Histone H3 trimethylation on lysine 27 immunostaining pattern in DICER1-associated tumors.

Background: DICER1-associated tumors are heterogeneous and affect several organs. DICER1-associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry. Methods: We explored the H3K27me3 immunostaining pattern in other DICER1-associated tumors. Twelve tumors from eleven patients with confirmed DICER1 mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody. Results: The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of DICER1-associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One DICER1-associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining. Conclusions: H3K27me3 expression is not universally lost in DICER1-associated tumors and thus is not predictive of DICER1 mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to DICER1-associated intracranial sarcoma.

Ferumoxytol-enhanced MR demonstration of changes to internal placental structure in placenta accreta spectrum: Preliminary findings.

INTRODUCTION: The goal of this pilot study is to determine if ferumoxytol-enhanced MR might provide a new approach to the diagnosis of placenta accreta spectrum (PAS), and if so, to identify signs of PAS. METHODS: Ten pregnant women were referred for MRI evaluation for PAS. MR studies consisted of pre-contrast SSFSE, SSFP, DWI, and ferumoxytol-enhanced sequences. Post-contrast images were rendered as MIP and MinIP images to separately display the maternal and fetal circulations respectively. Two readers examined the images for architectural changes to placentone (fetal cotyledon) that might distinguish PAS cases from normal. Attention was given to the size and morphology of the placentone, villous tree, and vascularity. In addition, the images were examined for evidence of fibrin/fibrinoid, intervillous thrombus, basal and chorionic plate bulges. Interobserver agreement was characterized with kappa coefficients and levels of confidence for feature identification was recorded on a 10-point scale. RESULTS: At delivery, there were five normal placentas and five with PAS (one accreta, two increta, two percreta). The ten changes of placental architecture in PAS included: focal/regional expansion of placentone(s); lateral displacement and compression of the villous tree; disruption of a regular pattern of normal placentones; bulging of the basal plate; bulging of the chorionic plate; transplacental stem villi; linear/nodular bands at basal plate; non-tapering villous branches; intervillous hemorrhage; and dilated subplacental vessels. All these changes were more common in PAS; the first five achieved statistical significance in this small sample. The interobserver agreement and confidence for the identification of these features was good to excellent except for dilated subplacental vessels. DISCUSSION: Ferumoxytol-enhanced MR imaging appears to depict derangements of the internal architecture of placentas with PAS, thereby suggesting a promising new strategy to diagnose PAS.

Ferumoxytol-enhanced magnetic resonance imaging with volume rendering: A new approach for the depiction of internal placental structure in vivo.

INTRODUCTION: Placental function is vitally important, but placental assessment is limited by current imaging methods in vivo. The goal of this study is to determine if ferumoxytol-enhanced MR studies might be used to depict placental structure during pregnancy. METHODS: Ten pregnant women were referred for MRI evaluation of abnormal placentation. The study group was composed five of these patients whose placentas were normal at pathology. MR studies consisted of pre-contrast SSFSE (single-shot fast spin-echo), SSFP (steady-state free procession), diffusion, and ferumoxytol-enhanced acquisitions. The post-contrast sequences were compared to pre-contrast SSFSE, SSFP, and diffusion acquisitions for features of correspondence. MR images were also compared to histopathology for anatomic landmarks including the three-ring pattern of the functional vascular exchange unit (the placentone) created by this central cavity surrounded by a ring of clustered villi, and an outer ring of dispersed villi corresponding to the maternal venous outflow channel. The measured sizes of these features on MR were compared to reported sizes. RESULTS: Post-ferumoxytol images showed enhancement of the maternal blood within the placenta, notably the intervillous space and the myometrial vessels. The unenhanced fetal vessels were most visible on the MinIP (minimum intensity projection) images; the enhanced maternal vessels were most visible on the MIP (maximum intensity projection) images. Composite MIP/MinIP images show the relation of maternal and fetal circulations. The signal intensities replicate the relative contributions from enhanced maternal blood and unenhanced chorionic villi. DISCUSSION: Ferumoxytol-enhanced MR imaging can depict the internal anatomy of the placenta in vivo of clarity and detail. This could represent a new diagnostic approach to placental disorders.

Normal placental structural anatomy: ultrasound and doppler features elucidated with US-MR image fusion and ferumoxytol-enhanced MRI.

PURPOSE: To elucidate ultrasound features of normal placental anatomy through correlation of gray-scale and ultrasound Doppler with ferumoxytol-enhanced MRI features using US-MR image fusion. METHODS: All patients referred to MR for ultrasound findings worrisome for PAS (placenta accreta spectrum) were included in this retrospective study. MR studies included a ferumoxytol-enhanced T1-weighted MRI. Ultrasound imaging included gray-scale, color Doppler, power Doppler, and spectral Doppler techniques. After the MR, US-MRI fusion was performed by co-registering a MR acquisition to real-time US, which allowed precise, point-to-point correlation of placental features. RESULTS: Fourteen patients at risk for PAS were studied using the US-MR image fusion. At delivery, there were six cases without PAS (gestational age range: 24 weeks 3 days to 34 weeks 0 days), and these composed the study cohort. Placental features that were on high signal intensity on post-ferumoxytol acquisitions represent spaces with maternal blood flow and corresponded to hypoechoic areas on ultrasound created by a paucity of reflective interfaces (villi). Color and spectral Doppler allowed the separation of maternal and fetal circulations in individual perfusional domains and demonstrated spiral artery inflow, circulation around the villous tree, and return of blood flow to the basal plate. Recognizable histopathologic features by ultrasound included the central cavity, villous tree, and venous return channels. CONCLUSION: Internal placental architecture can be discerned on ultrasound. This anatomy can be correlated and confirmed with ferumoxytol-MR through US-MR fusion. Understanding this structural anatomy on ultrasound could serve as a basis to identify normal and abnormal placental features.

Elevated Lactate Dehydrogenase Concentrations in Plasma Compared to Serum.

OBJECTIVE: To evaluate the difference in lactate dehydrogenase (LDH) concentrations in plasma vs serum specimens in our patient population. MATERIALS AND METHODS: We measured LDH in 110 paired plasma and serum specimens over a 2-week period. Hemolytic indices were performed on each specimen. These paired specimens were drawn in a single setting and stored under the same conditions. For the last 14 paired specimens, cell counts were performed on the plasma/serum. RESULTS: Plasma LDH was on average 22% higher than serum LDH. There was no difference in the hemolytic indices between the plasma and the serum specimens. In the last 14 specimens, cell counts revealed increased platelets in the plasma specimens compared to the serum specimens. CONCLUSION: We propose switching back to using serum for LDH testing because there was unpredictable elevation in plasma LDH concentrations. These elevations in LDH levels may be linked to the platelets present in plasma and that may lyse or become activated with storage at refrigerated temperature.

Catastrophic congenital hemangioma with severe coagulopathy leading to fatal cardiac failure: Case report and review.

We present a complex case of a neonate, delivered urgently for hydrops fetalis, with a large vascular mass of the extremity, diagnosed postnatally as a congenital hemangioma. The patient suffered immediate cardiac compromise and severe coagulopathy atypical for the diagnosis and subsequently died from these complications. Treatment was imperative but challenging due to a lack of a standardized treatment approach and few historical reports of equally critically ill patients. In this report, we review potential medical and surgical interventions and discuss treatment considerations in similar, life-threatening cases of congenital hemangiomas.

Chronic villitis of unknown etiology: Investigations into viral pathogenesis.

INTRODUCTION: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response. METHODS: We extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta. RESULTS: We detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE. DISCUSSION: These data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.

Correlation of Placental Magnetic Resonance Imaging With Histopathologic Diagnosis: Detection of Aberrations in Structure and Water Diffusivity.

OBJECTIVE: Noninvasive methods to identify placental pathologic conditions are being sought in order to recognize these conditions at an earlier stage leading to improved clinical interventions and perinatal outcomes. The objective of this study was to examine fixed tissue slices of placenta by T2- and diffusion-weighted magnetic resonance imaging (MRI) and correlate the images with placental pathologic findings defined by routine gross and histologic examination. METHODS: Four formalin-fixed placentas with significant placental pathology (maternal vascular malperfusion, chronic villitis of unknown etiology, and massive perivillous fibrin deposition) and 2 histologically normal placentas were evaluated by high-resolution MRI. Representative placental slices were selected (2 cm long and 10 mm wide) and rehydrated. Imaging was performed on a Bruker Avance 14.1 T microimager. Diffusion-weighted images were acquired from 16 slices using slice thickness 0.5 mm and in-plane resolution approximately 100 µm × 100 µm. T2 maps were obtained from the same slices. T2 relaxation time and apparent diffusion coefficient (ADC) were acquired from representative regions of interest and compared between normal and diseased placentas. RESULTS: In T2- and diffusion-weighted images, the placental microstructure differed subjectively between diseased and normal placentas. Furthermore, diseased placentas showed statistically significantly longer mean T2 relaxation times and generally higher mean ADC. CONCLUSION: Diffusion- and T2-weighted MRI can potentially be used to detect significant placental pathology by using T2 relaxation time and ADC as markers of altered placental microstructure.

The landscape of systematic reviews in urology (1998 to 2015): an assessment of methodological quality.

OBJECTIVES: To assess the quality of published systematic reviews in the urology literature (an extension of our previously reported work), as high-quality systematic reviews play a paramount role in informing evidence-based clinical practice. MATERIALS AND METHODS: Our focus was on systematic reviews in the urology literature that incorporated questions of prevention and therapy. To identify such reviews published during a 36-month period (2013-2015), we systematically searched PubMed and hand-searched the table of contents of four major urology journals. Two reviewers independently assessed the methodological quality of those reviews, using the 11-point 'Assessment of Multiple Systematic Reviews' (AMSTAR) instrument. We performed protocol-driven analyses of the data from our present study's 36-month period alone, as well as in aggregate with the data from our previously reported work's study periods (2009-2012 and 1998-2008). RESULTS: In our literature search of the 36-month period (2013-2015), we initially identified 490 possibly relevant reviews, of which 125 met our inclusion criteria. The most common topic of reviews for the 2013-2015 period was oncology (51.2%; n = 64), followed by voiding dysfunction (21.6%; n = 27). The mean [standard deviation (SD)] AMSTAR score in the 2013-2015 period (n = 125) was 4.8 (2.4); 2009-2012 (n = 113), 5.4 (2.3); and 1998-2008 (n = 57), 4.8 (2.0) (P = 0.127). In the 2013-2015 period, the mean (SD) AMSTAR score for the BJU International (n = 25) was 5.6 (2.9); for The Journal of Urology (n = 20), 5.1 (2.6); for European Urology (n = 60), 4.5 (2.2); and for Urology (n = 20), 4.4 (2.2) (P = 0.106). CONCLUSIONS: The number of systematic reviews published in the urology literature has exponentially increased, year by year, but their methodological quality has stagnated. To enhance the validity and impact of systematic reviews, all authors and editors must apply established methodological standards.