Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer.

Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).

Inguinal Node Metastasis of Low-Grade Endometrial Endometrioid Adenocarcinoma in a Morbidly Obese Patient.

BACKGROUND: The accurate preoperative evaluation of endometrial cancer is needed to inform disease staging, but the evaluation may be more prone to error if the physical signs of advanced stage disease are difficult to appreciate in morbidly obese patients. CASE: A morbidly obese (BMI = 56.9 kg/m2) 67-year-old woman with postmenopausal uterine bleeding was diagnosed with low-grade stage IB endometrial endometrioid adenocarcinoma after surgical staging. She received adjuvant vaginal brachytherapy. Fourteen months after surgery she presented with an ulcerating left inguinal mass. Fine-needle biopsy demonstrated adenocarcinoma consistent with her primary endometrioid adenocarcinoma. At the time of initial diagnosis, a preoperative physical examination was negative for inguinal lymphadenopathy and a computed tomography(CT) demonstrated inguinal lymphadenopathy that was not appreciated. CONCLUSION: In morbidly obese patients, the sensitivity of a physical examination is limited by body habitus. Obese patients with limited physical examinations may benefit from imaging studies to aid early diagnosis of extraperitoneal disease.

Incidental Finding of Synchronous, Benign, Metastasizing Leiomyoma with Distinct Cytogenetics in the Lung and Uterus.

This paper will present a case of benign metastasizing leiomyoma, incidentally found during the preoperative evaluation for acute cholecystitis. The preoperative chest X-ray revealed diffuse bilateral lung nodules suspicious for hematogenous metastasis and the densities measured 1-1.5 cm. A pelvis computed tomography (CT) scan showed in-homogeneous uterine mass with unusual vascular supply raising concern for leiomyosarcoma. Open lung biopsy revealed benign-appearing smooth-muscle neoplasm suggestive of metastatic leiomyoma. The patient was then treated with total abdominal hysterectomy with bilateral salpingo-oopherectomy which had identical pathology to the lung. As there were innumerable pulmonary metastases where complete resection was impossible, surgical castration appeared to be effective in reducing tumor size. The patient was also started on an aromatase inhibitor that subsequently improved her clinical outcome. Management strategies, cytogenetics, and histological diagnosis are discussed.

Endometrial Ablation for Aplastic Anemia-Associated Menorrhagia.

Aplastic anemia is characterized by bone marrow failure and pancytopenia. In women, this can lead to menorrhagia secondary to thrombocytopenia which may require treatment depending on its severity. We report a patient with aplastic anemia-associated menorrhagia requiring emergency inpatient endometrial ablation due to transfusion dependence. A 42-year-old G3P3003 female presented with severe anemia, thrombocytopenia, and metrorrhagia. Her subsequent bone marrow biopsy revealed aplastic anemia. Her menometrorrhagia progressively worsened and she remained transfusion dependent. In the hospital, the patient underwent an uneventful endometrial ablation to control her vaginal bleeding. Patient reports only minor spotting after the procedure. Endometrial ablation is a safe and effective technique of treating acute menorrhagia in patients with aplastic anemia. It can reduce vaginal bleeding and decrease transfusion dependence.

Metastatic Uterine Leiomyosarcoma Involving Bilateral Ovarian Stroma without Capsular Involvement Implies a Local Route of Hematogenous Dissemination.

Uterine sarcomas spread via lymphatic and hematogenous dissemination, direct extension, or transtubal transport. Distant metastasis often involves the lungs. Ovarian metastasis is uncommon. Here we present an unusual case of a large, high-grade uLMS with metastatic disease internal to both ovaries without capsular involvement or other abdominal diseases, and discovered in a patient with distant metastases to the lungs, suggesting likely hematogenous dissemination of uLMS to the ovaries in this case. Knowledge of usual uLMS metastases may influence surgical management in select cases.

Presence of both Mesenchymal and Carcinomatous Features in an In-vitro Model of Ovarian Carcinosarcoma Derived from Patients' Ascitic Fluid.

We have refined the technique for isolating and propagating cultures of primary ovarian carcinosarcoma cells (OSCs) derived from ascites, which allowed the cells to obtain the biphasic features of carcinosarcoma in cell culture conditions (presence of both carcinoma and mesenchymal morphologic types). This protocol involves a simple yet rapid method for the growth and propagation of ascites OSC in a basal culture medium. Autologous ascitic fluid was used as source of growth factors, and minimal manipulation was involved to establish the culture. The methodology allowed for the direct application of multiple molecular, cellular, and functional analyses within a few weeks of initial cell isolation, with the further potential of retrospective analyses of archived cells and tissues.

Feasibility, Sensitivity, and Specificity of Postprocedure Peritoneal Cytology.

The objective of this study was to determine the feasibility and diagnostic performance of cytopathologic evaluation of postprocedure washings collected after hysterectomy for gynecologic cancer. A total of 92 cases of hysterectomy for malignancy having cytology reports of both pre- and postprocedure washings were retrospectively identified. In all, 98.7% of preprocedure and 99.3% of postprocedure washings (P = 1.00) were satisfactory for cytopathology. Discordance regarding the observation of malignant cells between preprocedure and postprocedure washings was insignificant (P = .267). The sensitivity of postprocedure cytology for detecting malignant cells in cases of positive peritoneal histology was significantly lower than the sensitivity of preprocedure cytology (28.6% vs 57.1%, P = .041), with similar specificities (both 94%). Four patients with endometrial cancer having negative preprocedure peritoneal cytology were discovered to have positive postprocedure cytology. Postprocedure peritoneal cytology is feasible and may benefit patients with early-stage cancer by increasing the detection of microscopic peritoneal metastasis or cancer cell seeding during surgery.

Mullerian adenosarcoma of the cervix: Report of two large tumors with sarcomatous overgrowth or heterologous elements.

•Two cases of large cervical mullerian adenosarcoma with sarcomatous overgrowth or heterologous elements and contrasting survival outcomes are reported.•When the diagnosis of mullerian adenosarcoma is uncertain or suspected, review of pathology by a national expert may be considered.•Rhabdomyoblastic differentiation of mullerian adenosarcoma may be a more aggressive histologic type.

Genetic counseling for hereditary breast and gynecologic cancer syndromes at a community hospital.

Genetic screening and testing has been shown to be medically and emotionally beneficial for patients with a personal history or strong family history of breast, ovarian, and/or colorectal cancer. Gynecologic oncologists increasingly utilize genetic screening to modify their care and treatment plans of patients and their offspring based on inherited susceptibility to cancer. The U.S. Preventive Services Task Force (USPSTF) developed specific criteria that consider the medical, psychosocial, and ethical ramifications of genetic counseling of high-risk individuals. Genetic counseling and screening, along with early intervention, is of benefit to women with family histories suggestive of harboring breast cancer antigen (BRCA) mutations. The Western Connecticut Health Network (WCHN) Hereditary Cancer and Genetic Counseling Program provides a comprehensive cancer risk assessment and offers genetic screening as appropriate. This report describes trends in patient referrals, intake, results of genetic testing, and an expansion of services in a community-based genetic counseling program.

Vulvar metastasis of an early-stage well-differentiated endometrial cancer after minimally invasive surgery.

Endometrial cancer is the most common gynecologic malignancy, often manifesting as early-stage well-differentiated endometrioid adenocarcinoma associated with a high likelihood of long-term recurrence-free survival. Minimally invasive surgery for surgical staging of endometrial lesions is now routinely practiced, with laparoscopy the preferred surgical approach at many cancer centers. Recurrence or metastasis of early-stage well-differentiated endometrial endometrioid adenocarcinoma is uncommon, and may occur due to iatrogenic microscopic seeding of malignant cells during surgery, as suggested by previous reports of cancer metastasis to port sites after minimally invasive surgery, laparotomy incisions after open surgery, or intraperitoneal spread after hysteroscopy or uterine manipulation. Herein we report the only described case of isolated vulvar metastasis of an early-stage FIGO stage IB well-differentiated (histologic grade 1) endometrial endometrioid adenocarcinoma after minimally invasive surgery for surgical staging. The patient had recurrent endometrioid adenocarcinoma metastasis at the vulva 8 months after robotic-assisted total laparoscopic hysterectomy and surgical staging with specimen removal through the vagina. In selected cases, we suggest that use of a specimen bag during removal of the uterus through the vagina may limit seeding of malignant cells during minimally invasive surgery to treat cancer.

Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma.

Ovarian cancer remains the most common cause of gynecologic cancer-related death among women in developed countries. Nevertheless, subgroups of ovarian cancer patients experience relatively longer survival. Efforts to identify prognostic factors that characterize such patients are ongoing, with investigational areas including tumor characteristics, surgical management, inheritance patterns, immunologic factors, and genomic patterns. This review discusses various demographic, clinical, and molecular factors implicating longevity and ovarian cancer survival. Continued efforts at identifying these prognosticators may result in invaluable adjuncts to the treatment of ovarian cancer, with the ultimate goal of advancing patient care.

Human papillomavirusassociated cancers as acquired immunodeficiency syndrome defining illnesses.

The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV)-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS) defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

Clinical utility of chromogranin A and octreotide in large cell neuro endocrine carcinoma of the uterine corpus.

Primary neuroendocrine tumors of the female genital tract have been described in the cervix, ovaries and uterus. Large cell neuroendocrine carcinoma (LCNC) of the uterine corpus is the least common and appears to behave the most aggressively. We report a rare case of a large cell neuroendocrine tumor of the endometrium. These tumors are not well characterized, unlike neuroendocrine tumors of the uterine cervix. Consequently, the optimal management remains still unclear. The treatment of our case consisted of surgery, radiotherapy, chemotherapy, and octreotide. Despite the aggressive treatment, the patient died of disease progression 12 months after the initial diagnosis. We discuss the diagnosis, prognosis, and treatment options for LCNC of the genital tract, and potential future therapeutics.