Journal of Clinical Pathology

BackgroundHypercoagulability is becoming widely recognized as a major complication of COVID-19 infection as evidenced by high levels of fibrinogen degradation products and microthrombi identified within the lungs and kidneys of autopsy specimens from these patients. We report thromboelastography (TEG) testing on a cohort of patients with suspected COVID-19 infection at the time of admission to the intensive care unit. MethodsTEG testing was performed using the TEG 6s analyzer near or at the time of ICU admission. We also report the results of other coagulation or inflammatory related indices such as platelet count, prothrombin time, fibrinogen, D-dimer, C-reactive protein, ferritin, and procalcitonin. All laboratory testing was performed at the discretion of the attending physician in the course of normal patient care and retrospectively reviewed. ResultsWe found that maximum clot strength was consistently elevated in COVID-19 patients while normal in all patients found to be negative. We did not encounter significant prolongations of coagulation assays outside of those expectedly prolonged by heparin therapy nor was meeting the criteria for disseminated intravascular coagulation encountered. ConclusionsWe postulate that elevated maximum clot strength by TEG testing is predictive of COVID-19 status as within our cohort this perfectly predicted patients COVID-19 status despite a high level of suspicion in negative patients with normal TEG results. While these results require a larger cohort for confirmation, we feel that TEG testing could improve confidence in COVID-19 testing results in suspected patients possibly allowing for earlier de-escalation of infectious precautions and personal protective equipment utilization.

BackgroundUnited Kingdom Standards for Microbiology Investigations limits the pre-analytical delay of blood cultures to a maximum of four-hours between collection and incubation. Compliance with this delay standard is a measure of the ability of a microbiology service to support the management of sepsis which is a life-threatening complication of infection. A positive blood culture confirms the infection and an early result is critical to the effective management of the condition. Delayed results lead to the prolongation of empiric broad spectrum antimicrobial therapy which is considered a causal factor in the emergence of antimicrobial resistance. This retrospective observational study documents compliance with the standard by microbiology services in England in 2022/23. The impact of laboratory centralisation on the ability of microbiology services to comply with this standard is examined. MethodsFreedom of Information requests were submitted to 116 National Health Service Trusts/administrative units in England requesting retrospective audit data showing compliance with the recommended pre-analytical delay standard. Data relating to service configuration and cost were also requested. ResultsResponses were received from 89 Trusts (76.7%) managing 146 hospitals. Overall, the rate of compliance was low, with only four hospitals (2.7%) showing full compliance and 31.5% showing >80% compliance. ConclusionsPoor rates of compliance with the PAD standard are a concern as prompt attention to blood cultures improves patient outcomes from sepsis and supports antimicrobial stewardship. Laboratory centralisation has resulted in withdrawal of staff and facilities from some hospitals with insufficient investment in others, leading to a demonstrable inability of many hospitals to comply with this standard. Compliance will require investment in microbiology services. The financial implications of the improvements proposed should be evaluated in the context of overall health care and community benefits.

Public health emergency of SARS-CoV-2 has facilitated diagnostic testing as a related medical countermeasure against COVID-19 outbreak. Numerous serologic antibody tests have become available through an expedited federal emergency use only process. This paper highlights the analytical characteristic of an ELISA based assay by AnshLabs and three random access immunoassay (RAIA) by DiaSorin, Roche, and Abbott that have been approved for emergency use authorization (EUA), at a tertiary academic center in a low disease-prevalence area. The AnshLabs gave higher estimates of sero-prevalence, over the three RAIA methods. For positive results, AnshLabs had 93.3% and 100% concordance with DiaSorin or Abbott and Roche respectively. For negative results, AnshLabs had 69.7% and 73.0% concordance with DiaSorin and Roche or Abbott respectively. All discrepant samples that were positive by AnshLabs and negative by RAIA tested positive by all-in-one step SARS-CoV-2 Total (COV2T) assay performed on the automated Siemens Advia Centaur XPT analyzer. None of these methods, however, are useful in early diagnosis of SARS-CoV-2.

ObjectivesWe compared the Abbott ID NOW COVID-19 point-of-care test (POCT) with polymerase chain reaction (PCR)-based methods to assess the claimed sensitivity and specificity of POCT and to optimize test utilization in our regional health care system. MethodsAssuming PCR to be the gold standard, we used a convenience sampling of mostly symptomatic COVID-19 suspect hospital patients who had already been tested for internal validation and guideline development purposes by both PCR and POCT to calculate the sensitivity and specificity of POCT with Clopper-Pearson 95% confidence intervals (CI). ResultsDuring the study period, 113 paired patient samples met eligibility criteria. The sensitivity of POCT in this population was calculated to be 94.1% [CI 71.31-99.85%] and the specificity was 99.0% [CI 94.33-99.97%]. ConclusionsBased on the lower sensitivity of POCT and the estimated prevalence of COVID-19 in our symptomatic and asymptomatic hospital patients, we recommend a two-pronged testing approach in which COVID-19 suspect patients are tested by the more sensitive PCR, while asymptomatic patients with a low pre-test probability of infection are tested with POCT supplemented by PCR confirmation of positive results. Furthermore, isolation decisions should not be based on POCT results alone.

"The authors have withdrawn this manuscript because they discovered errors in the equations that no longer support the findings given in the paper. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author."

AbstarctO_ST_ABSBackgroundC_ST_ABSThe COVID-19 serological tests for IgG and IgM have been developed with several methodologies: Immunoenzymatic Assay (ELISA), Chemiluminescence, Electro Chemiluminescence, Fluorescent Lateral Flow Immunoassays and Immunochromatography. None of these tests should be used for the diagnosis or population screening of the disease, considering that the antibodies appear only on the 8th - 14th day of the disease onset. The present study evaluates a sample of immunofluorescent and immunochromatographic rapid tests to show their agreement in relation to Chemiluminescence. MethodsA diagnostic test evaluation assay was performed to establish the performance of five "rapid" tests (4 immunochromatographic and 1 immunofluorescent tests) for IgG and IgM serology for SARS-CoV-2 using a panel of 30 serum samples from patients received in the laboratory analysis routine. For the evaluation of clinical performance, the qualitative results of the "rapid" tests were compared against those obtained by chemiluminescence, dichotomized as positives ([&ge;] 10 AU / mL) or negative (<10 UA / mL). FindingsThe best agreement is seen in the immunofluorescent assay, for the IgG contrast, with a particularly good kappa index (0.85), without positive disagreements and a negative disagreement of about 15%. In the immunochromatographic methods Kappa index was 0.61 at best, with disagreements in negative findings of {approx}35% and in positive cases of up to {approx}70%. The IgM concordance behavior, on the other hand, reflects a weak to moderate Kappa concordance value (Kappa 0.2 to 0.6), with negative disagreements reaching up to 55% and positives of up to 84%, without any evaluated test reaching Kappa performance equal to or greater than 0.8. InterpretationSerological studies should be used in the clinical and epidemiological context and of other diagnostic tests. Given the high demand and supply in the market of "rapid serological tests", its evaluation against panels of serologically positive or negative samples established by Chemiluminescence or Electro chemiluminescence is essential to authorize its extensive use in populations FundingNone

In March 2020, the World Health Organization (WHO) declared a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the absence of effective treatment or biomedical prevention, understanding potential post infection immunity has important implications for epidemiologic assessments. For this reason, increasing number of in vitro diagnostic companies are developing serological assays to detect antibodies against SARS-CoV-2, but most of them lack the validation by third parties in relation to their quality, limiting their usefulness. We submitted to serological screening by two different immunochromatographic (IC) rapid testing for detection of IgG and IgM against SARS-CoV-2, 151 asymptomatic or minimally symptomatic healthcare workers previously tested positive for SARS-CoV-2 RT-PCR in order to evaluate the performance of rapid assays. Results showed discrepancies between molecular and IC results, and an inconsistency of immunoglobulins positivity patterns when compared to ELISA/CLIA results, highlighting the absolute necessity of assays performance validation before their marketing and use, in order to avoid errors in the results evaluation at both clinical and epidemiological level.

The clinical and epidemiological use of SARS-CoV-2 antibody assays is under debate with urgent need to validate and verify the performance of SARS-CoV-2 serologic assays. We aim to assess the clinical and analytical performance of three commercial serological assays of SARS-CoV-2, comparing three anti-SARS-CoV-2-IgG ELISA and identifying the seroconversion and seroprevalence in our population. A cross sectional study conducted from April 2020 to July 2020 at National Institute of Blood disease and Bone Marrow Transplantation Karachi, Pakistan with sample size of 404, enrolled consecutively. Participants were categorized into four groups namely convalescent plasmadonors (CPDs n=239), health care professionals (HCPs n=44), healthy blood donors (HBDs n=70) and from community (n=51). We evaluated the performance of Elecsys anti-SARS-CoV-2 electrochemiluminescence (ECLIA) assay on Cobas-e411 by Roche, three qualitative anti-SARS-CoV-2-IgG enzyme linked imunosorbant assay (ELISA) by (Generic assays, Euroimmun & Omega diagnostics), one quantitative ELISA assay by AESKU Diagnostics and two immune chromatography(ICT) kits namely InstaTest by CORTEZ and TEST IT by TURKLAB. From total 404 subjects, 322 (83.5%) were males. Mean age was 36.79{+/-}11.95 years. Among 239 in CPDs group, 202(84.5%) showed positive antibodies by ECLIA. The qualitative anti-SARS-CoV-2 IgG ELISA was positive in 174 (72.8%) and quantitative IgG in 180(75.3%) with mean titer of 56.7 {+/-}39.7 U/ml. Sensitivity and specificity of ECLIA were 97.44& 99%, ELISA by Generic assays were 67.85% and 89.9%; Euroimmun had 90.38% and 94.9%; Omega Diagnostics 96.4% and 95% and the AESKULISA 93.75% and 100% respectively. Seroconversion was found to be 53.8% and 77.77% within 7 -8 days and 12 to 14 days post onset of symptoms respectively. ICT had more specificity but less sensitivity. Seroprevalence was found to be 84.5%, 40.9% and 21.4% in CPDs, HCPs and HBDs respectively. The Roche ECLIA, qualitative ELISA by Omega Diagnostics & Euroimmun showed higher sensitivity as well as higher specificity. Quantitative ELISA has higher specificity and relatively high sensitivity. Significant numbers of COVID patients do not have detectable antibodies by all assays.

The last seventy years have been characterized by rapid advancements in computer technology, and the healthcare system has not been immune to this trend. However, anatomic pathology has remained largely an analog discipline. In recent years, this has been changing with the growing adoption of digital pathology, partly driven by the potential of computer-aided diagnosis. As part of an international collaboration, we conducted a comprehensive survey to gain a deeper understanding of the status of digital pathology implementation in Europe and Asia. A total of 127 anatomic pathology laboratories participated in the survey, including 75 from Europe and 52 from Asia, with 72 laboratories having established digital pathology workflow and 55 without digital pathology. Laboratories using digital pathology were thoroughly questioned about their implementation strategies and institutional experiences, including details on equipment, storage, integration with laboratory information system, computer-aided diagnosis, and the costs of going digital. The impact of the digital pathology workflow was also evaluated, focusing on turnaround time, specimen traceability, quality control, and overall satisfaction. Laboratories without access to digital pathology were asked to provide insights into their perceptions of the technology, expectations, barriers to adoption, and potential facilitators. Our findings indicate that while digital pathology is still the future for many, it is already the present for some. This decade may be a time when anatomic pathology finally embraces the digital revolution on a large scale. HIGHLIGHTSO_LILarger labs adopt digital pathology more C_LIO_LIFull digital transition is still rare nowadays C_LIO_LIMany initial concerns have not materialized after implementation C_LIO_LIMost non-digital laboratories plan to go digital soon C_LI

Aimto evaluate validity of digital quantification when compared with human fast-scoring in routine classification of chronic gastric wall inflammation. Method87 bariatric gastric samples coming from asymptomatic severe obese patients were examined and classified as normal, with unspecified chronic gastritis and lymphocytic gastritis using a fast-scoring, visual analogue scale method. Results were compared with digital diagnostic data (manual segmentation, supervised learning analysis based on intraepithelial lymphocytes count criteria). Discordant results were re-evaluated by the human pathologist by direct count (ground truth). Helicobacter Pylori diagnostic was performed in all cases (Giemsa). ResultsDigital analysis classified chronic inflammation as lymphocytic gastritis in 45 cases (mean 53 lymphocytes / 100 epithelial gastric cells {+/-}18). 30 cases were labeled as unspecific chronic gastritis (mean 25/100{+/-}2.8) (p<0.0001). Human fast-scoring classified 43 cases as lymphocytic gastritis and 20 as unspecific gastritis. Helicobacter Pylori was detected in 49% of lymphocytic gastritis cases and in 7% of chronic gastritis. 47 diagnostics were concordant (54%). In 36%, digital score was better than human fast-scoring. In 7%, digital results were false negative (all cases generated by technical artifacts). Overall, digital quantification had 89% accuracy and 96% precision when compared with ground truth. ConclusionIn our study, digital image analysis produced a fast and reproducible classification of chronic gastric inflammation with good precision and accuracy. Technical errors generated 6 cases of false negative results. Several other limitations of the study (use of only bariatric gastric fundus tissue, low number of cases, manual supervised learning segmentation) ask for an increased number of cases evaluation before validation and clinical use.

IntroductionSelf-collected capillary blood has numerous advantages over venous samples taken via phlebotomy, as such the use of this finger-prick testing has increased over recent years, driven in some part by Covid antibody testing. However, there is limited evidence that venous and capillary serum is comparable for many routine analytes. In this study we aimed to determine whether capillary sampling could offer an alternative sampling method to venous for the assessment of vitamin B12 in the form of holotranscobalamin, and if this analyte was stable in unspun capillary blood for three days, thus allowing for samples to be returned by the postal system. MethodsMatched pairs of capillary and venous blood samples were collected from 25 patients for the determination of holotranscobalamin, one set being processed on day zero, the other set being stored at ambient temperature and then processed on day three to mimic postal samples. Self-collected capillary blood was compared with phlebotomist-collected venous samples using correlation, Passing-Bablock regression, and Altman-Bland analysis. ResultsPassing-Bablock and Bland-Altman analysis showed holotranscobalamin levels in capillary and venous serum to be comparable and that the analyte was stable in unspun blood for at least three days at ambient temperatures. ConclusionsWe believe this is the first published study to determine if capillary blood sampling is an acceptable alternative to venous sampling for determining holotranscobalamin concentration; our data indicates that there is no significant difference in results from unspun venous and capillary blood stored at room temperature for at least 3 days compared to venous blood tested on the same day of collection.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529), creates a diagnostic vacuum, since differentiation of Omicron from Delta relies on relatively slow next generation sequencing (NGS) technology delaying epidemiologic understanding and therapeutic intervention. The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants. We demonstrate here that an immediately available RT-PCR assay for detection of spike gene N501Y and del69-70 can be utilized to rapidly differentiate Omicron from Delta variants in the proper epidemiologic context

ObjectiveRecently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid. MethodsBiopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists. ResultsAfter screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring <2 mm2, 79% were classified as discordant and 52% of the discordant biopsies measured <4 mm2. ConclusionHistological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies <4 mm2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.

ImportanceThe Verifying Accurate Leading-edge IVCT Development Act, if enacted, would create a unified regulatory oversight system for all in vitro clinical tests, including laboratory-developed tests. ObjectiveTo determine the frequency of use of laboratory-developed tests in an academic medical center system. DesignQuality improvement study analyzing 2021 test order data. SettingAcademic medical center (hospital, outpatient clinics, and cancer center) and non-profit national reference laboratory. Main Outcome(s) and Measure(s)Main outcome, not applicable; non-interventional study of retrospective data. Measures include assay type, assay methodology, compliance status (i.e., Food and Drug Administration cleared, approved, and/or authorized assay, laboratory-developed test, and standard method), test order volume, inpatient versus outpatient setting, and provider medical specialty. ResultsOf the 3,016,928 tests ordered in 2021, 2,831,489 (93.9%) were Food and Drug Administration cleared, approved, and/or authorized assays, 116,583 (3.9%) were laboratory-developed tests, and 68,856 (2.3%) were standard methods. Laboratory-developed tests were more commonly ordered in the outpatient versus inpatient setting and represented a higher proportion of the test volume at the cancer center compared to University Hospital (5.6% vs 3.6% respectively). The top 167 laboratory-developed test assays accounted for 90% of the laboratory-developed test volume (104,996 orders). Among the 20 most frequently ordered laboratory-developed tests were mass spectrometry assays and tests used in the care of immunocompromised patients. Internal/family medicine placed the greatest number of orders (1,044,642) and ordered one of the lowest proportions of laboratory-developed tests (3.2%). Non-infectious disease molecular testing made up 8.8% of laboratory-developed tests ordered. ConclusionsLaboratory-developed tests made up a small percentage of the total laboratory tests ordered within the academic health system studied. Regulatory reform proposals should consider the need for both safety and availability of laboratory-developed tests in clinical laboratory settings. KEY POINTSO_ST_ABSQuestionC_ST_ABSHow frequently are laboratory developed tests (LDTs) used in an academic medical center (AMC) setting? FindingsIn this quality improvement study looking at test orders in 2021, 93.9% of test orders were for FDA cleared, approved, or authorized assays, 3.9% were for LDTs, and 2.3% were for standard methods. The top 167 LDT assays accounted for 90% of the LTD volume. MeaningIn vitro diagnostic reform efforts will impact many LDTs assays with relatively low order volumes in AMC settings.

AimsDetermine if pathologic assessment of disease activity in steatohepatitis, performed using Whole Slide Images (WSIs) on the AISight Clinical Trials platform, yields results that are comparable to those obtained from the analysis performed using glass slides. Methods and ResultsThe accuracy of scoring for steatohepatitis (NAS [&ge;]4 with [&ge;]1 for each feature and absence of atypical features suggestive of other liver disease) performed on the WSI viewing platform was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement (OPA) with a consensus ground truth (GT) score, defined as the median score of a panel of 3 expert pathologists on glass slides. Each case was also read by 3 different pathologists, once on glass and once using WSIs with a minimum 2-week washout period between glass and WSI reads. It was demonstrated that the average OPA across 3 pathologists of WSI scoring with GT was non-inferior to the average OPA of glass scoring with GT (non-inferiority margin of -0.05, difference of -0.001, 95% CI of (-0.027,0.026), and p<0.0001). For each pathologist, there was a similar average OPA of WSI and glass reads with glass GT (pathologist A 0.843 and 0.849, pathologist B 0.633 and 0.605 and pathologist C 0.755 and 0.780), with intra-reader, inter-modality agreements per histologic feature being greater than published intra-reader agreements. ConclusionAccuracy of digital reads for steatohepatitis using WSIs is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system.

ObjectiveWe aimed to evaluate the performance of a cell free DNA (cfDNA) assay that uses next generation sequencing (NGS) with quantitative counting templates (QCT) for the clinical detection of the fetal RHD genotype in a diverse RhD-negative pregnant population in the United States (US). Study DesignThis retrospective cohort study was conducted in four US healthcare centers. The same NGS QCT cfDNA fetal RhD assay was offered to non-alloimmunized, RhD-negative pregnant individuals as part of clinical care. Rh immune globulin (RhIG) was administered at the discretion of the provider. The assays sensitivity, specificity, and accuracy were calculated considering the neonatal RhD serology results. ResultsA total of 401 non-alloimunized RhD-negative pregnancies who received clinical care in the period from August 2020 to November 2023 were included in the analysis. The D antigen cfDNA result was 100% concordant with the neonatal serology, resulting in 100% sensitivity, 100% positive predictive value (both 95% CI: 98.6%-100%), 100% specificity, and 100% negative predictive value (both 95% CI: 97.4%-100%). There were 10 pregnancies where the cfDNA analysis identified a non-RHD gene deletion, including RhD{Psi} (n=5) and RHD-CE-D hybrid variants (n=5). RhIG was administered to 93% of pregnant individuals with cfDNA results indicating an RhD-positive fetus compared to 75% of pregnant individuals with cfDNA results indicating an RhD-negative fetus, signifying providers were using the results to guide pregnancy management. ConclusionThis cfDNA analysis via NGS for detecting fetal RhD status is highly accurate with no false-positive or false-negative results in 401 racially and ethnically diverse pregnancies with 100% follow up of all live births. This study and prior studies of this assay support a recommendation to offer cfDNA screening for fetal Rh status as an alternative option to prophylactic RhIG for all non-alloimmunized RhD-negative individuals, which will result in more efficient and targeted prenatal care with administration of RhIG only when medically indicated.

BackgroundArtificial intelligence (AI) is rapidly fueling a fundamental transformation in the practice of pathology. However, AIs clinical integration remains challenging, with no AI algorithms to date enjoying routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. MethodsPerspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analyzed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FindingsConsensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AIs role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. InterpretationThis is the first systematic consensus study detailing the expected short/mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AIs successful clinical implementation. FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Gestational diabetes mellitus (GDM) affects 2-5% of all pregnancies and is known to place the fetus at risk for adverse fetal outcomes. Previous studies have reported the increased presence of villous immaturity in the placentas of women with gestational diabetes. Villous immaturity poses a great risk of restricted diffusion capacity across the placenta and may be a marker for some of the placental insufficiency associated with diabetes mellitus. The present study looks at the possibility of using fibrin stabilizing factor, or Factor XIII (FXIII), as a biomarker of villous immaturity. The aim of the present study is to establish a baseline pattern of FXIII expression in placentas of women in Saint John, NB with GDM, without villous immaturity using a scoring formula adapted from surgical pathology. While the small sample size precludes definitive conclusions regarding the expression of FXIII in normal placentas in women with GDM, there appears to a baseline of strong FXIII expression in normal placental tissues from the second and third trimester of pregnancy. Further study using a larger sample size is required to determine if a correlation exists between level of FXIII expression and degree of villous maturity in patients with GDM, which could improve the histologic assessment of placental development.

Backgroundto investigate endometrial carcinoma prognostic value of some histopathological and immunohistochemical factors, fairly easily accessible in every routinely pathology lab set. Methodswe considered patients affected by endometrial carcinoma with available clinical and radiological follow-up data after radical hysterectomy (S. Martino Polyclinic Hospital, Genoa, Italy, period 1/1/2013 - 1/7/2016). We analyzed the following histopathological items: histotype, stage (FIGO), type of infiltration (infiltrative/espansive), desmoplasia, intratumoral necrosis, tumor infiltrating lymphocytes and lymph vascular spaces invasion. Moreover, each case has been investigated with a panel of immunohistochemistry including estrogen receptor , progesteron receptor, Ki67, p53, {beta}-catenin, e-cadherin, bcl-2 and cyclin D1. Primary endpoints were disease free survival and overall survival. Resultsout of 99 cases eligible for our purpose, we found 69 low-grade endometrioid, 8 high-grade endometrioid and 22 other high-grade endometrial carcinomas. Disease free survival multivariate analysis showed a strong significant correlation between poor prognosis and advanced stage (p=0.0042). Advanced stage (p=0.0003) and presence of desmoplasia (p=0.04) resulted significantly correlated to a worse prognosis in overall survival multivariate analysis. In univariate model, the non-endometrioid histotype was significantly correlated with an unfavorable prognosis when compared to the endometriod type. Same for progesteron receptor low expression. Conclusionthe multivariate analysis confirmed the central prognostic role of stage in endometrial carcinoma. Moreover, other immunohistochemical markers in univariate analysis, have confirmed their easily reproducible usefulness, well integrating the recent TGCA molecular classification.

Cytomegalovirus (CMV) is a major opportunistic infection after liver transplantation and often mimics acute T cell-mediated rejection (TCMR), creating management uncertainty. We conducted a retrospective study to identify practical histologic features that distinguish CMV hepatitis from TCMR in routine practice. We included 10 recipients with CMV hepatitis and 5 with moderate to severe TCMR. Portal inflammation, bile duct injury, venous endotheliitis, lobular microgranulomas, neutrophilic microabscesses, and CMV inclusions were assessed. Clinical data were abstracted from the medical record. CMV hepatitis was diagnosed earlier after transplantation than TCMR (272 {+/-} 211 vs 549 {+/-} 522 days). Slides were available for 7 CMV and all 5 TCMR biopsies. Histologic findings and their diagnostic performance estimates were as follows: microgranulomas present in 7/7 CMV and 0/5 TCMR biopsies, sensitivity 100% and specificity 100%; bile duct injury minimal to absent in 6/7 CMV and 0/5 TCMR biopsies, sensitivity 86% and specificity 100%; neutrophilic microabscesses in 3/7 CMV and 0/5 TCMR biopsies, sensitivity 42.9% and specificity 100%. Antiviral therapy was administered in 9/10 CMV patients (90%); recurrent CMV viremia occurred in 4/10 (40%) and late chronic rejection in 2/10 (20%), while no CMV viremia occurred in the TCMR group. In routine practice, a pattern of portal lymphohistiocytic inflammation with lobular microgranulomas and minimal to absent bile duct injury supports CMV hepatitis over TCMR and can guide targeted search for inclusions and CMV PCR, which may help avoid unnecessary intensification of immunosuppression and enable timely antiviral therapy.