.3%, and 96.9%, and 62.5%, 97.3%, 83.3%, and 92.3%, respectively.ConclusionsIntraoperative ex vivo high-resolution sonography is a novel technique for assessing MI in EC. Its high sensitivity for deep MI could be useful as an adjunct to FS (enabling pathologists to obtain targeted FS slices) and could improve the accuracy of FS.

Cervical carcinoma, the second leading cause of cancer deaths in women worldwide, is associated with human papillomavirus (HPV). HPV-infected individuals are at high risk for developing cervical carcinoma; however, the molecular mechanisms that lead to the progression of cervical cancer have not been established. We hypothesized that in a multistep carcinogenesis model, HPV provides the initial hit and activation of canonical Wnt pathway may serve as the second hit. To test this hypothesis, we evaluated the canonical Wnt pathway as a promoting factor of HPV-induced human keratinocyte transformation. In this in vitro experimental cervical carcinoma model, primary human keratinocytes immortalized by HPV were transformed by SV40 small-t (smt) antigen. We show that smt-transformed cells have high cytoplasmic β-catenin levels, a hallmark of activated canonical Wnt pathway, and that activation of this pathway by smt is mediated through its interaction with protein phosphatase-2A. Furthermore, inhibition of downstream signaling from β-catenin inhibited the smt-induced transformed phenotype. Wnt pathway activation transformed HPV-immortalized primary human keratinocytes even in the absence of smt. However, activation of the Wnt pathway in the absence of HPV was not sufficient to induce transformation. We also detected increased cytoplasmic and nuclear staining of β-catenin in invasive cervical carcinoma samples from 48 patients. We detected weak cytoplasmic and no nuclear staining of β-catenin in 18 cases of cervical dysplasia. Our results suggest that the transformation of HPV expressing human keratinocytes requires activation of the Wnt pathway and that this activation may serve as a screening tool in HPV-positive populations to detect malignant progression.

There are several entities that can present with multiple nodular lesions within the peritoneal cavity, such as "disseminated peritoneal leiomyomatosis," "peritoneal fibrosis," "calcifying fibrous pseudotumor," and the recently described lesion of "reactive nodular fibrous pseudotumor of the gastrointestinal tract and mesentery." Here we present one such lesion in a 28-year-old woman with a history of dysmenorrhea and ergotamine use for migraine attacks. Intraoperative exploration of our patient disclosed numerous nodules located throughout the pelvic and abdominal peritoneum. Histopathologically, these lesions were fibrocollagenous nodules composed of sparse wavy spindle cells within hyalinized "keloid-like" collagen surrounded by an inflammatory infiltrate. Some of the nodules were associated with small foci of endometriosis. We believe this lesion is best described by the term "reactive nodular fibrous pseudotumor" and that endometriosis and the use of ergotamine derivatives may be contributing factors.

Objective The purpose of this study was to evaluate the prognostic factors, and the patterns of lymphatic metastasis in EOC patients who were treated with systematic pelvic and paraaortic lymphatic dissection. Methods A total of 420 EOC patients was retrospectively evaluated. Clinical factors available were evaluated for a possible significance in terms of lymphatic metastasis and paraaortic involvement. Results Two-hundred and three patients were found to have lymphatic metastasis. In multivariable analysis, stage ( P P P = 0.02 for mixed, and P = 0.04, for Brenner), and Ca-125 level higher than 500 U/ml ( P = 0.04) were found to be significantly related with the lymphatic involvement. Age and grade were significant factors for paraaortic metastasis both in univariable and multivariable analysis ( P = 0.003 and P = 0.02, respectively). Most of the patients with unilateral tumors had contralateral pelvic and/or paraaortic metastasis. There were eleven patients with lymphatic metastasis in stage I–II disease, and five had paraaortic metastasis while an additional five patients had contralateral pelvic nodal metastasis. However, there was no lymphatic involvement in Stage IA, Grade I–II disease (0/63). Survival analysis revealed no significant difference by the number of metastatic lymph nodes. Conclusion In multivariable analysis, lymphatic involvement was predicted independently by stage, histology, and Ca-125 level. In apparently stage I–II disease, a considerable part of patients were upstaged due to lymphatic involvement. Although routine systematic lymphadenectomy is suggested for patients with early stage disease, further series are needed for a definite regimen in patients with stage IA G1–2 disease since we did not detect any lymphatic involvement in this unique group.

Introduction: Mammary glands located in the vulvar region have been named as ectopic breast tissue or anogenital mammary glands by different authors. Literature on pathologies of ectopic breast tissue located in the vulvar region is rare. Most of the reports are about the malignancies arising from this ectopic tissue. Case Report: We report a case of fibrocystic disease of the mammary glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated during pregnancy. Conclusion: Ectopic breast tissue in the vulva is a rare entity and fibrocystic disease of this tissue has rarely been reported in the English literature.

Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.

To investigate the expression of Wilms' tumor 1 (WT1) protein in endometrial adenocarcinoma (EC) and endometrial intra-epithelial neoplasia (EIN).WT1 protein expression was determined on immunohistochemistry in 30 EC patients and in 20 EIN patients. WT1 protein expression in proliferative (n = 7), secretory (n = 9) and atrophic endometrium (n = 9) and benign endometrial polyps (n = 28) was used as the control group. Cellular and vascular WT1 staining was scored semiquantitatively.Cellular WT1 staining was 67% and vascular positivity was 73% in the EC group. In the EIN group the cellular staining was 100% and vascular staining was 85%. Although all EIN samples were positive for cellular WT1 staining, median cellular staining score was similar to that of EC (median, 2; range, 1-3; IQR, 1.75 vs 2, 0-3, 0.75, respectively). Increasing EC grade and stage were not associated with cellular or vascular WT1 staining score.WT1 is expressed in EIN.

OBJECTIVE Patients with endometrial intraepithelial neoplasia may have concurrent endometrial cancer if managed surgically or develop cancer in time if managed conservatively. Therefore, intraoperative assessment of the uterus may be helpful if a surgical approach is decided on. Our study aimed to investigate the role of frozen-section examination in patients with endometrial intraepithelial neoplasia. MATERIAL AND METHOD Patients with endometrial intraepithelial neoplasia who were subjected to hysterectomy with intraoperative frozen-section assessment were included. Main outcome measures were the rates of concurrent endometrial cancer and concurrent high-risk endometrial cancer as well as the efficacy of frozen-section in the detection of concurrent invasive disease and in the designation of low-risk and high-risk features. RESULTS The study group consisted of seventy-three patients. Permanent pathology revealed endometrial adenocarcinoma in 19.2% whereas only one patient (1.4%) had high-risk disease necessitating surgical staging. Frozen-section diagnoses were consistent with final pathology in 93.2% of patients in terms of the presence or absence of co-existent carcinoma. When frozen-section reports were further evaluated in terms of the presence or absence of high-risk endometrial carcinoma, consistency with the final pathology was seen in 98.6% of patients. CONCLUSION Co-existent endometrial cancer is not uncommon in endometrial intraepithelial neoplasia. Intraoperative frozen-section evaluation should therefore be considered whenever possible. Frozen-section is effective in the detection of coexistent invasive disease and in the designation of low-risk features. Although coexistent high-risk cancer is extremely rare, frozen-section assessment is not successful in determining high-risk features. Therefore, a re-staging surgery may be required on rare occasions.

Endocrine disease related tumors of female reproductive system mostly seen in ovary. Hormone producing ovarian tumors, ovarian tumor with functioning stroma, tumor related paraneoplastic and paraendocrine syndromes, paraganglioma and neuroendocrine tumors may include in this category. These tumors or its stroma can produce some hormones, which are led to endocrine manifestations. Rarely tumors associated with paraneoplastic and endocrine syndromes. Among these lesions, primary neuroendocrine tumors are rarely seen in the gynecologic tract, comprising 2% of gynecologic cancers. They have specific cytological and histopathological features that are usually helpful in differentiating them from epithelial tumors. Nevertheless, they still provide a diagnostic and clinical challenge, given their rarity. Accurate diagnosis of neuroendocrine tumor is essential for both therapeutic and prognostic purposes. In this review, we focused on neuroendocrine tumors of the gynecological tract and their morphological, immunohistochemical and molecular findings. In addition, we will briefly discuss paraganglioma and other endocrine diseases related tumors in the gynecological tract.