Occult symptomatic bilateral pure Leydig cell tumors in a postmenopausal woman: a case report.

BACKGROUND: Pure Leydig cell tumors (LCTs) represent 0.1% of ovarian masses. Postmenopausal patients typically present with virilization. Although LCTs can be challenging to locate on conventional imaging, positron emission tomography (PET) has been demonstrated to be effective. CASE: A 64-year-old postmenopausal woman presented with alopecia, facial hirsutism, and clitoromegaly. Laboratory findings included elevated testosterone and androstenedione. Ultrasound, computed tomography, and magnetic resonance imaging showed no adnexal masses. PET did not demonstrate ovarian fludeoxyglucose-avidity. Histopathology after bilateral salpingo-oophorectomy revealed bilateral Leydig cell tumors. Her testosterone normalized 2 weeks postoperatively. CONCLUSION: We describe the occult, symptomatic, bilateral ovarian Leydig cell tumors, an occurrence that has not been described in the literature. Virilizing tumors must be considered in patients with evidence of hyperandrogenism, even without pelvic masses on imaging.

Racial disparities in molecular subtypes of endometrial cancer.

OBJECTIVES: Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated. METHODS: Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients. RESULTS: There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients. CONCLUSIONS: The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities.

Impact of age at diagnosis on racial disparities in endometrial cancer patients.

INTRODUCTION: Although black patients with endometrial cancer (EC) have worse survival compared with white patients, the interaction between age/race has not been examined. The primary objective was to evaluate the impact of age at diagnosis on racial disparities in disease presentation and outcome in EC. METHODS: We evaluated women diagnosed with EC between 1991 and 2010 from the Surveillance, Epidemiology, and End Results. Mutation status for TP53 or PTEN, or with the aggressive integrative, transcript-based, or somatic copy number alteration-based molecular subtype were acquired from the Cancer Genome Atlas. Logistic regression model was used to estimate the interaction between age and race on histology. Cox regression model was used to estimate the interaction between age and race on survival. RESULTS: 78,184 white and 8518 black patients with EC were analyzed. Median age at diagnosis was 3-years younger for black vs. white patients with serous cancer and carcinosarcoma (P<0.0001). The increased presentation of non-endometrioid histology with age was larger in black vs. white patients (P<0.0001). The racial disparity in survival and cancer-related mortality was more prevalent in black vs. white patients, and in younger vs. older patients (P<0.0001). Mutations in TP53, PTEN and the three aggressive molecular subtypes each varied by race, age and histology. CONCLUSIONS: Aggressive histology and molecular features were more common in black patients and older age, with greater impact of age on poor tumor characteristics in black vs. white patients. Racial disparities in outcome were larger in younger patients. Intervention at early ages may mitigate racial disparities in EC.

Race-specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients.

BACKGROUND: The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC). METHODS: EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography-tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race-specific progression-free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log-rank testing. RESULTS: Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty-nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White-specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black-specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B). CONCLUSIONS: This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017;123:4004-12. © 2017 American Cancer Society.

Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients.

A majority of high-grade (HG) serous ovarian cancer (SOC) patients develop resistant disease despite high initial response rates to platinum/paclitaxel-based chemotherapy. We identified shed/secreted proteins in preclinical models of paclitaxel-resistant human HGSOC models and correlated these candidate proteins with patient outcomes using public data from HGSOC patients. Proteomic analyses of a HGSOC cell line secretome was compared to those from a syngeneic paclitaxel-resistant variant and from a line established from an intrinsically chemorefractory HGSOC patient. Associations between the identified candidate proteins and patient outcome were assessed in a discovery cohort of 545 patients and two validation cohorts totaling 795 independent SOC patients. Among the 81 differentially abundant proteins identified (q < 0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated in all models of paclitaxel-resistant HGSOC. Furthermore, elevated AKAP12 transcript expression was associated with worse progression-free and overall survival. Associations with outcome were observed in three independent cohorts and remained significant after adjusted multivariate modeling. We further provide evidence to support that differential gene methylation status is associated with elevated expression of AKAP12 in taxol-resistant ovarian cancer cells and ovarian cancer patient subsets. Elevated expression and shedding/secretion of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells, and elevated AKAP12 transcript expression is a poor prognostic and predictive marker for progression-free and overall survival in SOC patients.

Gene expression analysis of early stage endometrial cancers reveals unique transcripts associated with grade and histology but not depth of invasion.

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

Amniotic fluid as a vital sign for fetal wellbeing.

Introduction: Amniotic fluid, once thought to merely provide protection and room for necessary movement and growth for the fetus, is now understood to be a highly complex and dynamic system that is studied as a data point to interpret fetal wellbeing. Methods: Assessment of amniotic fluid volume is now routine when performing a sonographic evaluation of fetal status and is an important consideration in the assessment and management of perinatal morbidity and mortality.1,2 In this review, we will cover the dynamics that affect amniotic fluid volume, review methods for measurement and quantification of volume, review definitions for normative data as related to neonatal outcomes, and provide evidence based guidance on the workup and management options for oligoydramnios and polyhydramnios in singleton and twin pregnancies. Conclusions: When abnormalities of fluid exist, appropriate workup to uncover the underlying etiology should be initiated as adverse fetal outcomes are sometimes associated with these variations from normalcy.

The use of middle cerebral artery Doppler ultrasonography to guide delivery of a viable pregnancy complicated by metastatic gestational chroriocarinoma.

Background: Choriocarcinoma is a rare, aggressive subtype of gestational trophoblastic neoplasia. The diagnosis of metastatic choriocarcinoma in the setting of a viable intrauterine pregnancy is exceedingly rare and often associated with feto-maternal hemorrhage. Case: An otherwise healthy Gravida 1 Para 0 at 34 weeks gestational age presented with metastatic choriocarcinoma and a viable fetus. Measured Doppler peak systolic velocity of the middle cerebral artery was used to detect fetal anemia, thus optimising the timing of delivery. Conclusion: This is the first case report to our knowledge using Doppler ultrasonography to detect fetal anemia in an effort to guide delivery in a case of choriocarcinoma diagnosed during pregnancy. If choriocarcinoma is diagnosed during pregnancy, middle cerebral artery Doppler ultrasonography may serve as a critical tool to help detect anemia, allowing pregnancy prolongation to promote fetal maturity while screening for the development of feto-maternal hemorrhage.

Bilateral sciatic nerve palsy: a new presentation of toilet bowl neuropathy.

BACKGROUND: Presentations of lower extremity compression palsies are rare and exist only in case reports. The true incidence of emergency department (ED) presentations of bilateral sciatic nerve palsy, "toilet bowl neuropathy," is unknown. The following is a case of a 28-year-old active duty Navy woman who presented to our ED via ambulance with bilateral sciatic nerve palsy from prolonged immobility. OBJECTIVES: This discussion reviews the historical precedence for the diagnosis and details the work-up and prognosis. CASE REPORT: The patient presented complaining of bilateral lower extremity swelling, numbness, and an inability to walk after a prolonged, medication-facilitated sleep in an unusual position. She had significant weakness on examination and was admitted for further evaluation and care. Specialized neurologic studies were consistent with bilateral sciatic nerve palsy. CONCLUSION: Bilateral sciatic nerve palsy is an uncommon cause of lower extremity weakness. In the ED, other diagnoses such as Guillain-Barré syndrome, cauda equina, disk herniation, and gluteal compartment syndrome should be considered initially. The diagnosis of toilet bowl neuropathy, however, is dependent on obtaining an accurate history. This case report adds another perspective to the literature on sciatic nerve palsy recognition, diagnosis, and prognosis.

Borderline or marginal amniotic fluid index and peripartum outcomes: a review of the literature.

The predictive accuracy of a borderline amniotic fluid index (AFI) for an adverse pregnancy outcome is uncertain. Pregnancy outcomes of a borderline versus normal AFI suggest an increased risk of meconium-stained fluid, intrauterine growth restriction, cesarean delivery for a nonreassuring fetal heart rate, low Apgar scores, and neonatal intensive care unit admission with borderline fluid. These results are inconclusive because of study design variations, the absence of receiver-operating characteristic curves, our inability to calculate likelihood ratios, and a lack of randomized trials. There is currently insufficient evidence to recommend additional antenatal testing delivery based on a borderline AFI. Sonography could be considered for evaluating fetal growth until a definitive association or lack of an association between a borderline AFI and intrauterine growth restriction/small size for gestational age can be determined.