Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1.

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor type, along with a subset showing NF1 alterations. Five of 93 (5.4%) cases sequenced harbored TP53 mutations and RNA fusion analysis identified a single tumor containing an NTRK2 gene fusion, neither of which have been previously reported in HGAP. Clustering analysis revealed the presence of three distinct HGAP subtypes (or groups = g) based on whole-genome DNA methylation patterns, which we provisionally designated as gNF1 (n = 18), g1 (n = 72), and g2 (n = 54) (median ages 43.5 years, 47 years, and 32 years, respectively). Subtype gNF1 is notable for enrichment with patients with Neurofibromatosis Type 1 (33.3%, p = 0.0008), confinement to the posterior fossa, hypermethylation in the NF1 enhancer region, a trend towards decreased progression-free survival (p = 0.0579), RNA processing pathway dysregulation, and elevated non-neoplastic glia and neuron cell content (p < 0.0001 and p < 0.0001, respectively). Overall, our expanded cohort broadens the genetic, epigenetic, and clinical phenotype of HGAP and provides evidence for distinct epigenetic subtypes in this tumor type.

Coati Bodies: Cytoplasmic Hyaline Globules in the Ganglionic Neurons of Aging Captive Coatis.

Intensely eosinophilic and glassy intracytoplasmic inclusions were present in the neurons of the peripheral autonomic ganglia, Meissner's and Auerbach's plexus, and spinal ganglia in 20 aged white-nosed coatis ( Nasua narica, 7-19 years old) and in 4 of 7 brown-nosed coatis ( Nasua nasua, 2-21 years old) from multiple zoological institutions. Inclusions were single to numerous, sometimes distorting the cell. Pheochromocytomas were present in 5 of 16 white-nosed and 2 of 6 brown-nosed coatis, although no inclusions were present in the adrenal glands. Histochemically, immunohistochemically, and ultrastructurally, these inclusions were consistent with dense neurosecretory granules. Although similar inclusions have been reported sporadically in the adrenal medulla of humans and several other mammalian species as both incidental and pathologic findings, ganglionic inclusions reported herein appear to be unique and related to age in these species.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. RESULTS: Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION: Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Bacillus anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model.

BACKGROUND: Disseminated intravascular coagulation (DIC) appears to be important in the pathogenesis of Bacillus anthracis infection, but its causes are unclear. Although lethal toxin (LT) and edema toxin (ET) could contribute, B. anthracis cell wall peptidoglycan (PGN), not the toxins, stimulates inflammatory responses associated with DIC. METHODS AND RESULTS: To better understand the pathogenesis of DIC during anthrax, we compared the effects of 24-hour infusions of PGN, LT, ET, or diluent (control) on coagulation measures 6, 24, or 48 hours after infusion initiation in 135 rats. No control recipient died. Lethality rates (approximately 30%) did not differ among PGN, LT, and ET recipients (P = .78). Thirty-three of 35 deaths (94%) occurred between 6 and 24 hours after the start of challenge. Among challenge components, PGN most consistently altered coagulation measures. Compared with control at 6 hours, PGN decreased platelet and fibrinogen levels and increased prothrombin and activated partial thromboplastin times and tissue factor, tissue factor pathway inhibitor, protein C, plasminogen activator inhibitor (PAI), and thrombin-antithrombin complex levels, whereas LT and ET only decreased the fibrinogen level or increased the PAI level (P ≤ .05). Nearly all effects associated with PGN infusion significantly differed from changes associated with toxin infusion (P ≤ .05 for all comparisons except for PAI level). CONCLUSION: DIC during B. anthracis infection may be related more to components such as PGN than to LT or ET.

Prostate cancer: can multiparametric MR imaging help identify patients who are candidates for active surveillance?

PURPOSE: To determine whether multiparametric magnetic resonance (MR) imaging can help identify patients with prostate cancer who would most appropriately be candidates for active surveillance (AS) according to current guidelines and to compare the results with those of conventional clinical assessment scoring systems, including the D'Amico, Epstein, and Cancer of the Prostate Risk Assessment (CAPRA) systems, on the basis of findings at prostatectomy. MATERIALS AND METHODS: This institutional review board-approved HIPAA-compliant retrospectively designed study included 133 patients (mean age, 59.3 years) with a mean prostate-specific antigen level of 6.73 ng/mL (median, 4.39 ng/mL) who underwent multiparametric MR imaging at 3.0 T before radical prostatectomy. Informed consent was obtained from all patients. Patients were then retrospectively classified as to whether they would have met AS eligibility criteria or were better served by surgery. AS eligibility criteria for prostatectomy specimens were a dominant tumor smaller than 0.5 mL without Gleason 4 or 5 patterns or extracapsular or seminal vesicle invasion. Conventional clinical assessment scores (the D'Amico, Epstein, and CAPRA scoring systems) were compared with multiparametric MR imaging findings for predicting AS candidates. The level of significance of difference between scoring systems was determined by using the χ(2) test for categoric variables with the level of significance set at P < .05. RESULTS: Among 133 patients, 14 were eligible for AS on the basis of prostatectomy results. The sensitivity, positive predictive value (PPV), and overall accuracy, respectively, were 93%, 25%, and 70% for the D'Amico system, 64%, 45%, and 88% for the Epstein criteria, and 93%, 20%, and 59% for the CAPRA scoring system for predicting AS candidates (P < .005 for all, χ(2) test), while multiparametric MR imaging had a sensitivity of 93%, a PPV of 57%, and an overall accuracy of 92% (P < .005). CONCLUSION: Multiparametric MR imaging provides useful additional information to existing clinicopathologic scoring systems of prostate cancer and improves the assignment of treatment (eg, AS or active treatment).

Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury.

Warm ischemia/reperfusion (I/R) is a common clinical problem during liver transplantation and liver resection. Warm ischemia also occurs during trauma and shock. However, there is still no safe and promising strategy for protecting the liver from I/R injury. Signal transducer and activator of transcription 3 (STAT3) is a major immediate response molecule for protecting cell survival. In this study, we first confirmed that a pharmacological STAT3 inhibitor, (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), significantly reduced the survival of HepG2 cells, regardless of the serum condition. Furthermore, we created hepatocyte-specific STAT3-deficient mice with the cyclization recombination-locus of X-over P1 (Cre-LoxP) system to study the mechanisms of STAT3 in liver I/R injury. We found that the alanine aminotransferase level was significantly higher in hepatocyte-specific STAT3-deficient mice versus wild-type (WT) mice in a 70% liver I/R injury model. A histopathological examination showed that hepatocyte-specific STAT3-deficient mice suffered more severe damage than WT mice despite similar numbers of polymorphonuclear neutrophils in the 2 groups. These results indicate that endogenous STAT3 signaling in hepatocytes is required for protection of the liver in vitro and in vivo against warm I/R injury. In conclusion, endogenous STAT3 plays an important role in protecting the liver against I/R injury, and STAT3-targeting therapy could be a therapeutic approach to combating liver I/R injury.

Mimickers of neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspirate material: Need for caution.

Cytologic diagnosis of neuroendocrine tumors can be straightforward on cytologic preparations, given the classical neuroendocrine morphology and expression of neuroendocrine markers confirmed by immunohistochemistry. However, overreliance on neuroendocrine markers can lead to misdiagnosis even if individual cell features suggest a neuroendocrine tumor. We present three unusual cases, two of which were initially diagnosed as neuroendocrine tumors and the third one carried preliminary diagnosis of neuroendocrine tumor on endoscopic ultrasound-guided fine-needle aspirates. These cases subsequently turned out to be cholangioblastic cholangiocarcinoma, metastatic melanoma, and gastric glomus tumor, respectively. We suggest approaches that could have pointed us towards the correct diagnosis at the outset and discuss potential pitfalls.

Further refinement of the differentially methylated distant lung-specific FOXF1 enhancer in a neonate with alveolar capillary dysplasia.

Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80-90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that this enhancer segment is weakly methylated at ApT adenine, with about twice the frequency of methylation on the maternal versus paternal chr16. Our data provide further insight into the FOXF1 enhancer structure and function.

Correlation of magnetic resonance imaging tumor volume with histopathology.

PURPOSE: The biology of prostate cancer may be influenced by the index lesion. The definition of index lesion volume is important for appropriate decision making, especially for image guided focal treatment. We determined the accuracy of magnetic resonance imaging for determining index tumor volume compared with volumes derived from histopathology. MATERIALS AND METHODS: We evaluated 135 patients (mean age 59.3 years) with a mean prostate specific antigen of 6.74 ng/dl who underwent multiparametric 3T endorectal coil magnetic resonance imaging of the prostate and subsequent radical prostatectomy. Index tumor volume was determined prospectively and independently by magnetic resonance imaging and histopathology. The ellipsoid formula was applied to determine histopathology tumor volume, whereas manual tumor segmentation was used to determine magnetic resonance tumor volume. Histopathology tumor volume was correlated with age and prostate specific antigen whereas magnetic resonance tumor volume involved Pearson correlation and linear regression methods. In addition, the predictive power of magnetic resonance tumor volume, prostate specific antigen and age for estimating histopathology tumor volume (greater than 0.5 cm(3)) was assessed by ROC analysis. The same analysis was also conducted for the 1.15 shrinkage factor corrected histopathology data set. RESULTS: There was a positive correlation between histopathology tumor volume and magnetic resonance tumor volume (Pearson coefficient 0.633, p <0.0001), but a weak correlation between prostate specific antigen and histopathology tumor volume (Pearson coefficient 0.237, p = 0.003). On linear regression analysis histopathology tumor volume and magnetic resonance tumor volume were correlated (r(2) = 0.401, p <0.00001). On ROC analysis AUC values for magnetic resonance tumor volume, prostate specific antigen and age in estimating tumors larger than 0.5 cm(3) at histopathology were 0.949 (p <0.0000001), 0.685 (p = 0.001) and 0.627 (p = 0.02), respectively. Similar results were found in the analysis with shrinkage factor corrected tumor volumes at histopathology. CONCLUSIONS: Magnetic resonance imaging can accurately estimate index tumor volume as determined by histology. Magnetic resonance imaging has better accuracy in predicting histopathology tumor volume in tumors larger than 0.5 cm(3) than prostate specific antigen and age. Index tumor volume as determined by magnetic resonance imaging may be helpful in planning treatment, specifically in identifying tumor margins for image guided focal therapy and possibly selecting better active surveillance candidates.

Decision support system for localizing prostate cancer based on multiparametric magnetic resonance imaging.

PURPOSE: There is a growing need to localize prostate cancers on magnetic resonance imaging (MRI) to facilitate the use of image guided biopsy, focal therapy, and active surveillance follow up. Our goal was to develop a decision support system (DSS) for detecting and localizing peripheral zone prostate cancers by using machine learning approach to calculate a cancer probability map from multiparametric MR images (MP-MRI). METHODS: This IRB approved Health Insurance Portability and Accountability Act compliant retrospective study consisted of 31 patients (mean age and serum prostate specific antigen of 60.4 and 6.62 ng∕ml, respectively) who had MP-MRI at 3 T followed by radical prostatectomy. Seven patients were excluded due to technical issues with their MP-MRI (e.g., motion artifact, failure to perform all sequences). Cancer and normal regions were identified in the peripheral zone by correlating them to whole mount histology slides of the excised prostatectomy specimens. To facilitate the correlation, tissue blocks matching the MR slices were obtained using a MR-based patient-specific mold. Segmented regions on the MP-MRI were correlated to histopathology and used as training sets for the learning system that generated the cancer probability maps. Leave-one-patient-out cross-validation on the cancer and normal regions was performed to determine the learning system's efficacy, an evolutionary strategies approach (also known as a genetic algorithm) was used to find the optimal values for a set of parameters, and finally a cancer probability map was generated. RESULTS: For the 24 patients that were used in the study, 225 cancer and 264 noncancerous regions were identified from the region maps. The efficacy of DSS was first determined without optimizing support vector machines (SVM) parameters, where a region having a cancer probability greater than or equal to 50% was considered as a correct classification. The nonoptimized system had an f-measure of 85% and the Kappa coefficient of 71% (Rater's agreement, where raters are DSS and ground truth histology). The efficacy of the DSS after optimizing SVM parameters using a genetic algorithm had an f-measure of 89% and a Kappa coefficient of 80%. Thus, after optimization of the DSS there was a 4% increase in the f-measure and a 9% increase in the Kappa coefficient. CONCLUSIONS: This DSS provides a cancer probability map for peripheral zone prostate tumors based on endorectal MP-MRI. These cancer probability maps can potentially aid radiologists in accurately localizing peripheral zone prostate cancers for planning targeted biopsies, focal therapy, and follow up for active surveillance.

Use of a third-generation perfluorocarbon for preservation of rat DCD liver grafts.

BACKGROUND: Cold storage in any of the commonly used preservation solutions is not always adequate for donation after cardiac death (DCD) liver grafts due to prolonged warm ischemic time. In this study, we used a third-generation perfluorocarbon (PFC), Oxycyte, for DCD liver graft preservation in a rat model. MATERIALS AND METHODS: Twenty-eight rats (14 in each group) were used. Thirty minutes after cardiopulmonary arrest, livers were harvested and flushed with a cold and pre-oxygenated solution of either University of Wisconsin (UW) or UW + 20% PFC. After 8 h of cold preservation in either of the investigated solutions, liver graft specimens were analyzed for evidence of ischemic injury. Hemotoxylin and eosin staining (H and E), as well as immunohistochemical analysis with anti-cleaved caspase 3 antibody, was performed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the preservation solution were analyzed at 1 and 8 h during preservation. RESULTS: In the PFC group, the degree of cell congestion, vacuolization and necrosis were all significantly less than in the UW group (P = 0.002-0.004). The number of cells with a positive cleaved caspase 3 antibody reaction was reduced by about 50% in comparison with the UW group (P < 0.006). The AST level in the PFC group was significantly less than in the UW group after 8 h of preservation (P < 0.048). CONCLUSION: The addition of PFC to UW solution significantly decreases the degree of histologic damage in rat DCD liver grafts. This preservation strategy can be potentially helpful for organ preservation after prolonged warm ischemia.

Hydrogen-1 MR spectroscopy for measurement and diagnosis of hepatic steatosis.

OBJECTIVE: Hydrogen-1 MR spectroscopy ((1)H-MRS) is gaining acceptance as a noninvasive technique for assessment of hepatic steatosis, and the findings have been found to correlate closely with histopathologic grade. The aims of this study were to validate (1)H-MRS performed with a 3-T MRI system for quantifying hepatic steatosis and to determine threshold values of (1)H-MRS proton density fat fraction corresponding to standard histopathologic grade in patients undergoing diagnostic liver biopsy. SUBJECTS AND METHODS: We conducted a prospective cross-sectional liver MRS study with 52 subjects undergoing diagnostic liver biopsy. The diagnostic accuracy of (1)H-MRS was evaluated with receiver operating characteristic curves. RESULTS: The diagnostic accuracy of (1)H-MRS for hepatic steatosis was high with an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.88-1.0). Results were similar for three (1)H-MRS measurements obtained at different locations in the liver, for two independent pathologists, and whether fibrosis was present or absent. One third of participants had elevated transaminase concentrations of unknown cause, and (1)H-MRS estimates of steatosis had perfect agreement with histopathologic grade in this group. Calculated (1)H-MRS proton density fat fraction thresholds for histologic grades were less than 17% for grade 0 or trace steatosis, 17-38.6% for grade 1, and greater than 38.6% for grade 2 or higher. CONCLUSION: Hydrogen-1 MR spectroscopy is an effective, noninvasive technique that can be used to diagnose and quantify hepatic steatosis. Hydrogen-1 MR spectroscopy thresholds corresponded with histopathologic grades and may be useful in the workup of patients with elevated transaminase concentrations.

Response to Mesalamine Therapy in Pediatric Collagenous Gastritis and Colitis: A Case Report and Review.

Collagenous gastritis and collagenous colitis are 2 rare gastrointestinal disorders in pediatric patients. Both of these disease processes exist on a clinical spectrum, and are extremely rare to be present together in the pediatric population. Due to the rarity and unknown etiology of these disease processes, standardized treatment protocols and objective clinical biomarkers of disease progression are missing. This is the first report to describe a 16 year old female with CG and CC who responded well to mesalamine therapy, evident by decreasing calprotectin levels after initiation of therapy.

Cytological Diagnosis of Pancreatic Solid-Pseudopapillary Neoplasm: A Single-Institution Community Practice Experience.

INTRODUCTION: Pancreatic solid-pseudopapillary neoplasm (SPN) is a rare tumor that typically occurs in young females. Although a cytological diagnosis may be easily made in this age group when there are typical features, atypical clinical presentations and unusual cytological features may make this a challenging diagnosis. We present our single-institution experience in a cohort of these tumors, outlining both typical and atypical features. Awareness of unusual clinical and cytological features can help to avoid pitfalls during diagnosis. METHODS: We performed a review of all cases of pancreatic SPNs diagnosed over a 15-year period (January 2007 to December 2021). Detailed cytological, clinical, and follow-up histological features were presented and analyzed. RESULTS: Twenty-two cases of SPN were diagnosed at our institution during this 15-year period. Patients ranged from 12 to 73 years of age (mean 33 y, median 26 y) and included 19 females and 3 males. Seventeen patients had cytological material, and fourteen were diagnosed by EUS-FNA. Typical cytological features included papillary clusters with central capillaries, myxoid stroma, monomorphism, cercariform cells, and hyaline globules. Atypical or unusual cytological features that were seen in a few cases were multinucleated giant cells, clear cells, and/or foamy macrophages. A few cases showed features that were similar to pancreatic neuroendocrine tumors (PanNETs). Tumor cells were always positive for ß-catenin, CD10, CD56, cyclin-D1, progesterone receptor (PR), and vimentin by immunohistochemistry. They were always negative for chromogranin. Pancytokeratin and synaptophysin stains were positive in 9% and 46% of cases evaluated, respectively. All cases had histological confirmation on resection. The median follow-up duration was 69 months (a range of 2-177 months), with only three cases lost to follow-up. No recurrence or metastasis was identified. CONCLUSIONS: We present our experience with cytological diagnoses of SPN in a well-characterized cohort of 22 patients with histological correlation and follow-up data. These tumors occur over a wide range and show varied cytological features. SPNs can be confidently diagnosed on limited cytological material, with limited panel immunohistochemistry aiding diagnosis in atypical cases. Recognizing the associated degenerative changes is crucial in avoiding a misdiagnosis.

The effect of heparin administration in animal models of sepsis: a prospective study in Escherichia coli-challenged mice and a systematic review and metaregression analysis of published studies.

INTRODUCTION: If thrombosis contributes to sepsis, heparin titrated using activated partial thromboplastin times may be efficacious. We investigated heparin in preclinical models. METHODS AND MAIN RESULTS: In unchallenged mice (n = 107), heparin at 100, 500, or 2500 units/kg produced activated partial thromboplastin time levels less than, within, or greater than a prespecified therapeutic range (1.5-2.5 times control), respectively. In animals (n = 142) administered intratracheal Escherichia coli challenge, compared to placebo treatment, heparin at 100, 500, or 2500 units/kg were associated with dose dependent increases in the hazard ratios of death (hazard ratio [95% confidence interval]: 1.08 [0.66, 1.76]; 1.34 [0.80, 2.24]; 3.02 [1.49, 6.10], respectively) (p = .001 for the dose effect). Compared to normal saline challenge, E. coli without heparin (i.e., with placebo) increased the activated partial thromboplastin time (p = .002) close to the therapeutic range. While heparin at 100 and 500 units/kg with E. coli further increased activated partial thromboplastin time (p < .0001 vs. placebo) within or above the therapeutic range, respectively, these did not decrease inflammatory cytokines or lung injury. In metaregression analysis of published preclinical studies, heparin improved survival with lipopolysaccharide (n = 23, p < .0001) or surgically induced infection (n = 14, p < .0001) but not monobacterial (n = 7, p = .29) challenges. CONCLUSION: Coagulopathy with sepsis or other variables, such as type of infectious source, may influence the efficacy of heparin therapy for sepsis.

Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds.

PURPOSE: We determined the prostate cancer detection rate of multiparametric magnetic resonance imaging at 3T. Precise one-to-one histopathological correlation with magnetic resonance imaging was possible using prostate magnetic resonance imaging based custom printed specimen molds after radical prostatectomy. MATERIALS AND METHODS: This institutional review board approved prospective study included 45 patients (mean age 60.2 years, range 49 to 75) with a mean prostate specific antigen of 6.37 ng/ml (range 2.3 to 23.7) who had biopsy proven prostate cancer (mean Gleason score of 6.7, range 6 to 9). Before prostatectomy all patients underwent prostate magnetic resonance imaging using endorectal and surface coils on a 3T scanner, which included triplane T2-weighted magnetic resonance imaging, apparent diffusion coefficient maps of diffusion weighted magnetic resonance imaging, dynamic contrast enhanced magnetic resonance imaging and spectroscopy. The prostate specimen was whole mount sectioned in a customized mold, allowing geometric alignment to magnetic resonance imaging. Tumors were mapped on magnetic resonance imaging and histopathology. Sensitivity, specificity, positive predictive value and negative predictive value of magnetic resonance imaging for cancer detection were calculated. In addition, the effects of tumor size and Gleason score on the sensitivity of multiparametric magnetic resonance imaging were evaluated. RESULTS: The positive predictive value of multiparametric magnetic resonance imaging to detect prostate cancer was 98%, 98% and 100% in the overall prostate, peripheral zone and central gland, respectively. The sensitivity of magnetic resonance imaging sequences was higher for tumors larger than 5 mm in diameter as well as for those with higher Gleason scores (greater than 7, p <0.05). CONCLUSIONS: Prostate magnetic resonance imaging at 3T allows for the detection of prostate cancer. A multiparametric approach increases the predictive power of magnetic resonance imaging for diagnosis. In this study accurate correlation between multiparametric magnetic resonance imaging and histopathology was obtained by the patient specific, magnetic resonance imaging based mold technique.

Corpora amylacea in pleural effusion.

Corpora amylacea are predominantly found in the brain, prostate, and lung. Recent characterizations of their components suggest an important role in protection and clearing. We report the presence of corpora amylacea in pleural effusion in a patient with lupus. The differential diagnoses and potential significance are discussed.

Surgical Lung Biopsy for Interstitial Lung Disease. Safety and Feasibility at a Tertiary Referral Center.

Rationale: Video-assisted thoracoscopic surgery (VATS) remains the gold standard for interstitial lung disease (ILD) characterization when histology is deemed necessary. There is diminishing use of VATS owing to increased reliance on high-resolution computed tomographic patterns, as well as concerns regarding the potential morbidity and mortality of the procedure.Objectives: The goal of this study was to evaluate the safety and tolerability of VATS among a broad group of patients with ILD referred to a tertiary care center.Methods: Data for all patients with ILD who underwent VATS lung biopsies at Inova Fairfax hospital for the period from December 2012 to September 2019 were collected. Clinical, physiologic, and functional parameters as well as postoperative outcomes including any complications, hospital length of stay, and mortality were collated.Results: There were 268 diagnostic VATS biopsies performed during the period. The mean age of the cohort was 63 ± 13 years, 54% were male, and 25% were ultimately diagnosed with idiopathic pulmonary fibrosis. Two hundred twenty-nine patients were scheduled (85%, Elective VATS group) whereas 39 were inpatients (15%). In the elective group, the 1-month complication rate was 8%, whereas 4% had a severe complication, and there were no deaths. The only mortalities were in the group who were hospitalized before the VATS (4/39 = 10%). Complications were less frequent when VATS was requested by the tertiary referral ILD team. Of the elective group, 87% patients were discharged the same day.Conclusions: This report demonstrates the safety, tolerability, and feasibility of VATS lung biopsy as a same-day procedure in the modern era, especially if patients are first vetted by a team with expertise in the field of ILD. These results support a lower threshold to pursue a VATS biopsy when histology is required for an ILD diagnosis.

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Prostate cancer: value of multiparametric MR imaging at 3 T for detection--histopathologic correlation.

PURPOSE: To determine utility of multiparametric imaging performed at 3 T for detection of prostate cancer by using T2-weighted magnetic resonance (MR) imaging, MR spectroscopy, and dynamic contrast material-enhanced MR imaging, with whole-mount pathologic findings as reference standard. MATERIALS AND METHODS: This prospectively designed, HIPAA-compliant, single-institution study was approved by the local institutional review board. Seventy consecutive patients (mean age, 60.4 years; mean prostate-specific antigen level, 5.47 ng/mL [5.47 microg/L]; range, 1-19.9 ng/mL [1-19.9 microg/L]) were included; informed consent was obtained from each patient. All patients had biopsy-proved prostate cancer, with a median Gleason score of 7 (range, 6-9). Images were obtained by using a combination of six-channel cardiac and endorectal coils. MR imaging and pathologic findings were evaluated independently and blinded and then correlated with histopathologic findings by using side-by-side comparison. Analyses were conducted with a raw stringent approach and an alternative neighboring method, which accounted for surgical deformation, shrinkage, and nonuniform slicing factors in pathologic specimens. Generalized estimating equations (GEEs) were used to estimate the predictive value of region-specific, pathologically determined cancer for all three modalities. This approach accounts for the correlation among multiple regions in the same individual. RESULTS: For T2-weighted MR imaging, sensitivity and specificity values obtained with stringent approach were 0.42 (95% confidence interval [CI]: 0.36, 0.47) and 0.83 (95% CI: 0.81, 0.86), and for the alternative neighboring approach, sensitivity and specificity values were 0.73 (95% CI: 0.67, 0.78) and 0.89 (95% CI: 0.85, 0.93), respectively. The combined diagnostic accuracy of T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy for peripheral zone tumors was examined by calculating their predictive value with different combinations of techniques; T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy provided significant independent and additive predictive value when GEEs were used (P < .001, P = .02, P = .002, respectively). CONCLUSION: Multiparametric MR imaging (T2-weighted MR imaging, MR spectroscopy, dynamic contrast-enhanced MR imaging) of the prostate at 3 T enables tumor detection, with reasonable sensitivity and specificity values.