Pathology Commons^™

Spatial Profiling Of The Prostate Cancer Tumor Microenvironment Reveals Multiple Differences In Gene Expression And Correlation With Recurrence Risk, Vinay Kumar, Pavneet Randhawa, Robert Bilodeau, Dan Mercola, Michael Mcclelland, Anshu Agrawal, James Nguyen, Patricia Castro, Michael M Ittmann, Farah Rahmatpanah

Faculty, Staff and Students Publications

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …

The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi

Master of Medicine in Anatomic Pathology

Introduction: Breast Cancer (BC) is the most diagnosed cancer among women worldwide and in Kenya. It is a highly heterogeneous disease requiring patient specific treatment and strategies to monitor response to therapy, especially in the neoadjuvant (NAC) setting. Currently, there are no reliable markers in use that can predict response to chemotherapy among patients receiving NAC. Tumour Infiltrating Lymphocytes (TILs) and Cell free DNA (cfDNA) are biomarkers that could possibly bridge this gap. However, limited studies have been carried out on the African population. With the increasing mortality rates attributable to BC in Sub-Saharan Africa, coupled with the growing preference …

Acute Pericarditis And Acute Pleuritis/Empyema Following Submandibular Infection In A Covid-19 Positive Patient - An Autopsy Revealing The Danger Space Of The Neck, Jessica D. Anderson, Seyedalireza Fatemi, Joseph Fullmer, Ping I. Zhang

Posters

Acute pericarditis and empyema are life-threatening complications of severe odontogenic infections; reports of these findings from an autopsy perspective are rare. We report an autopsy case demonstrating infection from the mandibular molars to the pericardium and pleura in a patient following Covid-19 infection

Association Of Isolated Colitis With Non-Steroidal Anti-Inflammatory Drugs Usage, Ashbita Pokharel, Wei Li

Posters

Non-steroidal anti-inflammatory drugs (NSAIDs) have been known to produce various clinical gastrointestinal side-effects and histopathological changes. It has been reported that NSAIDs usage is associated with isolated colitis in periappendiceal orifice region. This study aims to further evaluate the clinicopathologic features of 16 patients with isolated colitis limited to the cecum or peri-appendiceal orifice region.

Cd30 Expression In Cutaneous B-Cell Lymphomas, Olabisi Afolayan-Oloye, Lili Zhao, Trilokraj Tejasvi, May P. Chan, Paul W. Harms, Douglas R. Fullen, Ryan A. Wilcox, Alexandra C. Hristov

Posters

CD30 expression has been infrequently described in cutaneous B-cell lymphomas (CBCL). We examined CD30 expression in reactive lymphoid hyperplasia (RLH) and CBCL and correlated expression with clinicopathologic features.

Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege

Master of Medicine in Clinical Pathology

Methodology: This cross-sectional study was carried out at Aga Khan University Hospital, Nairobi between July 1st 2020 and December 31st 2021. Participants were adults aged 18 years and above presenting to the emergency department with signs and symptoms suggesting an acute myocardial infarction. Patients were identified on the hospital management information system (CARE 2000) using test results for baseline high-sensitivity cardiac troponin I. The final diagnosis as well as secondary clinical data was obtained from both physical and electronic patient medical records. The reference standard for the diagnosis of acute myocardial infarction was taken as the final clinical diagnosis made …

Repeat Tracheal Aspirates In Pediatric Intensive Care Patients: Frequency, Resistance And Antimicrobial Use, Edward Lyon, Jennifer Goldman, Brian Lee, Margaret Campbell, Rangaraj Selvarangan, Elizabeth Monsees

Posters

Background: Tracheal aspirates (TA) are frequently obtained in the pediatric intensive care unit (PICU); however, no data exists on the frequency or clinical management of multiple TA cultures on the same PICU patient. In this study, we describe the frequency of repeat TAs in PICU patients, the emergence of multidrug resistant organisms (MDRO), frequently cultured pathogens of TAs, and associated antibiotic prescribing patterns. Methods: We identified 70 PICU patients between 2018-2019 who met our criteria for retrospective chart review with ≥2 TAs obtained during their hospitalization. The following information was collected: patient demographics, number of TAs per patient, microbiology with …

Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar

Department of Pathology and Laboratory Medicine

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster …

Increased Eosinophils In The Muscularis Propria Of Appendix May Indicate Early Symptomatic Appendicitis, Ping L. Zhang, Zhenhong Qu

Conference Presentation Abstracts

Background: The presence of neutrophils in muscularis propria is known to best correlate with clinical symptoms of acute appendicitis. Eosinophils present in the muscularis propria were noted in cases of acute appendicitis in 2000 (Carr, NJ. Annal of Diagnostic Pathology 2000;4:46–58), but the significance of their presence there has been unclear. The goal of this study was to investigate whether increased eosinophils in muscularis propria could be correlated with early symptoms of patients with clinical diagnosis of symptomatic appendicitis.

Methods: Seventeen patients with clinical diagnosis of acute appendicitis were identified as having acute symptomatology, but the resection specimens displayed a …

Paneth Cell-Like Granules In Clear Cell Renal Cell Carcinomas Are Cd68 And Lysozyme Positive Lysosomes, P L. Zhang

Conference Presentation Abstracts

Background:Paneth cells with features ofneuroendocrine differentiation can be seen inmultiple organs and various tumours. Paneth cell-likegranules in clear cell renal cell carcinomas (RCC)have previously been reported, but are found noexpression of neuroendocrine markers. Given thatclear cell RCC are rich in phagocytic factors, wehypothesized that the Paneth cell-like granules inclear cell RCC were associated with lysosomes.Methods:In this study, 72 different renal tumoursincluded 42 clear cell RCC, 16 papillary RCC, 5 clearcell papillary RCC, 6 chromophobe RCC, 2 urothelialcarcinomas and one unclassified RCC. All tumourswere evaluated for the Paneth cell-like granules onhaematoxylin & eosin stained sections. In addition,PAS-D staining, immunohistochemical stains andelectron …

Prevalence Of Allergic Fungal Sinusitis In Nonspecific Allergic Sinusitis, P L. Zhang, H D. Kanaan

Conference Presentation Abstracts

Background: Increased eosinophils in sinus contents are regarded as nonspecific allergic sinusitis. However there are only a few studies addressing the rate of fungal infection associated allergic fungal sinusitis in non-specific allergic sinusitis. This study was to identify the prevalence of allergic fungal sinusitis in the sinus content specimens with increased eosinophils. Methods: A computer search for allergic sinusitis was done over a 4 year period of time. And allergic fungal sinusitis was individually identified within listed allergic sinusitis cases. Each individual case of allergic fungal sinusitis was reviewed in correlation with sinus culture findings and the prevalence of allergic …

September 2022: Region 10 Emerging Special Pathogen Treatment Center (Resptc) At Providence Sacred Heart Medical Center & Children’S Hospital, Providence - Special Pathogens Program

Special Pathogens Newsletters

REGION 10 SPECIAL PATHOGENS NEWSLETTER

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …

Informing Healthcare Operations With Integrated Pathology, Clinical, And Epidemiology Data: Lessons From A Single Institution In Kenya During Covid-19 Waves, Allan Njau, Jemimah Kimeu, Jaimini Gohil, David Nganga

Pathology, East Africa

Pathology, clinical care teams, and public health experts often operate in silos. We hypothesized that large data sets from laboratories when integrated with other healthcare data can provide evidence that can be used to optimize planning for healthcare needs, often driven by health-seeking or delivery behavior. From the hospital information system, we extracted raw data from tests performed from 2019 to 2021, prescription drug usage, and admission patterns from pharmacy and nursing departments during the COVID-19 pandemic in Kenya (March 2020 to December 2021). Proportions and rates were calculated. Regression models were created, and a t-test for differences between …

Association Of Isolated Colitis With Nonsteroidal Anti-Inflammatory Drug Usage, Ashbita Pokharel, Wei Li

Conference Presentation Abstracts

Context: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been known to produce various clinical gastrointestinal side effects and histopathologic changes. It has been reported that NSAID usage is associated with isolated colitis in the periappendiceal orifice region. This study aimed to further evaluate the clinicopathologic features of 16 patients with isolated colitis limited to the cecum or periappendiceal orifice region.

Design: A retrospective review was performed on biopsy specimens from 16 patients with histologically proven colitis (focal active colitis with no chronicity) limited to the cecum or periappendiceal orifice. No significant pathologic changes in the terminal ileum or other parts of the …

Acute Pericarditis And Acute Pleuritis/Empyema Following Submandibular Infection In A Covid-19-Postive Patient: An Autopsy Revealing The Danger Space Of The Neck, Jessica Anderson, Seyedalireza Fatemi, Joseph Fullmer, Ping Zhang

Conference Presentation Abstracts

Acute pericarditis and empyema are life-threatening complications of severe odontogenic infections; reports of these findings from an autopsy perspective are rare. We report an autopsy case demonstrating infection from the mandibular molars to the pericardium and pleura in a patient following COVID-19 infection. A 53-year-old woman with history of COVID-19 (and on repeat testing at admission) presented with submandibular abscess that grew Streptococcus anginosus. Despite incision and drainage of the neck abscess and medical treatment, her condition deteriorated, with sudden death a week after admission. An autopsy with histologic analysis was performed. Externally, a surgical incision containing purulent drainage …

A Cost-Conscious Whole Slide Imaging System For Teaching And Teleconsultation In Pathology, Christopher Thorburn, Mustafa Deebajah, Keran Zhao, Zhenhong Qu

Conference Presentation Abstracts

Context: Whole slide imaging (WSI) systems can provide multiple users with concurrent access to slides without the need to be physically present at the same location. However, the cost of an all-in-one WSI system can be prohibitive for programs that do not already use WSI systems at a clinical scale. Here, we delineate a simple, inexpensive WSI system that is easy to implement and meets the need of a resident teaching environment.

Design: A digital camera (Basler acA2500, Mannheim, Germany) is mounted to a brightfield microscope with a 0.63× C-mount and connected to a computer with the manual WSI program …

Varieties Of Renal Diseases Identified In Renal Biopsies Of Patients Infected By Covid-19, Jessica Anderson, Wei Li, Hassan D. Kanaan, Ping Zhang

Conference Presentation Abstracts

Context: COVID-19 has been shown to cause renal pathology by multiple proposed mechanisms. However, studies evaluating renal biopsies for the effects of COVID-19 remain limited. We report our experience in our health system in a variety of renal pathologic diagnoses caused by COVID-19 infection.

Design: We performed detailed analysis of 5 renal biopsies related to COVID-19 infection, of 812 renal biopsies over the previous 22 months (0.6% of all cases).

Results: The first 3 patients were 2 African American men, 34 and 45 years old, and 1 48-year-old white male transplant recipient who developed acute kidney injury and nephrotic range …

Spectrum Of C3 Glomerulopathies: A Single-Center Experience, Mustafa Deebajah, Wei Li, Hassan D. Kanaan, Ping Zhang

Conference Presentation Abstracts

Context: C3GNs represent a rare type of glomerulopathy due to the activation of alternative complement pathway, including C3-dominant glomerulonephritis (C3D-GN) and dense deposit disease (DDD). The goal of this study was to demonstrate a spectrum of C3GNs.

Design: The study searched 3165 renal biopsies to identify C3GNs and their clinical indices over an 8-year period.

Conclusions: Our data indicate that C3GN cases had a consistent finding of dominant C3 staining, and low serum C3 in most, but exhibited a wide range of clinical and pathologic changes in pediatric to elderly patients. The findings support the previously reported characteristics of C3GN. …