Pan-cancer analysis of the effect of biopsy site on tumor mutational burden observations

Background Tumor mutational burden (TMB) has been proposed as a predictive biomarker of response to immunotherapy. Efforts to standardize TMB scores for use in the clinic and to identify the factors that could impact TMB scores are of high importance. However, the biopsy collection site has not been assessed as a factor that may influence TMB scores. Methods We examine a real-world cohort comprising 137,771 specimens across 47 tissues in 12 indications profiled by the FoundationOne assay (Foundation Medicine, Cambridge, MA) to assess the prevalence of biopsy sites for each indication and their TMB scores distribution. Results We observe a wide variety of biopsy sites from which specimens are sent for genomic testing and show that TMB scores differ in a cancer- and tissue-specific manner. For example, brain or adrenal gland specimens from NSCLC patients show higher TMB scores than local lung specimens (mean difference 3.31 mut/Mb; p < 0.01, 3.90 mut/Mb; p < 0.01, respectively), whereas bone specimens show no difference. Conclusions Our data shed light on the biopsied tissue as a driver of TMB measurement variability in clinical practice.

Clinical relevance of interdental papilla biopsy in chronic erosive gingivitis (desquamative gingivitis): retrospective bicentric study of 148 specimens

Background Chronic erosive gingivitis, also called desquamative gingivitis, defines a clinical picture that can be generated by several inflammatory and immune diseases. Pathology is therefore essential for the differential diagnosis. However, when the gingival lesion is initial, exclusive or predominant, selecting the biopsy site and protocol may be problematic due to tissue fragility. Especially since there are few studies on the subject, the aim of our study was to assess the protocol, diagnostic relevance and tolerance of an original protocol using interdental papilla biopsy. Methods We conducted a retrospective bicentric study, from October 2011 to July 2019, including all patients with a chronic erosive gingivitis who had received, for diagnostic purposes, a interdental papilla biopsy. Results The contribution levels for the two hospital departments were 94.7% and 97.1%, respectively. No postoperative complication was recorded in the short or long term. Conclusion The interdental papilla biopsy protocol is perfectly adapted to the anatomopathological examinations required to establish differential diagnosis of chronic erosive gingivitis. This surgical protocol is simple to perform, non iatrogenic with a very good tolerance and and accessible to all clinicians. It is highly efficient with an excellent contribution level. ClinicalTrials NCT04293718 (March 3, 2020). Health Data Hub N° F20201109083211 (November 9, 2020).

P–148 Effect of additional laser assisted drilling (LAD) during trophectoderm (TE) biopsy on mosaicism rate

Study question Does applying additional LAD during TE biopsy cause higher mosaicism rate in blastocysts? Summary answer Applying LAD during TE biopsy to create additional zona opening will produce more mosaic blastocysts. What is known already In Alpha IVF, laser assisted hatching (LAH) was done on day3 after ICSI for all pre-implantation genetic testing for aneuploidy (PGT-A) cycles. TE biopsy techniques used were laser+pulling (L+P), laser+flicking (L+F) and flicking only (F). At the time of biopsy, an extra step of creating additinonal artificial opening by LAD may be required when (a) blastocyst has very little herniated cells; (b) inner cell mass (ICM) is at the hatching point or biopsy site. Our internal study showed that biopsy using different techniques (L+P, L+F and F) does not affect mosaicism rate. Study design, size, duration This prospective study was designed to evaluate the effect of additional LAD during TE biopsy on the mosaicism rate. This study was conducted between 11th March–19th August 2019. Four hundred forty-three (443) patients had undergone oocyte retrieval and blastocyst culture after intracytoplasmic injection (ICSI) was done. A total of 824 hatching blastocyst (BG5) and fully hatched blastocyst (BG6) with at least a Grade A or Grade B TE (Gardner’s grading) were included in this study. Participants/materials, setting, methods LAH was done on day3 post-ICSI while biopsy was done on day5 and/or day6 for PGT-A. Laser pulse length used during LAH and biopsy was fixed at 400ms. The biopsied blastocysts were classified into 3 groups: (A) BG6 (n = 79), (B) BG5 without additional LAD during biopsy (n = 713) and (C) BG5 with additional LAD (n = 32). The number of biopsied cells ranged from 5–10 cells. Biopsied cells were tested using Next Generation Sequencing (Ion Torrent, USA). Main results and the role of chance The mosaicism rates for Group A, B and C were 19.0% (15/79), 23.4% (167/713) and 39.5% (15/38) respectively. Mosaicism rates of Group A and B were comparable (p = 0.4807), whilst Group C had significant higher mosaicism rate compared to Group A and B (p = 0.0238 and p = 0.0319 respectively). The mean age of Group A, B and C were 31.1, 31.4 and 27.1 respectively. The mean age between these 3 groups were not statistically significant (A vs B, p = 0.0713; A vs C, p = 0.06727; and B vs C, p = 0.4408). Limitations, reasons for caution Additional LAD during TE biopsy maybe be a confounding variable which affects the mosaicism rate. Moreover, the increase in mosaicism rate could be due to other unknown factors. A larger sample size is needed to confirm the results. Wider implications of the findings: Based on our study, additional LAD during TE biopsy is not recommended as this may increase mosaicism rate. Biopsy should be done when the blastocyst has more herniated cell or when the ICM leaves the hatching point/biopsy site. Trial registration number Not applicable

Feasibility, utility, and safety of transbronchial cryobiopsy for interstitial lung diseases in Japan

Background: Transbronchial lung cryobiopsy (TBLC) is a new technique that enables larger tissue collection than can be obtained by conventional transbronchial lung biopsy. TBLC is becoming popular worldwide and is performed for diffuse lung disease and lung cancer. However, only a few reports of TBLC have been published in Japan. This study was performed to evaluate the efficacy and safety of TBLC at our hospital and compare these findings with past reports.Methods: From April 2018 to January 2020, 38 patients who underwent TBLC for diffuse lung disease at our hospital were evaluated with respect to age, sex, biopsy site, biopsy size, diagnostic disease, and complications.Results: The patients who underwent TBLC constituted 20 men and 18 women with an average age of 63.7 years. The average sample size was 5.7 mm, and the diagnostic rate was 65.7% (25/38). Grade ≥2 complications included bleeding (15.8%), pneumothorax (2.6%), and atrial fibrillation (2.6%).Conclusions: TBLC was considered to be useful for the diagnosis of diffuse lung disease and could be safely performed.

Semi-Quantitative Characterization of Post-Transplant Lymphoproliferative Disorder Morphological Subtypes with [18F]FDG PET/CT

Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation classified according to the WHO as nondestructive, polymorphic, monomorphic, and classic Hodgkin Lymphoma subtypes. In this retrospective study, we investigated the potential of semi-quantitative 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/computed tomography (CT)-based parameters to differentiate between the PTLD morphological subtypes. Methods: 96 patients with histopathologically confirmed PTLD and baseline [18F]FDG PET/CT between 2009 and 2019 were included. Extracted semi-quantitative measurements included: Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean). Results: Median SUVs were highest for monomorphic PTLD followed by polymorphic and nondestructive subtypes. The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD (17.8, interquartile range (IQR):16) than in polymorphic subtypes (9.8, IQR:13.4) and nondestructive (4.1, IQR:6.1) (p = 0.04 and p ≤ 0.01, respectively). An SUVpeak ≥ 24.8 was always indicative of a monomorphic PTLD in our dataset. Nevertheless, there was a considerable overlap in SUV across the different morphologies. Conclusion: The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD than polymorphic and nondestructive subtypes. However, due to significant SUV overlap across the different subtypes, these values may only serve as an indication of PTLD morphology, and SUV-based parameters cannot replace histopathological classification.

Blind liver biopsy: a 17-year experience

Objectives: Liver biopsy is the gold standard for assessing liver inflammation, necrosis and fibrosis. The aim of the study is to evaluate clinical indications and histopathological results of percutaneus liver biopsy. Materials and methods: A total of 516 children who underwent blind liver biopsy were evaluated retrospectively. Results: Blind liver biopsy was performed for chronic active hepatitis B in 50% of the cases (n=260), neonatal cholestasis in 14% (n=68), autoimmune hepatitis in 7.7% (n=40), Wilson disease in 7.3% (n=38), isolated elevation of the liver enzymes in 5% (n=26), chronic active hepatitis C in 4.2% (n=22), metabolic disease in 3.4% (n=17), malignancies in 2.2% (n=11) and the others in 3.4% (n=17). Major complications were observed in 0.19% of the cases (n=1) and minor complications such as pain at the biopsy site in 13.5% of the cases (n=70), hypotension and tachycardia in 1.9% (n=10). Conclusions: Blind liver biopsy is a safe method in diagnosing liver diseases in childhood.