Do Exophytic and Endophytic Patterns in Borderline Ovarian Tumors Have Different Prognostic Implications? A Large Multicentric Experience.

Borderline ovarian tumor (BOT) accounts for 15-20% of all epithelial ovarian tumors. Concerns have arisen about the clinical and prognostic implications of BOT with exophytic growth patterns. We retrospectively reviewed all cases of BOT patients surgically treated from 2015 to 2020. Patients were divided into an endophytic pattern (with intracystic tumor growth and intact ovarian capsule) and an exophytic pattern (with tumor growth outside the ovarian capsule) group. Among the 254 patients recruited, 229 met the inclusion criteria, and of these, 169 (73.8%) belonged to the endophytic group. The endophytic group showed more commonly an early FIGO stage than the exophytic group (100.0% vs. 66.7%, p < 0.001). Furthermore, tumor cells in peritoneal washing (20.0% vs. 0.6%, p < 0.001), elevated Ca125 levels (51.7% vs. 31.4%, p = 0.003), peritoneal implants (0 vs. 18.3%, p < 0.001), and invasive peritoneal implants (0 vs. 5%, p = 0.003) were more frequently observed in the exophytic group. The survival analysis showed 15 (6.6%) total recurrences, 9 (5.3%) in the endophytic and 6 (10.0%) patients in the exophytic group (p = 0.213). At multivariable analysis, age (p = 0.001), FIGO stage (p = 0.002), fertility-sparing surgery (p = 0.001), invasive implants (p = 0.042), and tumor spillage (p = 0.031) appeared significantly associated with recurrence. Endophytic and exophytic patterns in borderline ovarian tumors show superimposable recurrence rates and disease-free survival.

Obstetrics outcomes after complete and partial molar pregnancy: Review of the literature and meta-analysis.

The hydatidiform mole is a rare gynecological disease rising from the trophoblastic. Post-molar pregnancies have an extremely variable course, varying from repeated abortions, stillbirths, preterm births, live births, or recurring in further molar pregnancies. Literature on obstetric outcomes following molar pregnancy is poor, often including monocentric studies, and with data collected from national databases. This review and meta-analysis aim to analyze the obstetric outcomes after conservative management of complete (CHM) and partial (PHM) molar pregnancies. The meta-analysis was performed following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Six studies met the inclusion. Of the total 25,222 patients, 13,129 complete (52.1 %) and 12,093 partial (47.9 %) molar pregnancies were included. Live births rate after CHM was statistically higher (p = 0.002) compared to the live births after PHM (53.6 % vs. 51.0 %, 3266 vs. 1807 cases, respectively). Studies showed heterogeneity I2 = 57.7 %, pooled proportion = 0.2 %, and 95 % Confidence Interval (CI) 0.6 to 0.9. No statistically significant difference was demonstrated for ectopic pregnancies (p = 0.633), miscarriage (p = 0.637), preterm birth (p = 0.865), stillbirth (p = 0.911), termination of pregnancy (p = 0.572), and complete molar recurrence (p = 0.580) after CHM and PHM. Partial molar recurrence occurred more frequently after PHM than CHM (0.4 % vs. 0.3 %, 52 vs. 37 cases, respectively, p = 0.002). Careful counseling on the obstetric subsequent pregnancies outcomes should be provided to patients eager for further pregnancy and further studies are needed to confirm these results.

Confounding factors of transvaginal ultrasound accuracy in endometrial cancer.

Endometrial cancer is the most frequently diagnosed gynecological tumour. Transvaginal ultrasound has a leading role in the preoperative evaluation of endometrial cancer patients. The study aimed to identify factors that can worsen the diagnostic accuracy of transvaginal ultrasound in endometrial cancer patients. We retrospectively analysed 290 patients with histological diagnosis of endometrial adenocarcinoma. Two-dimensional (2D) gray-scale ultrasound and power Doppler imaging were performed. Age, menopause status, obesity, parity, Figo stage and benign uterine disorders were evaluated as possible factors worsening the diagnostic accuracy of the ultrasonography. FIGO stage IB was the main significant confounding factor in the univariate analysis (p = .004). Furthermore, 2D transvaginal ultrasound showed worse diagnostic accuracy in endometrial cancer patients with concomitant benign uterine pathologies.Impact statementWhat is already known on this subject? Many studies have analysed the reliability and diagnostic accuracy of transvaginal ultrasound in predicting myometrial invasion, but few studies have underlined the importance of confounding factors. Shin et al. (2011) showed that diffuse fibromatosis is a quality ultrasound confounding factor. Furthermore, Fischerova et al. (2014) showed that body mass index (BMI) did not influence the diagnostic accuracy of ultrasound assessment.What do the results of this study add? FIGO stage IB is the main factor worsening the diagnostic accuracy of transvaginal ultrasound in endometrial cancer patients (p = .004). Among the 82 patients with histologically proven FIGO stage IB, 27 (32.9%) had a wrong ultrasound prediction of myometrial infiltration. Twenty-one (36.2%) patients in whom there was no agreement between ultrasound prediction of myometrial infiltration and pathological analysis had fibromatosis and/or adenomyosis (p = 0.04).What are the implications of these findings for clinical practice and/or further research? Two-dimensional ultrasound represents a useful tool in the correct pre-operative setting of patients with endometrial cancer. In FIGO stages IB endometrial cancer patients and in conjunction with benign uterine pathologies, 2D transvaginal ultrasound has less diagnostic accuracy. In these cases, MRI still plays a leading role.

Prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers: what is going on in a region of northern Italy?

BACKGROUND: BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40-45 for BRCA2 mutation carriers. STUDY QUESTION: Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. STUDY DESIGN: Multicentre data collection by invitation to report current RRSO practices. RESULTS: A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p =  0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42-68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. CONCLUSIONS: The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.

Long term complications following pelvic and para-aortic lymphadenectomy for endometrial cancer, incidence and potential risk factors: a single institution experience.

OBJECTIVE: To determine the incidence of long term lymphadenectomy complications in primary surgery for endometrial cancer and to elucidate risk factors for these complications. METHODS: A retrospective chart review was carried out for all patients with endometrial cancer managed at Parma University Hospital Unit of Gynecology and Obstetrics between 2010 and 2016. Inclusion criteria were surgical procedure including hysterectomy and lymphadenectomy (pelvic or pelvic and aortic). We identified patients with postoperative lymphocele and lower extremity lymphedema. Logistic regression analysis was used to identify predictive factors for postoperative complications. RESULTS: Of the 249 patients tested, 198 underwent pelvic lymphadenectomy (79.5%), and 51 (20.5%) of those underwent both pelvic and para-aortic lymphadenectomy. Among the 249 patients, 92 (36.9 %) developed lymphedema while 43 (17.3%) developed lymphocele. Multivariate analysis showed that addition of para-artic lymphadenectomy was an independent predictor for both lymphedema (odds ratio (OR) 2.764, 95% confidence interval (CI) 1.023 to 7.470) and lymphocele (OR 5.066, 95% CI 1.605 to 15.989). Moreover, postoperative adjuvant radiotherapy (OR 2.733, 95% CI 1.149 to 6.505) and identification of any positive lymph node (OR 19.391, 95% CI 1.486 to 253.0) were significantly correlated with lymphedema, while removal of circumflex iliac nodes (OR 8.596, 95% CI 1.144 to 65.591) was associated with lymphoceles occurrence. CONCLUSION: Although sentinel lymph node navigation is a promising option, lymphadenectomy represents the primary treatment in many patients with endometrial cancer. However, comprehensive nodal dissection remains associated with a high rate of long term complications, such as lymphedema and lymphocele. Avoiding risk factors that are related to the development of these postoperative complications is often difficult and, therefore, the strategy to assess lymph nodal status in these women must be tailored to obtain the maximum results in terms of oncological and functional outcome.

Psychophysiological Adjustment to Ovarian Cancer: Preliminary Study on Italian Women Condition.

This study aimed to evaluate the psychological and physiological adjustment in a sample of Ovarian Cancer survivors. For all we know, this is the first time that such analysis has been performed in Italy. We assessed psychological adjustment along with physiological adjustment, measured through the basal Heart Rate Variability at rest. We assessed 38 women overall, aged 29-80 years, in follow up for ovarian cancer. Each participant filled a psycho-oncological record, Multidimensional Scale of Perceived Social Support, Derridford Appearance Scale-59, Mental Adjustment to Cancer and EORTC Quality of Life Questionnaire LQ-30 Version 3.0. For each participant, we recorded Heart Rate Variability (5 min). These women have shown a high rate of perceived general social support (Me = 5.93) but they seem to have some general concern about their appearance (Me = 85.97, SD = 24.4). They have also shown a rather good total Quality of Life (QL2 Me = 66.32) with specific difficulties in emotional functioning (EF; Me = 69.19). Heart Rate Variability values, however, were lower of nearly 50% when compared to normative values. These women, then, seem to drag concerns and difficulties, in particular linked to the acceptance of their condition. Surprisingly enough, the best adjustment in these women seems to be related to the worst starting conditions. It is possible to suggest that the extremely negative conditions force these women to face cancer openly, as well as their condition of cancer survivors, pushing them "moving on" more than "trying to get back".

Immunohistochemical Detection of Hematopoietic Cell-specific Protein-Tyrosine Phosphatase (Tyrosine Phosphatase SHP-1) in a Series of Endometrioid and Serous Endometrial Carcinoma.

In this study, we evaluated the expression of SHP-1 (PTPN6) in endometrioid (Ec) and serous (Sc) subtypes of endometrial carcinoma by immunohistochemical analysis. In total, 114 patients with Ec carcinoma and 48 patients with Sc carcinoma were enrolled in this study. The correlation between the type of histology, the grade of tumor, the stage of development, and immunoreactivity to SHP-1 was evaluated. Kaplan-Meier and multivariate survival analyses, using a Cox regression model, were performed to establish whether this marker has prognostic value in these malignancies, on the basis of follow-up and stratification of the patients according to their SHP-1 immunoreactivity. A significantly higher SHP-1 expression was observed in the Ec group compared with the Sc group (P=0.0005, Fisher exact test). In the Ec group, SHP-1 immunoreactivity was correlated with grading, demonstrating that more differentiated lesions expressed SHP-1 more frequently than less differentiated neoplasms (G1 vs. G2, P=0.0243, statistically significant value, Fisher exact test; G1 vs. G3, P=0.0088, extremely significant value, Fisher exact test). Instead, in the Sc group, SHP-1 expression was not correlated with grading, as Sc is now defined as a high-grade carcinoma. SHP-1 expression did not change with neoplastic progression in Ec and Sc groups. From both univariate and multivariate analysis in the Ec group, expression of SHP-1 remained a positive prognostic factor (P=0.004, log-rank test) [HR=0.32 (0.11 to 0.94), P=0.039]. In contrast, in the Sc group, no correlation between SHP-1 expression and survival was noted (P=0.77, log-rank test). In this study, we observed that the absence of SHP-1 in immunohistochemical analysis might serve as a marker of poor prognosis for a subset of high-grade endometrial cancer.

Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation.

The aim of the current study was to diagnose the concomitant presence of adenomyosis (AM) in endometrioid endometrial cancer (EEC) in order to evaluate its value as an oncological prognostic marker. A retrospective analysis of 289 patients diagnosed with EEC who underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic-lymphadenectomy was conducted. The total cohort included 37 patients in Group A (those with concomitant AM and EEC) and 252 patients in Group B (those affected only by EEC). The following factors were evaluated: Presence or absence of AM, tumor grade, depth of myometrial invasion, tumor size, lymphovascular space involvement, lymph node status, peritoneal cytology, concomitant detection of endometrial atypical-hyperplasia or polypoid endometrial features and tumor stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Uterine examination of different sections of uterine cervix, corpus, myomas and cervical or endometrial polyps was performed. The diagnosis of AM was confirmed when the distance between the lower border of the endometrium and the foci of the endometrial glands and stroma was >2.5 mm. Parametric and nonparametric statistical tests were performed when possible; continuous variables were analyzed using a Student's t-test, and categorical variables were analyzed by the χ2 test or Fisher's exact test. The association between FIGO stage and group was determined to be significant: 83.8% of Group A patients were categorized as FIGO stage I, vs. 68.7% of Group B patients. In addition, Group A was associated with lower grades in FIGO stage, myometrial invasion, lymphovascular space involvement, lymph node involvement and tumor size. The findings suggest that the intraoperative evaluation of the presence of AM in patients with EEC may aid surgeons in estimating oncological risk and in selecting the most appropriate surgical treatment.

Tubal ectopic pregnancy: our experience from 2000 to 2013.

In this paper we summarize our experience in diagnosis and treatment of 402 retrospectively collected tubal EP and review the most recent topics from the literature. Systemic Methotrexate (MTX) was effective in 56 out of 65 patients (failure rate 13.8%), in whom hCG level was significantly lower when compared to the failure group (p<0,05); we performed 299 salpingectomies, 297 of whom through laparoscopic approach. MTX single-dose is safe and effective in eligible patients; surgery represents the treatment of most of the EPs, mainly through laparoscopic approach.

Quality of life in patients affected by endometrial cancer: comparison among laparotomy, laparoscopy and vaginal approach.

The aim of this study is to verify if the surgical approach (laparoscopy/laparotomy/vaginal) in stage-I endometrial cancer treatment, may have effects on intra- and post-operative outcomes and on the patient's quality of life. The study group consisted of patients with histological diagnosis of type-I endometrial adenocarcinoma, stage-I. They were divided into three groups according to surgical approach chosen (laparotomic/laparoscopic/vaginal). Every patient answered a telephone health survey (SF-36) at 30 and 180 days post-surgery. Surgical-operating times, hospitalization length and short/long-term complications after surgery were also compared. The SF-36 survey revealed a better performance status in patients who underwent laparoscopy as compared to those who received laparotomy or vaginal surgery. We found significantly better results considering General Health, Physical Functioning, Role-Physical and Bodily Pain in the laparoscopy group after 30 and 180 days. Patients who underwent laparoscopy had significantly shorter hospitalization and less post-operative complications even if laparoscopy required significantly longer surgical-operating times compared to vaginal surgery. Our data confirm the superiority of the laparoscopic approach respect to the laparotomic and vaginal ones both in term of hospitalization length and post-operative complications.

Conservative treatment for interstitial monochorionic twin pregnancy: case report and review of the published work.

Interstitial pregnancy is considered one of the most hazardous types of ectopic pregnancies, with a mortality rate of 2-2.5%. We describe a case of a viable monochorionic twin pregnancy in a 35-year-old woman successfully treated with systemic methotrexate associated with bilateral uterine arteries' embolization. ß-hCG was undetectable 67 days after the first administration of methotrexate and the ultrasonography performed on day 67 showed the remnant of the gestational sac in the right uterine horn, a thin endometrium and a normal myometrial vascularization. Conservative treatment allowed us to avoid surgical treatment and to preserve the patient's fertility.

Two cases of low-grade endometriod carcinoma associated with undifferentiated carcinoma of the uterus (dedifferentiated carcinoma): a molecular study.

Dedifferentiated carcinoma (DC) is an uterine neoplasm containing both low-grade endometrioid carcinoma (LGEC) and undifferentiated carcinoma (UC). DC is an aggressive tumour even when the UC component represents only 20% of the entire neoplasm. In this paper, two cases DCs at different stages of development, in 61- and 83-year-old women respectively were reported. In addition, in these uterine malignancies microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in order to explain its aggressive behavior, in both components. Case #1 presented metastases at diagnosis, while case #2 was at a lower stage. LGEC component was invasive in case #1 and intramucous in case #2. In both cases, UC components were characterized by a high degree of instability, in accordance of its aggressive behaviour and its architectural heterogeneity. Further studies with more numerous cases are mandatory to confirm these data.

Clinicopathologic implications of the epidermal growth factor receptor, cyclooxygenase 2 expression, and human papillomavirus status in squamous cell carcinoma of the uterine cervix in the elderly.

OBJECTIVES: To find information on invasive squamous cervical carcinoma in the elderly, 110 invasive squamous cervical carcinomas obtained from 2 groups of patients (aged <60 and >60 years) were analyzed for human papillomavirus (HPV) status by polymerase chain reaction study, for immunohistochemical epidermal growth factor receptor (EGFR), cyclooxygenase 2 (Cox-2) expression, and clinicopathologic features. METHODS: The HPV status and the expression of Cox-2 and EGFR in the younger and older women were compared and correlated with the grading, staging neoplasm, and lymph nodal status, using Fisher test and Spearman nonparametric correlation test. Overall survival curves were drawn using Kaplan-Meier estimates and were compared using log-rank tests in the whole series of 110 patients. Multinomial logistic regression was also used. RESULTS AND CONCLUSIONS: The number of neoplasms with higher staging was significantly greater than those in the younger women (P = 0.04). The mortality was higher in the older group than in the younger patients (P = 0.006).In the elderly, the presence of HPV DNA in 65% of cases, and in the absence of sexual activity, could be due to reactivation of latent HPV infection, which might be due to an impairment of host immunologic response.The overexpression of Cox-2 in a number of cases was significantly higher in the older group than in the younger group (P = 0.032, Fisher exact test), but this immunoreactivity is not related to the staging, grading, EGFR expression, or to the presence of HPV.The simultaneous expression of Cox-2 and EGFR had a poor prognostic significance, showing lower survival rates than cases without this immunoreactivity (P = 0.002), on univariate analysis.On multivariate analysis, Cox-2 and EGFR immunopositivity did not reveal any correlation between these markers and prognosis probably because the number of cases considered was not particularly high.

Randomised prospective study of abdominal wall closure in patients with gynaecological cancer.

BACKGROUND: Median laparotomy is the most common approach to the abdominopelvic cavity in patients with gynaecological tumours. AIMS: The primary endpoint of the study was to evaluate the onset of incisional hernia. The secondary endpoint was to evaluate the onset of infection, wound dehiscence, wound infection, and scar pain during the post-operative period. METHODS: A total of 191 patients were eligible for the study. They were divided into three groups. Group A underwent en bloc closure of the peritoneum and fascia with Premilene suture, Group B en bloc closure of the peritoneum and fascia with Polydioxanone suture, and Group C separate closure of the peritoneum and fascia with single stitches of Ethibond suture. Statistical analysis was performed using the Statistical Software Package for Social Sciences 12.0. RESULTS: Group A and Group B comprised 63 patients, and Group C included 65 patients. The three groups proved homogeneous on statistical analysis (P > 0.05). The statistical analysis did not reveal significant differences between the different suture types and techniques with respect to the incidence of incisional hernia (P > 0.05). CONCLUSION: In our study, the incidence of incisional hernia was 8%. Randomised patients were homogeneous for sample size and risk factors. No significant differences were found between suture types or techniques. Currently, there is no suture material or technique that can be considered superior to others. When possible, we believe that the best way to prevent incisional hernia is to preserve the integrity of the abdominal wall using minimally invasive techniques.

Uterine tumors resembling ovarian sex cord tumors: a case report of conservative management in young women.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are distinguished into two separate groups: endometrial stromal tumors with sex cord-like elements (Group I), which have an unfavorable prognosis; and UTROSCT proper (group II), with more than 40% sex cord-like differentiation and less endometrial component, which are biologically less aggressive than the tumors of the other group. We report the case of a young woman with UTROSCT treated by minimally invasive hysteroscopic surgery. This is one of the few cases reported in the literature that have been managed conservatively.

Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women.

AIM: In this article, for the first time, we investigate the presence of human papillomavirus (HPV) DNA in ovarian epithelial neoplasms from a group of 71 Italian women. The follow ups of the patients with or without HPV DNA were also considered to evaluate whether HPV DNA in these tumors could be an indicator of prognosis. METHODS: HPV DNA was evaluated by polymerase chain reaction (PCR). Additionally P16 immunoreactivity was evaluated in all positive cases to demonstrate the presence of HPV. RESULTS: Only three cases out of 71 epithelial ovarian neoplasms (4.22%) in this series were weakly HPV positive. The presence of HPV DNA in these cases did not seem to be related with the type of neoplasm, their grade of differentiation, staging of development, patient's age or survival. CONCLUSION: The presence of HPV could be an expression of a latent infection. In both positive and negative HPV ovarian neoplasms, cervix showed only chronic cervicitis and no signal for HPV DNA on PCR analysis.

Preoperative transvaginal ultrasonography and intraoperative gross examination for assessing myometrial invasion by endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy. The cornerstone of treatment remains surgery according to International Federation of Gynecology and Obstetrics staging. The aim of this study was to evaluate the concordance between myometrial infiltration detected by ultrasonography and gross examination with respect to definitive histologic examination and to select a population in which lymphadenectomy could be excluded. We also evaluated the concordance for the degree of tumor differentiation between diagnostic biopsy and final histologic results. METHODS: Our study included 75 patients with International Federation of Gynecology and Obstetrics stage I endometrial cancer. We evaluated preoperative and definitive grading and myometrial infiltration detected by ultrasonography and gross examination. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the procedures under study were determined with the Bayes theorem. To determine the predictive value of preoperative transvaginal ultrasonography and intraoperative gross examination for myometrial invasion, we used a multiple logistic regression model with a statistical software package. RESULTS: Our study showed 60% concordance between biopsy and histologic results. In 80% of the cases with discordant results, the tumor was undergraded. Ultrasonography had diagnostic accuracy of 73%, whereas gross examination correctly determined myometrial invasion in 82.6% of the patients, with sensitivity of 62% and specificity of 79%. CONCLUSIONS: Preoperative transvaginal ultrasonography and macroscopic gross examination appear to be simple, fast, and reliable methods to predict in myometrial invasion in patients with a low risk for lymph node metastasis, for which lymphadenectomy can reasonably be avoided.

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms.

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

Transitional cell carcinoma of the endometrium associated with benign ovarian brenner tumor: a case report with immunohistochemistry molecular analysis and a review of the literature.

Transitional cell carcinoma of the endometrium (TCCE) is a subtype of endometrial carcinoma, characterized by a prominent papillary pattern, resembling the papillary carcinoma of the urothelium. This neoplasm is very rare, with only 13 cases reported in the international literature. In this paper, a new case of TCCE associated with benign ovarian Brenner tumor is described. This association is extremely rare, with only 1 other case reported. A review of the literature is performed to delineate the clinico pathologic features of this malignancy. Moreover, immunohistochemical and molecular studies are carried out in the effort to establish the phenotype and etiology of this rare neoplasm. The molecular study, by polymerase chain reaction (PCR) failing to reveal the presence of HPV DNA, demonstrates that neither the TCCE nor the ovarian Brenner tumor is caused by an HPV infection. The association of TCCE with benign ovarian Brenner tumor could be a coincidental event. Conversely, this finding could be the manifestation of a multicentric metaplastic process (neometaplasia), involving both the coelomic epithelium of the ovary and the Mullerian epithelium of the uterus, or the evidence of "field effect" that manifests differently at different anatomical sites. In our view, other cases of TCCE associated with ovarian Brenner tumor should be reported to confirm the last 2 hypotheses.

P16(INK4a) overexpression independent of Human Papilloma Virus (HPV) infection in rare subtypes of endometrial carcinomas.

In the current study, we evaluated p16 expression in rare subtypes of endometrial carcinomas, whose HPV status has been previously examined in order to establish the role of this protein in their pathogenesis. These rare subtypes of endometrial carcinomas are primary squamous endometrial carcinoma (ESCC), endometrial mucinous microglandular adenocarcinoma (EMMA), and endometrial transitional cell carcinoma (ETCC). All tissues, obtained at the time of hysterectomy, were fixed in 10% phosphate-buffered formalin and embedded in paraffin. Serial sections were made for hematoxylin and eosin staining and for immunohistochemistry. Although a previous PCR study has demonstrated that none of these neoplasms showed any signal for HPV DNA, these malignancies did display immunoreactivity for P16(INK4a). In ESCC, P16(INK4a) immunoreactivity was diffuse in 100% of neoplastic cells. In two cases of EMMA, positivity for P16INK4a was zonal. In ETCC, scattered cells were positive for P16INK4a protein. These findings suggest that alteration of p16 could play an etiologic role, without any association to HPV infections, in these rare endometrial carcinomas. However, in our view, other cases of these rare malignancies should be investigated in order to confirm this hypothesis.