bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of cohabitation on adaptive and innate immune cell profiles in the Health and Retirement Study
Authors: Ramasubramanian Ramya , Meier Helen , Crimmins Eileen , Faul Jessica , Thyagarajan Bharat
Published: November 2022

Immune cells distribution is shaped by numerous factors including environmental factors, age, and genetics. Cohabitation has been associated with similar microbiomes, possibly due to dietary patterns and exposure to similar pathogens but has not been studied in the context of adaptive and innate immune systems previously. We used immunophenotyping data of 2283 households with participants living in the same household and compared it to 2283 randomly generated pairs of participants from the Health and Retirement study. The adaptive immune cells (subsets of T-cells and B-cells), and innate immune cells (monocytes, natural killer cells, and neutrophils) were compressed to two coordinates using multidimensional scaling. The Euclidean distances between participants in the same household were compared to the distances between the random pairs of participants using two sample independent t-tests. The mean distances of the immune coordinate points for adaptive immune cells between participants in the same household were lower than the randomly paired participants (p-value < 0.0001) and the variability of intra-household distances was lower than the random pairs (IQR: 7.18 vs 8.99). For the innate immune cells, the mean distances between participants in the same household were slightly lower than the randomly paired participants (p-value = 0.03) but the variability of the intra-household distances was higher than the random pairs (IQR: 4.08 vs 3.65). Variability in the adaptive immune system among participants living in the same household were substantially lower indicating the influence of shared environmental conditions in determining the adaptive immune profiles.
RecutClub 2.0: Deployment of a Trainee-Led, Didactic-Centered Whole Slide Imaging Platform
Authors: Hsu Jim , Christensen Paul , Long Scott
Published: November 2022

Objectives

The Houston Methodist Pathology training program encourages trainee participation in quality improvement (QI) projects for improving the didactics experience. One of these initiatives is RecutClub, a whole slide imaging (WSI) web-based platform for presenting surgical pathology unknown conference cases. With the evolving nature of pathology didactics in an ever-changing world where remote work plays an increasingly important role, several refinements were needed to ensure that the platform could continue to provide an unparalleled WSI experience for incoming trainees. Additionally, the burden of updating site content needed to be distributed from the site administrators to the end-users.

Methods

RecutClub is operated through Google Cloud via a Google App Engine instance. It connects to Google Cloud Databases to store persistent tabular data and Google Cloud Storage for pyramidal JPEG files used to display whole slide images in a web-browser. In the next generation platform (RecutClub 2.0), the largest change was to migrate case uploading from a developer-controlled solution to a decentralized, trainee-driven web portal. To ensure a superior user experience, the entire site as well as the upload form was migrated to Bootstrap 4. An AJAX-native, asynchronous uploader was built to interface the existing Google Cloud platform to a new upload portal that allows authorized trainees to build cases from scratch. Additionally, a tagging solution was implemented to allow for server-side persistent storage of trainee-selected cases, such as “interesting” cases or cases for further review. This tagging complements the existing region of interest (ROI) and case search functionalities.

Results

The deployment of RecutClub 2.0 involved multiple rounds of resident-led testing and feedback. Several regular testers offered ongoing user feedback and suggestions for visual layout and usability. The response from the general trainee population after deployment was overwhelming positive, with many trainees commenting on the “improved” visual aesthetics as well as the convenience of the upload functionality. Administrator involvement in case-upload time decreased from 2 hours/month to 0 hours/month due to enabling trainee-driven uploading.

Conclusions

The deployment of RecutClub 2.0 fulfilled the dual primary objectives of enabling straightforward trainee-led content updates, as well as decreasing administrator involvement in case-upload time. These and other changes ensure that RecutClub can continue to provide an unparalleled WSI experience for pathology trainees at Houston Methodist, while also providing fresh content in a landscape with several competing WSI platforms.
A multimodal genetic testing approach to a diagnosis of Roberts-SC phocomelia syndrome, an ESCO2 spectrum disorder
Authors: Killeen Trevor , Bower Matt , Berry Susan , Hirsch Betsy
Published: November 2022

Diagnosis of a genetic syndrome has traditionally relied upon the identification of characteristic phenotypic findings, followed by targeted laboratory testing. Shared clinical manifestations between genetically distinct syndromes and variable expressivity of findings within a single syndrome can complicate the diagnosis. Multiple testing modalities may be necessary, even when the putative gene(s) is known. We describe the multi-pronged genetic testing applied to a patient with a suspected diagnosis of Roberts- SC phocomelia syndrome (RBS). RBS is an autosomal recessive developmental disorder (OMIM 268300) caused by pathogenic variants in the “establishment of sister chromatid cohesion N-acetyltransferase” (ESCO2 ) gene mapped to chromosome 8p21.1. The ESCO2 enzyme product is a conserved protein with acetyltransferase activity required for formation of the cohesin complex, which, among other activities, maintains sister chromatid association during S-phase of the cell cycle. Because of the defective cohesin complex, RBS joins other syndromes referred to as cohesinopathies. The patient, a newborn male, was small for gestational age, with hypertelorism, cleft lip and palate, shortened forearms, absence of the radius and thumbs, and bilateral clubbed feet. All of these findings are established characteristics of RBS. Targeted Next Generation Sequencing revealed a single variant in exon 10 of ESCO2 (c.1654C>T, p.Arg552*) predicted to result in a loss of function. Chromosomal microarray was also performed and showed an estimated 15 Mb region of homozygosity (ROH) extending from 8p11.21 to 8p21.2, which spans ESCO2. The finding of this ROH supported the interpretation of homozygosity for the variant, as did a family history of consanguinity. Additional cytogenetic analysis documented premature sister chromatid separation and repulsion of heterochromatin chromosomal regions characteristic of RBS. These chromosomal findings served as a functional assay supporting pathogenicity of the ESCO2 variant. Interestingly, the only report of an identical variant within exon 10 of ESCO2 was described for two brothers diagnosed with Juberg-Hayward syndrome. Juberg-Hayward was considered allelic to, but a distinct entity from RBS. In contrast, our findings support the conclusion that RBS and Juberg-Hayward are not distinct syndromes, but rather represent variability within an ESCO2 syndrome spectrum. Such unification of diagnoses based on genomic findings has influenced numerous other clinical disorders. Further, our findings demonstrate the contributions of each of the genetic testing modalities, which may be applied, selectively or collectively, based on integration with clinical and family history data.
Machine Learning Models Accurately Predict PTHrP Results But Fail To Predict Physician Behavior
Authors: Spies Nicholas , Jackups Ron , Zaydman Mark
Published: November 2022

Quantification of circulating parathyroid hormone-related peptide (PTHrP) aids in the diagnosis of humoral hypercalcemia of malignancy. However, this test is often ordered in settings of low pre-test probability or mistakenly ordered when parathyroid hormone (PTH) was desired. To improve utilization, all PTHrP orders at our institutions are reviewed by a laboratory medicine resident. If the order appears to be inappropriate, the ordering physician is contacted to ask for permission to cancel. In this work, we attempted to automate this labor-intensive review process by developing machine learning models to predict the orders the physician is willing to cancel. We collected 2171 PTHrP orders that were subjected to manual review over the past 10 years. We removed any repeats, leaving 1649 first-time orders. For each order, we assigned a class label of ‘canceled’ or ‘completed’ based upon the notes in the resident’s documentation logs. For each order, we aggregated all data for the patient existing within the laboratory information system at the time of the first order (n = 40 million). Various strategies were applied to impute missing data, including leaving missingness as a feature, fill by medians, k-nearest neighbors, bagged trees, and linear regression. Class imbalances were adjusted using synthetic minority upsampling technique (SMOTE) and adaptive synthetic upsampling (ADASYN) for a final ratio of one:one. The dataset was partitioned into a 70:30 split between training and testing sets with five-fold cross-validation. Several machine learning algorithms were trained, including logistic regression, naive Bayes, random forest, and XGBoost. After training and cross-validation, the models were applied to the held-out test set, and performance was evaluated using the area under the receiver operating characteristic curve (AUC). XGBoost was the best performer at predicting the provider’s likelihood to cancel the test, but with an AUC of only 0.63. Surprised by this poor performance, we devised a second classification task of predicting the PTHrP results (normal vs abnormal, threshold = 4.2 pmol/L) for the subset of orders that were completed (n=1371). Using the same machine learning pipeline described above, we again observed that XGBoost was the best performer, but this time with an AUC of 0.89. The striking performance difference between the models trained on the two different targets suggests that the physician’s willingness to assent to our intervention may be unrelated to existing laboratory data or underlying biology. Likely explanations may include that our intervention is reaching a provider who is not the primary medical decision-maker or the correct provider at the wrong time when they are too busy to revisit details of prior work. In either case, a reflex order set that defines specific criteria for performing PHTrP upfront may be a more effective way to improve utilization.
Trends in Viral Respiratory Culture: Impacts of the SARS-CoV-2 Pandemic
Authors: Bradley Benjamin , Hymas Weston , Barker Adam
Published: November 2022

Introduction

Due to the increasing ease and availability of molecular assays, viral culture is rarely employed for the diagnosis of respiratory illnesses. Despite lower sensitivity than molecular techniques, viral culture may detect a wider array of viral pathogens at a lower cost relative to multiplex molecular panels. In this study, we examined the effects of the SARS-CoV-2 pandemic on viral respiratory culture ordering and trends in the rates of pathogen detection.

Methods

Viral respiratory culture results from Jan 1st, 2017 to February 28th, 2022 were analyzed for changes in the number of monthly orders, positivity rate, and incidence of individual pathogens. To determine changes in seasonal incidence and viral etiology, a comparison was made between winter (Dec-Feb) and summer (June-Aug) months as well as acute (Influenza A/B, RSV) and chronic (HSV, CMV) infections. Given SARS-CoV-2’s classification as a BSL-3 pathogen, our viral culture assay was not designed to detect this virus. As a surrogate method to measure rates of SARS-CoV-2 in viral culture specimens, we performed NAAT testing with the ThermoFisher TaqPath COVID-19, Flu A/B, RSV assay on negative specimens.

Results

Following the pandemic, testing volume decreased by 46.7% with the overall positivity rate decreasing from 6.67% to 4.85%. Among the 46 states for which more than ten orders were placed, monthly testing decreased in 38 states. Of the eight states with increased average monthly testing, the greatest increases were seen in Rhode Island, Nevada, and Montana. During the pre-pandemic timeframe, acute respiratory pathogens demonstrated a typical winter peak with low summer detection. Post-pandemic, there was an atypical increase of acute respiratory pathogens, driven primarily by RSV. The positivity rate for chronic viral infections increased from 3.43% pre-pandemic to 4.09% post-pandemic. Following the pandemic, HSV has replaced influenza as the most commonly detected pathogen during winter months. Molecular studies of 229 negative viral culture specimens identified 36 (15.7%) samples positive for SARS-CoV-2, 9 (3.9%) for RSV, and none for influenza A or B. Median cycle threshold values for SARS-CoV-2 samples were 21.3 (range: 9.1-36.5).

Conclusions

Following the SARS-CoV-2 pandemic, the number of respiratory virus cultures ordered significantly decreased. There has also been a statistically significant decrease in the positivity rate driven by the absence of acute viral respiratory pathogens, including influenza A/B and RSV. We also observed an offseason increase of RSV during the summer months of 2021. Detection rates of chronic viral pathogens including CMV and HSV have remained relative stable. The presence of SARS-CoV-2 in negative specimens raises concerns for inappropriate test utilization. While less sensitive than molecular methods, viral culture has the potential to offer a lower cost alternative for monitoring a broad range of viral pathogens.
Machine Learning Models Can Accurately Detect Crystalloid Contamination of Basic Metabolic Panels
Authors: Spies Nicholas , Zhang Ray , Farnsworth Christopher , Jackups Ron , Zaydman Mark
Published: November 2022

A common cause of erroneous laboratory results is preanalytical contamination of samples with intravenous crystalloids. Rules-based approaches, such as delta checks or feasibility cut-offs, can detect these errors, but rely on prior laboratory results and lack sensitivity. In this study, we aimed to improve the detection of crystalloid contamination using two machine learning workflows for the detection of contamination by the four most common crystalloids; normal saline (NS), lactated Ringer’s (LR), and their dextrose-containing counterparts (D5NS and D5LR). First, we employed a semi-supervised approach using manifold approximation and contrastive learning. To do this, we aggregated five years' worth of basic metabolic panel results (n = 67 million), then simulated contaminated samples by mixing random subsets of samples in silico with the crystalloid solutions at different ratios. The dataset was partitioned into a 70:30 split between training and testing sets with five-fold cross-validation. An autoencoder was trained to create an embedding of the data by minimizing the triplet loss. This embedding was then projected onto a two-dimensional manifold. When the four crystalloid solutions and the independent test set were mapped to the manifold, decision boundaries were drawn based on the threshold that maximized the F1 statistic, and labels were assigned. This method detected the 10% in silico mixtures with an area under the receiver operating characteristic curve (AUC) of 0.97, 0.94, 0.99, and 0.99 for NS, LR, D5NS, and D5LR respectively. Next, we evaluated a fully-supervised approach by training and validating Random Forest and XGBoost models using the same training and testing sets as above. Both models performed well, with XGBoost slightly outperforming Random Forest. The XGBoost model demonstrated AUCs of 0.992, 0.990, 0.998, and 0.996 for the NS, LR, D5NS, and D5LR mixtures. This high-level performance was maintained even as the proportion of mixed samples in the dataset was decreased from 50% to 1% to more accurately reflect real-world contamination rates. For NS and LR, the variables with the highest relative importance were calcium and chloride. For their D5 counterparts, glucose and calcium were most important. Creatinine and blood urea nitrogen were the least important variables in both approaches. Overall, the fully-supervised learning approach outperformed that of the contrastive embeddings for the specific task of identifying contamination from pre-defined crystalloids. One advantage of the semi-supervised approach is that it could be adapted to identify outliers that are not pre-defined. However, considering the relative ease of translating tree-based models into practice, we conclude that our XGBoost model offers the most promising solution and plan to prospectively validate this model for real-time detection of sample contamination.
Implementation and Assessment of a SmartZone Alert to Notify Clinicians of Critical Hyperbilirubinemia in Preterm Infants Less Than 35 Weeks Gestation
Authors: Xiao Yi , Palmucci Mandy , Carlin Lance , Lee Catherine , O'Gorman Maurice , Nair Srikumar , Yieh Leah , Leung Edward
Published: November 2022

Background

Neonatal jaundice, also known as hyperbilirubinemia in term and preterm infants, is treated with phototherapy when bilirubin results exceed gestational age- and age-specific medical decision levels (MDL) to prevent kernicterus and bilirubin-induced neurological damage. During phototherapy, unconjugated bilirubin is converted to water-soluble isomers that are excreted in the urine. Presently, the electronic medical record (EMR) at our hospital cannot use gestational age to stratify reference ranges thereby the associated flags and alerts would not be triggered, leading to delays in reviewing bilirubin results and placing phototherapy orders. The aim of this project is to replace the current manual assessment process for phototherapy with a newly designed alert to notify clinicians of elevated bilirubin results for preterm infants (<35 weeks gestation) and to minimize prolonged delays in placing phototherapy orders. We hypothesized that the SmartZone alert will encourage consistent and timely consideration of phototherapy.

Method

A SmartZone alert, built with Cerner command language and Discern Expert rules, evaluates total or neonatal bilirubin results for patients in the Newborn and Infant Critical Care Unit (NICCU), calculates the patient’s age using the recorded gestational age and birth time, and utilizes the following rules: 1) bilirubin result must exceed the pre-defined gestational age-specific MDLs, and 2) calculated gestational age is <35 weeks. Additionally, the SmartZone alert will not be triggered if there is an active phototherapy order. Once triggered, the alert will be visible for four hours to all caregivers who view the patient’s EMR. We compared the duration of time between verified bilirubin results and phototherapy orders before and after the implementation of the SmartZone alert.

Result

The SmartZone alert was implemented on 01/11/2022. Between 1/1/2021 - 1/11/2022, 95 preterm infants in the NICCU had neonatal and total bilirubin results, in which 19 met the criteria for the alert to be triggered, and 17 had phototherapy orders. Further analysis revealed that 12 orders were placed <24 hours, four orders were placed 24 - 72 hours, and one order was placed >72 hours after bilirubin results were verified. Between 1/12/2022 – 2/13/2022, 13 newly admitted preterm infants in the NICCU had neonatal and total bilirubin results, in which one triggered the alert, and phototherapy was ordered within 15 hours.

Conclusion

A SmartZone alert was implemented to encourage consistent and timely consideration of phototherapy for preterm infants <35 weeks with critical hyperbilirubinemia. The alert is functioning as intended. This alert will be continuously monitored to further optimize its functionality and utilization.
Development of a Novel Algorithm Using Red Blood Cell Indices for Screening of Alpha Globin Gene Deletions
Authors: Zhang Xi , Parikh Bijal
Published: November 2022

Distinguishing between different causes of microcytic anemia is essential for management of anemic patients. More than 20 different RBC indices have been used to screen thalassemia trait with inconsistent results. Differentiation between iron deficiency anemia (IDA) and alpha-thalassemia appears to be more challenging than differentiation between IDA and beta-thalassemia, based on RBC indices alone. Moreover, thalassemia and IDA may coexist. A highly sensitive screening algorithm is needed to select clinical cases for alpha globin gene analysis to reduce unnecessary testing and improve pre-test probabilities. A retrospective study was performed to evaluate the reliability of 22 RBC indices (RBC, MCV, RDW, MCH, Mentzer Index, RDW Index, etc) and formulae in differentiating cases with 1-2 alpha globin gene deletions from negative cases, in a cohort of 90 individuals with confirmatory alpha globin gene analysis results. The number of patients with each alpha globin gene deletion pattern were: 37 patients with alpha-thalassemia trait, 21 silent carriers (one gene deletion), 31 negative patients and 1 patient with triplicated alpha globin gene. The mean RBC count in each group were 4.79 +/- 0.65 (trait), 4.45 +/- 0.73 (carrier), and 4.21 +/- 0.84 (negative) (million/mm). The mean MCV in each group were 71.1 +/- 4.8 (trait), 76.1 +/- 5.9 (carrier), and 74.2 +/- 9.3 (negative) (fl). The mean RDW in each group were 16.5 +/- 3.0 (trait), 17.2 +/- 3.4 (carrier), and 18.3 +/- 4.9 (negative) (%). The mean MCH in each group were 22.0 +/- 1.8 (trait), 23.8 +/- 2.3 (carrier), and 23.5 +/- 3.7 (negative) (pg). None of the RBC indices showed significant difference between carrier and negative groups, while 20 RBC indices showed significant difference (p<0.05) between trait and negative groups. The sensitivities of the RBC indices in detecting 1-2 alpha globin gene deletions based on published cutoffs ranged between 3.4% and 81.0%, while the specificities ranged between 41.9% and 100%. A novel scoring algorithm based on the combination of 12 RBC indices and formulae achieved a sensitivity of 96.6% in detecting 1-2 alpha globin gene deletions, with a negative likelihood ratio of 0.15. The negative likelihood ratio of the scoring algorithm outperformed each of the 12 RBC indices at similar levels of sensitivities (>95%) based on revised cutoffs. The algorithm is a highly sensitive tool for screening of alpha globin gene deletions, including one gene deletion. It is more effective at identifying negative cases compared to individual RBC indices. Implementation of the algorithm could efficiently reduce 10.0% (9/90) of the test volume of alpha globin gene analysis. A more stringent version of the algorithm could achieve 100% sensitivity and reduce 5.6% (5/90) of the alpha globin gene analysis test volume.
Benign Multicystic Peritoneal Mesothelioma as a Rare Cause of Death
Authors: Webber M , Connor E , Singh A , Majari G , moroz K , craig R
Published: November 2022

Introduction/Objective

Benign multicystic peritoneal mesothelioma (BMPM) is a tumor arising from the serosa of the peritoneal cavity, often in the pelvis, and is comprised of multiple cysts lined by bland mesothelial cells. It is a rare entity with less than 200 cases reported. The clinical course is often indolent with nonspecific symptoms. It has a strong predilection for females (90%) and is commonly associated with endometriosis or prior surgeries. A high local recurrence rate (50%) following excision has been reported, but malignant transformation is rare.

Methods/Case Report

The decedent was a 53-year-old male with a history of multiple hernia repairs who presented following three days of diffuse abdominal pain and obstipation. Imaging showed large volume, complex ascites with multiple rim-enhancing fluid collections, diffuse peritoneal thickening, and a soft tissue density in the lower abdomen/pelvis. Exploratory laparotomy was congruent and revealed 2L of purulent ascites, numerous peritoneal cystic lesions, and a bulky tumor in the pelvis. Blood and ascites cultures later grew Bacteroides species, and Escerichia coli was also isolated from the blood. Postoperatively, the decedent continued to decline, and death occurred the following day. Autopsy demonstrated that the firm pelvic mass entrapped the bladder, rectum, and segments of the small intestine. Sectioning revealed numerous cystic spaces of varying size. Microscopically, they were lined by a single layer of benign cells with mild to focally moderate atypia. These cells stained positive for Calretinin, Pan-cytokeratin, and D2-40 and negative for CD31, which is characteristic of mesothelial cells. These findings are consistent with BMPM.

Results (if a Case Study enter NA)

NA.

Conclusion

The decedent’s death is the result of sepsis following acute peritonitis due to BMPM. Death resulting from this entity is exceedingly rare, and to our knowledge this case is only the second reported death due to BMPM.
Hemorrhagic Pancreatitis in Pediatric Heart Transplant Recipients
Authors: Schwietert M , Sanabria Nunez D , Petty D
Published: November 2022

Introduction/Objective

Acute pancreatitis is a known side effect of tacrolimus in solid organ transplant recipients, but can be difficult to detect as symptoms may be vague and poorly localized, or overlap with the underlying condition. This phenomenon has most frequently been described in adult kidney transplant recipients. We present two autopsy cases in which pediatric patients with history of orthotopic heart transplantation both developed hemorrhagic pancreatitis shortly following operative procedures. Both had received immunosuppressants including tacrolimus during therapy. Although the etiology of pancreatitis in these medically complex cases is likely multifactorial, tacrolimus may be an important contributor.

Methods/Case Report

Case 1: A 6-year-old male with hypoplastic left heart syndrome was admitted for two years for medical management while awaiting transplant. Prior to and following transplantation he received immunosuppressants including tacrolimus to reduce risk of transplant rejection. Two weeks post-operatively, he developed abdominal pain and elevated pancreatic enzymes, leading to a diagnosis of pancreatitis. Imaging revealed hemorrhage. Tacrolimus was suspected to have caused this, and was discontinued. Despite medical management and multiple attempts to embolize vessels around the pancreas, the decedent remained unstable and ultimately went into hypotensive bradycardic cardiac arrest. Autopsy revealed a large hemorrhagic cavity confluent with a necrotic pancreas, as well as coagulum adherent to bowel loops throughout the abdomen. Case 2: A 13-year-old male status post two orthotopic heart transplants presented for a dental procedure. Following this, he developed an anaphylactic-type reaction to medication, with hives and bradycardia followed by cardiac arrest. He was resuscitated, however, his cardiac function steadily declined throughout the remainder of his stay. Heart biopsy revealed no evidence of cell-mediated transplant rejection. Pancreatic enzymes were mildly elevated, and abdominal imaging was unremarkable. His tacrolimus levels were noted to be supratherapeutic, and this was discontinued. Shortly before passing, he developed severe abdominal pain with distension, nausea and vomiting. At autopsy, he was found to have nearly two liters of hemorrhage and clot within the peritoneum emanating from a necrotic and hemorrhagic pancreas.

Results (if a Case Study enter NA)

NA.

Conclusion

Close clinical monitoring of pancreatic function should be considered in solid organ transplant recipients receiving tacrolimus.
Histologic Features of a Solitary Fibrous Tumor in the Region of Oral Cavity and Maxillofacial Complex with Recurrence and Distant Metastasis: a Rare Case Report
Authors: Johnson A , Eltahir M , Xu Y
Published: November 2022

Introduction/Objective

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, and may involve many anatomic locations. Approximately 0.6% of SFTs in the oral cavity and maxillofacial complex may recur and/or develop distant metastasis. Here we report a case of SFT in oral cavity with local recurrence and distant metastasis.

Methods/Case Report

The patient was a 66-year-old male with a past medical history of left buccal mass status post excision with an unclear diagnosis in a foreign country 6 years ago. He presented with a recurrence of the left buccal mass. Computerized tomography (CT) of the head and chest demonstrated a 9 cm expansile mass centered in the left pterygopalatine fossa and a 1.7 cm mass in left upper lobe of the lung, respectively. Biopsy of the lung mass was performed first and displayed a hypercellular mesenchymal tumor, composed of spindle cells arranged in vague short fascicles, and scant fibrous stroma with thin-walled and staghorn-like vasculature. The tumor cells had mild nuclear atypia with 5 mitoses/10 high power fields. No necrosis is identified. There were trapped benign pneumocytes and bronchial epithelial cells in the tumor. The tumor is positive for CD34, CD99, Bcl-2 and STAT6 immunostains. The large left buccal mass was biopsied later and showed similar morphology. The diagnoses of metastatic SFT in the lung and recurrent SFT were rendered, respectively.

Results (if a Case Study enter NA)

NA.

Conclusion

The histologic findings of the recurrent SFT and the pulmonary metastasis are similar in our case. Although marked cellular atypia and necrosis are not observed in either tumor, other features including the large size of recurrent tumor, hypercellularity, and increased mitotic activity are associated with malignant behavior in this report, and warrant the need for long-term follow-up.
Giant Cell Tumor of Soft Tissue Arising from Breast with Distant Metastases Post-therapy: A Rare Entity
Authors: Platero Portillo T M , Benzi E , Dhamne S
Published: November 2022

Introduction/Objective

Giant-cell tumor of soft tissue (GCT-ST) is rare and indistinguishable from giant cell tumor of bone. GCT-ST arising in the soft tissue of breast is exceedingly rare, with only ten cases previously reported.

Methods/Case Report

We present a 46-year-old female with history of lupus, presenting with an enlarging mass in her left breast. Needle core biopsy showed a hypercellular proliferation of spindle cells arranged in fascicles and sheets with infiltrative borders. A primary diagnosis of high-grade spindle cell lesion was rendered. The patient’s clinical workup was negative for lesions elsewhere. The patient subsequently underwent a left segmental mastectomy. Histopathology revealed a tumor composed predominantly of high-grade spindled and epithelioid cells with tumor necrosis, a high mitotic rate, and several scattered multinucleated giant cells. Immunohistochemical stains showed positivity for CD68 and CD34 in giant cells only, while the tumor cells were positive for Vimentin and CD99. Pancytokeratin, cytokeratin 5/6, HMB-45, smooth muscle actin, myogenin, myo-D1, and desmin were all negative. Based on the morphology and immunohistochemistry, the tumor was diagnosed as a malignant GCT-ST. Adjuvantly, she underwent chemoradiation; however, within four months, she developed new nodules in the lung, left ventricle, and liver, radiologically consistent with metastases.

Results (if a Case Study enter NA)

NA

Conclusion

Although GCT-ST possesses a low malignant potential, its unpredictable behavior poses a challenge. Metastases may develop even after excision with adequate surgical margins. To our knowledge, this is the first case of primary malignant GCT-ST of the breast with distant metastases post-therapy. This entity, with its clinical complexities, remains a diagnostic and therapeutic challenge.
Hyperglycemia Alters the CD27:CD70 Axis of Human Immune Cells
Authors: Lerret N , Owaja C , Schulz M , Roback-Navarro E
Published: November 2022

Introduction/Objective

The exact mechanism that inflammation plays in the pathogenesis from obesity to Type 2 diabetes is unclear, however, activated immune cells and pro-inflammatory cytokines have been found in the adipose tissue of Type 2 diabetics, implicating their role in the disease process. While the CD27-CD70 axis is being explored in other models of chronic inflammation, such as rheumatoid arthritis and colitis, the role played in Type 2 diabetes remains unknown.

Objective

Evaluate whether hyperglycemia alters immune cells phenotype and effector function, specifically of the CD27:CD70 axis on human immune cells.

Methods/Case Report

Human peripheral blood from donors was divided into three groups. n=40 total those that have a healthy blood glucose value and are without any co-morbidities (normoglycemic), patients identified as having pre-diabetes per their hemoglobin A1c (HgbA1c) value (5.6-6.5%), and patients with diabetes, having an elevated blood glucose and HgbA1c value (> 6.5%). The blood was then stained with monoclonal antibodies towards cell surface markers associated with inflammation, including CD27/CD70 and analyzed via flow cytometry. Previous data using cell cultures of human PBMC-derived T cells and autologous dendritic cells exposed to varing concentrations of glucose to simulate hyperglycemia and pre-diabetes was compared to this data.

Results (if a Case Study enter NA)

1) T cells directly analyzed from pre-diabetic and hyperglycemia individuals down-regulate their CD27 expression. CD70 is up-regulated on immune cells directly analyzed from pre-diabetic individual when compared to immune cells from normoglycemic individuals. In accordance with the above resutls, CD4 T cells have an activated effector phenotype after co-culture with glucose stimulated dendritic cells. This includes down-regulation of CD27 on T cells and up-regulation of CD70 on dendritic cells.

Conclusion

Our data shows that certain markers of inflammation are up-regulated on the surface of immune cells from pre-diabetic and/or diabetic patients. Specifically, we demonstrate novel evidence that the CD27-CD70 axis is activated in diabetes or hyperglycemic conditions. These molecules may offer a potential target for therapeutics. Alternatively, our findings would allow a further way to characterize where a patient with an elevated blood glucose value is on the spectrum between pre-diabetes and full-blown diabetes.
Performance Evaluation of Two FDA-Approved Fentanyl Immunoassays against LC-MS/MS
Authors: Militello L , Zhang V
Published: November 2022

Introduction/Objective

The increased number of deaths caused by Fentanyl in recent years created the need for accurate, automated assays for fentanyl detection. Many products have been brought to market but there is concern over the sensitivity and specificity of the available immunoassays. Here we evaluate the performance of our current assay, the ARK Fentanyl II Assay (ARK), against the newly FDA-approved Fentanyl Immunoassay for Roche Cobas (Roche), using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the gold standard. To our knowledge, this is the first study to evaluate the performance of the Roche fentanyl immunoassay.

Methods/Case Report

We collected discarded patient urine samples screened for fentanyl using ARK over 3 months to get a total of 100 positive and 100 negative results. All samples were stored at -20 °C and later tested again using ARK, Roche and in-house LC-MS/MS assays. Both immunoassays were performed on Roche Cobas c501 chemistry analyzer. In-house LC-MS/MS assay gave quantitative measurements for both fentanyl and norfentanyl with a limit of quantification of 1 ng/mL for both. Samples with results above 1 ng/mL of either analyte were considered positive for the presence of fentanyl. The upper limit of quantification of the LC-MS/MS assay was 2000 ng/mL. The results obtained from LC-MS/MS were considered as reference values to determine the sensitivity and specificity of the immunoassays, which were calculated by dividing the number of positive and negative samples correctly identified by immunoassay by total positive and negative samples based on LC-MS/MS results, respectively. ARK is designed to detect fentanyl with a cutoff of 1 ng/mL. Roche is designed to detect norfentanyl with a cutoff of 5 ng/mL.

Results (if a Case Study enter NA)

Analytical sensitivity and specificity were 91.9% and 99.3% for ARK and 96.8 and 98.6% for Roche. Fentanyl and norfentanyl levels by LC-MS/MS ranged from <1 to >2000 ng/mL with a mean of 57 and 232 and standard deviation of 235 and 578, respectively. False positives were seen in 1 sample for ARK and 2 samples for Roche. False negatives were seen in 5 samples for ARK and 2 samples for Roche. Roche accurately identified 6 positive samples that had norfentanyl concentrations less than the cutoff of 5 ng/mL, indicating a potential greater sensitivity than stated.

Conclusion

Both immunoassays performed reasonably well, showing great specificity. Roche displayed greater sensitivity.
Extramedullary Hematopoiesis Identified in Pleural Fluid of a Patient with Bilateral Pleural Effusions and Associated Myelofibrosis
Authors: Marshall C , Liu Y
Published: November 2022

Introduction/Objective

Extramedullary hematopoiesis (EMH) is the formation of blood cells outside of the bone marrow medullary spaces. EMH is typically seen in the spleen or liver and in association with bone marrow replacement disorders, hemoglobinopathies, and other hematological disorders. Rarely EMH can occur in the pleural cavity of patients resulting in subsequent pleural effusions. These cases can accurately be diagnosed with identification of megakaryocytes and other hematopoietic elements in the pleural fluid.

Methods/Case Report

We present a 67 year old male with a past medical history of pericardial effusion, Jak 2 positive Myelofibrosis (Post PV/ET), and type II diabetes mellitus, who presented with complaint of shortness of breath for 10 days. The patient did not require oxygen at home and denied any cough or hemoptysis. In the emergency department a Chest X ray was ordered which showed bilateral pulmonary effusions. These effusions were attributed to worsening congestive heart failure, and diuretic therapy was started. With no resolution of the pleural effusions, the decision was made to conduct a thoracentesis and remove the fluid. Interventional radiology then performed a thoracentesis removing 1000 mL from each the left and right pleural spaces. Cytological preparation of the fluid demonstrated myeloid and erythroid precursors as well as occasional megakaryocytes. The diagnosis of extramedullary hematopoiesis was made and the effusion did not recur.

Results (if a Case Study enter NA)

NA.

Conclusion

Extramedullary hematopoiesis of the pleural space is rare. However it must be considered in the differential diagnosis of a patient with persistent effusions and concomitant bone marrow replacement disease such as myelofibrosis. Prompt removal and cytological evaluation of the pleura fluid for hematopoietic elements should be performed in order to diagnose and manage the patient most effectively.
CeruminousSyringocystadenoma papilliferum: An Extremely Rare Neoplasm of the External Ear
Authors: Ajmal I , Sonani H , Al Hmada Y
Published: November 2022

Introduction/Objective

Syringocystadenoma papilliferum (SCAP) is a rare benign adnexal tumor derived from the apocrine or the eccrine sweat glands on the face or the scalp. Ceruminous glands are modified apocrine glands in the external auditory canal and produce cerumen that helps the ear canal against physical damage and microbial invasion. Neoplastic transformation of these glands is even rarer among these benign tumors.

Methods/Case Report

Here we report a case of a 29-year-old female with a three-month history of progressively worsening right-sided ear pain, muffled hearing, aural fullness, and right-sided shooting aches. She reported that her ear felt sensitive to touch and was painful if she lay on it. Previous treatments included steroids and oral antibiotics without any improvement in symptoms. A physical exam revealed a right narrow ear canal with a cystic mass to the superior lateral canal wall. A CT Temporal Bone showed a 1 cm oval soft tissue lesion in the lateral osseous portion of the right external auditory canal with no underlying osseous erosions identified. This is nonspecific, and neoplasm cannot be excluded. The decision was made for excision. The mass ruptured during excision with dishwater appearing fluid. Microscopic examination showed papillae lined by bilayered glandular epithelium projecting into a cystic lumen. Well defined myoepithelial cell layer is appreciated. Decapitation secretions and plasma cells are noted to be present in the stroma. A final diagnosis of Syringocystadenoma papilliferum is made.

Results (if a Case Study enter NA)

NA.

Conclusion

Ceruminous Syringocystadenoma papilliferum is an extremely rare benign tumor of the ceruminous glands of the external ear. Complete excision is the treatment of choice
Racial Disparity in Antibody Against High Prevalence Antigen; Anti-U
Authors: Abdelmonem M , Cai W , Yunce M , Tang M , Shan H , Cabungan M
Published: November 2022

Introduction/Objective

Anti-U is an IgG antibody directed against the U antigen, which usually forms after exposure to U antigen via blood transfusion and/or pregnancy. U antigen is located on glycophorin B (GYPB) as part of the MNS blood group system. Approximately 2% of the African American population lacks this antigen, making them prone to developing anti-U. Anti-U can cause hemolytic disease of fetus and newborn (HDFN) and hemolytic transfusion reactions (HTR).

Methods/Case Report

A 60-year-old African American male underwent aortic valve surgery. The patient was A Pos with a negative antibody screen. During surgery, the patient was transfused with 3 random units of packed red blood cells (PRBCs). The postoperative course was uncomplicated, and the patient was discharged home. 6 months later, the patient was admitted for another procedure and was expected to require blood products. Thus, a type and screen test was ordered, revealing pan reactivity on screening cells. This prompted further investigation. Antibody detection was performed with the solid-phase technique followed by the tube method with Polyethylene glycol (PEG) as an enhancement medium. PEG technique is the next choice of method if the solid phase requires extended antibody work up, which was the case in our patient. PEG tube method successfully identified Anti-U, and the patient's phenotype was confirmed to be U negative.

Results (if a Case Study enter NA)

N/A.

Conclusion

It is imperative to stress the importance of racial disparity while investigating antibodies against high prevalence. In our case, our suspicion was high for Anti-U, given that patient was of African American descent. Tube methods with PEG and Solid Phase techniques are usually used for antibody identification. It is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they have to prevent further exposure.
A Scalp Metastatic Follicular Thyroid Carcinoma with a Silent Thyroid History and Normal Thyroid Uptake by PET-CT
Authors: Huang H , Salehiazar S , Peng S
Published: November 2022

Introduction/Objective

Follicular thyroid carcinoma (FTC) accounts for 10%-15% of all primary thyroid cancers. Follicular thyroid cancer is known to metastasize hematogenously, with distant metastasis occurring in 6-20% of cases. Scalp metastasis with an underlying thyroid carcinoma is an exceedingly rare clinical entity; there are less than 15 case reports in the literature. 1-2. Here, we present a case of widely invasive FTC with skull metastases located on the parietal calvarium. The scalp mass was confirmed as follicular thyroid carcinoma via microscopic morphology and positive immunoreactivity for Vimentin, TTF1, thyroglobulin, and PAX8. We present this case not only because of the diagnostic challenge and rare scalp metastasis, but also because of the patient’s unusual “silent” thyroid medical history and no abnormal thyroid uptake by PET-CT.

Methods/Case Report

81-year-old female presenting 2-year history of right parietal scalp mass, which was previously suspected for lipoma with attempted resection in Mexico but interrupted due to severe hemorrhage. No palpable thyroid nodule was noted. PET-CT showed avid lesions of the right breast with nipple retraction, as well as avid suspicious lesions of bilateral lungs, calvarium, xiphoid process, right acetabulum, T spine most c/f widely metastatic cancer, most likely a breast primary; evaluation of the neck demonstrates physiologic FDG-activity in the thyroid. Thyroid studies showed hyperthyroidism: TSH (L) <0.010 uIU/mL; Free T3 (H) 4.7 pg/mL and Free T4 1.00 ng/d. The patient was performed Ultrasound-guided FNA and core biopsy of the large parietal scalp lesion, however, FNA of the cystic component was nondiagnostic (no malignant cells seen).

Results (if a Case Study enter NA)

NA.

Conclusion

Core biopsy of the large parietal mass the tumor cells tend to form follicular or microfollicular architecture with colloid present, but no papillary nuclear features. Rare mitotic figures are seen. IHC stain of tumor cells are positive for AE1/AE3, Cam5.2, CK7, TTF1, thyroglobulin, PAX8, and Vimentin, which show strong evidence for metastatic follicular thyroid carcinoma (FTC) origin. Tumor cells are negative for Napsin-A, P63, Synaptophysin, Ck5/6, Ck20, EMA, WT1, CDX2, GATA3, Mammaglobin, ER, PR, and BRST2, which helps rule out the primary malignancy from lung, breast, neuroendocrine or other adenocarcinomas.
Gastric Spindle Cell Neoplasms With Mast Cells - A Pitfall In Diagnosis Of Gastric Biopsies.
Authors: Bal S K , Sieber S C
Published: November 2022

Introduction/Objective

Undifferentiated sarcoma, previously known as malignant fibrous histiocytoma (MFH), is a very rare primary neoplasm of stomach. It usually arises from soft tissue of extremities with an incidence of 1- 2/100,000, typically presenting in the 5th-7th decades of life with a slight male predominance. We report a case of gastric undifferentiated sarcoma which was interpreted as gastrointestinal stromal tumor (GIST) on initial biopsy.

Methods/Case Report

A 84 year old female presented to the Danbury Hospital emergency department with hematemesis and melena. Upper gastrointestinal endoscopy revealed a pedunculated mass in the cardia of stomach with ulceration, followed by a computed tomographic scan of chest and abdomen revealing a 2.9 cm mass along the proximal lesser curvature of the stomach. An endoscopic biopsy revealed a spindle cell neoplasm with immunohistochemical staining for c-kit consistent with GIST. She later underwent partial gastrectomy. Histopathology of the resected gastric tumor showed tumor cells arranged in sheets and storiform pattern, exhibiting spindled to polygonal morphology with marked nuclear pleomorphism, high mitotic activity (20 mitoses per 10 high power fields) and Touton type giant cells. Immunohistochemical stains demonstrated absence of staining for c-kit, DOG-1, CD34, actin, desmin, S100, cytokeratin AE1/AE3, CD3, CD5, CD20, CD21, CD15, CD30, ALK1, myeloperoxidase, CD1a and LCA. Numerous mast cells within the tumor stained for c-kit. Molecular testing for c-kit and PDGFRA mutations were negative. A final diagnosis of undifferentiated sarcoma with features of myxofibrosarcoma was rendered.

Results (if a Case Study enter NA)

NA.

Conclusion

Undifferentiated sarcomas are high grade malignant mesenchymal neoplasms without clear cellular differentiation or immunohistochemical marker. Only 4% of the total cases of undifferentiated sarcoma have been reported to be arising primarily from the gastrointestinal tract. They carry a poor prognosis with a 5 year survival of 47%. The main pitfall in our case was the positive uptake of c-kit stain by mast cells which led to the diagnosis of GIST in first gastric biopsy. We want to stress the importance of entertaining this diagnosis in the differential when encountered with a malignant gastric spindle cell neoplasm along with careful interpretation of c-kit stains in small biopsy specimens as the treatment and prognosis differs greatly from GIST.