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FACTORS PREDICTING INACCURACY BETWEEN FROZEN SECTION ANALYSIS AND POSTOPERATIVE PATHOLOGY RESULTS: A TERTIARY CENTER EXPERIENCE ABSTRACT Objective: To evaluate the diagnostic accuracy and to identify the factors determining the inaccuracy between FS analysis and postoperative pathology results in our hospital. Materials and Methods: This study included 1435 patients with pelvic masses who underwent surgical intervention and FS consultation. Results: On univariate analysis, menopausal state, abnormal uterine bleeding, preoperative serum Ca125 level, preoperative leukocyte value, preoperative neutrophil value, tumor size, presence of cystic component, pathological findings in Doppler USG, ascites and cell type were found to have statistical significance for benign / borderline / malign discrimination. Menopausal state (p lt;0.0001), preoperative serum Ca125 level (p lt;0.0001) and tumor size (p lt;0.0001) were identified as independent predictors for determining inaccuracy between intraoperative and postoperative pathological evaluation. Inconsistency increased 2.5 times with a serum Ca125 gt; 35 IU/ml, 3.8 times with tumor size gt; 79 mm and 5 times in postmenopausal patients. For the discrimination of benign / borderline / malign definitions, FS results and final pathology results were compatible in 1250 (87%) patients while it was not in 185 (13%) patients. Conclusions: Increased preoperative serum Ca125 level was a predictor for inaccuracy between FS examination and postoperative pathology results. Also, tumor size ≥80 mm and menopausal state were related to misdiagnosis in FS results. Maximal effort should be done to minimize preventable errors during intraoperative FS analysis. Keywords: Frozen section, Pelvic mass, Inaccuracy, Borderline tumors

Background and objectives Epithelial ovarian cancer (OC) is a clinically, morphologically, and molecularly heterogeneous disease. Estrogen receptor (ER) β is highly represented in normal ovarian epithelial cells and benign tumors, but ERα is the main form expressed in OC. ERα-positive OC had a favorable outcome. Progesterone receptor (PR) expression in ovarian tumors is a good prognostic marker associated with longer progression-free survival. Human epidermal growth-factor receptor (HER) 2 expression is associated with a worse prognosis. The aim of the study was to evaluate immunohistochemical (IHC) expression of ER, PR, and HER2/neu in ovarian epithelial tumors and to correlate their expression with different demographic, clinical, and pathological parameters. Patients and methods Sixty cases of primary ovarian epithelial tumors were studied according to their expression to ER, PR, and HER2/neu. Results There was a statistically significant relation between ER IHC and histopathological type of borderline tumor cases and also between PR IHC and histopathological types of both borderline and malignant tumor cases. A statistically significant relation was found between PR IHC and tumor grade and FIGO stage. Triple-negative tumors are significantly associated with mucinous carcinoma and with FIGO stage IV. Interpretation and conclusion Larger studies on a wider scale of patients, especially those with triple-negative ovarian tumor cases, are needed in order to elucidate the exact role of ER, PR, and HER2/neu as a possible prognostic marker in epithelial OC. Other markers are recommended to be used in association with ER, PR, and HER2/neu in order to improve test sensitivity.

ImportanceCardiac-specific death from radiation caused by radiation therapy (RT) in patients with malignant tumors has received extensive attention, however, little is known regarding the potential cardiotoxic effects of RT in patients with non-malignant tumors.Objectives and methodsIn this study, we used the SEER data to explore the incidence of post-radiation cardiovascular complications in patients with non-malignant tumors of central nervous system (CNS), and identify the influencing factors of cardiac-specific death.ResultsUltimately 233, 306 patients were included (97.8% of patients had brain tumors and 2.2% had spinal cord tumors). For patients with non-malignant tumors of CNS, RT {yes (odds ratio [OR] 0.851, 95% confidence interval [CI] 0.774–0.936, p = 0.001, before propensity score matching (PSM); OR 0.792, 95% CI 0.702–0.894, p < 0.001, after PSM) vs. no} was associated with lower risk of cardiac-specific death, other clinical features affecting cardiac death similar to those in patients with non-malignant tumors of CNS receiving RT. For patients with non-malignant tumors of CNS receiving RT, female, married status, Hispanic ethnicity, surgery, and tumor site (brain exclude nerve and endocrine, nervous system) were associated with lower risks of cardiac-specific death, while earlier year of diagnosis, older age of diagnosis, Black, larger tumor and bilateral tumor were risk factors for cardiac-specific death.ConclusionsOur study shows the influencing factors for cardiac-specific death in patients with non-malignant tumors of CNS, and found RT is associated with lower risk of cardiac-specific death. These results can facilitate the identification of patients with non-malignant tumors of CNS who can benefit from RT while avoiding cardiovascular events. In addition, this study helps to enhance the clinical use of RT in these populations, especially in patients who may have impaired cardiac function due to CNS tumors.

Background and objectives Epithelial ovarian cancer (OC) is a clinically, morphologically, and molecularly heterogeneous disease. Estrogen receptor (ER) ß is highly represented in normal ovarian epithelial cells and benign tumors, but ERa is the main form expressed in OC. ERa-positive OC had a favorable outcome. Progesterone receptor (PR) expression in ovarian tumors is a good prognostic marker associated with longer progression-free survival. Human epidermal growth-factor receptor (HER) 2 expression is associated with a worse prognosis. The aim of the study was to evaluate immunohistochemical (IHC) expression of ER, PR, and HER2/neu in ovarian epithelial tumors and to correlate their expression with different demographic, clinical, and pathological parameters. Patients and methods Sixty cases of primary ovarian epithelial tumors were studied according to their expression to ER, PR, and HER2/neu. Results There was a statistically significant relation between ER IHC and histopathological type of borderline tumor cases and also between PR IHC and histopathological types of both borderline and malignant tumor cases. A statistically significant relation was found between PR IHC and tumor grade and FIGO stage. Triple-negative tumors are significantly associated with mucinous carcinoma and with FIGO stage IV. Interpretation and conclusion Larger studies on a wider scale of patients, especially those with triple-negative ovarian tumor cases, are needed in order to elucidate the exact role of ER, PR, and HER2/neu as a possible prognostic marker in epithelial OC. Other markers are recommended to be used in association with ER, PR, and HER2/neu in order to improve test sensitivity. [ABSTRACT FROM AUTHOR]

Ovarian Cancer (OC) constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of OC. Intraoperative frozen section (FS) diagnosis is widely used to decide the surgery course. We aimed to assess the reliability of intraoperative FS diagnosis for treatment planning of patients with suspected OC from a multidisciplinary perspective. The clinical consequences of reclassification and the multidisciplinary management of the therapy plan, is the secondary aim of this study. To our knowledge, this information is sparely investigated. A single-center, retrospective population-based study of patients who underwent surgery for suspected OC between 2018 and 2020. Histopathological outcomes were classified as benign, borderline, or malignant. The FS diagnosis was the diagnostic test, and the final histopathology report was the gold standard. Diagnostic capability for treatment planning was assessed, and modifications made possible by overall clinical knowledge were discussed. A total of 358 patients were identified, of whom 187 were included in the FS group. Overall accuracy was 89.8%, and 19 patients were reclassified; the malignancy grade of 15 tumors was underestimated. Prevalence, sensitivity, specificity, positive predictive value, and negative predictive value for invasive malignancies on FS were 54.0% (CI 46.6–61.3%), 88.1% (CI 80.2–93.7%), 98.8% (CI 93.7–99.9%), 98.9% (CI 92.7–99.8%), and 87.6% (CI 80.6–92.4%), respectively. Tumors incorrectly graded by FS tended to be of borderline-related. The reliability of the FS methodology was an accurate test to help perform appropriate surgery and plan swift oncological treatment. FS is a reliable method to diagnose invasive malignancies and benign pathology. The communication between the pathologist, surgeon, and medical oncologist is highly important for both intraoperative decision-making and postoperative patient care. [ABSTRACT FROM AUTHOR]

In thyroid pathology, the great variety of types and the wide range of aggressiveness of thyroid cancers complicate both diagnosis and management. In 2016, a subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid tumor with papillarylike nuclear features (NIFTP) to reduce overtreatment of this low-risk tumor that follows a benign course after surgery. Starting from a paradigmatic clinical case, in this short review, we will summarize the ultrasonography, cytological, histological and molecular features of this new entity. In the preoperative settings, the recognition of some peculiar elements may only suggest the possibility of a NIFTP, thus favoring a less aggressive surgical approach. However, the diagnosis of NIFTP can only be made after complete resection of the lesion by detecting well-defined inclusion and exclusion histopathological criteria. Since NIFTP is not 'malignant,' surgery may be considered curative with no further treatment or surveillance needed. NIFTP-related issues, including nodule size, multifocality, oncocytic changes, heterogeneous incidence across different geographical areas and its occurrence in the pediatric age, will be discussed. [ABSTRACT FROM AUTHOR]

Aim: To examine the clinicopathological features of ovarian seromucinous borderline tumors (SMBTs) and compare them with those of mucinous borderline/atypical proliferative mucinous tumors (MB/APMTs). Patients and Methods: Patients with SMBT between 2014 and 2018 and those with MB/APMT between 1988 and 2018 who underwent surgery at our Institution were identified. Pathological review was conducted using the 2014 World Health Organization criteria. Clinical features were compared retrospectively between SMBT and MB/APMT. Results: In total, 11 (12.9%) patients with SMBT and 74 (87.1%) patients with MB/APMT were included in our study. The diagnosis of six patients with SMBT and 73 patients with MB/APMT was not revised on review. SMBT was diagnosed at a younger age (p=0.04), was of smaller size (p<0.01) and bilateral (p=0.03), coexisted with endometriosis (p<0.01), and more frequently recurred than MB/APMT (p=0.04). Conclusion: SMBT might be more aggressive than MB/APMT. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the characteristics of patients who underwent surgery due to the presence of a large pelvic-abdominal mass over a 5-year period in a university clinic. Material and Methods: Among 3476 gynecologic operations, intraoperative findings were evaluated retrospectively. Uterine and/or adnexal masses smaller than 20 cm were excluded to refine "large" tumors and 74 patients with large tumors were enrolled in the study group. Demographic characteristics, intraoperative findings, and results of histopathologic examinations were recorded. Moreover, preoperative and intraoperative findings were compared among tumors with adnexal origin according to their final histopathologic results. Results: The mean age of the patients was 46 years. The most common symptom was abdominal pain, as recorded in 38 (51.4%) patients. Among all patients, 31 (41.9%) had coexisting illness and 13 (17.6%) had a history of surgery. The mean tumor diameter was 25.9±8.6 cm (20-60) and 60 (78.9%) tumors were of adnexal origin. The ratios of malignancy for large adnexal and uterine tumors were 34.4% and 12.5%, respectively. When the large adnexal tumors were re-evaluated, the mean cancer antigen (CA) 125 level was significantly higher, and ascites was more frequently detected in malignant tumors (p<0.01) then in benign and borderline tumors. Conclusion: Benign and borderline tumors are more common among large abdominopelvic masses, although the presence of ascites and elevated CA 125 may present malignancy in large gynecologic tumors. Further studies with larger sample sizes are needed to define the characteristics of large tumors and their malignant potentials. [ABSTRACT FROM AUTHOR]

Objectives: Malignant and borderline ovarian tumors of epithelial origin are rarely encountered among prepubertal girls and adolescents. The aim of this population-based study was to elucidate their clinicopathological characteristics and prognosis using a multi-institutional tumor registry.Study Design and Outcomes: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was accessed and a cohort of females aged <=19years old, diagnosed between 1988 and 2013 with a borderline ovarian tumor (BOT) or a malignant epithelial ovarian carcinoma (EOC) was accessed. Observed survival (OS) was assessed using the Kaplan-Meier method. Comparisons were made using the log-rank test.Results: A total of 114 cases diagnosed with BOT between 1988 and 2000 were identified; 61/114 (53.5%) and 51/114 (44.8%) of BOT were of serous or mucinous histology respectively. Ten-year OS for those with BOT was 97.3%. A total of 140 cases of EOC were identified. Median age was 17 years and the most common histological subtypes were mucinous 79/140 (56.4%) and serous 29/140 (20.7%) adenocarcinoma. Most had stage I disease 92/131 (70.2%) and fertility-sparing surgery was commonly performed. Five-year OS for those with stage I disease was 93.6% compared to 48.3% for cases with exta-ovarian tumor spread (p<0.001).Conclusions: BOT and EOC are exceedingly rare in the pediatric and adolescent population. In this age group EOC consists mostly of low-grade mucinous and serous tumors confined to the ovary. OS survival for those with stage I disease is excellent. [ABSTRACT FROM AUTHOR]

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Objective: This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT). Methods: Women with borderline and malignant MOTwere identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study. Data were collected from the electronic patient record and case notes. Results: Of 310 women identified with MOT, 203 patients with benign MOT were excluded. Of the remaining 107 patients, 15 patients with previous appendicectomy were also excluded. The study population consisted of 92 patients. There were 57 (62%) patients with borderline MOT and 35 (38%) patients with malignant MOT. In the borderline subgroup, 40/57 (70%) patients had appendicectomy of whom 8 (20%) had macroscopically abnormal appendices. One patient had pseudomyxoma peritonei secondarily involving the appendix and 7 patients had a histologically normal appendix. Normal histology was found in all macroscopically normal appendices. In the malignant subgroup, 29/35 (83%) patients had an appendicectomy. There were 8 (27.5%) macroscopically abnormal appendices with a malignant pathology in 7 (87.5%) patients and 1 patient had a resolving appendicitis. There were 21 macroscopically normal appendices of which, serrated adenomawas found in 1 (4.8%) patient, whereas the remaining 20 (95.2%) patients had normal histology. Conclusions: InMOT, an abnormal appearing appendix should be excised. If the appendix is grossly normal, our data do not support performing an appendicectomy as part of a surgical staging procedure. [ABSTRACT FROM AUTHOR]

Highlights • Case of incidental diagnosis of a giant borderline ovarian mucinous tumor, with a mass of over 6500 g is presented. • Compressive symptoms or visible abdominal mass are the most frequent observations of giant mucinous ovarian tumors. • Borderline mucinous tumors, when diagnosed in Stage I, present a recurrence rate of 1%. • Diagnostic symptoms are described in literature, but are not related with prognosis, while asymptomatic cases are not often related to earlier diagnosis or with better results. Abstract Introduction Cases of giant mucinous ovarian tumors are rarely described in literature, with different clinical manifestations. Compressive symptoms or visible abdominal mass are the most frequent observations, with higher surgical risks and life-threatening complications. Presentation of case We report a case of a 69-year-old female with a giant borderline ovarian mucinous tumor, with peculiarity of absence of clinical manifestation, in front of a mass of over 6500 g. The patient underwent exploratory laparotomy where a giant cystic mass with solid lesions measuring more than 50 cm was found. It originated from the left ovary and extended up to mesocolon. Excision of the tumor intact wall, without fluid aspiration, abdominal hysterectomy with bilateral ooforectomy was performed. No hemodynamic and cardiac intraoperative modifications were observed. There were no significant early or late postoperative complications. Patient was well 12 months after surgery. The pathological examination showed a giant cystic neoplasm measuring 60 × 50 × 40 cm, weighing 6500 g. This histological study showed a mucinous neoplasm of borderline malignancy, with epithelial cells mainly of endocervical type with focal development of intestinal epithelium with goblet cells. Discussion Giant ovarian lesions are often related with compressive symptoms and need resection with high-risk of mortality. Although optimal imaging evolution, rarely rapid growth and abnormal mucina production can determine giant evolution. Conclusion Our case report is paradigmatic for absence of symptoms at diagnosis, although dimension of lesion, for borderline mucinous histotype, that determined a good prognosis in this patient, and for safe operative treatment. [ABSTRACT FROM AUTHOR]

Objective: The clinical value of human epididymis protein 4 (HE4) and the possibility of its use in the differential diagnosis in patients with benign, borderline and epithelial ovarian cancer in early International Federation of Gynaecology and Obstetrics (FIGO) stages.Study Design: The study group consisted of 205 women, including 60 with ovarian cancer, 18 with borderline tumors, 77 with benign lesions and 50 healthy subjects. In all the patients, before the treatment and in control groups, we determined CA 125 and HE4 in serum by electrochemiluminescence on the basis of the COBAS e601 system. For comparison of two independent groups, we used the U Mann-Whitney test. The analysis of the diagnostic power of the assessed parameters has been determined using the MedCalc statistical program. The probability of disease free survival (DFS) was evaluated using the log-rank test and Cox regression model.Results: Concentrations of HE4, CA 125 and Risk of Ovarian Malignancy Algorithm (ROMA) value were significantly higher in early ovarian cancer than in patients with benign (P<0.0001) and borderline tumors (P<0.002), the receiver operating characteristics (ROC) curves, demonstrated the highest diagnostic sensitivity for the ROMA score, as well post (AUC=0.817) as pre-menopausal (AUC=0.806). HE4 concentrations (P<0.021) and the value of the ROMA score (P<0.004) were significantly higher in patients with relapse than in patients in remission. There was no connection between concentrations of the studied tumor markers and DFS.Conclusions: Determination of HE4 serum concentrations has a significant clinical value, especially in patients with benign lesions and elevated CA 125 levels. The combined assessment of HE4, CA 125 and the ROMA algorithm is helpful in differentiating benign tumors and borderline pelvic tumors from epithelial ovarian cancer in early FIGO stages. Determination of HE4, CA 125 and ROMA algorithm is not helpful in differentiating patients with borderline from benign lesions. [ABSTRACT FROM AUTHOR]

Cadherin-11 (CDH11, OB-cadherin) is a mesenchymal cadherin found to be upregulated in various types of tumors and implicated in tumor progression and metastasis. In order to determine the role of CDH11 expression in ovarian tumors, we performed a combined reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemical study on a large cohort of benign, borderline and invasive ovarian tumors. The RT-qPCR and western blot analysis demonstrated that the CDH11 expression was high in benign cystadenomas and decreased with increasing malignancy. This may be explained by the different tumor-stroma ratios, since immunohistochemistry revealed strong staining of stromal cells, particularly vascular smooth muscle cells and endothelial cells, but only weak cytoplasmic or nuclear immunoreactivity of cancer cells. Within the group of invasive carcinomas, high CDH11 protein expression, as detected by western blot analysis, was found to be significantly correlated with advanced stage and nodal involvement. However, the recurrence-free and overall survival analyses did not reveal any prognostic or predictive significance. In conclusion, in contrast to other tumor types, CDH11 does not play an important role in ovarian cancer progression. [ABSTRACT FROM AUTHOR]

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Objetivo: avaliar alguns aspectos epidemiológicos, do diagnóstico e do prognóstico em mulheres com tumores epiteliais ovarianos borderline e francamente invasores. Métodos: foram revisados os prontuários de 198 pacientes tratadas no CAISM/UNICAMP de 1986 a 1996. Para análise estatística foram utilizados os testes chi², exato de Fisher, t de Student e curvas de sobrevida pelo método de Kaplan-Meyer comparadas pelo teste log-rank. O seguimento médio das pacientes foi de 50 meses (de 11 a 168). Dos 198 casos, 24 eram tumores borderline (12%) e 174 (88%) carcinomas francamente invasores. Resultados: a média de idade das pacientes com tumores borderline foi significativamente menor que a das mulheres com carcinoma francamente invasor: 43 ± 14,8 anos vs 52 ± 12,6 anos (pPurpose: to determine some epidemiological, diagnostic and prognostic aspects in women with borderline and invasive epithelial ovarian tumors. Methods: the charts of 198 women treated at CAISM/UNICAMP from 1986 to 1996 were revised. For statistical assessment, chi², Fisher's exact and t Student's tests were used when appropriate, followed by survival curves by the Kaplan-Meyer method, compared by the log-rank test. The mean follow-up was 50 months (11 to 168). Results: the overall rate of borderline tumors was 12% (24 cases), and for invasive carcinoma, 88% (174 cases). The mean age of the patients with borderline tumors was significantly lower than that of those with invasive carcinoma (43 ± 14.8 years vs. 52 ± 12.6 years, p

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Introduction: Ovarian cysts are commonly encountered lesions. They are amongst the most frequent cause of hospitalization and surgery in gynecologic practice. One cannot confidently distinguish a benign lesion from a malignant one on the basis of clinical, radiological or gross characteristics alone so a histopathology examination is a must as it guides therapy. The study was undertaken to determine the morphologic spectrum of the cystic lesions of the ovary. Methods: This is a descriptive study which was carried out at Kathmandu Medical College Teaching Hospital for a period of two years from 1st January 2011 to 31st December 2012. A Total of 135 cases of ovarian cysts were received and processed in the Pathology Department. Hematoxylin and Eosin stained slides were examined. Results: Among the 135 ovarian cystic lesions, 119 cases (88.15%) were unilateral and 16 cases (11.85%) were bilateral. There were 59 cases (43.7%) of benign cysts, 69 cases (51.1%) of benign tumors, 5 cases (3.7%) of malignant tumors and 2 cases (1.5%) of borderline epithelial tumors. The age of patients ranged from 13 years to 73 years with mean age of presentation of 43 years. Among the ovarian cystic lesions the incidence of mature cystic teratoma was the highest (30%). The most common non-neoplastic cyst was endometriotic cyst (39%), while the most common benign tumor was mature cystic teratoma (58%). The malignant tumor encountered in the study was serous cystadenocarcinoma. Two cases of borderline epithelial tumors (1.5%) were also observed in the study. Conclusion: The most common cystic lesion that were encountered in the study was benign tumor followed by benign cyst. Of the benign tumors, mature cystic teratoma was the most frequently observed lesion. Among the non-neoplastic cysts, endometriotic cyst was the most frequently observed lesion. [ABSTRACT FROM AUTHOR]

Importance: Cardiac-specific death from radiation caused by radiation therapy (RT) in patients with malignant tumors has received extensive attention, however, little is known regarding the potential cardiotoxic effects of RT in patients with non-malignant tumors., Objectives and Methods: In this study, we used the SEER data to explore the incidence of post-radiation cardiovascular complications in patients with non-malignant tumors of central nervous system (CNS), and identify the influencing factors of cardiac-specific death., Results: Ultimately 233, 306 patients were included (97.8% of patients had brain tumors and 2.2% had spinal cord tumors). For patients with non-malignant tumors of CNS, RT {yes (odds ratio [OR] 0.851, 95% confidence interval [CI] 0.774-0.936, p = 0.001, before propensity score matching (PSM); OR 0.792, 95% CI 0.702-0.894, p < 0.001, after PSM) vs. no} was associated with lower risk of cardiac-specific death, other clinical features affecting cardiac death similar to those in patients with non-malignant tumors of CNS receiving RT. For patients with non-malignant tumors of CNS receiving RT, female, married status, Hispanic ethnicity, surgery, and tumor site (brain exclude nerve and endocrine, nervous system) were associated with lower risks of cardiac-specific death, while earlier year of diagnosis, older age of diagnosis, Black, larger tumor and bilateral tumor were risk factors for cardiac-specific death., Conclusions: Our study shows the influencing factors for cardiac-specific death in patients with non-malignant tumors of CNS, and found RT is associated with lower risk of cardiac-specific death. These results can facilitate the identification of patients with non-malignant tumors of CNS who can benefit from RT while avoiding cardiovascular events. In addition, this study helps to enhance the clinical use of RT in these populations, especially in patients who may have impaired cardiac function due to CNS tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Ye, Zhao, Ma, Wei, Wang, Zhang and Wang.)

The question whether the appendix should be removed at the time of surgery for apparent early-stage ovarian cancer is controversial. Removal of the appendix in the setting of mucinous histologic type is primarily driven by the existing challenge to distinguish between primary ovarian mucinous neoplasm and metastatic appendiceal carcinoma to the ovary.To evaluate the value of an appendectomy at the time of surgery for ovarian mucinous borderline tumors or carcinoma.A retrospective single institute-based study was conducted. We identified patients who were operated on by a gynecologic oncologist for an abnormal pelvic mass, which was diagnosed as mucinous adenocarcinoma or mucinous borderline tumor between January 2000 and December 2010. Cases were included in the study if an appendectomy was performed at the time of initial surgery.Seventy-seven cases meeting the inclusion criteria were identified. The ovarian mass of 11 patients (14%) was diagnosed as metastatic appendiceal carcinoma involving the ovary. Evidence of metastatic disease, abnormal-looking appendix, or pseudomyxoma peritonei, were identified at the time of surgery for all of these cases. The condition of 30 patients (39%) and 36 patients (47%) were diagnosed as mucinous borderline ovarian tumor and invasive or microinvasive mucinous ovarian carcinoma, respectively. Evidence of metastasis from the ovary to the appendix was not identified in any of the cases.Our data suggest that in cases of apparent early-stage mucinous ovarian borderline tumors and cancer, adding an appendectomy at the time of surgery is not warranted in the absence of a grossly abnormal appendix or evidence of metastatic disease. [ABSTRACT FROM AUTHOR]

Objective: To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Design: Case-control study (Mayo Clinic Ovarian Cancer Study). Setting: Ongoing academic study of ovarian cancer. Patient(s): A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. Intervention(s): None. Main Outcome Measure(s): Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Result(s): Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. Conclusion(s): We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Frozen section (FS) diagnosis of mucinous tumors of the ovary can be quite difficult due to the size of these tumors, heterogeneity and potential risk of metastasis from gastrointestinal (GI) neoplasms. Given the paucity of data on this subject, our objective was to determine the reliability of FS diagnosis in ovarian mucinous tumors. Methods: A retrospective review of 73 consecutive ovarian mucinous tumors submitted for frozen section (FS) evaluation between January 2004 and November 2009 was conducted. FS and final pathology results, in addition to patient characteristics, were collected. Univariate analysis was performed evaluating predictors of FS reliability. Results: The average tumor size was 19.7cm (0.8–50cm). The FS and final pathology diagnosis were concordant in 66% (48/73) of the cases. Of the 25 (34%) discordant cases, 8 (11%) were downgraded and 17 cases (23%) were upgraded. Of the 44 tumors interpreted as LMP on FS, 14 (32%) were malignant at final diagnosis (26% ovarian, 7% GI) and 8 (18%) were benign. Of the 23 benign tumors on FS, 13% were upgraded to either LMP or malignant at final diagnosis. Tumors with a malignant diagnosis on FS were 100% concordant with final diagnosis. Univariate analysis did not reveal any correlation with the FS diagnosis and patient age, tumor size or presence of bilateral disease. Conclusions: Our study showed a 34% rate of discordance between FS and final diagnosis. Given that 5 cases (7%) were of GI origin, intraoperative assessment of the appendix should be performed in all mucinous ovarian tumors. [Copyright &y& Elsevier]

Summary: Recent morphologic, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. Type I tumors comprise low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas, and Brenner tumors. They are generally indolent, present in stage I (tumor confined to the ovary), and are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN, PIK3CA, ARID1A, and PPP2R1A, which target specific cell signaling pathways. Type I tumors rarely harbor TP53 mutations and are relatively stable genetically. Type II tumors comprise high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. They are aggressive, present in advanced stage, and have a very high frequency of TP53 mutations but rarely harbor the mutations detected in type I tumors. In addition, type II tumors have molecular alterations that perturb expression of BRCA either by mutation of the gene or by promoter methylation. A hallmark of these tumors is that they are genetically highly unstable. Recent studies strongly suggest that fallopian tube epithelium (benign or malignant) that implants on the ovary is the source of low-grade and high-grade serous carcinoma rather than the ovarian surface epithelium as previously believed. Similarly, it is widely accepted that endometriosis is the precursor of endometrioid and clear cell carcinomas and, as endometriosis, is thought to develop from retrograde menstruation; these tumors can also be regarded as involving the ovary secondarily. The origin of mucinous and transitional cell (Brenner) tumors is still not well established, although recent data suggest a possible origin from transitional epithelial nests located in paraovarian locations at the tuboperitoneal junction. Thus, it now appears that type I and type II ovarian tumors develop independently along different molecular pathways and that both types develop outside the ovary and involve it secondarily. If this concept is confirmed, it leads to the conclusion that the only true primary ovarian neoplasms are gonadal stromal and germ cell tumors analogous to testicular tumors. This new paradigm of ovarian carcinogenesis has important clinical implications. By shifting the early events of ovarian carcinogenesis to the fallopian tube and endometrium instead of the ovary, prevention approaches, for example, salpingectomy with ovarian conservation, may play an important role in reducing the burden of ovarian cancer while preserving hormonal function and fertility. [Copyright &y& Elsevier]

There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers. [ABSTRACT FROM AUTHOR]

Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGβ3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.Oncogene (2005) 24, 4672–4687. doi:10.1038/sj.onc.1208214 Published online 30 May 2005 [ABSTRACT FROM AUTHOR]

Background: Benign tumors of the pancreas are rare, accounting for only 1–2% of primary pancreatic lesions. Up to now, partial duodenopancreatectomy is still one of the established forms of treatment of benign tumors of the pancreas. We applied duodenum-preserving pancreatic head resection in 12 patients with benign pancreatic tumors to evaluate the feasibility, morbidity and recurrence rates after this less aggressive method. Methods: Between April 1984 and December 1999, 12 patients with benign and borderline tumors of the pancreatic head were operated on by duodenum-preserving pancreatic head resection. Results: All five patients with serous cystadenoma are free of recurrence 4.4 years after primary resection. One of two patients with mucinous cystadenoma and one of three patients with intraductal papillary mucinous tumor developed recurrent tumor within the former pancreatic head 5 years and 6 years, respectively, after the primary operation. Both patients were resected a second time. One of two patients with gastrinoma still has elevated serum gastrin levels. There was no hospital or long-term mortality. Conclusion: For a symptomatic serous cystadenoma, duodenum-preserving pancreatic head resection is a good alternative to partial duodenopancreatectomy. In borderline tumors with malignant potential, we would rather suggest a more radical duodenum-preserving segmental resection. A video clip (3 min) is attached demonstrating the basic steps of duodenum-preserving pancreatic head resection. [ABSTRACT FROM AUTHOR]

Abstract Background Even though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies. Methods GPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ERα and ERβ mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In addition, IHC was evaluated in a tissue microarray (TMA) of 150 primary malignant ovarian tumors. Results All tumor samples contained GPER mRNA. The content of mRNA was not different between benign and malignant tumors, but one third of malignant samples over-expressed GPER mRNA. The content of ERα mRNA was higher in malignant than in benign tumors, whereas ERβ mRNA was higher in benign than in malignant tumors. GPER mRNA was detected in all seven ovarian cancer cell lines with highest levels in TOV21G and TOV112D cells. Similar expression pattern was seen for ERβ mRNA. Western blot demonstrated GPER protein in all tumor samples. Semi-quantification showed no difference between benign and malignant tumors, but about one third of malignant samples over-expressed GPER protein. GPER staining was localized mainly in epithelial cells. In the TMA study we found no correlation between GPER staining and clinical stage, histological grade or patient survival. Conclusions GPER mRNA as well as GPER protein is present in both benign and malignant ovarian tumor tissue. About one third of malignant tumors over-expressed both GPER mRNA and protein. This, however, correlated neither with histological or clinical parameters nor with patient survival.

The prognostic significance of DNA ploidy in relation to clinical and histopathologic factors was evaluated in a retrospective study of 370 patients treated at the Norwegian Radium Hospital from 1970 to 1982 with complete follow-up of median 149 months. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the primary tumor were obtained in 321 cases, 293 (91%) were diploid and 28 (9%) were aneuploid. Aneuploidy was associated with older age, more advanced disease and non-serous histologic types. By multivariate analysis the only parameters with prognostic significance for corrected survival (death from disease) were ploidy, stage, histologic type and age. The patients with aneuploid tumors had a 19-fold increased risk of dying of disease compared with patients with diploid tumors. In tumor-free operated patients the extent of surgery had no influence on survival, neither had postoperative treatment. Using the prognostic factors the patients could be divided into risk groups. The large group of patients with diploid stage I tumors belonged to the low risk group. Fertility-saving operations can be offered to patients with diploid stage IA tumors, all others should have bilateral salpingo-oophorectomy and omentectomy with or without hysterectomy. Patients with diploid stage I tumors should not receive adjuvant treatment. The value of adjuvant chemotherapy in the high risk group needs further investigation. [ABSTRACT FROM AUTHOR]

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5-272 U ml-1). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5-272 U ml-1) and in all 11 with mucinous tumors (median 62, range 41-157 U ml-1). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3-6 weeks after primary laparotomy, were significantly lower than the preoperative ones (P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26-87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients. [ABSTRACT FROM AUTHOR]

Cytokeratins are one of the intermediate cytoplasmic filaments which contribute to the cytoskeleton. Keratins have recently been demonstrated in normal and neoplastic tissues as well as in human cell lines. It has been suggested that the cellular location of keratin may reflect tissue-specific or epithelial type differentiation. Twenty-three examples of human ovaries containing the full spectrum of epithelial proliferations from inflammatory reactive processes to malignant neoplasia were studied for the cellular distribution of cytokeratin using antisera to human keratin. Nineteen cases contained immunoreactive keratin which was limited to the epithelial cells: 2/2 inflammatory, 8/10 benign tumors, 5/7 borderline tumors, 4/4 carcinomas. There was marked regional heterogeneity in keratin expression such that adjacent morphologically-identical cells could be functionally distinguished by the immunoreactive staining. The predominant cellular localization of keratin varied between histological tumor types in the benign neoplasms: serous=apical, subciliary; endometrioid=apical; mucinous=basal. This pattern was lost in the cytological progression to borderline and malignant tumors. In borderline tumors, the most intense reactivity was noted in areas of cellular atypia and proliferation. In borderline and malignant tumors, keratin was usually present in basal cytoplasmic regions contiguous with stroma. [ABSTRACT FROM AUTHOR]