Diagnostic Histopathology Research Articles

An Investigation of the Cause of Wild Turkey Mortality in Mississippi.

Lymphoproliferative disease virus (LPDV) is an exogenous alpharetrovirus that sporadically causes fatal lymphoid neoplasia in affected turkeys. Previous studies of wild turkeys (Meleagridis gallopavo) in the United States have demonstrated geographically widespread LPDV infection and frequent coinfection with avian poxvirus (APV) and reticuloendotheliosis virus (REV). This study was conducted to better understand health risks to Mississippi wild turkeys, including the relative importance of LPDV, APV, and REV in contributing to mortality. Thirteen wild turkeys, which died naturally or were euthanized due to illness, were submitted to Mississippi State University's Poultry Research and Diagnostic Laboratory for postmortem examinations. Birds originated from nine counties across the state over the past 5 yr. Carcasses were submitted as fresh (nonfrozen) or frozen. At autopsy, 9 of 13 turkeys had severe, proliferative cutaneous lesions on the head and neck, with diphtheritic or proliferative oral and esophageal lesions. Samples were collected for molecular diagnostic testing (LPDV and REV PCR), histopathology, and bacterial culture and isolation. External and internal parasites were preserved in formalin for identification. APV (cutaneous and/or diphtheritic forms) was diagnosed in 9 of 13 birds by identification of pathognomonic histologic lesions (including intracytoplasmic inclusion bodies). Interestingly, all birds with APV were also REV PCR positive. Furthermore, eight turkeys were positive for LPDV, and LPDV was commonly associated with coinfections with APV and REV.

Histomorphological Analysis of Gestational Trophoblastic Disease Spectrum with Clinicopathological Correlation at a Teaching Hospital

Introduction: Clinically, all trophoblastic lesions are frequently combined under a broad spectrum of gestational trophoblastic diseases (GTDs) without the use of specific pathological terms. However, studies now demonstrate that various forms of GTDs demonstrate differences in etiology, histogenesis, morphology, and clinical behavior. Thus, the need for diagnostic histopathology of these lesions to distinguish gestational trophoblastic neoplasms from nonneoplastic lesions and molar pregnancies and also for early anticipation for early anticipation, risk category stratification, prognostication, management, and prediction of persistent GTD. Our study aimed to study the histomorphological patterns of various types of GTD with light microscopy and the pattern of occurrence of GTDs in relation to age, parity, and gestation. Materials and Methods: The present study was conducted in the department of pathology, from January 2020 to April 2022. All GTDs confirmed by histopathological examination by hematoxylin- and eosin-stained slides were included. Results: The spectrum of GTDs found in this study was seventy cases of hydatidiform mole (92.10%), three cases of exaggerated placental site (EPS) reaction (3.94%), and two cases of choriocarcinoma (2.63%) and one case (1.31%) of placental site trophoblastic tumor (PSTT). The most common presenting symptom was vaginal bleeding (93.42%). Conclusion: Hydatidiform mole forms the most common type of GTD with an incidence of complete moles more than partial moles. Histomorphological examination and analysis are helpful for confirmatory diagnosis. The most common clinical presentation of GTD was vaginal bleeding followed by amenorrhea. Emphasis on detailed descriptive morphological assessment can help in the histological distinction of benign lesions such as EPS reaction and placental site nodule and avert such cases from being erroneously diagnosed as neoplastic. The Ki-67 proliferation index helped in distinguishing the EPS reaction from neoplastic lesions such as PSTT which requires surgical intervention and chemotherapy.

Gastroduodenal neuroendocrine neoplasms including gastrinoma - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne żołądka i dwunastnicy z uwzględnieniem gastrinoma - uaktualnione zasady postępowania (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

After another meeting of experts of the Polish Network of Neuroendocrine Tumours, updated recommendations for the management of patients with gastric and duodenal neuroendocrine neoplasms, including gastrinoma, have been issued. As before, the epidemiology, pathogenesis and clinical symptoms of these neoplasms have been discussed, as well as the principles of diagnostic procedures, including biochemical and histopathological diagnostics and tumour localisation, highlighting the changes introduced in the recommendations. Updated principles of therapeutic management have also been presented, including endoscopic and surgical treatment, and the options of pharmacological and radioisotope treatment. The importance of monitoring patients with gastric and duodenal NENs, including gastrinoma, has also been emphasised.

Perioperative outcomes in dogs and cats undergoing pancreatic surgery: 81 cases (2008-2019).

To identify and describe the type and frequency of perioperative factors in dogs and cats undergoing pancreatic surgery under referral care. Medical records from a small animal surgical referral practice were retrospectively reviewed to identify dogs and cats that underwent pancreatic surgery between 2008 and 2019. Inclusion criteria included complete medical record, histopathology results and follow-up of at least 14 days postoperatively or until death. Variables collected included signalment, history, presenting complaint, preoperative diagnostic results, intraoperative complications, surgical findings/procedures, postoperative complications and histopathology results. Cases were excluded if pertinent information or a histopathology report was missing from the medical record. The frequency of these variables was reported. There were 81 client-owned animals identified that met the inclusion criteria (57 dogs and 24 cats). The most common pancreatic procedure performed in dogs was partial pancreatectomy 63.2% (36/57) and in cats was pancreatic biopsy 62.5% (15/24). The most common histologic diagnosis in dogs was pancreatic islet cell carcinoma 50.9% (29/57) and in cats was pancreatitis 41.7% (10/24). The overall mortality rate was 13.6% (11/81), with a 10.5% (6/57) mortality rate in dogs and a 20.8% (5/24) mortality rate in cats. In this series of dogs and cats, pancreatic surgery under referral care carried a low to moderate mortality rate.

Rapid access to biomarker data in a community setting: Integration of next-generation sequencing into routine pathologic workflow.

3143 Background: Biomarker data in the form of next generation sequencing (NGS) are critical to the delivery of precision cancer care. Onsite testing is often limited to large academic centers, requiring smaller community centers to rely on samples send outs. Turnaround time for biomarkers can be lengthy and can adversely affect the delivery of optimal therapy in many tumor types. This study aims to evaluate the feasibility of rapidly delivered comprehensive NGS in a community center using a novel workflow in the laboratory by integrating NGS into the routine immunohistochemistry (IHC) service. Methods: An automated NGS workflow utilizing the Genexus integrated sequencer with the Oncomine precision assay GX (OPA, Thermofisher Scientific), was validated for clinical use and integrated into the routine diagnostic IHC service. During the study period (Oct 2020 – Oct 2021), NGS biomarker data was generated and reported alongside IHC biomarkers where applicable. A retrospective chart review was performed to assess the early experience and performance characteristics of this novel approach to biomarker testing. Results: A total of 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR 2-5). The majority (n = 481, 83%) of cases were resulted in fewer than 5 business days. Tumor types included lung cancer (n = 310, 54%), melanoma (n = 97, 17%), and colorectal cancer (n = 68, 12%). Specimen types included surgical resections (n = 104, 18%), core biopsies (n = 411, 71%), and cytology specimens (n = 63, 11%). NGS testing detected key driver alterations at expected prevalence rates in respective tumor types; lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAFwild-type (33%), among others. Conclusions: This is the first study demonstrating the clinical feasibility and turnaround time statistics of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry in a community setting. This novel approach of integrating biomarkers, IHC, and morphology offers rapid turnaround by removing the need for outsourcing biomarker data. This model could be adopted by other community centers to improve rapid access to biomarker data and therapeutic decision making.

Are We Only Detecting the Tip of the Iceberg? A Nationwide Study on Primary Aldosteronism with up to 8-Year Follow-up

ABSTRACT Background Long-term follow-up studies on primary aldosteronism (PA) are lacking. Objective We aim to review results of diagnostic procedures and histopathology for patients diagnosed during 2012–2016 in Iceland, compare unilateral (UD) and bilateral disease (BD) and assess treatment response. Methods Thirty-two patients aged 28–88 were diagnosed and treated according to guidelines. Results The majority had BD. Everyone needed potassium supplementation at case detection. We saw a reduction in systolic blood pressure (p < .001, both groups), antihypertensive agents (p = .002 UD and p = .04 BD) and potassium supplementation (p < .001, both groups). Conclusion Similar treatment response was seen in both subgroups. Ratio of hypokalemia and number of cases indicates severe PA underdiagnosis in Iceland.

3D Visualization of Human Blood Vascular Networks Using Single-Domain Antibodies Directed against Endothelial Cell-Selective Adhesion Molecule (ESAM).

High-quality three-dimensional (3D) microscopy allows detailed, unrestricted and non-destructive imaging of entire volumetric tissue specimens and can therefore increase the diagnostic accuracy of histopathological tissue analysis. However, commonly used IgG antibodies are oftentimes not applicable to 3D imaging, due to their relatively large size and consequently inadequate tissue penetration and penetration speed. The lack of suitable reagents for 3D histopathology can be overcome by an emerging class of single-domain antibodies, referred to as nanobodies (Nbs), which can facilitate rapid and superior 2D and 3D histological stainings. Here, we report the generation and experimental validation of Nbs directed against the human endothelial cell-selective adhesion molecule (hESAM), which enables spatial visualization of blood vascular networks in whole-mount 3D imaging. After analysis of Nb binding properties and quality, selected Nb clones were validated in 2D and 3D imaging approaches, demonstrating comparable staining qualities to commercially available hESAM antibodies in 2D, as well as rapid and complete staining of entire specimens in 3D. We propose that the presented hESAM-Nbs can serve as novel blood vessel markers in academic research and can potentially improve 3D histopathological diagnostics of entire human tissue specimens, leading to improved treatment and superior patient outcomes.

Assessment of Ki-67 proliferation index with deep learning in DCIS (ductal carcinoma in situ)

The proliferation index (PI) is crucial in histopathologic diagnostics, in particular tumors. It is calculated based on Ki-67 protein expression by immunohistochemistry. PI is routinely evaluated by a visual assessment of the sample by a pathologist. However, this approach is far from ideal due to its poor intra- and interobserver variability and time-consuming. These factors force the community to seek out more precise solutions. Virtual pathology as being increasingly popular in diagnostics, armed with artificial intelligence, may potentially address this issue. The proposed solution calculates the Ki-67 proliferation index by utilizing a deep learning model and fuzzy-set interpretations for hot-spots detection. The obtained region-of-interest is then used to segment relevant cells via classical methods of image processing. The index value is approximated by relating the total surface area occupied by immunopositive cells to the total surface area of relevant cells. The achieved results are compared to the manual calculation of the Ki-67 index made by a domain expert. To increase results reliability, we trained several models in a threefold manner and compared the impact of different hyper-parameters. Our best-proposed method estimates PI with 0.024 mean absolute error, which gives a significant advantage over the current state-of-the-art solution.

Point of Care Molecular Testing: Community-Based Rapid Next-Generation Sequencing to Support Cancer Care.

Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care.

Histopathological evaluation of nonalcoholic fatty liver disease : Automated evaluation of liver biopsies

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with arising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment.

Feasibility of EBUS-TBNA for histopathological and molecular diagnostics of NSCLC-A retrospective single-center experience.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive bronchoscopic procedure, well established as a diagnostic modality of first choice for diagnosis and staging of non-small cell lung cancer (NSCLC). The therapeutic decisions for advanced NSCLC require comprehensive profiling of actionable mutations, which is currently considered to be an essential part of the diagnostic process. The purpose of this study was to evaluate the utility of EBUS-TBNA cytology specimen for histological subtyping, molecular profiling of NSCLC by massive parallel sequencing (MPS), as well as for PD-L1 analysis. A retrospective review of 806 EBUS bronchoscopies was performed, resulting in a cohort of 132 consecutive patients with EBUS-TBNA specimens showing NSCLC cells in lymph nodes. Data on patient demographics, radiology features of the suspected tumor and mediastinal engagement, lymph nodes sampled, the histopathological subtype of NSCLC, and performed molecular analysis were collected. The EBUS-TBNA specimen proved sufficient for subtyping NSCLC in 83% and analysis of treatment predictive biomarkers in 77% (MPS in 53%). The adequacy of the EBUS-TBNA specimen was 69% for EGFR gene mutation analysis, 49% for analysis of ALK rearrangement, 36% for ROS1 rearrangement, and 33% for analysis of PD-L1. The findings of our study confirm that EBUS-TBNA cytology aspirate is appropriate for diagnosis and subtyping of NSCLC and largely also for treatment predictive molecular testing, although more data is needed on the utility of EBUS cytology specimen for MPS and PD-L1 analysis.

Screening for Early Detection of Cervical Cancer in Women Living with HIV in Mumbai, India - Retrospective Cohort Study from a Tertiary Cancer Center

Abstract Introduction Women living with human immunodeficiency virus (HIV) have an increased risk of persistent human papillomavirus infection (HPV) of developing cervical cancer precursors and are, therefore, considered at higher risk for cervical cancer. Despite the higher risk, screening for cervical cancer is extremely low among HIV-positive women in India. Objectives Given the limited usefulness of cytology-based screening programs, the current study retrospectively evaluated the comparative performance of visual inspection with 5% acetic acid (VIA), conventional cytology, and human papillomavirus (HPV) testing among HIV-positive women attending the cancer screening clinic at the tertiary cancer center. Materials and Methods Retrospective analysis of 291 HIV-positive women attending cervical cancer screening services in a tertiary cancer center in Mumbai was undertaken. All underwent simultaneous screening with VIA, Pap cytology, and HPV DNA testing, followed by diagnostic colposcopy and histopathology. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to detect cervical intraepithelial neoplasia (CIN) 2/3 on histology were estimated. Results The screen positivity rate for cervical cancer screening by VIA, high-risk HPV DNA, and Pap cytology was 35.7, 34.4, and 6.2% respectively. At the CIN2+ disease threshold, the sensitivity, specificity, PPV, and NPV estimates were 80.00% (59.30–93.17), 68.42% (62.46–73.96), 19.23% (15.46–23.67), 97.33% (94.30–98.77) for VIA; 80.00% (68.78–97.45), 70.68% (64.81–76.08), 22.00% (18.22–26.32), 98.43% (95.58–99.45) for HPV DNA; and 64.00% (42.52–82.03), 98.12% (95.67–99.39), 76.19% (56.13–88.89), 96.67% (94.50–98.00) for cytology (HSIL cutoff). Conclusion The diagnostic performance of VIA and HPV DNA was comparable and better than cytology indicating that VIA as a cost-effective cervical cancer screening test can be incorporated within the services under sexually transmitted diseases /HIV testing and counseling centers within the country.

Mycotic abdominal aortic aneurysm caused by Borrelia afzelii: a case report

BackgroundInflammatory aneurysms and mycotic aneurysms make up a minority of abdominal aortic aneurysms. Mainly autoimmune mechanisms are proposed in the pathogenesis of inflammatory aneurysms, and it is not routine to check for infectious agents as disease culprits.Case presentationA 58-year-old European male with complaints of abdominal and back pain for 8 weeks was admitted after a semi-urgent computed tomography scan revealed an 85 mm inflammatory abdominal aortic aneurysm. The patient had normal vital signs, slightly elevated inflammatory markers, and mild anemia on admission. Clinical examination revealed a tender pulsating mass in his abdomen. His clinical condition was interpreted as impending rupture and urgent repair of the aneurysm was deemed necessary. Due to the patient’s relatively young age and aneurysm neck morphology, open aortic repair was preferred. Preoperatively, the aneurysm appeared inflamed, with fibrous wall thickening and perianeurysmal adhesions. Aneurysm wall biopsies were sent to histopathological and microbiological diagnostics. Routine cultures were negative, but 16S rRNA gene real-time polymerase chain reaction was positive and Borrelia afzelii was identified by DNA sequencing of the polymerase chain reaction product. B. afzelii was also identified by sequencing the polymerase chain reaction product of a Borrelia-specific groEL target. Immunoglobulin G and M anti-Borrelia antibodies were present on serological analysis. Histopathological analysis displayed loss of normal aortic wall structure and diffuse infiltration of lymphocytes and plasma cells. The patient had an uneventful recovery and was discharged after 1 week to a regional rehabilitation facility. Though the patient fares clinically well and inflammatory markers had normalized, antimicrobial treatment with doxycycline continues at 3 months follow-up due to remaining radiologic signs of inflammation.ConclusionsBorrelia infection in the setting of acute aortic pathology is a rare entity. To our knowledge, this is the first case report to demonstrate a mycotic abdominal aortic aneurysm as a rare manifestation of Lyme disease. Aortic wall biopsies and real-time polymerase chain reaction analysis of the specimen were essential for accurate diagnosis. This finding may contribute to the understanding of the etiology of inflammatory aneurysmal disease and abdominal aneurysms in general.

Clinical utility of linear endosonography in patients with unexplained biliary dilatation and negative MRCP, with predictors for detection of neoplastic lesions

Background and study aimsUnexplained biliary dilatation (UBD) frequently represents a diagnostic dilemma. Linear endosonography (EUS), with its close proximity to the pancreaticobiliary system and the ability for tissue acquisition, could have a role in revealing etiologies of UBD particularly in the context of negative other non-invasive modalities. However, in such patients, the decision for this semi-invasive procedure is usually debatable and often needs justification. Thus, we aimed to evaluate the diagnostic utility of linear EUS in patients with UBD after negative magnetic resonance cholangiopancreatography (MRCP) and to delineate predictors for EUS ability to detect neoplastic lesions.Patients and methodsThis was a prospective diagnostic observational study between 2018 and 2021. Included patients with evidence of biliary dilatation on abdominal ultrasound and negative MRCP underwent linear EUS examination. Results were compared to the final diagnosis relied on histopathology after EUS-guided biopsy or surgery for neoplastic lesions, while ERCP, diagnostic EUS criteria plus histopathology for autoimmune pancreatitis, Rosemont criteria for chronic pancreatitis, and/or follow-up for 6 months were the gold standard tests for non-neoplastic etiologies. Logistic regression was conducted to reveal predictors of neoplasm detection by EUS.ResultsSixty-one patients (mean age 60 years, 32 females) were enrolled; 13.1% of them were asymptomatic. The final diagnosis was categorized into 29 patients with and 32 without neoplasms. Sensitivity, specificity, positive, negative predictive values (PPV, NPV), and accuracy of EUS-positive findings were 98.3%, 100%, 100%, 66.7%, and 98.3%, respectively. Corresponding results for neoplasm identification were 100%, 93.8%, 93.5%, 100%, and 96.7%, respectively. The most common neoplastic etiologies were small pancreatic and ampullary masses. Common bile duct (CBD) diameter > 12.9mm and CA19-9 > 37.1 u/ML were independent predictors for pancreaticobiliary neoplasm at multivariate regression analysis.ConclusionLinear EUS appears to have a high accuracy in detecting etiologies of UBD, with higher sensitivity for small pancreatic, ampullary lesions, and CBD stones. CBD diameter > 12.9 mm and elevated CA19-9 > 37.1 u/ML should raise a concern about the presence of occult pancreaticobiliary neoplasm, and then, EUS may be warranted even in asymptomatic patients.

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors.

Terminal deoxynucleotidyl transferase (TdT) is aunique type of DNA polymerase predominantly expressed in precursor lymphoid cells and acute lymphoblastic leukemia. It participates in the junctional diversity of T-cell receptors and immunoglobulins. Recently, aberrant TdT expression was found in seminomas. Here, we evaluated the expression of TdT in our cohort of germ cell tumors (GCTs) with two anti-TdT antibody clones. We included 173 cases of testicular GCTs, 5 ovarian dysgerminomas, and one gonadoblastoma in the study. Tissue microarrays containing representative tumor samples were constructed and subsequently stained with anti-TdT monoclonal rabbit antibody EP266 (Dako) and TdT rabbit polyclonal antibody (Cell Marque). Expression was assessed with the H-score. No specific nuclear reaction was observed for the polyclonal anti-TdT antibody. The H-score values varied between the histological subtypes for the EP266 antibody. Positive nuclear staining was consistently seen in germ cell neoplasia in situ , seminoma, dysgerminoma, and embryonal carcinoma. Pure tumors had higher TdT H-scores than the mixed ones. Teratomas, yolk sac tumors, and choriocarcinomas were almost uniformly negative. Our study confirms that aberrant expression of TdT by testicular and ovarian GCTs exemplifies apotential diagnostic pitfall in histopathological diagnostics.

Infrared Spectroscopic Analysis in the Differentiation of Epithelial Misplacement From Adenocarcinoma in Sigmoid Colonic Adenomatous Polyps

Purpose:The differential diagnosis of epithelial misplacement from invasive cancer in the colon is a challenging endeavour, augmented by the introduction of bowel cancer population screening. The main aim of the work is to test, as a proof-of concept study, the ability of the infrared spectroscopic imaging approach to differentiate epithelial misplacement from adenocarcinoma in sigmoid colonic adenomatous polyps.Methods:Ten samples from each of the four diagnostic groups, normal colonic mucosa, adenomatous polyps with low grade dysplasia, epithelial misplacement in adenomatous polyps and adenocarcinoma, were analysed using IR spectroscopic imaging and data processing methods. IR spectral images were subjected to data pre-processing and cluster analysis based segmentation to identify epithelial, connective tissue and stromal regions. Statistical analysis was carried out using principal component analysis and linear discriminant analysis based cross validation, to classify spectral features according to the pathology, and the diagnostic attributes were compared.Results:The combined 4-group classification model on an average showed a sensitivity of 64%, a specificity of 88% and an accuracy of 76% for prediction based on a ‘single spectrum’, whilst a ‘majority-vote’ prediction on an average showed a sensitivity of 73%, a specificity of 90% and an accuracy of 82%. The 2-group model, for the differential diagnosis of epithelial misplacement versus adenocarcinoma, showed an average sensitivity and specificity of 82.5% for prediction based on a ‘single spectrum’ whilst a ‘majority-vote’ classification showed an average sensitivity and specificity of 90%. A 92% area under the curve (AUC) value was obtained when evaluating the classifier using the Receiver Operating Characteristics (ROC) curves.Conclusions:IR spectroscopy shows promise in its ability to differentiate epithelial misplacement from adenocarcinoma in tissue sections, considered as one of the most challenging endeavours in population-wide diagnostic histopathology. Further studies with larger series, including cases with challenging diagnostic features are required to ascertain the capability of this modern digital pathology approach. In the long-term, IR spectroscopy based pathology which is relatively low-cost and rapid, could be a promising endeavour to consider for integration into the existing histopathology pathway, in particular for population based screening programmes where large number of samples are scrutinised.

Diagnostic Accuracy of the Vulvoscopy Index for Detection of Vulvar Dermatosis (DATRIV Study, Part 1)

Three rings vulvoscopy (TRIV) has previously been described to facilitate the diagnosis and treatment of vulvar discomfort. The distinction between outer, middle, and inner vulvar rings is based on differences in anatomy, histology, and embryology. The vulvoscopy index was designed considering the patient's history, clinical exam, and assessment of the specificity and localization of the lesion relative to the vulvar ring. This paper evaluated the sensitivity, specificity, and diagnostic accuracy of the vulvoscopy index in detecting vulvar dermatosis compared with histopathology as a reference test. Structured ISSVD vulvodynia pattern questionnaire and TRIV form data were utilized for the study. The data obtained were analyzed using StatSoft (Dell, Austin, Texas), Statistica 12 (TIBCO®, Palo Alto, CA), and SPSS 20 (IBM, Armonk, NY). Ethical approval for the study was obtained from the Institutional Review Board of Polyclinic Harni, and all patients provided written informed consent. The histopathological diagnosis of vulvar dermatosis was confirmed in 72 patients at first biopsy. Lesions specific for vulvar dermatosis were visible by TRIV in 82 patients. The resulting difference of ten patients were participants with early vulvar dermatosis. In six of them, vulvar dermatosis was confirmed at a later biopsy during the study period. There was no statistically significant difference between the scores of points (median and range), frequency and relative frequency of vulvar findings within one item of the vulvoscopy index and histopathology, except for ten patients with early forms of vulvar dermatoses. The sensitivity, specificity, and diagnostic accuracy of the vulvoscopy index for detecting vulvar dermatosis were 100%, 96.1%, and 96.9%, respectively. The positive and negative predictive values were 0.88 and 1.00, respectively. The vulvoscopy index represents a compelling clinical test for detecting vulvar dermatoses. Differences between vulvoscopic and histopathological diagnostics implicate the impossibility of histopathology in recognizing early forms of vulvar dermatoses. Accordingly, early dermatoses could represent a key area for applying this test. ClinicalTrials.gov Identifier: NCT02732145.

Clinical Value of the N-S-P Scheme for Diagnosing Vulvar Dermatosis (DATRIV Study, Part 2)

The DATRIV study aimed to create a basis for developing standard outcome measures in vulvoscopy to facilitate the diagnosis and treatment of vulvar discomfort. For this purpose, the three rings vulvoscopy (TRIV) was introduced, and the vulvoscopy index and N-S-P scheme were designed as outcome parameters. In this paper, the clinical value of collecting and managing data obtained during TRIV in normal and patients with chronic vulvar distress was carefully examined by introducing the N-S-P scheme. Complex ISSVD vulvodynia pattern questionnaire and TRIV form data were methodically performed for data gathering. The collected data were explored using StatSoft (Dell, Austin, Texas), Statistica 12 (TIBCO®, Palo Alto, CA) and SPSS 20 (IBM, Armonk, NY). Ethical permission for the study was acquired from the Institutional Review Board of the Polyclinic Harni, and all patients gave written informed consent. In addition to TRIV, lesions specific to vulvar dermatosis were detected in 82 patients. Histopathology diagnosed vulvar dermatosis at the first biopsy in 72 patients. The resulting difference of ten patients consisted of patients with early vulvar dermatosis. Six of these ten subjects were diagnosed with vulvar dermatosis on a second biopsy during the study period. Statistical tests did not show a significant difference between normal findings or the presence of any type of lesion (nonspecific and specific) concerning the three vulvar rings, except in ten patients with early vulvar dermatoses. The N-S-P scheme accurately recognized the disease in all patients showing 100% sensitivity in detecting vulvar dermatoses. Patients without histopathological verified vulvar dermatosis at the first biopsy were classified as false positives, so the specificity of the test was 96.1%. Overall, the diagnostic accuracy of the N-S-P scheme in detecting vulvar dermatosis was 96.9%. Positive and negative predictive values were 0.88 and 1.00, respectively. The N-S-P scheme and TRIV are convincing clinical tests to detect vulvar dermatoses. Differences between vulvoscopy and histopathological diagnostics imply a lack of specificity of tissue transformations within early forms of vulvar dermatoses sufficient to distinguish them microscopically from normal findings. Consequently, early dermatoses could be a critical area for proposing this test. ClinicalTrials.gov Identifier: NCT02732145.

Role of fine needle aspiration cytology (FNAC) in diagnosing Pancreatic lesions in a tertiary care institution

OBJECTIVE- FNAC is an accurate and rapid technique for diagnosing pancreatic masses. Pancreatic carcinoma represents the seventh leading cause of cancer death in the world, responsible for more than 300,000 deaths per year.[1] Worldwide, both the incidence and death rates of pancreatic cancer are increasing. The aim of this study was early diagnosis of these lesions and to evaluate its burden and study the global, regional, and national patterns. These would further aid in policy making , better resource allocation for controlling pancreatic cancer risk factors and formulating more effective treatments.[2]&#x0D; METHODS- This was a retrospective observational study performed at a tertiary care hospital over a period of one and a half year. A total of 86 patients with pancreatic lesions were subjected to image guided FNA . 35 of these patients underwent diagnostic histopathology in addition to FNA.&#x0D; RESULTS- The 86 cases analyzed were in the age group of 61-70 years with mean age distribution of 57.34 years. Male predominance was seen with M:F ratio of 2.18:1. Head was the most common area to be aspirated followed by tail and least number of lesions were in body of pancreas. Maximum cases were found to be malignant (55) in etiology. Only 2 were non diagnostic because one of them had insufficient cellularity and other had necrosis mainly on histopathology. Adenocarcinoma was the most common malignancy found followed by one case each of lymphoma and solid pseudo papillary neoplasm of pancreas. Histo pathological correlation was obtained in 91.42% cases proving that FNA is a very useful tool in early diagnosing pancreatic lesions.

Using a convolutional neural network for classification of squamous and non-squamous non-small cell lung cancer based on diagnostic histopathology HES images

Histological stratification in metastatic non-small cell lung cancer (NSCLC) is essential to properly guide therapy. Morphological evaluation remains the basis for subtyping and is completed by additional immunohistochemistry labelling to confirm the diagnosis, which delays molecular analysis and utilises precious sample. Therefore, we tested the capacity of convolutional neural networks (CNNs) to classify NSCLC based on pathologic HES diagnostic biopsies. The model was estimated with a learning cohort of 132 NSCLC patients and validated on an external validation cohort of 65 NSCLC patients. Based on image patches, a CNN using InceptionV3 architecture was trained and optimized to classify NSCLC between squamous and non-squamous subtypes. Accuracies of 0.99, 0.87, 0.85, 0.85 was reached in the training, validation and test sets and in the external validation cohort. At the patient level, the CNN model showed a capacity to predict the tumour histology with accuracy of 0.73 and 0.78 in the learning and external validation cohorts respectively. Selecting tumour area using virtual tissue micro-array improved prediction, with accuracy of 0.82 in the external validation cohort. This study underlines the capacity of CNN to predict NSCLC subtype with good accuracy and to be applied to small pathologic samples without annotation.