Inadequate Biopsy Research Articles

Late breaking abstracts

Late breaking abstracts

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

Abstract 4537: Cryogenic biopsy device for preservation of labile biomarkers

Abstract Background: Preanalytical factors such as the handling of biospecimens between resection and analysis can have a significant impact on assay results which may adversely affect patient care. Global phosphoprotein analysis indicates that a 5 minute delay in time-to-stabilization (ischemia time) can impact 20% of phospho-serine and 50% of phospho-tyrosine residues in kinases. Consequently, inadequate tumor biopsy processing is a significant impediment to the use of phosphorylated biomarkers in oncology. We aim to develop new biopsy devices and methodologies to stabilize highly dynamic biomarkers and minimize the influence of preanalytical factors. Methods: A cryobiopsy device (CBD) was developed by integrating a 19G cryoablation needle with a 16G cutting cannula of a clinical biopsy device. The device enables in-situ freezing of the tissue sample before it is cut and removed from the tumor. We measured the stabilization of a highly labile biomarker, phosphorylated-MET (pMET), to compare between percutaneous biopsy samples acquired by the CBD (zero ischemic time) and by a clinical grade 18G biopsy device (Temno) (10-20 second ischemic time). The animal protocol was approved by the FNLCR's IACUC. Athymic nude mice (nu/nu NCr) were implanted with human gastric carcinoma cell line SNU-5. Tumors were biopsied 3 weeks after implantation (tumor size range 150-250mm3). The needle was passed through the skin into the tumor, a tissue sample was collected, and the biopsy needle was retracted. The tissue sample of the Temno device was rapidly frozen in a cryovial that was precooled in liquid nitrogen [1]. The already frozen tissue sample of the CBD was rapidly transferred to a second precooled cryovial. The vials were sealed and returned to liquid nitrogen. Frozen specimens were stored at −80°C until processing. Each tumor was biopsied once and the animal was euthanized. The methodology to determine the pMET/MET levels in the biopsy samples is detailed in [2]. Results: The pMET/MET ratio was not significantly different between samples acquired by the CBD and by the Temno device (mean±st dev): pY1234/35-MET/MET ratio: CBD 0.75±0.11; Temno 0.71±0.10 pY1356-MET/MET ratio: CBD 0.56±0.08; Temno 0.50±0.06 pY1235-MET/MET ratio: CBD 0.90±0.15; Temno 0.83±0.14 Conclusions: Past studies showed that tissue levels of highly labile biomarkers like pMET can change significantly in 1-2 minutes from the time of tissue harvesting [2]. The current study demonstrates that rapid freezing of the tissue within less than 20 seconds from tissue harvesting maintains the in-vivo levels of pMET similarly to tissue freezing before tissue harvesting. This result suggests that devices that rapidly freeze tissue samples after removal from the body, which are more suitable for clinical use, may be sufficient for preservation and accurate quantitation of highly labile biomarkers. 1. PMID: 18980982 2. PMID: 27001313 Supported by NCI Contracts HHSN261200800001E and HHSN261201200050C Citation Format: Erez Nevo, Melinda G. Hollingshead, Katherine Ferry-Galow, Jeevan P. Govindharajulu, Shoshan Nevo, Kay D. Gray, Ralph E. Parchment, James H. Doroshow, Apurva K. Srivastava. Cryogenic biopsy device for preservation of labile biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4537.

The Value of Negative Diagnosis in Thyroid Fine-Needle Aspiration: a Retrospective Study with Histologic Follow-Up.

The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy of less than 5% in thyroid nodules with a benign diagnosis on fine-needle aspiration (FNA). However, recent series have suggested that the true rate of malignancy might be significantly higher in this category of patients. We reviewed our experience by performing a retrospective analysis of patients with benign thyroid FNA results who underwent thyroidectomy between 2008 and 2013 at a large academic center. Information including demographics, ultrasound features, FNA diagnosis, and surgical follow-up information were recorded. Slides were reviewed on cytology-histology discrepant cases, and it was determined whether the discrepancy was due to sampling or interpretation error. A total of 802 FNA cases with a benign diagnosis and surgical follow-up were identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found to be neoplastic, including 117 malignant cases. False negative, defined as interpretation error and inadequate biopsy of the nodule harboring malignancy, was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were excluded from the analysis, false-negative rate was 5%. When microPTC cases were excluded, false-negative rate was 3% and was slightly less than 3% when both microPTC and NIFTP cases were excluded from the analysis. Retrospective review of neoplastic cases showed that 57% were due to sampling error and 43% were due to interpretation error. Interpretation error was more likely to occur in follicular patterned neoplasms (75%), while sampling error was more common in non-follicular variants of papillary thyroid carcinoma (non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were still more likely to occur in follicular neoplasms (79%) but there was no significant difference in sampling error between non-FVPTC (37%) and follicular patterned neoplasms (42%). Tumor size was larger in cases with interpretation error (mean = 2.3cm) compared to cases with sampling error (mean = 1.4cm). This study shows that the false-negative rate of thyroid FNA at our institution is not significantly above the rate suggested by the BSRTC. Interpretation errors were more likely to occur in follicular patterned neoplasms, while non-FVPTC was more frequently found in false negative cases due to inadequate sampling.

A case of chronic ulcer due to subcutaneous arteriolosclerosis in an obese patient mimicking pyoderma gangrenosum.

The differential diagnosis of chronic ulcers covers a wide range of diseases and poses a diagnostic challenge. Subcutaneous ischemic arteriolosclerosis can lead to local ischaemia and ulceration as a result of arteriolar narrowing and reduction of tissue perfusion. This pathophysiological feature can be seen in eutrophication (nonuremic calciphylaxis) in morbid obesity, hypertensive ischemic leg ulcer (Martorell ulcer) and calciphylaxis in chronic renal insufficiency. All of the ulcers happened in this way can be wrongly diagnosed as pyoderma gangrenosum because of clinical similarity and inadequate biopsies. We report a case of chronic ulcer due to subcutaneous arteriolosclerosis in morbid obesity, wrongly diagnosed as pyoderma gangrenosum. It can be detrimental to misdiagnose the ulcers due to subcutaneous arteriolosclerosis as pyoderma gangrenosum since they need a diametrically different approach.

Abstract No. 608 Value of performing outpatient CT-guided percutaneous lung biopsy at a large, tertiary care center after unsuccessful outside hospital biopsy attempt

To determine the value of performing outpatient CT-guided percutaneous lung biopsy (CTLB) at a large, tertiary care center after unsuccessful outside hospital biopsy attempt. Retrospective review of 402 consecutive patients undergoing outpatient CTLB at MD Anderson Cancer Center for the 120-day period ending June 15, 2017 was undertaken. The reason for biopsy was determined based upon the interventional radiology preprocedure clinic note. Demographics, procedure and imaging variables, complications, and pathology results were collected. Of the total number of patients biopsied during this period, 5% (20/402) were either denied biopsy at an outside hospital (OSH) or had an inadequate biopsy result which precluded treatment decision planning. 3 patients were denied biopsy at OSH for high risk and/or technical difficulty; 9 patients underwent repeat biopsy for prior non-diagnostic biopsy at OSH; and 8 patients underwent repeat biopsy for incomplete biopsy at OSH. The mean age was 66 years (15 – 90), 50.7% were female, and 17.2% had history of COPD. Median lesion size was 1.5 cm (0.5 – 9.4). Biopsy was performed with core in 98.0%, fine-needle aspiration (FNA) in 51.0%, and both core and FNA in 49.0% of cases. Median number of core samples was 3 (1 – 8) using a median 20-gauge (18 – 20) needle and median number of FNA samples was 3 (1 – 8) using a 22-gauge needle. Of these 20 patients, 3/20 (15.0%) developed PTX (CTCAE Grade 1) and 1/20 (5.0%) required chest tube placement for expanding PTX (CTCAE Grade 2). All 20 patients (100.0%) had a successful diagnostic biopsy based on histology and/or requested molecular testing. 20 patients underwent CTLB at MD Anderson Cancer Center after unsuccessful outside hospital biopsy attempt. The advanced experience of providers allowed for aggressive biopsy sampling with complication rates within the expected thresholds of the institution and yielded meaningful pathology outcomes based on histology and/or requested molecular testing. On an annualized basis, this represents 60 previously unserved patients that could safely receive a diagnosis, demonstrating the value of higher level care centers in the broader healthcare value chain.

Abstract P2-02-12: Cell free DNA analysis identifies actionable ERBB2 amplifications in patients with HER2 negative breast cancer

Abstract Identification of ERBB2 (HER2) overexpression in metastatic breast cancer informs utilization of HER2 targeted therapy. The NCCN recommends HER2 expression re-evaluation at the first disease recurrence in patients with negative or equivocal tissue status given results discrepancies due to inadequate tissue biopsy, tumoral heterogeneity, biopsy technique or fixation as well as discordance in ERBB2 (HER2) expression between primary and metastatic lesions. We examined the incidence of ERBB2 (HER2) negative to positive “flips” (e.g. to ERBB2-amplified in plasma) in a cohort of patients who underwent a blood-based cell-free DNA (cfDNA) assay at a CLIA-certified/CAP-accredited/NYSDOH-approved molecular diagnostic laboratory. Laboratory database was queried for samples from patients with a breast cancer diagnosis. The query was filtered to ensure patients with multiple cfDNA timepoints were counted only once. Patients without a pathology report submitted at any cfDNA collection timepoint or the pathology report did not include ERBB2 (HER2) status, results were inconclusive or quantity not sufficient were excluded. Between March 2014 and April 2017, 1,853 unique patients were identified with reported ERBB2 (HER2) status. For patients with more than one cfDNA timepoint collected (N=349; 18.8%), the earliest pathology report was referenced. 1,386 patient tumor samples were negative for HER2 overexpression (74.8%), 325 (17.5%) were positive, and 142 (7.7%) were equivocal. Twenty-nine of the 1,386 patients with reported tumor negative HER2 status had amplification on subsequent cfDNA analysis (2.1%). All 29 patients were female. Most patients (N=21) had a single cfDNA timepoint collected. Median age at cfDNA blood draw was 58 years (range 28–68). Median length of time between reported tissue negative status and cfDNA blood draw was 405 days (range 21–4,060). Median plasma ERBB2 copy number was 2.44 (greater than 50th-centile per laboratory data) (range 2.15–16.5). Clinical follow-up was obtained for 19 patients (65%). Nine patients were lost to follow-up or succumbed to disease prior to initiation of a new therapeutic regimen. One patient was known HER2 positive prior to receipt of the cfDNA results. In the remaining nine patients, six initiated targeted HER2 therapy following receipt of the cfDNA results, with five of six (83%) demonstrating a clinical response. In one patient with known ER/PR positive, HER2 negative disease, progressing through multiple lines of therapy, addition of trastuzumab and pertuzumab to her paclitaxel regimen following identification of the cfDNA ERBB2 amplification resulted in a significant reduction in CEA levels (238 to 37.9 ng/mL) by week five. In a second patient, following identification of the cfDNA ERBB2 amplification, she was treated with trastuzumab and pertuzumab along with docetaxel and had a dramatic response. She continues on trastuzumab and pertuzumab alone. Although a modest sample size, this is the second cfDNA series demonstrating that ERBB2 (HER2) status may flip from negative to positive upon recurrence or metastasis, and that targeting plasma-detected ERBB2 amplification with anti-HER2 has clinical benefit. cfDNA is a viable alternative to tissue rebiopsy in this patient population. Citation Format: Raymond VM, Diaz J, Banks KC, Ahn E, Brufsky A, Ellis M, Lippman M, Lee C, Pluard T, Schreeder M, Schwab R, Lanman RB. Cell free DNA analysis identifies actionable ERBB2 amplifications in patients with HER2 negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-12.

In vitro Comparison of Ethanol Metabolism in Precision Cut Liver Slices from C57Bl/6, Balb/c, DBA/2J and 129S1/SvlmJ Mice

Percutaneous biopsy is a key diagnostic tool for both native and allograft kidney diseases. Adequacy criteria vary, but at a minimum, a biopsy should allow the pathologist to reach a diagnosis and provide prognostic information such as the degree of interstitial fibrosis and tubular atrophy (IF/TA) and percentage of glomerulosclerosis. Whereas most studies use glomerular counts as a surrogate for biopsy adequacy, the amount and preservation of tubulointerstitium is equally important, considering IF/TA is a major prognostic parameter for most medical renal diseases. Many studies have compared the diagnostic adequacy of different gauge needles; however few have investigated performance differences between same gauge needles. In this study, we retrospectively analyzed 235 renal biopsies performed at a single center in Canada over 2 years to compare the utilization, safety, diagnostic and prognostic performance of two 18-gauge needles in native and allograft kidney biopsies. We found no significant difference in needle utilization between native and allograft kidneys, or between trainees and staff radiologists. The total tissue yielded area, glomerular counts, percentage of inadequate biopsies and number of passes were similar; however the number of cases in which IF/TA evaluation was deemed not possible was higher for biopsies using disposable instrument needles (4.3% vs. 0%; p = 0.01). These also showed greater number of tissue fragments (median 4 for reusable vs 3 for disposable; p = 0.04). We postulate that the increased tissue fragmentation might have impaired the pathologists ability to accurately assess interstitial fibrosis and tubular atrophy in biopsies obtained with the disposable instrument needles.

Utility of Genomic Assessment of Blood-Derived Circulating Tumor DNA (ctDNA) in Patients with Advanced Lung Adenocarcinoma.

Purpose: Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next-generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications.Results: Seventy-two patients (82%) had ≥1 ctDNA alteration(s); among these, 75% carried alteration(s) potentially actionable by FDA-approved (61.1%) or experimental drug(s) in clinical trials (additional 13.9%). The most frequent alterations were in the TP53 (44.3% of patients), EGFR (27.3%), MET (14.8%), KRAS (13.6%), and ALK (6.8%) genes. The concordance rate for EGFR alterations was 80.8% (100% vs. 61.5%; ≤1 vs. >1 month between ctDNA and tissue tests; P = 0.04) for patients with any detectable ctDNA alterations. Twenty-five patients (28.4%) received therapy matching ≥1 ctDNA alteration(s); 72.3% (N = 16/22) of the evaluable matched patients achieved stable disease ≥6 months (SD) or partial response (PR). Five patients with ctDNA-detected EGFR T790M were subsequently treated with a third generation EGFR inhibitor; all five achieved SD ≥ 6 months/PR. Patients with ≥1 alteration with ≥5% variant allele fraction (vs. < 5%) had a significantly shorter median survival (P = 0.012).Conclusions: ctDNA analysis detected alterations in the majority of patients, with potentially targetable aberrations found at expected frequencies. Therapy matched to ctDNA alterations demonstrated appreciable therapeutic efficacy, suggesting clinical utility that warrants future prospective studies. Clin Cancer Res; 23(17); 5101-11. ©2017 AACR.

Colorectal endometriosis: Five years’ experience in this enigmatic problem

Introduction Endometriosis affects primarily women of reproductive age and is responsible for impairing their quality of life. Presence of severe symptoms, stenosis of the intestinal lumen, diagnostic difficulty (suspicion of malignancy) and intolerance to hormonal therapy are indications for surgery. Despite numerous studies concerning endometriosis, there is still considerable controversy about its incidence, pathogenesis, diagnosis and optimal treatment. Methods This retrospective observational study includes 11 patients who were diagnosed with intestinal endometriosis between January 2009 and December 2013. Demographic data, clinical presentation, diagnostic modalities, localization of the disease and intraoperative data were collected. Results Median age of the patients was 43 (34–63). Eight patients had intermittent abdominal pain, seven had change in bowel habits and three had for rectal bleeding. Seven patients were operated on for severe stenosis of the intestinal lumen (intestinal obstruction) and three for a suspected malignancy. Postoperatively all of the patients who underwent resection were free of pain. No patient had any disease recurrence on USG or CT images. Discussion Intestinal endometriosis should be considered in female patients of reproductive age presenting with constipation, rectal bleeding and abdominal pain. Also repeated inadequate biopsies should raise suspicion of intestinal endometriosis. Intestinal endometriosis is a rare disease with diagnostic difficulties and despite medical management, treatment options are usually surgery. But in patients who were diagnosed preoperatively and did not have intestinal obstruction, medical therapy may be tried.

Audit of Oral Histopathology Service at a Nigerian Tertiary Institution over a 24-Year Period.

Biopsies are often essential for definitive diagnosis of oro-facial lesions and are a part of oral diagnostic procedures carried out in histopathology laboratories. At present, there is paucity of literature on the audit of oral histopathology services in Nigeria. The objectives of this study were to determine the prevalence of biopsied oral lesions in a Nigerian tertiary institution. Also to profile the usage of oral pathology service and to identify challenges that may be present in an oral histodiagnostic service. This was a retrospective study performed at the Oral Pathology Department of the University of Ibadan/ University College Hospital, Ibadan, Nigeria. Reports of all biopsies submitted at the Oral Pathology laboratory, for the period 1990-2014, were reviewed and data extracted. Descriptive analysis was done using SPSS software, version 20. The total number of reports was 1,998; invalid reports constituting 220(11%) were subsequently excluded leaving 1,778(89%) valid reports. The mean age of patients was 36.70±19.79, while the peak age of presentation was in the 3rd decade. Male to female ratio was 1:1.1, and the mandible was the most common site of lesions 619(34.8%). These services were mainly utilized by oral surgeons (83.9%) and ameloblastoma (11.5%) was the most frequently diagnosed lesion. CD45 (16.7%) was the most frequently requested immuno-diagnostic test. Biopsied oral lesions were more prevalent in females, while oral and maxillofacial surgeons utilized these services the most. Inadequate biopsy specimens or unrepresentative specimens and deficient documentation were challenges identified in this study.

The detection and significance of EGFR and BRAF in cell-free DNA of peripheral blood in NSCLC.

ObjectiveAlthough driver mutation status is crucial to targeted therapy decision-making in non-small cell lung cancer (NSCLC), due to unavailable or inadequate biopsies, there are still many patients with unknown mutation status. A promising way to solve this problem is liquid biopsy, such as cell-free DNA (cfDNA) in peripheral blood. Additionally, due to the little amount of cfDNA, detecting methods with high sensitivity, specificity and economy are required in clinical practice. Here, we explored the feasibility of Competitive Allele-Specific TaqMan® PCR (CastPCR) detecting driver mutations in cfDNA from plasma in lung adenocarcinoma patients.ResultsSensitivity, specificity, concordance, PPV and NPV of CastPCR detecting EGFR mutations in cfDNA was 56.4% (31/55), 94.2% (49/52), 74.8% (80/107), 91.2% (31/34) and 67.1% (49/73), respectively. Notably, specificity and PPV for p.T790M both reached 100.0%. For BRAF detection, it was 28.6% (2/7), 93.0% (93/100), 88.8% (95/107), 22.2% (2/9) and 94.9% (93/98), respectively.Materials and MethodsPlasma specimens of 107 lung adenocarcinoma patients and their matched tumor formalin fixed paraffin embedded (FFPE) samples were analyzed. CastPCR was used to detect EGFR (c.2235_2249del, c.2236_2250del, c.2369C>T p.T790M, c.2573T>G p.L858R) and BRAF (c.1406G>C p.G469A, c.1799T>A p.V600E, c.1781A>G p.D594G) mutations. Mutation results of tumor tissue was set as gold standard, and the sensitivity, specificity, concordance, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each mutation.ConclusionsFor patients whose tumor tissue is unavailable or inadequate, EGFR mutation detection in cfDNA with CastPCR could be first choice. Mutation positive results may provide reference for further clinical medication. While negative results indicate that detection in tissue should be considered as the following step. In this way, tumor tissue could be economized to the maximum extent and the risk of repeated percutaneous transthoracic lung biopsy could also be lowered to the maximum extent. For BRAF detection in cfDNA, CastPCR is a specific method while the sensitivity needs further exploration.

Diagnostic utility of fine-needle aspiration cytology of lesions involving bone.

Fine-needle aspiration (FNA) is utilized in the diagnostic work-up of bone lesions in a number of institutions, either in isolation or in conjunction with core biopsy. We report our experience with FNA of bone-based lesions, including comparison of this approach with concurrent core biopsy specimens. Retrospective review over a 5-year period (2011-2015) revealed 233 cases of bone FNAs. The most commonly encountered diagnosis was malignant neoplasm (160 cases, 68.7%); within this group of malignancies, 103 cases (64.4%) represented metastatic carcinoma. Benign lesions were encountered infrequently (9 cases, 3.9%). While 37 cases (15.9%) revealed "no evidence of malignancy," 12 cases (5.2%) showed atypical findings, 3 cases (1.3%) demonstrated inflammatory conditions, and 12 aspiration biopsies were deemed nondiagnostic (5.2%). In 202 cases, concurrent core biopsies were performed following FNA and rapid on-site evaluation (ROSE). Comparison of the FNA and core biopsy diagnoses among malignant neoplasms revealed 19 diagnostic discrepancies, including 16 cases with a false-negative FNA (7.9% of all FNAs with concurrent core biopsy) and 3 cases with a false-negative core biopsy (1.5% of all cases with corresponding FNA). Our findings indicate that FNA of bone lesions is a useful diagnostic technique with high sensitivity, particularly when the cytologic findings are interpreted in conjunction with the core biopsy and pertinent clinical and radiologic findings. In addition, ROSE followed by open, dynamic communication with the performing radiologist leads to an extremely low rate of inadequate core biopsy specimens, resulting in optimal patient diagnosis and management. Diagn. Cytopathol. 2017;45:608-613. © 2017 Wiley Periodicals, Inc.

Effectiveness and safety of two 18-gauge needle types on native and allograft renal biopsies.

Percutaneous biopsy is a key diagnostic tool for both native and allograft kidney diseases. Adequacy criteria vary, but at a minimum, a biopsy should allow the pathologist to reach a diagnosis and provide prognostic information such as the degree of interstitial fibrosis and tubular atrophy (IF/TA) and percentage of glomerulosclerosis. Whereas most studies use glomerular counts as a surrogate for biopsy adequacy, the amount and preservation of tubulointerstitium is equally important, considering IF/TA is a major prognostic parameter for most medical renal diseases. Many studies have compared the diagnostic adequacy of different gauge needles; however few have investigated performance differences between same gauge needles. In this study, we retrospectively analyzed 235 renal biopsies performed at a single center in Canada over 2years to compare the utilization, safety, diagnostic and prognostic performance of two 18-gauge needles in native and allograft kidney biopsies. We found no significant difference in needle utilization between native and allograft kidneys, or between trainees and staff radiologists. The total tissue yielded area, glomerular counts, percentage of inadequate biopsies and number of passes were similar; however the number of cases in which IF/TA evaluation was deemed not possible was higher for biopsies using disposable instrument needles (4.3% vs. 0%; p=0.01). These also showed greater number of tissue fragments (median 4 for reusable vs 3 for disposable; p=0.04). We postulate that the increased tissue fragmentation might have impaired the pathologists ability to accurately assess interstitial fibrosis and tubular atrophy in biopsies obtained with the disposable instrument needles.

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48%) were classified as malignant and 9 cases (1.49%) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76%). There were 26 (4.3%) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95%). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.

PWE-038 Validation of Multiparametric MRI in The Assessment and Staging of Non-Alcoholic Fatty Liver Disease: Abstract PWE-038 Table 1

Introduction Hepatic fibrosis is an important determinant of outcome in non-alcoholic fatty liver disease (NAFLD). The severity of non-alcoholic steatohepatitis (NASH) has relevance to clinical follow up intensity and assessment of the effectiveness of treatment interventions. Magnetic resonance imaging (MRI)-acquired T1 measurement has been shown to correlate with hepatic fibrosis and is also increased by inflammation, indicating potential as a tool to stratify NAFLD. Methods Patients undergoing liver biopsy (LB) were invited for MRI and blood sampling prior to LB. Iron accumulation has been shown to reduce T1 independent of fibrosis, so an iron corrected hepatic T1 (cT1) was calculated using LiverMultiscan (Perspectum Diagnostics, Oxford). Histology was graded by two expert liver histopathologists according to the NASH-CRN system. Results 50 patients had complete data sets following exclusions (1 inadequate biopsy, 3 MRI data unavailable). 28 (56%) patients were male. Median age 54 years. 26 (52%) patients had type-2 diabetes. Mean (±SD) body mass index was 33.6 (±5.1) Kg/m2. Median (IQR) of ALT, fasting glucose and cholesterol were 54 (52) u/L, 6.2 (4.0) mmol/L and 4.8 (1.5) mmol/L, respectively. 38 (76%) LBs demonstrated NASH and the remainder simple steatosis (SS). Mean(±SD) cT1 for NASH and SS were 1007(±95) milliseconds (ms) and 907(±120) ms, respectively (p = 0.004). The correlation between cT1 and NAS was highly significant (Rho = 0.51, p F1) and advanced (>F2) fibrosis cT1 had an AUROC (95% CI) of 0.65 (0.48–0.83) and 0.62 (0.47–0.78), respectively. To identify patients with SS and no significant fibrosis cT1 had an AUROC (95%CI) of 0.75 (0.56–0.93). Conclusion Multiparametric MRI using LiverMultiscan has the ability to non-invasively stage fibrosis in patients with NAFLD. The additional benefit of this novel technology is the ability to concurrently establish the severity of NASH. The correlation of cT1 and NAS suggests that multiparametric MRI has potential for monitoring the effectiveness of treatment interventions in NAFLD. Disclosure of Interest P. Eddowes: None Declared, N. McDonald: None Declared, N. Davies: None Declared, S. Semple: None Declared, S. Hubscher: None Declared, T. Kendall: None Declared, C. Kelly Employee of: Perspectum Diagnostics, M. Mavar Employee of: Perspectum Diagnostics, A. Herlihy Employee of: Perspectum Diagnostics, P. Newsome: None Declared, S. Olliff: None Declared, J. Fallowfield: None Declared, G. Hirschfield: None Declared

Differential diagnosis of panniculitides

Panniculitides are diseases of the subcutaneous tissue with heterogeneous etiology. They may develop consequent to infections, as areaction to drugs, after thermal injury, as part of autoimmune diseases, in metabolic disorders or due to infectious organisms. The clinical presentation with subcutaneous nodules is often nonspecific. Moreover, the differentiation from vasculitides of medium-sized vessels can be clinically challenging. Microscopic examination of biopsy specimens is of high importance in the differential diagnosis of panniculitides. Histopathologically, panniculitides can be classified according to the predominantly infiltrated area in septal and lobular panniculitides and they can be separated from vasculitides of medium-sized vessels. Diagnostic difficulties arise from inadequate biopsy specimens and from lack of clinicopathological correlation. This article summarizes diagnostic criteria of frequent and clinically important panniculitides.

Suction rectal biopsy yields adequate tissue in children

Background/purposeHirschsprung disease (HD) is diagnosed by rectal biopsy, with suction rectal biopsy (SRB), the preferred technique in neonates. Reported SRB adequacy has varied overall with concern for decreased diagnostic yield in older children. The study aim was to assess SRB adequacy by age in children with the current device used at our institution. MethodsFollowing IRB approval, a retrospective cohort of children (1 to 18years) evaluated by SRB for HD was identified through billing records. Data regarding demographics, procedure, results, and complications were collected and analyzed using SPSS. Results56 children (median age 3.9years) underwent SRB with an 80.4% overall success rate. Patients older than 5years had 90.5% adequacy rate compared to 74.3% in those younger. Univariate analysis revealed weak association of inadequate specimens with younger age and males, and no association with insurance, race/ethnicity, weight–height or BMI percentile, sedation type, or procedure location. SRB under general anesthesia (GA) had 100% adequacy (n=6). Patients with inadequate initial biopsy achieved diagnosis by SRB with increased sedation (n=5) or full thickness biopsy under GA (n=5). ConclusionWith adequacy of 80.4% overall and 90.5% for patients greater than 5years, SRB is effective in evaluating the older child for HD.

SAT-421 - The Histological Quantification of Alpha-Smooth Muscle Actin Predicts Future Graft Fibrosis in Pediatric Liver Transplant Recipients

Histological quantification of apha smooth muscle actin predicts future graft fibrosis in pediatric liver transplant recipients Varma S1, Stephenne X1, Komuta M2, Bouzin.C3, Ambroise J4, Smets F1, Reding R5, and Sokal EM1 Universite Catholique de Louvain, Cliniques Universitaires St Luc, 1Service de Gastroenterologie et Hepatologie Pediatrique and Pediatric Research Unit, 2Service de Anatomopathologie, 3 Imaging Platform (2IP) Institut de Recherche Experimentale et Clinique (IREC) , 4 Centre for Applied Molecular Technologies (CTMA), Institut de Recherche Experimentale et Clinique (IREC) 5 Unites de Chirurgie Pediatrique, Brussels, Belgium Aims: To evaluate significance of alpha smooth muscle actin (ASMA) expression on liver biopsy as predictor of future graft fibrosis in pediatric liver transplant (LT) recipients. Background: Activated hepatic stellate cells express cytoplasmic protein-alpha smooth muscle actin (ASMA) and subsequently secrete collagen leading to liver fibrosis. As activation of stellate cells precedes collagen deposition, we hypothesize that quantification of ASMA can predict the severity of future fibrosis. Patients: Stable pediatric LT recipients transplanted between 2006-20012, with two protocol biopsies less than two years apart and first being at more than 1year post LT. Patients with biliary, vascular complications, autoimmune hepatitis, hepatitis B or C infection, re-transplantation, or those with inadequate biopsy size were excluded. Methods: Metavir and liver allograft fibrosis scoring (LAFSc) used for fibrosis assessment. Automated staining for ASMA followed by digital quantification of ASMA positive area percentage was done. Fibrosis on initial biopsy specimen was labelled “current fibrosis” and on next biopsy labelled “prospective fibrosis”. The change between “current” and “prospective” fibrosis score was “prospective change in fibrosis”. Bile duct proliferation, lobular inflammation and portal tract infiltration was also evaluated. Results: 32 biopsy specimens, from 18 patients stained for ASMA and 56 evaluated for fibrosis. Significant association between the ASMA positive area percentage on initial biopsy and “prospective change in fibrosis” was seen; using Metavir (p-value = 0.02), LAFSc cumulative (p-value = 0.02) and LAFSc-portal (p-value=0.01) scores. AUROC analysis suggested ASMA positive area percentage > 1.05 to predict increased fibrosis on the next biopsy (60.0 % sensitivity, 90.0 % specificity). Conclusion: ASMA quantification on biopsy in liver transplant recipients predicts the future course of fibrosis, specifically portal fibrosis.

Rectal biopsy for Hirschsprung's disease: a review of techniques, pathology, and complications.

Hirschsprung's disease (HD) is one of the most common congenital anomalies of colorectal function, affecting approximately 1 in 5000 live births, with a 4:1 male predominance. HD is characterized by aganglionosis that is most often limited to the rectosigmoid, but can extend proximally along the colon and, in rare instances, reach into the small intestine. A clinical history of delayed passage of meconium beyond 48 hours after birth, physical exam findings of abdominal distention and vomiting, and a contrast enema demonstrating a transition zone are highly suggestive of HD. We searched databases including PubMed, Google Scholar, and Scopus for the following key words: Hirschsprung's disease, rectal biopsy, pathology, ganglion cell, nerve trunk hypertrophy, pediatric constipation, and selected publications written in English that were relevant to the scope of this review. Based on the data presented in the literature, we reviewed 1) biopsy techniques for the diagnosis of Hirschsprung's disease, addressed inadequate biopsies, and complications from rectal biopsy, and 2) pathologic and histologic interpretation of biopsy specimens for the diagnosis of Hirschsprung's disease. A well-executed rectal biopsy with expert pathologic evaluation of the specimen remains the gold standard for the diagnosis of Hirschsprung's disease and is the subject of this review.