Adequate Biopsy Research Articles

Efficacy, Safety, and Adequacy of EUS-guided Liver Biopsy

Efficacy, Safety, and Adequacy of EUS-guided Liver Biopsy

Optimal route planning for image-guided EBUS bronchoscopy

The staging of the central-chest lymph nodes is a major lung-cancer management procedure. To perform a staging procedure, the physician first uses a patient's 3D X-ray computed-tomography (CT) chest scan to interactively plan airway routes leading to selected target lymph nodes. Next, using an integrated EBUS bronchoscope (EBUS = endobronchial ultrasound), the physician uses videobronchoscopy to navigate through the airways toward a target node's general vicinity and then invokes EBUS to localize the node for biopsy. Unfortunately, during the procedure, the physician has difficulty in translating the preplanned airway routes into safe, effective biopsy sites. We propose an automatic route-planning method for EBUS bronchoscopy that gives optimal localization of safe, effective nodal biopsy sites. To run the method, a 3D chest model is first computed from a patient's chest CT scan. Next, an optimization method derives feasible airway routes that enables maximal tissue sampling of target lymph nodes while safely avoiding major blood vessels. In a lung-cancer patient study entailing 31 nodes (long axis range: [9.0 mm, 44.5 mm]), 25/31 nodes yielded safe airway routes having an optimal tissue sample size = 8.4 mm (range: [1.0 mm, 18.6 mm]) and sample adequacy = 0.42 (range: [0.05, 0.93]). Quantitative results indicate that the method potentially enables successful biopsies in essentially 100% of selected lymph nodes versus the 70–94% success rate of other approaches. The method also potentially facilitates adequate tissue biopsies for nearly 100% of selected nodes, as opposed to the 55–77% tissue adequacy rates of standard methods. The remaining nodes did not yield a safe route within the preset safety-margin constraints, with 3 nodes never yielding a route even under the most lenient safety-margin conditions. Thus, the method not only helps determine effective airway routes and expected sample quality for nodal biopsy, but it also helps point out situations where biopsy may not be advisable. We also demonstrate the methodology in an image-guided EBUS bronchoscopy system, used successfully in live lung-cancer patient studies. During a live procedure, the method provides dynamic real-time sample size visualization in an enhanced virtual bronchoscopy viewer. In this way, the physician vividly sees the most promising biopsy sites along the airway walls as the bronchoscope moves through the airways.

Global Glomerulosclerosis in Kidney Biopsies With Differing Amounts of Cortex: A Clinical-Pathologic Correlation Study

Rationale & ObjectiveThe number of glomeruli is often used to determine the adequacy of a kidney biopsy (eg, at least 10 glomeruli). It is often assumed that biopsy specimens with limited amounts of cortex are too imprecise for detection of focal pathology.Study DesignClinical-pathologic correlation (cross-sectional).Setting & ParticipantsLiving kidney donors who underwent a needle core biopsy of their kidney at the time of donation.ExposureThe amount of cortex biopsied as determined by either the number of glomeruli or area of cortex on histology.OutcomeThe percentage of globally sclerotic glomeruli, density of interstitial fibrosis foci, and severity of arteriosclerosis were determined.Analytical approachA beta-binomial model assessed how the mean percentage of globally sclerotic glomeruli and patient variability in percentage of globally sclerotic glomeruli differed with the number of glomeruli on the biopsy specimen. Additional models assessed the association of interstitial fibrosis and arteriosclerosis with number of glomeruli.ResultsThere were 2,915 kidney donors studied. Fewer glomeruli on the biopsy specimen associated with higher mean percentage of globally sclerotic glomeruli and higher patient variability in percentage of globally sclerotic glomeruli. Smaller cortical volume on imaging correlated with both less cortex on biopsy and higher percentage of globally sclerotic glomeruli. Based on a statistical simulation, the probability of patient percentage of globally sclerotic glomeruli ≥ 10% if the biopsy percentage of globally sclerotic glomeruli is ≥10% (positive predictive value) was 45% with 1 to 9 glomeruli versus 31% with 10 or more glomeruli; the negative predictive value was 91% versus 98%. Fewer glomeruli also associated with more interstitial fibrosis and arteriosclerosis.LimitationsThe study was limited to living kidney donors. Patient variability in percentage of globally sclerotic glomeruli was based on a statistical model because multiple biopsy specimens per patient were not available.ConclusionsThe amount of cortex on a needle core biopsy is not completely random. Chronic changes from loss of cortex contribute to low amounts of cortex on a kidney biopsy specimen.

SAT-308 RENAL BIOPSY ADEQUACY AND COMPLICATIONS IN CHILDREN

Renal biopsy is commonly used in the diagnosis of kidney diseases. Increasingly in paediatric practice, biopsies are performed under general anaesthetic by interventional radiologists, who perform their own ultrasound compared to nephrologists who use ultrasonographer-guided ultrasound in a sedated child. The sample adequacy and complication rates have not been determined in the two groups. This study aimed to compare biopsy size and adequacy between interventional radiologists and nephrologists and to compare complication rates. We examined consecutive kidney biopsies performed between January 2008 and December 2017 and probed the electronic medical records of patients for data regarding complications. In native biopsies, successful processing for light microscopy, immunofluorescence, and electron microscopy were used as proxy for specimen adequacy. In transplant biopsies, adequate specimens contained at least 10 glomeruli and 2 arteries, based on the Banff criteria. Data were analysed using Mann–Whitney U test, Pearson’s chi-squared test, and Fisher’s exact test in SPSS. Interventional radiologists performed 112 of the 355 biopsies obtained. Interventional radiologists made more passes (median number 3 vs 2, p < 0.01) and obtained more renal cores (median number 3 vs 2, p < 0.01). They obtained more total glomeruli (median number 32 vs 15, p < 0.01) and more glomeruli per core (median number 12.0 vs 7.0, p < 0.01). No differences in specimen adequacy of native renal biopsies were observed between the two groups, but interventional radiologists obtained more adequate transplant biopsy specimens (95.0% vs 51.4%, p < 0.01). There were no significant differences in complications, including de novo haematuria, pain requiring analgesia, unplanned overnight stay, transfusion requirement, biopsy-related infections, or AV fistula formation between the two groups. A statistically lower rate of perinephric haematoma (20.5% vs 31.9%, p = 0.03) was detected in the interventional radiologist group. However, they self-report haematoma, whereas ultrasonographers report haematoma for nephrologists. Interventional radiologists obtained significantly larger specimens than nephrologists. There were no significant differences in post procedural complications other than perinephric haematoma.

Abstract 311: Diverse biological mechanisms drive resistance to Lorlatinib in ALK-rearranged Lung Cancer

Abstract Background: ALK rearrangements occur in 3-6% of patients (pts) with lung adenocarcinoma. Lorlatinib, is a novel third generation ALK tyrosine kinase inhibitor (TKI) with proven efficacy for patients previously treated with second generation ALK TKI. Methods: The MATCH-R study is a prospective single-institution trial aiming to identify mechanisms of resistance to targeted agents and immunotherapy in pts with advanced cancer (NCT02517892). Patients that achieve an initial partial or complete response or stability of disease for at least 6 months with selected agents are included upon disease progression. Tumor biopsies are performed and serial blood samples are collected. Extensive molecular profiling with panel next-generation sequencing (NGS), whole exome sequencing (WES) and RNA sequencing (RNAseq) is performed on tumor samples. Patient-derived xenografts (PDX) in NOD scid gamma (NSG) or nude mice and patient-derived cell lines are developed. We report mechanisms of resistance in a cohort of pts with ALK-rearranged lung cancer treated with lorlatinib. Results: From June 29th 2015 to November 15th 2018, 113 pts treated with a TKI were included in the MATCH-R study, of which 14 (12%) received treatment with ALK TKI, 6 pts treated with lorlatinib and with adequate tumor biopsies for molecular analysis were included. Tumor types studied were lung adenocarcinoma (n=4), anaplastic thyroid carcinoma (ATC, n=1) and myofibroblastic inflammatory tumor (MIT, n=1). An NF2 frame-shift deletion was detected by NGS in the ATC sample and a TNIK Q674 missense mutation was detected in the MIT sample. In the four pts with lung cancer treated with lorlatinib, we identified novel ALK G1202R/F1174L compound mutations from the tumor biopsy in one case and characterized them with Ba/F3 models (ctDNA analysis will be presented). Induction of epithelial mesenchymal transition (EMT) with lorlatinib exposure was responsible for resistance in one patient-derived model and susceptible to combined ALK/SRC inhibition. This cell line also had ALK C1156Y/G1269A compound mutations, not contributing to lorlatinib resistance. In a third case, double deleterious events in NF2 were identified in temporo-spatial distinct tumor biopsies on progression to lorlatinib. We further validated the effect of these events in patient-derived cell lines developed from two different biopsies. Downstream mTOR pathway activation conferred resistance to lorlatinib, and was reversible with mTOR inhibitors. We performed NF2 knockout in H3122 cells using Crispr-Cas9 gene editing to validate these findings. The resistance mechanism to lorlatinib treatment is yet to be elucidated in one patient-derived model. Conclusions: Mechanisms of resistance to lorlatinib can be diverse and complex, involving compound mutations, EMT and bypass activation. The present evidence could provide new insights for the development of tailored treatments for patients. Citation Format: Gonzalo Recondo, Laura Mezquita, David Planchard, Anas Gazzah, Francesco Facchinetti, Ludovic Bigot, Ahsan Z. Rizvi, Jean-Paul Thiery, Jean-Yves Scoazec, Rosa L. Frias, Tony Sourisseau, Linda Mahjoubi, Justine Galissant, Aurelie Abou-Lovergne, Gilles Vassal, Rastislav Bahleda, Antoine Hollebecque, Claudio Nicotra, Maud Ngocamus, Stefan Michiels, Ludovic Lacroix, Catherine Richon, Nathalie Auger, Thierry De Baere, Frederic Deschamps, Eric Solary, Ken A. Olaussen, Eric Angevin, Alexander Eggermont, Fabrice André, Christophe Massard, Jean-Charles Soria, Benjamin Besse, Luc Friboulet. Diverse biological mechanisms drive resistance to Lorlatinib in ALK-rearranged Lung Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 311.

Advanced Pneumonic-type Lung Carcinoma: A Retrospective Study of Clinical-radiological-pathological Characteristics with Survival Analysis in A Single Chinese Hospital

背景与目的肺炎型肺癌是一种临床和影像表现特殊的肺癌。本研究旨在总结此类肺癌的临床、影像及病理学特征，诊断手段，治疗方案及预后情况。方法肺炎型肺癌定义为：肺部计算机断层扫描（computed tomography, CT）以磨玻璃或实变影为主要表现，经组织学或细胞学明确诊断的肺癌。收集2013年1月1日-2018年8月30日期间，就诊于北京协和医院呼吸与危重症医学科的晚期肺炎型肺癌病例，回顾性分析这些患者临床资料并进行生存随访。结果共纳入46例患者，均为肺腺癌。咳嗽（41/46, 89.1%）、咳痰（35/46, 76.1%）是最常见的临床表现。胸部CT常见表现为磨玻璃影（87.0%）、实变影（84.8%）、以及多发磨玻璃结节（84.8%），多发囊样变和空洞分别为40.0%和13.0%。同侧及对侧肺转移分别见于95.3%和84.8%的病例。从出现症状到明确诊断的中位时间为214天（95%CI: 129-298）。CT引导肺穿刺活检及外科肺活检的确诊率为100%，支气管镜下的支气管肺泡灌洗（BAL）联合经支气管肺活检（TBLB）的确诊率为80.9%（17/21），痰液病理学检查的确诊率为45.0%（9/20）。病理亚型，26例（26/46, 56.5%）为浸润性粘液腺癌，20例患者因缺乏足够的病理标本量而无法进一步区分亚型。38例进行了EGFR基因检测，6例（6/38, 15.8%）有突变。33例进行ALK基因检测，仅1例（1/33, 3.0%）有ALK重排。中位总生存期（overall survival, OS）为522天（95%CI: 424-619）。EGFR野生型或ALK融合基因阴性的患者，化疗明显延长中位OS（HR=0.155, P=0.002, 2），接受化疗者中位OS 547天（95%CI: 492-602），不接受化疗者中位OS 331天（95%CI: 22-919）。结论肺炎型肺癌由于其临床和影像特征与肺部感染相似而经常导致延误诊断。支气管镜下的BAL联合TBLB有相当高的确诊率。浸润性粘液腺癌为肺炎型肺癌的主要病理亚型。肺炎型肺癌EGFR突变及ALK重排发生率很低。对于无明确驱动基因的患者，应积极行化疗，延长患者生存期。

Predictors of adequate percutaneous liver biopsy specimens: a single-center experience

BackgroundPercutaneous liver biopsy is one of the widely accepted procedures to find any disorder, infection, and disease. Understanding the correlation between biopsy factors and adequacy rate will improvize efficacy and safety of biopsy.ObjectivesThis study was carried out to find the effect of needle size on the adequacy rate of biopsy and also to establish the association of factors such as BMI, cumulative length, and the number of cores to adequacy rate of biopsy.Materials and methodsThis retrospective review study was carried out at King Abdul-Aziz Medical City, MNGHA, Jeddah, Saudi Arabia. The data were acquired on adult patients who underwent percutaneous liver biopsy for 2010–2016 time periods. The data were analyzed by using the statistical package for social sciences, version 23.ResultsNo significant difference was observed in the adequacy rate of biopsy among samples of different needles (P=0.998). Similarly, BMI and guidance did not significantly (P=0.860 and 0.873) affect the adequacy rate. However, the number of cores (P<0.001) and cumulative length (P<0.001) had a significant effect on adequacy rate. Finally, only cumulative length (2.4 cm) was significantly correlated (P<0.05) to the adequacy rate of Percutaneous liver biopsy (PLB).ConclusionThe adequacy rate significantly depends on cumulative length and the number of cores. However, further studies are required to establish a conclusive relationship between factors and adequacy rate.

Needle Biopsy Adequacy in the Era of Precision Medicine and Value-Based Health Care.

Needle biopsy of diseased tissue is an essential diagnostic tool that is becoming even more important as precision medicine develops. However, the capability of this modality to efficiently provide samples adequate for diagnostic and prognostic analysis remains quite limited relative to current diagnostic needs. For physicians and patients, inadequate biopsy frequently leads to diagnostic delay, procedure duplication, or insufficient information about tumor biology leading to delay in treatment; for health systems, this results in substantial incremental costs and inefficient use of scarce specialized diagnostic resources. To review current needle biopsy technology, devices, and practice with a perspective to identify current limitations and opportunities for improvement in the context of advancing precision medicine. PubMed searches of fine-needle aspiration and core needle biopsy devices and similar technologies were made generally, by tissue site, and by adequacy as well as by health economics of these technologies. Needle biopsy adequacy can be improved by recognizing the importance of this diagnostic tool by promoting common criteria for needle biopsy adequacy; by optimizing needle biopsy procedural technique, technologies, clinical practice, professional education, and quality assurance; and by bundling biopsy procedure costs with downstream diagnostic modalities to provide better accountability and incentives to improve the diagnostic process.

Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists.

In vivo microscopy (IVM) allows direct, real-time visualization of tissue histology in living patients without the need for tissue removal, processing, or staining. The IVM technologies in clinical use include confocal microscopy and optical coherence tomography. These technologies also show promise for use with pathology specimens (ex vivo microscopy [EVM]). However, few systems designed for EVM are commercially available, at least in part because of the lack of defined minimal functional requirements (FRs). To develop minimal FRs for likely high-volume pathology applications of EVM. The IVM Committee of the College of American Pathologists identified potential EVM pathology applications based on the published literature. A subcommittee of IVM and EVM early adopters and experts then defined FRs for the most likely EVM applications. Potential EVM applications include assessment of margins, adequacy of needle biopsies and aspirates for diagnosis, and transplant tissues; selection of tissue for molecular studies or biorepository; and guidance in block selection from gross specimens. The first 3 applications were selected for development of FRs. The FRs were identified based on existing laboratory practices and guidelines and input from experts in the field and included device footprint and portability, specimen preparation, imaging time, field of view or resolution, morphologic diagnostic capability, yield, accuracy, ease of use, safety, and cost. Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.

Comparison of EUS-guided versus percutaneous and transjugular approaches for the performance of liver biopsies

BackgroundLiver biopsy through endoscopic ultrasound (EUS) has become a novel approach for tissue acquisition. We aim to evaluate the adequacy of EUS-guided liver biopsies in comparison to those obtained through interventional radiology (IR) techniques. MethodsA retrospective single-center analysis was performed of all IR (transjugular or image-guided percutaneous) and EUS-guided liver biopsies performed at an academic medical center from January 2016 to January 2018. Patient demographics, histologic characteristics, and clinical outcomes were collected. Results152 procedures were included for analysis. 45% of liver biopsies were performed through EUS-guidance. The most common indication for liver biopsy was NASH fibrosis staging (n = 64). IR-guided biopsies contained a higher number of complete portal triads (13.6 vs. 10.8 p ≤ 0.01) while EUS-guided biopsies produced an increased total specimen length (4.6 cm vs. 3.6 cm p ≤ 0.01).47% of biopsy samples were fragmented with the majority of these (72%) occurring with EUS-guided procedures (p ≤ 0.01). IR-guided biopsies led to more complications in comparison to EUS-guided procedures (p = 0.03) ConclusionLiver biopsies performed through EUS-guidance are comparable to IR-guided liver biopsies and may have an enhanced safety profile with acceptable tissue acquisition characteristics. Standardization of techniques and needles is needed for optimization of tissue sampling.

Cryoprobe transbronchial lung biopsy with flexible bronchoscope using Arndt endobronchial blocker.

Cryoprobe transbronchial lung biopsy (TBLB)/transbronchial lung cryobiopsy (TBLC) is increasingly being described as an alternative to surgical lung biopsy and provides larger lung biopsy samples as compared with conventional TBLB in patients with diffuse parenchymal lung diseases. The technique for cryoprobe TBLB procedure has not yet been standardized, and various authors describe different modalities. However, the use of an artificial airway (rigid bronchoscope or endotracheal tube) is preferred for airway protection. In addition, the use of an occlusion balloon provides safety to prevent excessive bleeding. The exclusive use of rigid bronchoscopy may limit the widespread adoption of this diagnostic modality. We describe a method to perform cryoprobe TBLB with exclusive use of a flexible bronchoscope and utilization of Arndt endobronchial blocker as an occlusion balloon. The procedure was performed in two patients under moderate conscious sedation. Adequate lung biopsies were obtained in both the cases without any complications. This modality may allow safe performance of cryoprobe TBLB with a flexible bronchoscope. Herein, we describe the technical and procedural considerations of this modality.

Revisiting Bone Marrow Core Biopsy Adequacy Criteria in the Era of Extensive Ancillary Testing.

Bone marrow core biopsy is a routine component of comprehensive marrow evaluation, and adequacy criteria have been recommended. However, the effectiveness of these adequacy criteria for diagnostic bone marrow evaluation needs to be reassessed in the current era of extensive ancillary testing. We aimed to determine the impact of core biopsy length and intertrabecular area of evaluable bone marrow on overall adequacy for diagnostic marrow evaluation at our tertiary care institution. Five hundred sequential cases of iliac crest bone marrow sampling were identified by retrospective re-view at our tertiary care institution. In this cohort, 470 core biopsies were obtained for histologic evaluation. Data including gross core biopsy length, number of intertrabecular 40x high power fields of evaluable marrow, and other pathologic/clinical parameters were compiled. The mean core biopsy length was 1.2 cm, and only 23% measured the recommended ≥ 1.5 cm. However, 96% of the core biopsies were interpretable and contributed to the comprehensive bone marrow evaluation. Notably, 100% of biopsies with ≥ 5.5 intertrabecular areas were contributory. Ancillary testing including immunophenotypic, cytogenetic, and/or molecular studies were performed in > 99% of cases. When histology was integrated with ancillary testing, the overall diagnosis was substantially limited in only 0.4% of cases and material deemed entirely insufficient in 0.4%. The number of intertrabecular 40x areas of evaluable marrow is a better predictor of adequacy than core biopsy length, and adequacy criteria should be revised in this era of extensive ancillary testing.

Kidney Biopsy Adequacy: A Metric-based Study.

There are differences in renal biopsy yield related to on-site evaluation, tissue division, and operator, among others. To understand these variations, we collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. Proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in our region were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086). Biopsies in which inadequate or marginal cortical tissue was submitted for LM had only minor decreases in the amount of cortex submitted for immunofluorescence and electron microscopy, revealing an opportunity for improved specimen triaging when limited tissue is obtained. In conclusion, both on-site evaluation/division and proceduralist significantly affect quantitative kidney biopsy metrics, which in turn affects the pathologist's ability to render an accurate diagnosis with appropriate prognostic information for the patient and treating nephrologist.

Comparing laparoscopic and percutaneous renal biopsy for diagnosing native kidney disease: A matched pair analysis

Percutaneous renal biopsy is a well-established diagnostic procedure in patients with underlying medical renal disease. Aim of this study is to compare the adequacy of the biopsy material, the diagnostic yield, and the complication rates of the trans-peritoneal laparoscopic approach and the image-guided percutaneous approach to renal biopsy in the diagnosis of native kidney disease. We performed a matched-pair analysis matching 1:3 40 patients who underwent trans-peritoneal laparoscopic renal biopsy to 120 patients who underwent percutaneous renal biopsy in the same years. Patients were retrospectively analyzed. Differences in adequacy of biopsy material (i.e. number of glomeruli, continuous), diagnostic yield (categorical) and postoperative complications across the two groups were assessed using Wilcoxon Rank sum or χ2 test. Laparoscopic biopsy was associated with a higher number of harbored glomeruli (median 50, IQR 20-77) compared to the percutaneous approach (median 10, IQR 7-15), P<0.001. Adequate biopsies containing at least ten glomeruli were obtained in a significantly higher percentage of patients in the laparoscopic group versus the percutaneous group (92.5% vs. 57.1%, P<0.001). The laparoscopic approach was also associated with a significantly higher diagnostic yield than the percutaneous approach (82.5% vs. 63.5%, P=0.027). Patients who underwent laparoscopic biopsy had no perioperative or postoperative complications, resulting in a significantly lower complication rate than percutaneous biopsy (0% vs. 4%, P<0.001), particularly in the need for transfusion for post-procedure bleeding (0% vs. 1.8%, P<0.001). In this retrospective matched-pair analysis comparing patients undergoing renal biopsy for medical kidney disease, trans-peritoneal laparoscopic renal biopsy was safer and more effective for the diagnosis of medical renal diseases compared to percutaneous renal biopsy. Prospective trials with a good follow-up are needed to define the best candidate for each approach. 4.

Teaching FNA techniques and ultrasound guided FNA

Teaching FNA techniques and ultrasound guided FNA

The Role of Molacular Genetic Examination in Differential Diagnosis and Prognostic Prediction in Patints with B-Cell Chronic Lymphoproliferative Disorders: A Restrospective Study of 1592 Patients

Background: B-cell chronic lymphoproliferative disorders (BCLPD) are a heterogeneous group of mature B-cell malignancies characterized by monoclonal proliferation in the bone marrow (BM) or peripheral blood (PB). The overlapped clinical features and the lack of individual diagnostic markers make diagnosis challenging, especially in patients who have difficulty to get adequate non-BM biopsy specimens or patients manifest as leukemic onset without nodes-involvement. It is necessary to explore novel methods to make precise diagnostic classification and prognostic prediction through simply PB/BM examination.Methods and results: A total of 1592 patients with newly diagnosed BCLPD were enrolled from January 1998 to December 2016, of which chronic lymphocytic leukemia (CLL) accounted for 39%, leukemic marginal zone lymphoma (l-MZL)occupied 13%, and Waldenstrom's macroglobulinemia/ lymphoplasmacytic lymphoma (LPL/WM), leukemic follicular lymphoma (l-FL) and mantle cell lymphoma (l-MCL) were 13%, 9% and 8%, respectively. There are 14% patients failed to fit into any of the categories and remaining unclassified which defined as BCLPDU. The median age at diagnosis was 58 years old. The male/female ratio of all BCLPD patients was 1.84:1. Male predominance was pronounced in WM/LPL, l-MCL and HCL with a M/F ratio of 2.5-2.7, while with balance gender in l-MZL and l-FL.FISH analyses were performed in 1234 patients. 17p and 11q deletion were most common in l-MCL (36% and 17%), while 13q deletion and trisomy 12 were most frequent in CLL (35% and 21%). Patients with 17p deletion showed significantly adverse survival in CLL and l-MCL (p<0.05), but the phenomenon was not found in other types of BCLPD. Instead, complex karyotype showed better predictive capability of worse survival than 17p deletion in patients with l-FL, l-MZL and BCLPDU.A total of 665 patients had been successfully amplified the IGHV-IGHD-IGHJ rearrangements. Based on a cut-off value of 98% homology, the IGHV mutated proportion in patients with l-MCL was 48.6%, which was higher than other BCLPDs, following CLL 33.3% and l-MZL 28.6%, while most of WM and l-FL were unmutated. The most frequent rearrangement in l-MZL were IGHV1-2*01, which was seldom found in other subtypes. Also, DH2-2 and VH3-7 were mainly found in CLL and l-MCL respectively. Besides, we have identified several stereotyped IGH CDR3 which were specific for the certain BCLPD subtype. About 23% unclassified patients could acquire further diagnosis according to the special mutation status, VDJ rearrangements or stereotyped CDR3 sequencing.With a median follow-up of 50.3 months, 522 patients (38.0%) had disease progression or died. Patients with lMCL have a significant worse survival than other entities, with a 3-year overall survival (OS) rate of 58%. Following , patients with WM/LPL had relatively poorer prognosis with a 5-year OS rate of 68.2%, while the prognosis for l-MZL, l-FL and CLL were relatively favourable, with a 5-year OS of 80%.The OS of the B-CLPD had improved over time due to the emergence of immunotherapy and novel (3-year OS improved from 82.1% to 92.2%). The improvement of l-MCL and WM was obvious but not for CLL and l-MZL.Conclusion: Non-BM biopsy specimens are not available for part of BCLPD patients. Overlapped magnification of BM/PB brings on difficulties in differential diagnosis. Besides morphology and immunophenotype, comprehensive analysis of FISH, karyotype, IGHV, MYD88 or BRAF mutation and other molecular examination might contribute to further differential diagnosis and prognostic prediction. Moreover, it might provide advice for the initial time and strategy of treatment. DisclosuresNo relevant conflicts of interest to declare.

Adequacy and Accuracy of Core Biopsy in Children: A Radiologic/Pathologic Correlation Study.

Core biopsy (CB) is increasingly popular for assessing solid lesions in children. To date, pediatric literature is limited regarding factors contributing to diagnostically inadequate or inaccurate CB. Therefore, we retrospectively examined radiologic/pathologic factors associated with adequacy/accuracy of CB in pediatric patients. A search of the surgical pathology database for CB between January 2007 and December 2014 yielded 134 CB from 99 patients. Age, sex, anatomic site of lesion, CB diagnosis, and final diagnosis were acquired from the electronic medical record. Image guidance modality, lesion size, and CB sampling device were obtained from radiology records. CB hematoxylin and eosin slides were reviewed for fragmentation, percentage of fibrosis, and percentage of necrosis. Overall, CB length was measured using cellSens software and a DP71 camera. Groups were compared using 2-sided homoscedastic Student's t tests; 87.3% (117/134) CB were diagnostic; final diagnosis was available for 105 cases, with a concordance rate of 80.0% (84/105). Image guidance modality, lesion site (extremity vs nonextremity), and CB needle gauge did not significantly differ between diagnostic versus nondiagnostic CB or concordant versus discordant CB. Diagnostic CB had less necrosis and fibrosis than did nondiagnostic CBs (6.8% vs 29.7%, P = .0002 and 10.3% vs 29.1%, P = .0006). Nondiagnostic and discordant CB were more likely to be from bony lesions than soft tissue ( P = .01 and P = .0248). CB is valuable for diagnosing solid lesions in children, with good overall diagnostic rates regardless of lesion size, location, or imaging modality used for biopsy. Nondiagnostic and discordant CB were more often obtained from bony lesions; sampling via open biopsy may be more useful in that setting. Nondiagnostic and discordant CB have more necrosis and fibrosis, suggesting that on-site evaluation of CB tissue viability-for example, by touch imprint or fine needle aspiration-may be useful in further enhancing CB utility.

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4).

Background:α-synuclein is a lead Parkinson’s disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).Objective:To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study.Methods:Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded.Results:The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred.Conclusion:Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.

Diagnosis of Hirschsprung's disease in children: Preliminary evaluation of a novel endoscopic technique for rectal biopsy.

Background and AimThe diagnosis of Hirschsprung's disease (HD) relies on anorectal manometry and rectal biopsy. The role of endoscopic biopsy is uncertain for the diagnosis of HD in children. In this study, we evaluated the adequacy of biopsies procured by endoscopic mucosal resection (EMR) for the diagnosis of HD.MethodsConsecutive children with suspected HD from January 2013 to January 2018 were enrolled in the study. EMR was performed using the standard band ligation device at a distance of about 3 cm from dentate line in rectum. All samples were assessed macroscopically and microscopically. An adequate sample was defined as those measuring >3 mm and including adequate submucosa.ResultsA total of 132 children underwent evaluation for constipation in the study period. Of these, 10 children (median age, 4.25 years) underwent EMR using the band ligation device for the evaluation of HD. EMR was performed with and without submucosal lifting injection in four and six children, respectively. All the samples were adequate macroscopically (>3 mm). Absence of ganglion cells was noted in six children. Of these, three children underwent full‐thickness rectal biopsy followed by surgery. Three children did not undergo surgery. Ganglion cells were identified in four children, thereby excluding the diagnosis of HD.ConclusionRectal biopsy using EMR with a band ligation device is feasible, safe, and provides adequate sample for the evaluation of HD in children.

An Evaluation of the Quality of Esophageal Biopsies in Patients with Eosinophilic Esophagitis

Introduction: Eosinophilic esophagitis (EoE) is a clinicopathologic diagnosis based on the presence of ≥15 eosinophils per high power field (hpf) in the epithelium. Additional changes include microabscesses, lamina propria (LP) papillae elongation, basal zone hyperplasia, intercellular edema, and LP fibrosis. Recent studies have shown the importance of subepithelial fibrosis as this correlates with clinical and endoscopic findings of EoE, disease duration and response to therapy. We sought to determine the adequacy of esophageal biopsies, defined as the presence of LP, among patients with EoE. Methods: This was a single-center, retrospective, observational study at a tertiary referral center. The pathology database was interrogated to identify pathology records from 2014-2015 that contained ≥15 eosinophils/hpf. All records were reviewed by one expert GI pathologist for the presence of lamina propria. We investigated factors that could influence acquisition of deeper esophageal biopsies including type of sedation, trainee involvement, procedure duration and seniority of attending endoscopist. Results: We reviewed 119 pathology records that were contributed by 109 patients. Within the pathology records, 244 esophageal biopsies were reviewed and classified by location (proximal, distal, and other; note that a pathology record could contribute multiple location biopsies). Only 98 biopsies had the presence of LP (40%). Breakdown according to location: proximal biopsies 25/66 (38%); distal biopsies 34/90 (38%); and other biopsies 39/88 (44%) had the presence of LP. Univariable generalized linear mixed models were used to estimate the odds of a higher number of LP biopsies. Patient demographics, trainee involvement, seniority of attending endoscopist, sedation used, and procedure time were not associated with odds of a higher number of LP biopsies. When analyzed by location of biopsies, senior attending physicians (defined as > 3 years in practice) were 3.74 (95% CI: 1.45 - 9.65) times as likely to obtain a positive distal biopsy with LP when compared to junior attendings (p = 0.01). Conclusion: The majority of biopsies did not contain LP. Senior attendings were more likely to obtain quality distal biopsies. Duration of procedure, sedation type, and trainee involvement did not affect depth of biopsy. As esophageal biopsy remains the gold standard for monitoring disease activity, quality of mucosal sampling is essential to providing accurate information to guide clinical management.395_A Figure 1. Odds of a higher count of lamina propria biopsies395_B Figure 2. Odds of a positive LP on distal biopsy