Routine Histopathological Analysis Research Articles

BN SO04 - The value of routine histopathology analysis of gallbladder specimens after elective and emergency laparoscopic cholecystectomy

Abstract Background Gallbladder cancer is not among the 20 most common cancers in the UK, accounting for less than 1% of all new cancer cases with a peak rate at 85-89 years of age. There is a dominant routine conception among surgeons to send the gallbladder specimen for histopathology even if there is no gross features that raise suspicion for neoplasm. In this study, we are trying to get evidence of the value of routine histopathology analysis of gallbladder specimens after elective and emergency laparoscopic cholecystectomy surgeries in Warwick hospital. Method The record of all the patients who underwent laparoscopic cholecystectomy ( elective, expiated and emergency ) in Warwick hospital in the period between 01/07/2023 – 30/01/2024 ( 7 months) were collected, reviewed and underwent data analysis Results A total of 171 specimens were sent for histo-pathology analysis. Only one patient had low grade dysplasia with no malignant features. No routine follow-up decided for him/her after upper GIT MDT discussion. The incidence rate was 0% of neoplasm and 0.6% of low-grade dysplasia. Conclusion No specimen in the study had suspicious gross features of malignancy. Using a selective system is more logical and economic than the routine sending for histopathology after elective and emergency laparoscopic cholecystectomy if there are no suspicious features in the specimen.

ThP6.3 - Is routine histopathological analysis required following cholecystectomy?

Abstract Aims To identify incidental gall bladder cancers (IGBC) in elective cholecystectomy specimen. Preoperative presentations were observed to see if a selective approach can be adopted when requesting histopathological examination (HPE) following elective cholecystectomy. Methods Retrospective data was gathered for all patients undergoing cholecystectomy in 2022 at a single university teaching hospital. Histology reports and preoperative presentations were analysed. The total sample size was 505. Results Within the 505 patients, six operations did not occur, and five other patients underwent pancreaticojejunostomy. In the remaining 494 patients who underwent successful cholecystectomy 130 were males. Two (0.4%) patients were found to have IGBC (poorly differentiated adenocarcinoma). Both were females aged 57 and 75 years with grossly thickened gall bladder at operation. One patient underwent portal lymphadenectomy and segmental liver resection whilst the other patient was commenced on palliative chemotherapy. Conclusions We found very low incidence of IGBC following routine elective cholecystectomy. This is particularly rare in young patients (< 50 years) found to have a thin-walled gallbladder on ultrasound examination or at laparoscopy. Hence routine HPE following elective cholecystectomy does not seem necessary. We recommend requesting HPE if any mucosal abnormality is identified on inspecting the specimen after removal or if the gallbladder is thick-walled at laparoscopy or preoperative imaging, or patient is over 50 years of age. In the absence of level 1 evidence, such a pragmatic approach appears safe, cost-effective, and offers good use of valuable resources.

Periodic Acid Schiff Staining to Detect Mott Cells, Aberrant Plasma Cells Containing Immunoglobulin Inclusions Called Russell Bodies.

Hematoxylin and eosin staining is widely used for routine histopathological analysis under light microscopic examination to determine alterations of tissue architecture and cellular components in animal studies. Aside from hematoxylin/eosin staining, periodic acid Schiff (PAS) staining is used to detect polysaccharides and carbohydrate-rich macromolecules, and is essential in immunological fields for evaluation of glomerular lesions of kidneys in autoimmune animals. Since erythrocytes are not stained by PAS, this stain is also helpful for identifying changes in immune cells in the red pulp of the spleen, which is filled with erythrocytes. This article describes a protocol to detect Mott cells, bizarre plasma cells containing immunoglobulin inclusion bodies (Russell bodies) in the cytoplasm. The protocol can be used for formalin-fixed, paraffin-embedded tissue sections, frozen tissue sections, tissue-touch preparations, blood films, and cytocentrifuged cell smears. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Detection of Mott cells by PAS staining in formalin-fixed, paraffin-embedded tissue sections Basic Protocol 2: Detection of Mott cells by PAS staining in frozen tissue sections, touch preparations, blood films, and cytocentrifuged cell smears.

Real-time in vivo confocal laser endomicroscopic imaging of equine endometrium: Preliminary observations and feasibility study

Endometrial health is vital for the reproductive efficiency of broodmares and accurate diagnostic testing is crucial for directing the best treatment options and outcomes. Confocal laser endomicroscopy (CLE) is an endoscopic technique for obtaining in-vivo, real-time microscopic imaging of tissues using a fiber optic probe. CLE relies on induced tissue fluorescence and fluorescein sodium, given intravenously, is the contrast agent most used in human medicine. This study aimed to determine the feasibility of CLE for imaging equine endometrium and determine a standard dose of fluorescein sodium to achieve optimal cellular imaging. In-vivo CLE was performed on 44 mares, and the images were compared with routine histopathological analysis of endometrial biopsies. No adverse reactions occurred after IV fluorescein sodium administration and a dose of 4 mg/kg was established (0.04 mL/kg of 10 % fluorescein sodium solution) to achieve optimal image contrast. CLE enabled multiple regions of the endometrium to be assessed quickly. Distinct tissue architecture patterns could be appreciated using CLE, and the luminal epithelium could be assessed for integrity (ulceration) and exocytosed inflammatory cells. Endometrial gland distribution, density, shape, and epithelial height were evaluated. Blood vessels were clearly outlined, and inflammatory cells and fibrosis were discernable within the interstitium. Image quality varied between mares, and the stage of oestrous cycle may have been a factor of influence. This novel imaging modality enables collection of “virtual” biopsies and facilitates critical assessment of multiple regions of the uterus compared with the standard histopathologic assessment of a single random tissue biopsy.

Cost Analysis of Routine Histopathologic Evaluation of Specimens Following Total Ankle Arthroplasty.

Routine histopathologic examination of orthopaedic surgical specimens is a standard practice at many institutions. Previous studies have demonstrated that this practice seldom altered patient management for several orthopaedic procedures. As a result, the value of such practices has come into question. The purpose of this study is to determine the cost-effectiveness of routine histopathologic analysis of specimens obtained during total ankle arthroplasty (TAA). A retrospective analysis was performed of patients who underwent uncomplicated primary TAA at a large, academic, health system between January 2015 and December 2021. The postoperative histopathologic diagnoses were compared with the respective patient's preoperative clinical and intraoperative diagnoses. The prevalence of concordant, discrepant, and discordant diagnoses was determined. Cost-effectiveness analysis was conducted to assess the financial implications of obtaining routine specimens for histopathologic examination for TAA. A total of 85 TAAs were identified in 85 individual patients and were included in the present study. A total of 172 specimens were sent for routine histopathologic review. On histopathologic analysis, a final diagnosis was confirmed in 82 (96.5%) of the total specimens reviewed. A discrepant diagnosis was discovered in 3 (3.5%; 2 cases of gout/pseudogout and 1 case of osteonecrosis) cases and 0 (0%) discordant diagnoses were discovered, corresponding to positive and negative predictive values of 97% and 100%, respectively The total estimate of costs incurred for the routine analysis of all specimens included in the study was between $12 299.20 and 17 846.00. The estimated cost to establish each discrepant diagnosis ranged between $4099.73 and $5948.67, and the cost for a discordant diagnosis was unable to be established. Routine histopathologic analysis of specimens obtained during TAA rarely revealed a discordant diagnosis and resulted in no alterations to patients' plan of care. Furthermore, the additional costs of routine histopathologic examination are significant. As such, it is recommended that such interventions in TAA should be performed on a per-case basis at the operating surgeon's discretion.

Ultrasound-guided photoacoustic (US-PA) tomography of the breast: Biochemical differentiation using intrinsic tissue markers—lipids, collagen and hemoglobin with histopathologic correlation

In this pilot study, we investigated the utility of handheld ultrasound-guided photoacoustic (US-PA) imaging probe for analyzing ex-vivo breast specimens obtained from female patients who underwent breast-conserving surgery (BCS). We aimed to assess the potential of US-PA in detecting biochemical markers such as collagen, lipids, and hemoglobin, and compare these findings with routine imaging modalities (mammography, ultrasound) and histopathology results, particularly across various breast densities. Twelve ex-vivo breast specimens were obtained from female patients with a mean age of 59.7 ± 9.5 years who underwent BCS. The tissues were illuminated using handheld US-PA probe between 700 and 1100 nm across all margins and analyzed for collagen, lipids, and hemoglobin distribution. The obtained results were compared with routine imaging and histopathological assessments. Our findings revealed that lipid intensity and distribution decreased with increasing breast density, while collagen exhibited an opposite trend. These observations were consistent with routine imaging and histopathological analyses. Moreover, collagen intensity significantly differed (P < 0.001) between cancerous and normal breast tissue, indicating its potential as an additional biomarker for risk stratification across various breast conditions. The study results suggest that a combined assessment of PA biochemical information, such as collagen and lipid content, superimposed on grey-scale ultrasound findings could aid in distinguishing between normal and malignant breast conditions, as well as assist in BCS margin assessment. This underscores the potential of US-PA imaging as a valuable tool for enhancing breast cancer diagnosis and management, offering complementary information to existing imaging modalities and histopathology.

Is routine histopathological analysis of hemorrhoidectomy specimens necessary? A systematic review and meta-analysis.

Hemorrhoidectomy is a common procedure used to treat symptomatic hemorrhoids. However, the necessity and cost-effectiveness of routinely conducting histopathological analysis on excised tissue samples are uncertain. A systematic review was conducted using MEDLINE and EMBASE up to December 2023 for studies assessing the histopathological outcomes of hemorrhoidectomy specimens. Meta-analysis was performed on articles with combinable results to determine the pooled proportions of cancer and anal intraepithelial neoplasia (AIN) using the random effects model. From 2974 initial search results, 12 studies were included in the review, with 48,365 resected specimens from hemorrhoidectomy. Among these, there were 11 retrospective studies and one prospective study. A meta-analysis of 11 studies revealed that the prevalence of anal cancer was low, at 0.13% (95% CI: 0.05%-0.31%). The prevalence of anal cancer and AIN combined was 1.16% (95% CI: 0.53%-2.52%). This literature review estimated the probability of malignancy detection in hemorrhoid specimens sent for histopathological evaluation. The low incidence of malignant findings implies that routine analysis of hemorrhoidectomy samples may not be cost-effective. However, existing studies have yet to establish definitive risk factors for abnormal histological diagnoses to aid in the selection of specimens for selective histopathology.

Effect of Histopathological Findings of Gastric Specimens Resected During Laparoscopic Sleeve Gastrectomy on Weight Loss Success: A Retrospective Analysis of 599 Patients.

Even though there aren't enough studies on long-term outcomes, laparoscopic sleeve gastrectomy (LSG)is the most common procedure amongweight loss surgeries. In this study, we aimed to evaluate the histopathological results of resected stomach specimens of patients who underwent LSG and to analyze the effect of histopathological results on weight loss success. The patients were divided into two groups according to histopathological results of the pathology specimens: abnormal (chronic active gastritis, chronic inactive gastritis, neoplasias) and normal. If the excess weight loss percentage (EWL%) values were over 70% at the end of the first year following LSG, the patients were considered successful in terms of weight loss. The groups were compared in terms of age, gender, preoperative body mass index (BMI) value, as well as postoperative first-year BMI, EWL%, total weight loss percentage (TWL%), and successful patient percentage. A total of 599 patients were included in this study. When the patients were dichotomized according to their pathology results as normal or abnormal, 101 (%83.5) of the patients with normal pathology results had EWL% greater than 70%. On the contrary, 356 (74.5%) of the patients with abnormal pathology results had EWL% greater than 70%, and this difference was statistically significant (p=0.038). Patients with normal histopathologic examination results of resected gastric specimens after LSG are more successful than the patient population with abnormal histopathologic results in terms of the percentage of patients with EWL% above 70 at the end of the first postoperative year. We recommend routine histopathologic analysis of gastric specimens after LSG in severely obese patients.

Upper Lip Nodule as the First Manifestation of Sarcoidosis: A Case Report

Introduction: Sarcoidosis is a chronic disorder characterized by the presence of multiple granules, which could affect different systems and tissues. These granules are histologically characterized by non-caseous granulomatous inflammation; however, their etiology is still unknown. Previous reports state that different antigens may be involved. Sarcoidosis has been rarely reported in the Brazilian population. The objective of this study was to report a clinical case of sarcoidosis presenting with oral manifestations as the first sign and symptom. Case Presentation: An 85-year-old, nonsmoking, white woman was referred to the Department of Stomatology of our clinic in 2019, complaining of a persistently growing nodule on the upper lip and in the right arm subcutaneous tissue lasting for three months. Both lesions were painless and non-mobile/cohesive nodules with borrachoid consistency on palpation, well-delimited margins, and overlying normal-colored mucosa/skin. The oral nodule was surgically excised and sent for routine histopathological analysis, revealing granulomatous inflammation, the presence of central lobules of activated macrophages, epithelioid histiocytes, multinucleated Langerhans cells, and a peripheral cuff of mononuclear cells (lymphocytes). There was no evidence of central necrotic areas; however, asteroid bodies (i.e., starry inclusions) were rarely interspersed within multinucleated Langerhans cells. Warthin-Starry, Fite, and PAS special staining did not show any evidence of granulomatous pathogens, which was compatible with non-infectious granulomatosis. Complementary tests revealed hypercalcemia and elevated serum levels of alkaline phosphatase and angiotensin-converting enzyme. Conclusions: Sarcoidosis can manifest itself in several ways, so the diagnostic process needs to be thorough and comprehensive to confirm the disease. In addition, disease progression should be regularly monitored in patients.

Routine Histopathologic Examination of Bone Obtained During Elective Primary Total Knee Arthroplasty May Not Be Necessary.

Many institutions require the routine collection of pathology samples from every primary total knee arthroplasty (TKA) performed. These policies are controversial, and their cost-effectiveness is difficult to define. We sought to judge the cost-effectiveness of one such policy according to World Health Organization recommendations. We analyzed 3200 consecutive primary TKAs, comparing our presumed preoperative diagnoses against the diagnoses made by the pathologist. Diagnoses were categorized as concordant (matching), discrepant (not matching but without impact to patient management), or discordant (not matching and resulting in a direct change to patient management). An incremental cost-utility ratio analysis was performed to determine the cost-effectiveness of our institution's policy to routinely collect pathology samples from every primary TKA performed. Cost-effectiveness was defined by World Health Organization guidelines as a cost of less than $228,090 per quality-adjusted life year gained. Twelve pathology samples were lost before reaching a pathologist. From the remaining 3188 samples, we identified 3158 concordant cases, 29 discrepant diagnoses, and 1 discordant diagnosis. It cost an estimated $10,522.60 to identify each discrepant diagnosis and an estimated $305,155.36 to diagnose one discordant case in our cohort. Our incremental cost-utility ratio analysis revealed that we spent $305,155.36 to gain 0 quality-adjusted life years for our patients. Routine histopathologic analysis of TKA samples was cost-ineffective in our patient cohort and may not be necessary during routine TKA.

Topic: Education/Training Abstract ID: 18 The Efficacy and Yield of Routine Duodenal Biopsy Sampling and Histopathological Analysis Versus Endoscopic Gestalt for the Diagnostic Evaluation of Celiac Disease in Patients With Normal Endoscopic Findings: An Experience at a Tertiary Care Center

Topic: Education/Training Abstract ID: 18 The Efficacy and Yield of Routine Duodenal Biopsy Sampling and Histopathological Analysis Versus Endoscopic Gestalt for the Diagnostic Evaluation of Celiac Disease in Patients With Normal Endoscopic Findings: An Experience at a Tertiary Care Center

Necropsy-based study on dairy cow mortality—Underlying causes of death

The worldwide problem of increasing dairy cow mortality is widespread in modern production systems, it causes economic losses, and indicates problems with herd health and welfare. Most studies on causes of dairy cow mortality are limited as they are based on secondary register data, or questionnaires for producers or veterinarians, and neither necropsies nor histopathologic analyses are usually performed. For this reason, no definite causes for dairy cow deaths have been determined making it difficult or impossible to implement effective preventive measures. The objectives of this study were to (1) determine the causes of on-farm mortality of Finnish dairy cows, (2) determine the usefulness of routine histopathologic analysis in bovine necropsies, and (3) assess how reliable producers' perception about the cause of death is. Underlying diagnoses of on-farm deaths were determined through necropsy of 319 dairy cows at an incineration plant. The necropsy data were combined with background information obtained from online questionnaires covering cow and herd records. Mastitis was the most common underlying diagnosis of death (26.6%), followed by digestive disorders (15.4%), other known disorders (13.8%), calving-associated disorders (12.2%), and locomotion disorders (11.9%). The underlying diagnoses of death varied during different stages of lactation and with parity. A large proportion of the study cows (46.7%) died during the first 30 d after calving, and of those, 63.6% died during the first 5 d. A routine histopathologic analysis was performed in every necropsy, and it changed the preliminary gross diagnosis in 18.2% of the cases. Producers' perception about the cause of death agreed with the necropsy-based underlying diagnosis of death in 42.8% of the cases. It was most consistent for mastitis, calving disorders, locomotion diseases, and accidents. In cases where producers had no insights about the cause of death, necropsy revealed the final underlying diagnosis in 88.2% of cases, demonstrating the usefulness of necropsy. Based on our findings, necropsies provide useful and reliable information to develop control programs for cow mortality. Including routine histopathologic analysis in necropsies, more accurate information may be obtained. Furthermore, targeting preventive measures on transitional cows may be most effective, as the number of deaths was highest at this time.

Immunohistochemical investigation of parainfluenza 3 virus in sheep pneumonia.

The aim of this study was to determine the prevalence of parainfluenza 3 (PI3) virus antigen through histopathological and immunohistochemical (IHC) methods in sheep lung samples collected from Erzurum province, Türkiye. Between August and November 2017, 1462 sheep were dissected in the slaughterhouse and their lungs were examined macroscopically. In total, 100 of the lung samples with pneumonia were selected. Routine histopathological and IHC analyses of the collected lung tissues with pneumonia were performed. Pneumonia observed through macroscopical and histopathological examinations of the lung samples was classified as purulent-catarrhal bronchopneumonia (14.00%), fibrinous bronchopneumonia (23.00%), interstitial pneumonia (69.00%), granulomatous pneumonia (7.00%), verminous pneumonia (19.00%) and pulmonary adenomatosis (6.00%). Two or three types of pneumonia were observed in many of the same cases. The PI3 virus antigen positivity rate in the IHC analysis of sheep lung samples was 19.00%. In the IHC tracing, positivities were found mostly in the alveolar macrophages and cytoplasm of bronchial, bronchiolar and alveolar epithelial cells. As a result, the prevalence of PI3 virus in sheep in Erzurum province, Türkiye, was determined to be 19.00% using KLN BVB IHC method.

Cortical Pathology in Vanishing White Matter.

Vanishing white matter (VWM) is classified as a leukodystrophy with astrocytes as primary drivers in its pathogenesis. Magnetic resonance imaging has documented the progressive thinning of cortices in long-surviving patients. Routine histopathological analyses, however, have not yet pointed to cortical involvement in VWM. Here, we provide a comprehensive analysis of the VWM cortex. We employed high-resolution-mass-spectrometry-based proteomics and immunohistochemistry to gain insight into possible molecular disease mechanisms in the cortices of VWM patients. The proteome analysis revealed 268 differentially expressed proteins in the VWM cortices compared to the controls. A majority of these proteins formed a major protein interaction network. A subsequent gene ontology analysis identified enrichment for terms such as cellular metabolism, particularly mitochondrial activity. Importantly, some of the proteins with the most prominent changes in expression were found in astrocytes, indicating cortical astrocytic involvement. Indeed, we confirmed that VWM cortical astrocytes exhibit morphological changes and are less complex in structure than control cells. Our findings also suggest that these astrocytes are immature and not reactive. Taken together, we provide insights into cortical involvement in VWM, which has to be taken into account when developing therapeutic strategies.

Favorable Effects of Virgin Coconut Oil on Neuronal Damage and Mortality after a Stroke Incidence in the Stroke-Prone Spontaneously Hypertensive Rat.

Stroke is consistently one of the top ten causes of morbidity and mortality globally, whose outcomes are quite variable, necessitating case-specific management. Prophylactic diets before the onset of stroke have been implicated to work. In this research, the effects of virgin coconut oil (VCO) on stroke were evaluated using a stroke-prone spontaneously hypertensive rat (SHRSP) model. Eight-week-old SHRSPs were subjected to the repeated oral administration (5 mL/kg/day) of either 1% Tween 80 (group A) or VCO (group B). An early stroke onset was observed due to hypertension that was aggravation by the administration of 1% NaCl in water ad libitum. The following data were collected: the days until stroke occurred, the survival rate until the animal died, and blood pressure (BP) every two weeks using the tail-cuff method. After necropsy, the organs were harvested, and the brain was processed for a routine histopathological analysis. VCO delayed the incidence of it and prolonged their survival. Compared to group A, group B showed a significantly lowered BP by 20 mmHg at four weeks after the start of VCO treatment. Lastly, the brain histopathology showed that the structurally damaged areas were smaller in group B than they were in group A. The VCO could have protective effects on the brain before and even after stroke incidence.

Routine pathologic evaluation of circular stapler anastomotic rings is not useful after resection for colorectal cancer: retrospective study and systematic review with meta-analysis.

BackgroundCircular staplers are commonly used for reconstruction after radical resection for colorectal cancer. Pathological analysis of the anastomotic rings is common practice, although the benefits are unclear. The purpose of this study was to evaluate the usefulness of routine histopathological analysis of anastomotic rings in an original series and in a systematic review of the literature.MethodThe retrospective study was performed at two university-associated academic hospitals in Winnipeg, Canada, including patients investigated for colorectal cancers (within 30 cm of the anal verge) who underwent resection between 2007 and 2020. The systematic review involved Ovid MEDLINE, Embase, Scopus, and Web of Science databases, selecting for adult human studies involving analysis of anastomotic rings in elective colorectal cancer resections. The main outcome measure was the proportion of patients with cancer in the anastomotic ring specimens. The frequency of benign pathology findings and changes to patient management were also examined.ResultsOut of 673 eligible patients, 487 were included in the retrospective analysis. No patients had cancer within the anastomotic ring specimens. Twenty-five patients (5.1 per cent) had benign pathological findings within the anastomotic ring specimens, and patient management was never affected. In the systematic review, 27 articles were included in the final analysis out of 5848 records reviewed. The rate of cancer within anastomotic ring specimens was 0.34 per cent, and the rate of change in patient management was 0.19 per cent.ConclusionThe likelihood of finding cancer within anastomotic rings is rare and their histopathological examination seldom changes patient management.

Routine Histopathologic Analysis of Hip and Knee Bone Specimens After Total Joint Arthroplasty.

Total hip and total knee arthroplasties (THA/TKA) are some of the most common elective surgeries done in the United States. Routine histopathologic analysis of hip and knee bone specimens after total joint arthroplasty commonly occurs to identify unexpected pathologic findings and serves as a quality assurance measure. As the most common indication for THA and TKA is osteoarthritis, the practice of routine histopathologic analysis may not be routinely warranted. There is no clear consensus on the cost-effectiveness of this practice, and the literature has questioned both the clinical relevance of discrepancies between surgeon diagnosis and histopathological diagnosis and raised concerns about variance in the histological evaluation of resected specimens by pathologists. Femoral head analysis in the setting of femoral neck fractures has been previously reported, yet there is no clear overview for this topic in the setting of elective THA. The histopathologic features of bone specimens during routine total joint arthroplasty, the cost-effectiveness, and current recommendations will be reviewed.

LGG-14. LOGGIC (Low Grade Glioma in Children) Core BioClinical Data Bank: Establishment and added clinical value of an international molecular diagnostic registry for pediatric low-grade glioma patients

BACKGROUND: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data. In addition to routine histopathological and molecular analyses, LOGGIC Core determines the driver alteration as precisely as possible to support treatment decisions and participation in interventional trials. Hence, the question arises whether comprehensive implementation of RNA sequencing using Fresh Frozen (FF) tumor tissue to identify underlying gene fusions improves diagnostic accuracy and provides a clinical benefit. METHODS: Establishment of an international molecular and clinical registry including the logistical and analytical pipeline. First analysis of all patients age 0 to 18, which were included in Germany as part of the German HIT-LOGGIC-program between April 2019 and February 2021, and for whom FF tissue was available. This included histopathological evaluation, immunohistochemistry, 850k methylation analysis, gene panel sequencing, RNA sequencing using FF tissue. RESULTS: FF tissue was available in 178/379 included cases. RNA sequencing was performed on 125 samples. In this prospective, population based cohort, we confirmed KIAA1549:BRAF-fusion (57%), BRAFV600E-mutation (9%) and FGFR1-changes (10%) as most frequent alterations. 12% of cases presented rare gene fusions (e.g. TPM3:NTRK1, EWSR1:VGLL1, GOPC:ROS1, SH3PXD2A:HTRA1, PDGFB:LRP1). In 19% of cases, RNA sequencing detected an actionable target not identified by conventional methods. CONCLUSION: The addition of RNA sequencing reveals clinically relevant alterations including rare gene fusions. By demonstrating improvement of diagnostic accuracy and making precision oncology studies (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible, the added value for pLGG patients becomes apparent. LOGGIC Core is currently being rolled out internationally and aims to define the new state of the art standard molecular diagnostics. We propose to include RNA sequencing as part of routine diagnostic procedures for all pLGG patients, especially in tumors where no common MAPK alteration was identified.

Diagnostic efficacy of deep learning-based prediction of origin for patients with cancers of unknown primary.

e13560 Background: Despite of routine medical history inquiry, laboratory analysis, histopathological analyses, endoscopy and imaging methods, 3-5% of metastatic cancers are diagnosed with unknown primary (CUP). It poses a considerable challenge as modern therapeutic options for patients with CUP are mainly limited to empirical chemotherapy (paclitaxel, carboplatin, etc.), leading to an overall poor prognosis. In current clinical trials (CUPISCO trial, PACET-CUP trial) targeting CUP for precision therapy, genomic data suggest that only 31% of CUP patients could be matched for at least one targeted or immune agent. The determination of primary tumor origin and genetic mutations could probably provide more therapeutic choices and help to significantly improve the outcome in CUP patients. Methods: To identify the primary lesion of CUP, we built a weighted ensemble model by Automated machine learning, including 13 models ( XGBoost, RandomForestGini, ExtraTreesGini, etc.), using genetic and clinical datasets containing 22,018 patients of 28 tumor types, enrolled between 2016-2021. Our genetic and clinical datasets contained 10 features including age, tumor site, gene alteration, TMB, etc. Among them, 813 sites related to tumor were covered by gene alteration. The 5-fold Cross-Validation method was used to estimate the accuracy of our diagnosis models. Results: The models were evaluated using top-k differential diagnosis accuracy, which measured how frequently the top-k predictions capture any of the primary diagnoses in the reference standard. Our diagnostic model was then performed on 8 CUP patients. All of them were successfully confirmed their diagnosis of primary origin tumor. Among these patients, 2/8 CUP patients have begun relevant systemic therapy based on the confirmed diagnosis: 1 patient with diagnosis of esophageal squamous cell carcinoma receiving the immune combination TP Regimen (Albumin paclitaxel plus cisplatin) and achieved a 9-month PFS; another patient diagnosed as colorectal cancer achieved a 2-month PFS after treatment with Oxaliplatin-based chemotherapy regimen. Preliminary results of our study demonstrated the efficiency of this Artificial Intelligence model for the diagnosis in CUP patients. Conclusions: We developed a diagnostic model on CUP using deep learning based on genomic and clinical data and preliminarily applied in clinic. Genetic characterization of CUP patients contributes to the selection of targeted therapies under unclear diagnosis, whereas our diagnosis model could equally adjust more proper precision treatment for CUP patients. In CUP patients, the combined strategy of deep learning-predicted diagnosis and genetic mutations-based therapy could help to maximize the clinical benefit in a clinical setting and optimize the clinical development of innovative therapies.

Evaluation of the Cost Effectiveness of Routine Histopathologic Femoral Head Analysis in Hip Arthroplasty.

PurposeHistopathologic analysis of femoral head specimens following total hip arthroplasty (THA) is a routine practice that represents a significant use of health care resources. However, it occasionally results in discovery of undiagnosed hematopoietic malignancy and other discrepant diagnoses such as avascular necrosis. The purpose of this study was to determine the rate of discordant and discrepant diagnoses discovered from routine histopathological evaluation of femoral heads following THA and perform a cost analysis of this practice.Materials and MethodsA review of patients undergoing primary THA between 2004-2017 was conducted. A comparison of the surgeon’s preoperative and postoperative diagnosis, and the histopathologic diagnosis was performed. In cases where the clinical and histopathology differed, a review determined whether this resulted in a change in clinical management. Medicare reimbursement and previously published cost data corrected for inflation were utilized for cost calculations.ResultsA review of 2,134 procedures was performed. The pathologic diagnosis matched the postoperative diagnosis in 96.0% of cases. Eighty-three cases (4.0%) had a discrepant diagnosis where treatment was not substantially altered. There was one case of discordant diagnosis where lymphoma was diagnosed and subsequently treated. The cost per discrepant diagnosis was $141,880 and per discordant diagnosis was $1,669 when using 100% Medicare reimbursement and Current Procedural Terminology (CPT) code combination 88304+88311.ConclusionHistopathologic analysis of femoral head specimens in THAs showed an association with high costs given the rarity of discordant diagnoses. Routine use of the practice should be at the discretion of individual hospitals with consideration for cost and utility thresholds.