BACKGROUND:The diagnosis of pancreatic tumors is often complicated because of sampling and interpretive challenges.The current study was performed to determine the rates, types, and causes of diagnostic discrepancies. METHODS: The authors retrospectively reviewed cytology cases from 2004 to 2010 using matched surgical resection cases as the gold standard. RESULTS: A total of 733 cases were divided into 3 categories: 1) positive or suspicious (290 cases); 2) negative or atypical (403 cases); and 3) unsatisfactory (40 cases). Of these cases, 101 fine-needle aspiration (FNA) cases had matched surgical resections including 58 positive diagnoses, 39 negative diagnoses, and 4 unsatisfactory diagnoses. All 19 discrepant cases represented false-negative diagnoses without any false-positive cases noted, which included 2 cases with interpretive errors (10%) and 17 cases with sampling errors (90%). All matched cytology cases were divided into 5 subgroups based on the type of lesion or type of error and were analyzed for sensitivity and specificity. The sampling error rate in cystic lesions (8 of 24; 33%) was significantly higher than that in solid lesions (9 of 73; 12%). The falsenegative rate in the interpretive error group (3%) was significantly lower than that in the sampling error group (23%). CONCLUSIONS:The results of the current study confirm that pancreatic endoscopic ultrasound-guided FNA diagnosis has a very low false-positive rate but a relatively high false-negative rate using matched surgical resections as the gold standard. The major cause of a false-negative cytology diagnosis is sampling error and the rate of sampling error in cystic lesions is significantly higher than that in solid lesions. Cancer (Cancer Cytopathol) 2013;121:449-58. V C 2013 American Cancer Society.KEY WORDS: false-negative; endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the pancreas; cystic lesion; solid lesion; pancreatic resection.

BackgroundAutomated screening of Papanicolaou tests (Pap tests) improves the productivity of cytopathology laboratories. The ThinPrep® Imaging System (TIS) has been widely adopted primarily for this reason for use on ThinPrep® Pap tests (TPPT). However, TIS may also influence the interpretation of Pap tests, leading to changes in the frequency of various interpretive categories. The effect of the TIS on rates of TPPT interpretation as atypical squamous cells of undetermined significance (ASC-US) is of concern because any shift in the frequency of ASC-US will alter the sensitivity and specificity of the Pap test. We have sought to determine whether automated screening of TPPT has altered ASC-US rates in our institution when compared with manual screening (MS) of TPPT.MethodsA computerized search for all ASC-US with reflex Human Papillomavirus (HPV) testing over a one-year-period (7/1/06 to 6/30/07) was conducted. Cases included both TPPT screened utilizing TIS and screened manually. HPV test results for both groups were recorded. Pertinent follow-up cervical cytology and histology results were retrieved for the period extending to 11/30/07. Automated screening was in clinical use for 10 months prior to the start of the study.ResultsAutomated screening was performed on 23,103 TPPT, of which 977 (4.23%) were interpreted as ASC-US. Over the same period, MS was performed on 45,789 TPPT, of which 1924 (4.20%) were interpreted as ASC-US. Reflex HPV testing was positive for high risk (HR) types in 47.4% of the TIS cases and 50.2% of MS cases. Follow-up cervical dysplasia found by colposcopy was also distributed proportionally between the two groups. Cervical intraepithelial neoplasia (CIN) was found on follow-up biopsy of 20.1% of the TIS cases (5.2% CIN 2/3) and 21.2% of MS cases (5.1% CIN 2/3). None of these differences were statistically significant.ConclusionUse of the ThinPrep® Imaging System did not appreciably change ASC-US rates or follow-up reflex HPV test results in our laboratory. This demonstrates that the benefits of automated screening may be obtained without increasing the rate of referral to colposcopy for ASC-US follow-up.

Cervical screening with combined cytology and high-risk human papillomavirus (HR-HPV) detection has been approved for women 30 years or older. We investigated the clinical use of cotesting for women with negative Papanicolaou tests. Follow-up cytology, HR-HPV test, and biopsy findings were identified during an 18-month period. In 1 year, 2,719 cotests from 2,686 women were identified; 146 were positive for HR-HPV. Among women with positive HR-HPV testing, 120 had follow-up, including 70 with repeated cotesting, and 3 had high-grade dysplasia identified (2.5% of women with follow-up). In 1,334 women with initial double-negative cotest results who had repeated cytologic testing within 18 months, 2 high-grade dysplasias were found (0.1%). The vast majority of cotest results are double-negative. Among tests that show HR-HPV positivity, the prevalence of underlying high-grade dysplasia is low. About half of all women who undergo cotesting receive follow-up that is not in accord with published guidelines.

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Background The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. Methods This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to ‘deep phenotyping’ (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonally- and spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/immediately after birth and 6 weeks after birth. Conclusions To accelerate progress towards the women’s and children’s health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health.

ObjectivesThe AMANHI study aims to seek for biomarkers as predictors of important pregnancy–related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available.MethodsAMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8–19 weeks of gestation) for population–based follow–up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field workers will collect very detailed phenotypic and epidemiological data from the pregnant woman and her family at scheduled home visits during pregnancy (enrolment, 24–28 weeks, 32–36 weeks & 38+ weeks) and postpartum (days 0–6 or 42–60). Trained phlebotomists will collect maternal and umbilical blood samples, centrifuge and obtain aliquots of serum, plasma and the buffy coat for storage. They will also measure HbA1C and collect a dried spot sample of whole blood. Maternal urine samples will also be collected and stored, alongside placenta, umbilical cord tissue and membrane samples, which will both be frozen and prepared for histology examination. Maternal and newborn stool (for microbiota) as well as paternal and newborn saliva samples (for DNA extraction) will also be collected. All samples will be stored at –80°C in the biobank in each of the three sites. These samples will be linked to numerous epidemiological and phenotypic data with unique study identification numbers.Importance of the studyAMANHI biobank proves that biobanking is feasible to implement in LMICs, but recognises that biobank creation is only the first step in addressing current global challenges.

Background:programmed death-ligand 1 (PD-L1) is a ligand for the inhibitory programmed cell death protein 1 (PD-L1), which are targeted by several anti-PD-1 and PD-L1 drugs for lung cancer treatment. In clinical practice, many lung cancer cases only have cytology samples available to test PD-L1. Our current study compared the PD-L1 immunohistochemistry (IHC) between paired cytological and surgical samples.Materials and Methods:Formalin-fixed lung cancer tissue microarray and paired cell blocks and surgical specimens from the same patients with a confirmed diagnosis of lung squamous cell carcinoma (SCC, n = 29) and adenocarcinoma (AC, n = 23) were sectioned for PD-L1 IHC.Results:PD-L1 was expressed on tumor cells in 16 of 29 (55%) SCC surgical specimens and 18 of 29 (62%) paired cytologic specimens with 83% matched immunostains. PD-L1 was expressed on tumor cells in 13 of 23 (57%) AC surgical specimens and in 17 of 23 (74%) paired cytologic specimens with 79% matched immunostains. The PD-L1 was expressed on inflammatory cells in 20 of 23 (87%) AC surgical specimens and in 15 of 23 (65%) paired cytologic specimens with 70% matched immunostains. The PD-L1 was expressed on inflammatory cells in 18 of 29 (62%) SCC surgical specimens and in 12 of 29 (41%) paired cytologic specimens with 79% matched immunostains.Conclusions:PD-L1 immunostain in cytology samples matched very well with paired surgical samples in both SCC and AC cases. The cytologic samples present slightly higher sensitivity for PD-L1 immunostain on tumor cells as compared to surgical biopsies.

Context College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. Objective To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. Design Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. Results A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. Conclusions There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.