Margin Status Post Cervical Conization Predicts Residual Adenocarcinoma In Situ (AIS) and Occult Adenocarcinoma in a Predominantly Hispanic Population.

Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment.

Variability in the identification of lymphovascular space invasion for early stage cervical cancer.

OBJECTIVE: To evaluate the inter- and intra-rater variability of lymphovascular space invasion (LVSI) in early stage cervical cancer. METHODS: We identified invasive cervical cancer tissue samples from radical hysterectomies in our institutional pathology database. The cases were stained with Hematoxylin & Eosin (H&E) and immunostains (CD-31 and D2-40). They were evaluated for the presence of LVSI by 6 pathologists on 3 separate occasions: with H&E staining only, then with H&E and immunostained specimens, and finally using a shared written criterion for diagnosis of LVSI. With 80 cases, a two-sided 95% confidence interval for the Kappa of 0.7 with a precision of 0.1 on each side was estimated. RESULTS: Stage distribution was: IA 10%, IB 85%, and IIA 5%. The majority of cases were squamous cell carcinoma (55%), followed by adenocarcinoma (39%) and adenosquamous or other histology (6%). The mean inter-rater Kappa was 0.41 (95% CI: 0.37-0.45) for H&E. Usage of immunohistochemistry made a statistically significant improvement in the mean Kappa, but it still remained low: 0.52 (p = 0.02). Adding evaluation criteria for LVSI did not significantly increase the mean Kappa: 0.49 (p = 0.16). The mean intra-rater variability of H&E staining alone compared with H&E staining plus immunostaining was 0.53 (range: 0.43-0.64). The mean Kappa comparing H&E staining and H&E staining with criteria was 0.50 (range: 0.40-0.59). CONCLUSIONS: We noted high inter- and intra-rater variability in the diagnosis of LVSI underscoring the challenges of LVSI diagnosis. Considering the significance assigned to LVSI and its implication for treatment, comprehensive guidelines with regards to determination of LVSI status are of paramount importance.

Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study.

OBJECTIVES: To explore whether the metabolic switches proceed or succeed the histological changes in precancerous lesions. To validate pyruvate kinase isoform 1 (PKM1) and pyruvate kinase isoform 2 (PKM2) as a histological biomarker to predict the progression of endometrial hyperplasia into invasive cancer status. METHODS: The records of 56 patients with a primary diagnosis of complex hyperplasia with atypia after endometrial biopsy were selected and analyzed retrospectively. A set of 3 consecutive sections at 4-µm thickness were cut and studied with immunohistochemical stains. From each case, 2 to 3 fields with a diagnosis of complex hyperplasia with atypia were selected and compared. A single pathologist blinded to the final diagnosis assigned the scoring. RESULTS: Positive immunostaining for PKM1 was observed in 31.25% (10 out of 32) of initial endometrial biopsy with the diagnosis of complex hyperplasia with atypia and final diagnosis of endometrial cancer, while 91.67% (out of 24) of patients with final diagnosis of negative endometrial cancer had endometrial biopsy with positive PKM1 staining ( P < .001). Positive immunostaining for PKM2 was observed in 100% of patient with endometrial biopsy result of endometrial hyperplasia with atypia (56 of 56). CONCLUSIONS: Lack of staining with PKM1 expression may help to predict the fate of endometrial hyperplasia. The disappearance of this marker is associated with the progression of hyperplasia toward cancer phenotype. Further studies are needed to understand the causes and potential mechanisms for suppressing Pyruvate Kinase Isoform 1 expression in endometrial hyperplasia.

Adenoid Cystic Carcinoma of Bartholin's Gland: Case Report.

Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare gynecologic malignancy. We report a case of locally advanced ACC of Bartholin's gland. A 62-year-old presented with left Bartholin's gland carcinoma and underwent left radical vulvectomy, left-sided inguinal-femoral lymph node dissection, posterior pelvic exenteration, and pedicle abdominal muscle flap. On her 3 months follow-up exam she was disease free.Pelvic exenteration for thetreatment of this rare disease in the vulva is a potential curative option.

Safety, feasibility and learning curve of robotic single-site surgery in gynecology.

BACKGROUND: Robotic single-site (RSS) surgery has emerged as a novel minimally invasive approach in gynecology. METHODS: Retrospective cohort study of consecutive RSS gynecologic procedures undertaken between October 2013 and March 2014. RESULTS: The 25 RSS completed cases consisted of 11 adnexal and 14 hysterectomy cases of which three included pelvic lymphadenectomies. Mean age, body mass index and estimated blood loss were 51 years, 25 kg/m(2) , 30 mL in the adnexal group, respectively, and 58 years, 27 kg/m(2) , 96 mL in the hysterectomy group, respectively. Mean console time was 20 and 45 min and mean total operative time was 56 and 93 min in adnexal and hysterectomy cases, respectively. The CUSUM method identified two learning phases with significant reduction in console time after the 7th adnexal case and the 5th hysterectomy. CONCLUSION: When performed by advanced minimally invasive surgeons and in appropriately selected patients, RSS surgery is feasible and safe. Copyright © 2015 John Wiley & Sons, Ltd.

Bevacizumab-induced transient sixth nerve palsy in ovarian cancer: A case report.

We report a case of transient sixth nerve palsy after systemic administration of bevacizumab. Two days after systemic administration of bevacizumab in conjunction with gemcitabine and carboplatin in a 67-year-old woman with recurrent primary ovarian cancer, the patient developed sixth nerve palsy. After bevacizumab was stopped, the complete left sixth nerve palsy resolved spontaneously over the course of 3 months. This is the first reported case of bevacizumab-induced cranial sixth nerve palsy in the treatment of gynecologic malignancy.

Pilonidal cyst of the clitoris.

A pilonidal cyst is an epithelialized sinus tract or cyst containing hair follicles with a surrounding inflammatory reaction. It usually develops in the sacrococcygeal region with few reports of its development in the genitalia. We present a case of a periclitoral pilonidal cyst in a young woman and its management.

Expression of H1.5 and PLZF in granulosa cell tumors and normal ovarian tissues: a short report.

PURPOSE: Ovarian granulosa cell tumors (GCTs) typically exhibit an excellent prognosis, but their recurrences are associated with high mortality rates. In the past, immunohistochemistry (IHC)-based approaches have been used to facilitate the distinction between GCTs and other, more frequently occurring, primary or metastatic tumors. The purpose of this study was to assess the added value of H1.5 and PLZF protein expression in the correct delineation of GCTs. METHODS: Consecutive 5-µm thick sections from routinely fixed and paraffin embedded tissues from 30 GCTs and 33 benign ovaries were processed for IHC using anti-PLZF and anti-H1.5 monoclonal antibodies. The respective protein staining intensities and distributions were quantified into reported scores for all tissue samples. Student's t-test and Fisher's exact test were used to compare the mean scores for each group. A p-value of <0.05 was considered statistically significant. Also, both the sensitivity and the specificity of the two antibodies were evaluated. RESULTS: A statistically significant difference in the expression of H1.5 between the GCT and normal ovary groups was observed (p < 0.0001). Normal ovarian tissues were found to strongly express H1.5, whereas GCTs were found to weakly express this protein. In contrast, PLZ expression was not found to be significantly different between both study groups. CONCLUSIONS: From our results we conclude that H1.5 is down-regulated in GCTs compared to normal ovarian tissues. Additional investigations on larger and more heterogeneous study populations, and on the molecular mechanism (s) underlying down-regulation of the H1.5 protein, may further substantiate the use of H1.5 as a diagnostic/prognostic marker and, in addition, provide insight into the pathogenesis of GCTs.

Immunohistochemical detection of promyelocytic leukemia zinc finger and histone 1.5 in uterine leiomyosarcoma and leiomyoma.

OBJECTIVES: The accurate distinction of leiomyoma from leiomyosarcoma is essential for patient management. However, the distinction can be difficult to make, particularly in tissue biopsy samples. Immunohistochemistry has been established as a useful technique to aid in the diagnosis of malignancies. The advantages of immunohistochemical studies are their ease of use and interpretation. This study is the first to evaluate the utility of the promyelocytic leukemia zinc finger (PLZF) protein and the histone 1.5 (H1.5) protein as potential diagnostic immunohistochemical markers for distinguishing leiomyosarcoma from leiomyoma. METHODS: Tissue samples from 21 leiomyosarcomas and 26 leiomyomas were studied. The student t-test and the Fisher exact test were used to calculate the differences in staining between the 2 groups. RESULTS: Statistically significant differences were found in the staining indices of anti-PLZF and anti-H1.5 when comparing benign and malignant tumors (P < .0001 and P < .0001, respectively). The mean H1.5 staining score in leiomyosarcomas was 158.3, compared to 28.3 in leiomyomas. The mean PLZF score in leiomyosarcomas was 1.5 in contrast to 71.5 in leiomyomas. For H1.5 at a score ≥60, the sensitivity and specificity were 90.5% and 84.6%, respectively. For PLZF, a score ≤15 had a test sensitivity and specificity of 100% and 80.8%, respectively. This suggests that staining for H1.5 or PLZF can serve as a good screening test. Additionally, combining the 2 immunostains results in a sensitivity and specificity of 90.5% and 97.5%, respectively, in differentiating between leiomyoma and leiomyosarcoma. CONCLUSIONS: We describe immunostaining for PLZF and H1.5 in benign and malignant uterine smooth muscle tumors. Statistically significant differences in staining patterns were found, suggesting utility in distinguishing leiomyosarcomas from leiomyomas.

Multicystic benign cystic mesothelioma presenting as a pelvic mass.

Background. Benign cystic mesothelioma (BCM) is a rare tumor that arises from the abdominal peritoneum with a predilection to the pelvic peritoneum. For this reason, it can often mimic gynecologic malignancies. Case. A 47-year-old perimenopausal female presented reporting several weeks of abdominal distention associated with abdominal tenderness and constipation. Computed tomography revealed a 24 cm multiloculated pelvic mass, and tumor markers were notable for an elevated CA-125. The patient was taken to the operating room for an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingoophorectomy, and removal of pelvic mass. Final pathologic evaluation revealed a benign cystic mesothelioma. Conclusion. Classically these tumors present as large multicystic masses with thin-walled septations and on preoperative evaluation BCM can mimic many different disease entities including ovarian malignancies and cystic lymphangioma. Often diagnosis can only be made at time of surgery.

The role of liver resection at the time of secondary cytoreduction in patients with recurrent ovarian cancer.

OBJECTIVE: The aim of this study is to determine the role of liver metastatectomy in the morbidity and survival of patients with recurrent ovarian carcinoma. METHODS: We retrospectively reviewed the records of all patients who had undergone hepatic resection for liver metastases from ovarian carcinoma at the time of cytoreductive surgery at our institution from 1988 to 2012. The Kaplan-Meier method was used for survival analysis. A total of 76 patients met the inclusion criteria and had undergone liver resection as part of cytoreductive surgery for ovarian carcinoma during the study period. Of these 76 patients, 27 underwent liver resection at the time of secondary cytoreduction, and these patients that are the focus of this analysis. RESULTS: Median overall survival for the study group from the time of diagnosis to the last follow-up or death was 56 months (range, 12-249 months). Twenty died of the disease with an overall median survival of 12 months from the time of the liver resection (2-190 months), and 7 patients were alive with the disease at the time of the last follow-up. Based on Kaplan-Meier survival analysis, the factors associated with the longest survival after the liver resection (2-190 months) were the interval from the primary surgery of less than 24 months versus more than 24 months (P = 0.044) and secondary cytoreduction to residual disease of less than 1 cm (P = 0.014). CONCLUSIONS: Based on our analysis of a single institution's series of ovarian cancer patients with hepatic metastasis, liver resection is feasible and safe and should be considered as an option in selected patients at the time of secondary cytoreduction.

Survival analysis of robotic versus traditional laparoscopic surgical staging for endometrial cancer.

OBJECTIVE: The purpose of this study was to compare the survival of women with endometrial cancer managed by robotic- and laparoscopic-assisted surgery. STUDY DESIGN: This was a retrospective study conducted at 2 academic centers. Primary outcomes were overall survival, disease-free survival (DFS), and disease recurrence. RESULTS: From 2003 through 2010, 415 women met the study criteria. A total of 183 women had robotic and 232 women had laparoscopic-assisted surgery. Both groups were comparable in age, body mass index, comorbid conditions, histology, surgical stage, tumor grade, total nodes retrieved, and adjuvant therapy. With a median follow-up of 38 months (range, 4-61 months) for the robotic and 58 months (range, 4-118 months) for the traditional laparoscopic group, there were no significant differences in survival (3-year survival 93.3% and 93.6%), DFS (3-year DFS 83.3% and 88.4%), and tumor recurrence (14.8% and 12.1%) for robotic and laparoscopic groups, respectively. Univariate and multivariate analysis showed that surgery is not an independent prognostic factor of survival. CONCLUSION: Robotic-assisted surgery yields equivalent oncologic outcomes when compared to traditional laparoscopic surgery for endometrial adenocarcinoma.

Placental abruption and fetal demise secondary to placental metastases from unknown primary: a case report.

BACKGROUND: Although maternal malignancy is relatively common, maternal metastases to the products of conception remains a rare event. There is no available literature that describes the incidence of placental metastases as a cause of abruption and fetal death. importanc CASE: We present an unusual case of placental abruption and disseminated intravascular coagulation leading to fetal demise secondary to placental metastases of unknown origin. CONCLUSION: In our case placental abruption likely resulted from metastases to the intervillous space.

Five-millimeter balloon trocar site herniation: report of two cases and review of literature.

Trocar site herniation is a well-known potential complication of minimally invasive surgery. We present the cases of two herniations after use of 5-mm non-bladed balloon trocars. In both patients, surgical management was required, with no subsequent sequelae to date. The hernias were attributed to excessive fascial stretching and compression by the balloon. We recommend full-thickness closure of 5-mm ports if a balloon is used or if there was extensive intraoperative manipulation.

Biomarkers for early detection of ovarian cancer.

Ovarian cancer is the most lethal gynecological malignancy. However, effective screening strategies have not been established and continue to be elusive. A good screening test must adequately address validity, reliability, yield, cost, acceptance and follow-up services. An ideal screening test for ovarian cancer must have a high sensitivity in order to correctly diagnose all women with the disease and a high specificity to avoid false-positive results. The current screening modalities of bimanual examination, CA-125 and transvaginal ultrasonography together allow us to detect only 30-45% of women with early-stage disease. Recent developments in proteomic and genomic research have identified a number of potential biomarkers. Although panels of tumor markers and proteomic-based technologies may improve the positive predictive value, all markers require validation and interfacing with newly developed diagnostic imaging technologies. While a large amount of information on miRNAs has been promising, much remains to be elucidated. This review will examine the current status of biomarkers and technologies of interest in the effort of early detection of ovarian cancer.

Burns, hypertrophic scar and galactorrhea.

An 18-year-old woman was admitted to Motahari Burn Center suffering from 30% burns. Treatment modalities were carried out for the patient and she was discharged after 20 days. Three to four months later she developed hypertrophic scar on her chest and upper limbs. At the same time she developed galactorrhea in both breasts and had a disturbed menstrual cycle four months post-burn. On investigation, we found hyperprolactinemia and no other reasons for the high level of prolactin were detected.She received treatment for both the hypertrophic scar and the severe itching she was experiencing. After seven months, her prolactin level had decreased but had not returned to the normal level. It seems that refractory hypertrophic scar is related to the high level of prolactin in burns patients.

Primary pulmonary carcinoid tumor with metastasis to endometrial polyp.

INTRODUCTION: A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE: We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION: This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION: This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp.

Does the type of surgery for early-stage endometrial cancer affect the rate of reported lymphovascular space invasion in final pathology specimens?

OBJECTIVE: Laparoscopically assisted vaginal hysterectomy (LAVH), which usually involves the use of an intrauterine manipulator for optimal surgical control, has been shown to be as effective and safe as conventional total abdominal hysterectomy (TAH) for the staging of endometrial carcinoma. The purpose of this study was to determine whether the use of an intrauterine manipulator was associated with an increase in the pathologic reporting of lymphovascular space invasion (LVSI), which is an important determinant in choosing adjuvant therapy. We hypothesized that intracavitary manipulation and an increase of the intrauterine pressure could cause pseudolymphovascular invasion. STUDY DESIGN: We performed a retrospective chart review of endometrial cancer patients treated at our institution from January 1996 through January 2006. Records were reviewed for patient's age, preoperative diagnosis, procedure type, final surgical staging, and final pathology report. Using the 2009 International Federation of Gynecology and Obstetrics staging, we included all patients having stage IA or IB endometrioid-type endometrial cancer who had undergone either a TAH or LAVH with or without pelvic and paraaortic lymph node dissection. The χ2 and Fisher exact tests were used to measure the association between risk of positive lymphovascular invasion and surgical groups. RESULTS: Of 568 women identified as having endometrioid-type endometrial cancer, 486 (85.6%) met criteria for stage IA-IB endometrioid histology, grade 1, 2, or 3. LVSI was reported in 553/568 cases, with LVSI positivity in 16.9% (n = 96/568). The mean ages of the LAVH and TAH groups were significantly different (59.4 vs 62.4 years, respectively, P = .0050). Also, mean estimated blood loss and uterine weight significantly varied between TAH and LAVH groups (P = .0001 and .008, respectively). For stage IA, 17/220 (7.7%) who had been treated with LAVH had positive LVSI compared with 20/199 (10.1%) of patients receiving TAH (P = .73). For stage IB, 11/25 (44.0%) of patients treated with LAVH had positive LVSI compared with 10/31 (32.3%) of patients receiving TAH (P = .53). The stage I cancer patients were further subdivided into histological grades 1, 2, and 3, and LVSI was not significantly different between TAH and LAVH groups per grade of cancer. We found no differences between TAH and LAVH in early-stage endometrial cancer (stage IA and IB), with respect to the presence of positive peritoneal washings. CONCLUSION: In early-stage endometrial cancer (stage IA and IB), there were no differences between TAH and LAVH in the final pathologic report of LVSI. The use of an intrauterine manipulator for LAVH was not associated with an increased detection of LVSI.

A meta-analysis of the relationship between endometrial thickness and outcome of in vitro fertilization cycles.

OBJECTIVE: The objective was to evaluate the relationship between endometrial thickness on the day of human chorionic gonadotropin administration and pregnancy outcome in in vitro fertilization cycles. DESIGN: This was a systematic review and meta-analysis. MATERIALS AND METHODS: We identified 484 articles using Cochrane library, PubMed, Web of Science, and Embase searches with various key words including endometrial thickness, pregnancy, assisted reproductive technology, endometrial pattern, and in vitro fertilization. A total of 14 studies with data on endometrial thickness and outcome were selected, representing 4922 cycles (2204 pregnant and 2718 nonpregnant). The meta-analysis with a random effects model was performed using comprehensive meta-analysis software. We calculated the standardized mean difference, odds ratio (OR), and 95% confidence intervals (CIs). RESULTS: There was a significant difference in the mean endometrial thickness between pregnant and nonpregnant groups (P<0.001), with a standardized mean difference of 0.4 mm (95% CI 0.22-0.58). The OR for pregnancy was 1.40 (95% CI 1.24-1.58). CONCLUSIONS: The mean endometrial thickness was significantly higher in pregnant women compared to nonpregnant. The mean difference between two groups was <1 mm which may not be clinically meaningful. Although there may be a relationship between endometrial thickness and pregnancy, implantation potential is probably more complex than a single ultrasound measurement can determine.

Burn injuries during pregnancy in Iran.

OBJECTIVE: To report on maternal and fetal outcome in 53 pregnant women seen at a referral burn center. METHODS: Possible links between outcome and maternal age, level of education, marital status, percentage of total body surface area (TBSA) burned, inhalation injury, source and intentionality of the burn, and trimester of pregnancy at the time of the burn were assessed. RESULTS: Of 5,497 women, 53 (1.3%) were pregnant at the time of admission. Maternal and fetal deaths occurred at significantly higher rates in cases of inhalation injury (P=0.001). The mean percentage of TBSA burned was significantly higher in cases of maternal or fetal death (P<0.001 for both), and when the burn has a suicidal intent (P=0.006). The maternal and fetal mortality rates were also higher when the burn was suicidal (P=0.001 and P=0.005). CONCLUSION: Inhalation injury, suicidal burn injury, and percentage of TBSA burned were correlated with a higher maternal and fetal mortality.