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Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and β-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant β-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered β-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant β-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant β-catenin expression were frequent events in SRCCs of various organs, and that the altered β-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/β-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.

Using a comprehensive next-generation sequencing pipeline (143 genes), Oncomine Comprehensive v.2, we analyzed genetic alterations on a set of vulvar squamous cell carcinomas (SCCs) with emphasis on the primary and metastatic samples from the same patient, to identify amenable therapeutic targets. Clinicopathologic features were reported and genomic DNA was extracted from 42 paraffin-embedded tumor tissues of 32 cases. PD-L1 expression was evaluated in 20 tumor tissues (10 cases with paired primary and metastatic tumors). Fifteen (88%) of 17 successfully analyzed HPV-unrelated SCCs harbored TP53 mutations. 2 different TP53 mutations had been detected in the same tumor in 4 of 15 cases. Other recurrent genetic alterations in this group of tumors included CDKN2a mutations (41%), HRAS mutations (12%), NOTCH1 mutations (12%) and BIRC3 (11q22.1-22.2) amplification (12%). Six HPV-related tumors harbored PIK3CA, BAP1, PTEN, KDR, CTNNB1, and BRCA2 mutations, of which, one case also contained TP53 mutation. Six cases showed identical mutations in paired primary site and distant metastatic location and four cases displayed different mutational profiles. PD-L1 expression was seen in 6 of 10 primary tumors and all 6 paired cases showed discordant PD-L1 expression in the primary and metastatic sites. Our results further confirmed the genetic alterations that are amenable to targeted therapy, offering the potential for individualized management strategies for the treatment of these aggressive tumors with different etiology. Discordant PD-L1 expression in the primary and metastatic vulvar SCCs highlights the importance of evaluation of PD-L1 expression in different locations to avoid false negative information provided for immunotherapy.

Despite mounting evidence that large intramural leiomyomas decrease fecundity during in vitro fertilization cycles, few studies have demonstrated a mechanism for this impact. We hypothesize that large intramural leiomyomas (IM) decrease the expression of endometrial implantation factors during the window of implantation. We prospectively recruited sub-fertile patients with IM 3 cm or greater in size planning myomectomy and performed endometrial biopsies the day of planned myomectomy (n = 9). Preoperative screening demonstrated no intercavitary lesions. Control endometrial samples were obtained from young, normally menstruating women free of uterine leiomyomas (n = 8). Endometrial samples were obtained in the mid-secretory phase (average cycle day for control patients and intramural leiomyoma patients were 24.5 and 21.3, respectively). Expression of implantation markers HOXA10, leukemia inhibitory factor (LIF), ER-α, and PR was compared using quantitative immunohistochemistry. Standard descriptive statistics were used to compare H-scores between the cohorts. Patients with intramural leiomyomas were found to have decreased LIF compared to controls (p value

The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3.Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue.Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort.pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy.

Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare but extremely aggressive tumor. While high-risk human papillomavirus (HPV) is involved at an early stage of oncogenesis in many tumors, additional driving events have been postulated to facilitate the progression of SCNECs. Identification of oncogenic drivers could guide targeted therapy of this neoplasm. Clinicopathologic features of 10 cervical SCNECs are reported. Analyses included immunohistochemical evaluation of p16, p53, synaptophysin, and chromogranin expression; in situ hybridizations and polymerase chain reaction for high-risk HPV and/or HPV 18; and next-generation sequencing based on a 637-gene panel. The patients ranged in age from 28 to 68 years (mean, 45.6 y; median, 40.5 y). All tumors had diffuse p16 and synaptophysin expression. All but 1 tumor was positive for chromogranin (extent of staining ranged from focal to diffuse). HPV 18 was detected in 6 tumors and HPV 35 in 1 tumor. At least 1 driver mutation was detected in 8 tumors. Four cases harbored TP53 somatic mutations, 3 of which correlated with an aberrant p53 staining pattern. Four PIK3CA mutations (p.G106A, p.N345T, p.E545K, and p.E545D) were detected in 3 tumors, 2 of which also harbored TP53 mutations. Oncogenic driver mutations involving KRAS, Erbb2, c-Myc, NOTCH1, BCL6, or NCOA3 were detected in 4 tumors. Mutations in caretaker tumor suppressors PTEN, RB1, BRCA1, BRCA2, and ARID1B were also identified in 4 tumors that commonly coharbored activating oncogenic mutations. Targeted next-generation gene sequencing identified genetic alterations involving the MAPK, PI3K/AKT/mTOR, and TP53/BRCA pathways in SCNECs. The presence of genetic alterations that are amenable to targeted therapy in SCNECs offers the potential for individualized management strategies for treatment of this aggressive tumor.

To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon.Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA.Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01% to 0.07%.In this pilot study, DNA derived from tumor was detected in the vaginas of 60% of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.

// Zachary C. Dobbin 1,2 , Ashwini A. Katre 1 , Adam D. Steg 1 , Britt K. Erickson 1 , Monjri M. Shah 1 , Ronald D. Alvarez 1 , Michael G. Conner 3 , David Schneider 4 , Dongquan Chen 5 and Charles N. Landen 6 1 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham 2 NIH Medical Scientist Training Program, University of Alabama at Birmingham 3 Department of Pathology, University of Alabama at Birmingham 4 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham 5 Division of Preventative Medicine, Department of Medicine, University of Alabama at Birmingham 6 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Virginia, Charlottesville, VA Correspondence: Charles N. Landen Jr, email: // Keywords : Ovarian Cancer, Patient-derived xenograft, cancer stem cells, chemoresistance, animal models of cancer Received : August 08, 2014 Accepted : August 18, 2014 Published : August 19, 2014 Abstract A cornerstone of preclinical cancer research has been the use of clonal cell lines. However, this resource has underperformed in its ability to effectively identify novel therapeutics and evaluate the heterogeneity in a patient’s tumor. The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy, but also basic tenets of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of six pair of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer

OBJECTIVE. Carcinosarcomas are rare and aggressive ovarian malignancies. Treatment recommendations, which include surgical cytoreduction followed by platinum based chemotherapy, have been based on small amounts of retrospective data or extrapolated from experience with high-grade epithelial ovarian adenocarcinoma. Our objective was to determine the effects of radical primary cytoreduction on progression-free survival (PFS) and overall survival (OS). METHODS. Following IRB approval, records of women with ovarian carcinosarcomas diagnosed between 2000 and 2012 at our institution were reviewed. Demographics, tumor characteristics, treatments, PFS, and OS were collected. Patients were divided into three groups based on the amount of residual disease: N1 cm of disease, ≤1 cm of disease, or no visible disease. Chi-square and student’s t-test were used to compare variables among groups. Kaplan–Meier survival curves were generated and compared with the log-rank test. RESULTS. 51 patients with ovarian carcinosarcoma were identified and all underwent primary cytoreductive surgery. Following surgical cytoreduction, 18 patients (35%) had no visible disease, 20 (39%) had ≤1 cm of disease, and 13 (25%) had >1 cm of residual disease. Median PFS varied significantly among groups: 29 vs. 21 vs. 2 months (p = 0.036) as did median OS: 57 vs. 32 vs. 11 months (p = 0.015). When patients with stage 3 disease were analyzed separately, median OS still varied significantly among groups: 57 versus 31 versus 3 months (p = 0.009). CONCLUSION. Degree of surgical cytoreduction appears to correlate with PFS and OS. Radical surgery resulting in no visible disease is recommended for the upfront surgical treatment of ovarian carcinosarcoma.

We report a case of extramedullary hematopoiesis (EMH) in uterine leiomyoma and associated numerous intravascular thrombi. A 29-year-old nulliparous female presented with heavy vaginal bleeding and a hematocrit of 22%. No bone marrow biopsy has been performed. She had a history of uterine leiomyomata and menorrhagia for a year. A transvaginal ultrasound confirmed the presence of a uterine leiomyoma. The patient was treated conservatively with oral contraceptive pills due to desire for fertility. However, she continued to have heavy vaginal bleeding and developed bilateral upper extremity deep vein thrombosis and multiple superficial vein thromboses after two months. An exploratory laparotomy with uterine myomectomy was performed. Gross examination of the specimen revealed a single nodular mass measuring10.0×9.5×7.5 cm with a white-tan swirling cut surface. Microscopic examination revealed benign smooth muscle consistent with leiomyoma and numerous intravascular thrombi both with areas of EMH. Immunohistochemical stains confirmed the presence of all three benign lineages of hematopoietic cells. Occurrence of EMH in uterine leiomyoma and intravascular thrombi is very rare. It may be related to systemic hematopoietic stimulation due to severe chronic anemia and local presence of hematopoietic growth factors and/or cytokines.

Advanced cases of epithelial ovarian, primary peritoneal, and primary tubal malignancies have a relatively poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Although traditionally thought of as one disease process, ongoing research suggests that there is not 1 single site or cell type from which these cancers arise. A majority of the serous tumors appear to originate from dysplastic lesions in the distal fallopian tube. Therefore, what we have traditionally considered “ovarian” cancer may in fact be tubal in origin. In this article, we will review epithelial ovarian cancer classification and genetics, theories regarding cells of origin with a focus on tubal intraepithelial carcinoma, and implications for prevention and screening.

Malignant transformation in a mature cystic teratoma (MCT) is rare, with a reported incidence of approximately 1% to 3%. To our knowledge, no case has been reported previously with the invasion of malignant tumor of MCT into the adjacent small intestine. We report a case of squamous cell carcinoma arising within a MCT and invading into the adjacent small bowel. The patient is a 73-yr-old African American woman who noted the presence of a relatively asymptomatic abdominal mass over the past 40 yr. The mass had become more symptomatic over the past several months, with right-sided abdominal pain and constipation. She underwent an exploratory laparatomy, which demonstrated a cystic abdominal mass measuring 24 cm in diameter and weighing 8 kg. The mass contained necrotic debris, a cloudy fluid, hair, and cartilage. It was adherent to the small intestine in an area associated with focal thickening of the cystic wall of the mass. Histologically, the mass demonstrated a MCT within which arose a well-differentiated squamous cell carcinoma. At the point of attachment to the small intestine, histologic sections demonstrated a transmural invasion of the squamous cell carcinoma into the attached segment of the small intestine through the muscularis propria and the submucosa reaching the mucosal surface. Thirteen regional lymph nodes were isolated near the portion of the small intestine involved with the tumor; however, none of them exhibited metastatic carcinoma.

• HVO focuses on the education, surgical training and development of research skills of surgical oncology residents.

This study aimed at evaluating the expression of tyrosine kinase receptors c-kit, (platelet-derived growth factor receptor-alpha (PDGFR-alpha), and PDGFR-beta in ovarian granulosa cell tumors (GCTs).Primary ovarian GCT specimens were obtained for immunohistochemical staining.The expressions of c-kit, PDGFR-alpha, and PDGFR-beta were analyzed and scored by a semiquantitative (SQ) method. Normal ovarian tissue from the same patients' specimens served as internal controls.A total of 21 specimens were available for evaluation. C-kit was expressed in only 2 samples, whereas both PDGFR-alpha and PDGFR-beta stained positive in 100% of tumors. PDGFR targets demonstrated strong positive expression in intensity and amount of tissue stained. Normal ovarian tissue demonstrated complete absence of staining for all 3 antibodies evaluated.The data demonstrated significant expression of PDGFR targets of imatinib mesylate in GCTs, whereas normal ovarian tissues had a complete absence of staining.This expression profile provides the rationale to investigate the role of imatinib mesylate in PDGFR-positive GCTs.

In this report, we present the case of a 32-year-old woman with Wegener's granulomatosis of the uterine cervix, review the literature, and discuss the differential diagnosis.

Describe the effect of 50 mcg vaginal 17-β-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse.Seventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-β), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP).Serum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p=0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p=0.03) and itching (p=0.02) improved. Tissue biomarker levels did not change (TGF-β p=0.35, NFKB p=0.74, eNOS p=0.80, iNOS p=0.24, TSP p=0.80).Vaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.

To prospectively evaluate in a blinded fashion the accuracy of frozen section in endometrial cancer.Sixty patients with endometrial cancer or complex atypical hyperplasia were consecutively enrolled. Intraoperatively, a frozen section was obtained, processed, and stored for interpretation by blinded pathologists. Final pathologic diagnosis was conducted in the usual fashion with the pathologists blinded to frozen results. Histologic grade and myometrial invasion on frozen section was correlated with final pathology.Median age was 61 years (range, 39-82 years). Fifty-seven percent of patients were white, and mean body mass index was 40 mg/kg2. Depth of invasion on frozen correlated with final pathology in 67% (95% confidence interval [CI] 55-79%). Twenty-eight percent (95% CI 17-39%) of patients were upstaged from frozen to final. Patients with no invasion on frozen were upstaged in 46% (95% CI 28-64%). Histologic grade on frozen correlated with final pathology in 58% (95% CI 46-70%); 38% (95% CI 26-50%) of patients were upgraded by final grade. Patients with frozen grade 1 histology or less were upgraded in 61% (95% CI 45-77%). Clinically relevant upstaging occurred in 11 patients (18%) (95% CI 8-28%).Frozen section for histologic grade and depth of myometrial invasion in endometrial cancer correlates poorly with final pathology. Because a large number of patients are potentially understaged with the use of frozen section with a subsequent risk of over and under treatment, we recommend consideration of comprehensive surgical staging for all patients with endometrial cancer.II-2.

Aging in humans is characterized by a selective decline in circulating levels of adrenal androgens. The results of in vivo studies are suggestive of reduced adrenal 17,20-lyase activity in aging men and women.We sought to determine whether there are changes in the distribution and/or expression of cytochrome B5 (CytB5), an accessory protein important in the regulation of 17,20-lyase activity, in the adrenals of aging humans.Comparison between younger and older adrenal glands.The study was conducted in a University Center.Adrenal glands obtained at autopsy after sudden death as a result of trauma from 46 young (age 20-40 yr) and 26 older (age 50-91 yr) humans were obtained and fixed within 24 h postmortem.Paraffin sections were stained with hematoxylin and eosin and also were subjected to immunohistochemical staining for CytB5. All sections were quantitatively evaluated using an image capture and analysis program and qualitatively evaluated with respect to staining intensity.To determine whether there are any changes in CytB5 distribution in the adult human adrenal cortex during the aging process using qualitative and quantitative analysis with respect to age, gender, race, and postmortem interval.CytB5 immunoreactivity was found in cells that corresponded to those of the zona reticularis. The percentage of the adrenal cortex immunoreactive for CytB5 decreased with aging (38.6 +/- 7.6% for young and 30.1 +/- 5.9% for older, mean +/- sd; P0.0001) as did the percentage of adrenocortical tissue comprising the zona reticularis (36.8 +/- 10.8% for young and 27.2 +/- 5.9% for older; P0.001). However, there was no apparent change in the staining intensity of CytB5 among those cells that were immunopositive for this factor with aging.There appears to be a reduction in the proportion of the adrenal cortex that expresses CytB5 with aging, and this likely corresponds to a shrinkage of the zona reticularis. The mechanism and cause for this cortical regression are unknown.

A 23-year-old female underwent a cesarean section for breech presentation at term. Her postpartum course was complicated by multiple admissions for pelvic pain presumed to be endometritis. Her symptoms were temporarily alleviated with intravenous antibiotics during each hospitalization. Imaging to evaluate persistent abdominal pain revealed a large cystic right lower quadrant mass adjacent to the ovary. Findings at diagnostic laparoscopy included a 15-cm × 4-cm appendix with pathology confirming myxoglobulosis. This case describes the only reported case of myxoglobulosis of the appendix presenting as a rare cause of pelvic pain in a postpartum patient. (J GYNECOL SURG 20:127)

Androgens are an integral part of human physiology. The de novo production of androgens is generally limited to the adrenal cortex and the gonads. Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17, which catalyzes both 17 hydroxylase and 17,20 lyase activities. 17,20-lyase activity is relevant to the regulation of androgen production, and is allosterically modulated through the action of an accessory protein, cytochrome b5 (CytB5). Our objective was to determine the cellular localization of P450c17 and CytB5 in androgen-synthesizing tissues of the human. Immunohistochemical analyses of P450c17 and CytB5 were performed on fetal and adult human adrenals, ovaries, and testes. In the fetal adrenal, CytB5 and P450c17 were both found in the cells of the fetal zone, but not in the neocortex. In the adult adrenal, the zona fasciculata was immunoreactive for P450c17 only, whereas the zona reticularis was immunopositive for both P450c17 and CytB5. In the adult gonads, P450c17 and CytB5 were colocalized in the Leydig cells of the testis, theca interna cells of the follicle, theca lutein cells, and isolated cell clusters in the ovarian stroma. Whereas P450c17 and CytB5 were colocalized in the Leydig cells of the fetal testes, there was no immunostaining for either in the midgestational fetal ovary. Our findings of colocalization of CytB5 and P450c17 are strongly supportive of the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human.

Background: Despite its favorable prognosis, endometrial stromal sarcoma (ESS) commonly recurs in the abdomen and pelvis. Rarely, it recurs in the cardiovascular system. A case of isolated cardiac ESS recurrence without concurrent vascular or abdominal disease is presented in this report. Case: A 53-year-old woman with previously diagnosed and treated ESS presented to her physician with tachycardia and fatigue. Transthoracic echocardiogram revealed an intra-atrial pedunculated mass without caval involvement. Results: Surgical resection was performed successfully with alleviation of the patient'sher symptoms. Pathology confirmed isolated intracardiac recurrent ESS. Conclusions: This is the first documented case of intracardiac recurrence of ESS without concurrent abdominal or intracaval disease. This isolated recurrence supports a hematogenous mechanism of spread for ESS rather than intracavitary diffusion. Aggressive surgical management continues to be an option for treatment. (J GYNECOL SURG 28:140)

Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Coexisting pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent “normal” cervical epithelium from six formalin-fixed paraffin-embedded (FFPE) samples were selected. Tissues from these 18 samples were isolated using laser capture microdissection, RNA was extracted and sequenced. RNA-sequencing (RNA-seq) generated 2.4 billion raw reads in 18 samples, of which approximately 50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one third of the sample pairs (same direction and FDR p

Objective. The Wnt/β-catenin pathway is known to regulate cellular proliferation and plays a role in chemoresistance. Niclosamide, an FDA approved salicyclamide derivative used for the treatment of tapeworm infections, targets the Wnt/β-catenin pathway. Therefore, the objective of this study was to investigate niclosamide as a potential therapeutic agent for ovarian cancer. Methods. Tumor cells isolated from 34 patients' ascites with primary ovarian cancer were treated with niclosamide (0.1 to 5 μM) ± carboplatin (5 to 150 μM). Cell viability was assessed using the ATP-lite assay. LRP6, Axin 2, Cyclin D1, survivin and cytosolic free β-catenin levels were determined using Western blot analysis. Tumorspheres were treated, and Wnt transcriptional activity was measured by the TOPflash reporter assay. ALDH and CD133 were analyzed by Flow cytometry and IHC. ALDH1A1 and LRP6 were analyzed by IHC in solid tumor and in ascites before and after treatment with niclosamide. Results. Combination treatment produced increased cytotoxicity compared to single agent treatment in 32/34 patient samples. Western blot analysis showed a decrease in Wnt/β-catenin pathway proteins and the expression of target genes. A significant reduction of Wnt/β-catenin signaling was confirmed by TOPflash assay. There was increased staining of ALDH1A1 and LRP6 in ascites compared to solid tumor which decreased after treatment. Conclusion. This study demonstrates that niclosamide is a potent Wnt/β-catenin inhibitor. Targeting the Wnt/β-catenin pathway led to decreased cellular proliferation and increased cell death. These findings warrant further research of this drug and other niclosamide analogs as a treatment option for ovarian cancer.

Nonpuerperal uterine inversion is an extremely rare gynecologic event. The vast majority of nonpuerperal inversions occur in association with a uterine tumor, of which approximately 20% are malignant. The case of a 74-year-old patient with suspected primary cervical sarcoma is presented. At the time of surgery, nonpuerperal uterine inversion was identified. High-grade endometrial stromal sarcoma was confirmed on pathologic examination. The etiologic factors that constitute the differential diagnosis are discussed, as well as strategies for managing this unusual entity.

Background. Clear cell adenocarcinoma (CCA) of the vagina is traditionally treated with radical surgical resection with tailored postoperative radiation when indicated. Due to a bimodal distribution, women of reproductive age are frequently affected and could benefit from radical trachelectomy to preserve fertility. Case. A 22 year old female was diagnosed with clinical stage I vaginal clear cell adenocarcinoma in the left fornix abutting the cervix. The patient desired future fertility; therefore, she underwent radical abdominal trachelectomy and upper vaginectomy. Twenty-eight months after initial surgery, she has no evidence of recurrence with regular menstrual cycles. Conclusion. For patients with CCA of the upper vagina, where removal of the cervix is necessary, a radical trachelectomy with upper vaginectomy should be considered to conserve fertility.

Background. Although mature cystic teratoma is the most common tumor of the ovary, squamous cell carcinoma arising from a mature teratoma is a rare event. Prognosis depends on clinical stage, grade, and recently described mode of tumor infiltration. Case. This case involves a 52-year-old woman with stage II squamous cell carcinoma arising in a mature cystic teratoma of the left ovary. Final pathology demonstrated poorly differentiated squamous cell carcinoma with gamma mode of tumor infiltration. The patient completed adjuvant chemotherapy and subsequently died of progressive disease. Conclusion. Squamous cell carcinoma arising from a benign cystic teratoma is a rare event. Studies have shown stage, grade, and mode of infiltration to be predictors of recurrence and prognosis. This case supports the growing evidence linking the mode of tumor infiltration with overall prognosis of survival.

Background Positron emission tomography (PET) is commonly used to detect occult or recurrent malignancy, including tumors of the female genital tract. Recently, there have been reports of PET scans used in patients with Gestational Trophoblastic Disease (GTD). Case A 22-year-old female presented with vaginal bleeding and elevated β-hCG 7 months after a spontaneous vaginal delivery of a healthy infant. She had a history of molar pregnancy and persistent GTD requiring multi-agent chemotherapy. Metastatic evaluation with computed tomography and magnetic resonance imaging showed no evidence of GTD. A positron emission tomography/computed tomography (PET/CT) scan revealed a focus of metabolic activity in the left pelvis. The patient underwent an exploratory laparotomy that revealed metastatic choriocarcinoma in the left broad ligament. Conclusion PET/CT may be useful in the evaluation of occult choriocarcinoma when conventional imaging fails to identify metastatic disease.

To determine the radiographic characteristics of ovarian granulosa cell tumors (GCTs) and to evaluate the use of CA125 levels35 in combination with imaging as an algorithm for preoperative diagnosis.A retrospective analysis of women from two academic medical centers who were diagnosed with ovarian GCT between January 1998 and August 2012 was conducted. Clinical data included tumor appearance on pre-operative imaging and CA125 levels. Ovarian cysts were defined as complex if imaging exhibited multicystic areas, hemorrhagic, solid, or cystic and solid components. A CA125 level35 was abnormal.One hundred and fifteen women were diagnosed with GCTs, of whom 63 underwent pre-operative imaging. Median age at surgery was 46 years (12-87). Forty women had preoperative ultrasounds, 43 had CT scans and 20 underwent both modalities. GCTs were almost exclusively classified as complex cysts in 62 (98%) cases. The most common morphology was solid and cystic (n=44 (70%)). Forty-four (70%) patients had tumors10 cm. Forty-two patients had a pre-operative CA125 performed. Eighteen (43%) patients had complex masses and CA12535. Twenty-three (55%) had CA12535 with a complex mass, and one (2%) had a unilocular cyst with a CA12535.In this study, there was a near equal distribution of patients with complex masses and CA125 levelsor35. If established strategies to predict malignancy are applied to GCTs, we will frequently fail to make the diagnosis pre-operatively. Additional research is necessary to generate an appropriate algorithm to guide pre-operative referral to a gynecologic oncologist.

Managed mental health care cost-containment practices of risk-benefit analysis, provider usage, manipulation of supply and demand, gate keeping, medical necessity, and formulation have adversely affected quality of care. Improved mental health services are dependent upon redefining mental health problems and understanding inequities created by medicalization as means to limit access to services. This dilemma can be addressed by development of mental health policy, public education, and political advocacy. An immediate role for professional psychology is found in the creation of a research agenda that documents empirically supported interventions for specific mental health problems, mechanisms of effective and acceptable service-delivery, and identification of providers with demonstrated clinical skills, including cultural competencies.

Altered glycosylation is a key hallmark of tumor cells; still, the role of individual glycosyltransferases remains unclear. ST6Gal-I is a tumor-associated sialyltransferase which catalyzes the addition of a sialic acid sugar to substrate glycoproteins. Addition of the negatively-charged sialic acid by ST6Gal-I has been shown to alter receptor conformation, clustering, and surface retention, leading to changes in downstream signaling. In this study we assayed ST6Gal-I by immunohistochemistry and report the great majority of patient ovarian and pancreatic tumors express this enzyme. In contrast, the normal epithelium expresses minimal ST6Gal-I. Enzyme expression in ovarian cancers is enriched during metastasis and correlates with worse progression-free and overall survival. Recent evidence points to ST6Gal-I activity in stem/progenitor cells. In light of this, we investigated whether ST6Gal-I functionally promotes a cancer stem cell (CSC) phenotype, i.e. resistance to chemotherapy, survival as tumorspheroids, and ability to initiate tumors. We previously reported that ST6Gal-I activity confers resistance to cisplatin; we now show its activity additionally confers resistance to gemcitabine in pancreatic tumor cells. ST6Gal-I expressing cells are enriched in patient derived xenografts (PDX) treated with gemcitabine suggesting that these cells preferentially survive chemotherapy in vivo. In addition to chemoresistance, ST6Gal-I promotes the growth of pancreatic and ovarian cell lines in tumorspheroid culture. Moreover, ST6Gal-I expressing primary tumor cells isolated from ovarian cancer ascites or PDX tumors survive in tumorspheroid culture, whereas ST6Gal-I negative cells do not. Conversely, forced expression of ST6Gal-I protects tumor cells exposed to the ascites fluid milieu in vitro, while non-ST6Gal-I expressing cells succumb to this inflammatory environment. In a limiting dilution tumor initiating assay, ST6Gal-I expressing cells have a higher tumor incidence and form larger tumors compared to cells with ST6Gal-I knockdown. We next created a conditional mouse model with forced ST6Gal-I expression in the intestinal tract and used AOM-DSS chemically-induced carcinogenesis model to evaluate tumor formation. Compared with wildtype mice, ST6Gal-I knock-in mice have a greater tumor burden, evidenced by increased tumor number and area. As a novel mechanistic link beteween ST6Gal-I and the CSC phenotype, direct modulation of ST6Gal-I levels in tumor cells regulates the expression of stem-related transcription factors, Sox9 and Slug, implicated in tumor progression. The finding that a distinct glycosyltransferase governs the expression of key transcription factors highlights the tumor glycome as a driving factor in CSC behavior. Citation Format: Matthew J. Schultz, Andrew T. Holdbrooks, Asmi Chakraborty, William E. Grizzle, Charles N. Landen, Donald J. Buchsbaum, Michael G. Conner, Rebecca C. Arend, Karina J. Yoon, Chris A. Klug, Daniel C. Bullard, Robert A. Kesterson, Patsy G. Oliver, Amber K. O’Connor, Bradley K. Yoder, Susan L. Bellis. The tumor associated sialyltransferase ST6Gal-I promotes a cancer stem cell phenotype and upregulates stem-related transcription factors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3327.

Purpose: Endoglin (CD105) is a membranous protein overexpressed in tumor-associated endothelial cells, chemoresistant populations of ovarian cancer cells, and potentially stem cells. Our objective was to evaluate the effects and mechanisms of targeting endoglin in ovarian cancer. Experimental Design: Global and membranous endoglin expression was evaluated in multiple ovarian cancer lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline comet assay, γ-H2AX foci formation, and quantitative PCR. In an orthotopic mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and without carboplatin. Results: Endoglin expression was surprisingly predominantly cytoplasmic, with a small population of surface-positive cells. Endoglin inhibition decreased cell viability, increased apoptosis, induced double-stranded DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and SIRT1. BARD1 was also associated with platinum resistance, and was induced by platinum exposure. In vivo, antiendoglin treatment decreased tumor weight in both ES2 and HeyA8MDR models when compared with control (35%–41% reduction, P < 0.05). Endoglin inhibition with carboplatin was associated with even greater inhibitory effect when compared with control (58%–62% reduction, P < 0.001). Conclusions: Endoglin downregulation promotes apoptosis, induces significant DNA damage through modulation of numerous DNA repair genes, and improves platinum sensitivity both in vivo and in vitro. Antiendoglin therapy would allow dual treatment of both tumor angiogenesis and a subset of aggressive tumor cells expressing endoglin and is being actively pursued as therapy in ovarian cancer. Clin Cancer Res; 19(1); 170–82. ©2012 AACR.

BACKGROUND: Uterine leiomyosarcoma is an aggressive tumor that has a propensity for distant metastasis. Distant sites of spread include the lung, liver, brain, and bone. CASE: A woman in her 5th decade was diagnosed with stage IV leiomyosarcoma of the uterus. Distant metastasis in the chest was confirmed by thoracotomy at the time of her original diagnosis. She subsequently experienced multiple episodes of metastasis including metastatic disease to her thyroid. She survived 71 months after diagnosis of stage IV disease. CONCLUSION: Our case represents the first reported experience with uterine leiomyosarcoma metastatic to the thyroid. Additionally the case is notable because the patient experienced multiple episodes of asymptomatic stable disease after repetitive chemotherapeutic regimens.

Purpose: Within heterogeneous tumors, subpopulations often labeled cancer stem cells (CSC) have been identified that have enhanced tumorigenicity and chemoresistance in ex vivo models. However, whether these populations are more capable of surviving chemotherapy in de novo tumors is unknown. Experimental Design: We examined 45 matched primary/recurrent tumor pairs of high-grade ovarian adenocarcinomas for expression of CSC markers ALDH1A1, CD44, and CD133 using immunohistochemistry. Tumors collected immediately after completion of primary therapy were then laser capture microdissected and subjected to a quantitative PCR array examining stem cell biology pathways (Hedgehog, Notch, TGF-β, and Wnt). Select genes of interest were validated as important targets using siRNA-mediated downregulation. Results: Primary samples were composed of low densities of ALDH1A1, CD44, and CD133. Tumors collected immediately after primary therapy were more densely composed of each marker, whereas samples collected at first recurrence, before initiating secondary therapy, were composed of similar percentages of each marker as their primary tumor. In tumors collected from recurrent platinum-resistant patients, only CD133 was significantly increased. Of stem cell pathway members examined, 14% were significantly overexpressed in recurrent compared with matched primary tumors. Knockdown of genes of interest, including endoglin/CD105 and the hedgehog mediators Gli1 and Gli2, led to decreased ovarian cancer cell viability, with Gli2 showing a novel contribution to cisplatin resistance. Conclusions: These data indicate that ovarian tumors are enriched with CSCs and stem cell pathway mediators, especially at the completion of primary therapy. This suggests that stem cell subpopulations contribute to tumor chemoresistance and ultimately recurrent disease. Clin Cancer Res; 18(3); 869–81. ©2011 AACR.

To evaluate patterns of failure and overall survival for patients with surgical stage I uterine carcinosarcoma managed conservatively without adjuvant therapy. A computerized database identified 27 patients whose conditions have been diagnosed with surgical stage I uterine carcinosarcoma from 1993 to 2002. Charts were abstracted for patient demographics, tumor characteristics, recurrence, and survival. Of 27 patients, 23(85%) did not receive adjuvant therapy after undergoing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. Five patients were stage IA, 14 were stage IB, and 4 were stage IC. Fourteen patients had either poorly differentiated endometrioid carcinoma alone or in combination with papillary serous carcinoma (61%) as their epithelial tumor component. The median nodal count was 9 (range, 3-21). Eleven patients are alive without evidence of disease with a median follow-up of 63 months (range, 12-164 months). Eleven patients had recurrence with a median time to recurrence of 13 months (range, 6-39 months), and all are dead of disease. Univariate analysis demonstrated that poorly differentiated epithelial or papillary serous histologic diagnosis was the only predictor variable associated with recurrence and, consequently, death (P = 0.04). Approximately 50% of patients with surgical stage I carcinosarcoma who are observed without adjuvant therapy will experience a recurrence. Because most patients will recur distantly, systemic chemotherapy should be considered for patients with early stage uterine carcinosarcoma.

Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (HE) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed HE alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using HE diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for HE/p16/Ki-67 combined were comparable to that of HE alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, HE/p16/Ki-67 combined, and HE alone.Interobserver agreement for diagnosis of AIN was fair when based solely on HE preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with HE, Ki-67, and HE/p16/Ki-67 combined.

Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is the most common hereditary cancer syndrome in the United States and Europe. More than 50% of women diagnosed with Lynch syndrome will present with a gynecologic malignancy as their sentinel cancer; the majority of these cancers will be endometrial cancer.1 HNPCC is caused by a germline mutation in the DNA mismatch repair mechanism that works to ensure the fidelity of the genome during cell division.2 The most common mutations are MLH1, MSH2, MSH6, and PMS2; defects in these genes result in microsatellite instability.3 Per the Modified Bethesda criteria recommendations, patients less than age 50 diagnosed with colorectal cancer should undergo testing to determine whether they have a genetic mutation associated with Lynch syndrome (see the Box). Although approximately 11% of patients under the age of 50 diagnosed with endometrial cancer will have a mutation consistent with Lynch syndrome,4 no recommendations for genetic testing exist specific to endometrial cancer.5 Modified Bethesda Criteria Tumors from individuals should be tested for microsatellite instability in the following situations: Colorectal cancer diagnosed in a patient who is less than 50 years of age. Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors,* regardless of patient age. Colorectal cancer with the microsatellite instability-H–like histology diagnosed in a patient who is less than 60 years of age. Colorectal cancer diagnosed in a patient with one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed before the age of 50. Colorectal cancer diagnosed in a patient with two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age. *HNPCC-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain tumors; sebaceous gland adenomas and keratoacanthomas in Muir-Torre syndrome; and carcinoma of the small bowel. The purpose of this study was to estimate the frequency of mismatch repair deficiencies detected by immunohistochemistry and microsatellite instability testing in women less than age 50 with endometrial cancer. Additionally, we sought to evaluate whether obesity affected the frequency of mismatch repair deficiencies.

Umbilical endometriosis is rare and can be a challenging diagnosis in the absence of classic signs and symptoms.A case of severe, primary, spontaneous umbilical endometriosis with foci of plasma cell endometritis and diffuse stromal lymphovascular presence occurred.Despite a lengthy differential, endometriosis must be considered in the evaluation of an umbilical mass. The presence of plasma cell endometritis and stromal lymphovascular elements in the absence of pelvic endometriosis lends evidence to the theory of lymphovascular transport as an etiology of extrapelvic endometriosis.

This chapter will be devoted to infrequently encountered lesions of the female reproductive tract. Some of these will be lesions that are rarely seen, while others will be lesions that you may anticipate seeing from time to time, although certainly not everyday.

The purpose of this study was to explore whether endometrial microbial colonization and plasma cell endometritis are risk factors for adverse pregnancy outcomes, and whether these outcomes are influenced by interactions between interconceptional antibiotics and the micro-flora.Subgroup analyses of data from a double-blind, randomized, placebo-controlled trial of a course of metronidazole plus azithromycin given every 4 months to women with a prior preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histology were obtained at randomization and repeated 2 weeks after the first treatment. Fifty-nine on antibiotics versus 65 on placebo had pregnancy outcomes. Prevalence of adverse pregnancy outcomes (pregnancy loss or preterm birth37 weeks) was stratified by treatment group and endometrial characteristics. Subgroups were assessed and screened for potential interaction (P values for significance set a priori at.01), prior to formal statistical testing for interaction (P values.05).The prevalence of adverse pregnancy outcome was 62.7% in the presence of endometrial microbial colonization at baseline (any microbe) and 50% in the absence of colonization (RR = 1.25; 99% CI 0.42-3.7). Prevalence of adverse pregnancy outcomes was 61.9% with plasma cell endometritis, and 70.8% without; RR = 0.87 (0.50-1.5). There was a nonsignificant reduction in adverse pregnancy outcome in the absence of Gardnerella vaginalis or gram-negative rods with RR (95% CI) = 0.60 (0.3-1.2) and 0.66 (0.4-1.2), respectively. In the presence of these microbes, antibiotics appeared to increase adverse outcomes: RR = 1.5 (1.1-2.0) and 1.5 (1.1-2.1), respectively. This reversal of impact represents a crossover interaction.Neither baseline endometrial microbial colonization nor plasma cell endometritis were risk factors for adverse pregnancy outcome. However, colonization with specific microbes interacted with antibiotics to increase adverse outcomes.

OBJECTIVE A pilot study to determine genomic microarray differences in patients with normal cervical tissue and cervical intraepithelial neoplasia (CIN) 3. MATERIALS AND METHODS After institutional review board approval, patients referred to the University of Alabama at Birmingham Colposcopy Clinic for a loop electrosurgical excisional procedure were identified. Tissue biopsies of both normal tissue and CIN 3 from fresh loop electrosurgical excisional procedure specimens were obtained and sent to pathology for histological confirmation. Procurement of these 2 types of tissue from the same patient controls for different types of human papillomavirus infection, smoking and nutritional status, age, immunocompetency, and other microenvironment factors (i.e., the patient serves as their own control). Standard RNA extraction techniques (Qiagen, Inc., Valencia, CA) were used to prepare the tissue specimens for microarray analysis with the Affymetrix GeneChip U133A expression array (Affymetrix, Inc., Santa Clara, CA). Paired samples were eligible for microarray analysis only when both normal tissue and CIN 3 were confirmed by pathology. The data were then subsequently subjected to a log-like transformation and analyzed with a t test. For this study, p

The purpose of this study was to evaluate the impact of an interconception antibiotic regimen on endometrial microbial flora and histologic type.This was a secondary analysis of a double-blind randomized placebo-controlled trial of prophylactic metronidazole plus azithromycin that was given to 241 women (antibiotics, 118 women; placebo, 123 women) with a previous preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histologic types were obtained at randomization and 2 weeks after treatment. The prevalence of either the new acquisition or the resolution of individual microbes, categories of microbes, and plasma cell endometritis were compared by chi-square or Fishers' exact tests.Overall, antibiotics were associated with lower acquisition and higher resolution of microbes. Of women without Gardnerella at baseline, 14% of the women who received antibiotics vs 34% of the women who received placebo had positive endometrial culture for the organism after treatment (P.05); of those women with G. vaginalis at baseline, 57% of the women who received antibiotics vs 33% of the women who received placebo (P.05) had a negative follow-up culture. Other gram-negative rods, especially aerobes in general, manifested similar patterns. The impact on anaerobes and plasma cell endometritis was not definitive, but there was a trend toward the increased resolution of the former (77% vs 55%) and reduced acquisition of the latter (28% vs 50%).The antibiotic regimen prevented the acquisition and promoted the resolution, but not the eradication, of gram-negative rods such as G. vaginalis and the aerobic subcategory.

Background Inflammatory pseudotumor is a rare benign cause of lymphadenopathy previously reported in several anatomic locations that can simulate malignant neoplasm. Case A postmenopausal woman presented with abdominal pain, generalized malaise, leukocytosis, and intermittent fevers up to 102 degrees F. A 5-day course of antibiotics was given with persistence of symptoms. Computed tomography of the abdomen and pelvis demonstrated an ill-defined, retroperitoneal soft-tissue density, and lymphadenopathy. She underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and unilateral pelvic and paraaortic lymphadenotomy. Histologic examination revealed inflammatory pseudotumor of the lymph nodes, with immunohistochemical studies demonstrating actin-positive myofibroblastic cells. Four months after surgery, the patient remains asymptomatic without evidence of disease. Conclusion Inflammatory pseudotumor of the pelvic lymph nodes is a rare entity and should be included in the differential diagnosis of patients with persistent fever and lymphadenopathy.

Background. Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that is generally resistant to conventional chemotherapeutic treatment. Patients with localized disease are usually managed with hysterectomy. Case. A 29-year-old female presented with vaginal bleeding and an elevated serum human chorionic gonadotropin (HCG). After initial observation, the patient experienced continued vaginal bleeding and a persistently elevated HCG. Therefore, she underwent a dilation and curettage and final pathology revealed PSTT. Since the patient desired future fertility, the patient received combination chemotherapy with etoposide, methotrexate, actinomycin-D followed by etoposide and cisplatin (EMA-EP). The patient had a complete response to chemotherapy and subsequently delivered a term infant 2 years after completion of therapy. Conclusion. PSTT is thought to be a chemoresistant disease and the preferred method of treatment is hysterectomy or local uterine resection. However, combination chemotherapy is a reasonable option in a properly counseled patient who strongly desires future fertility.