Pathology Commons^™

Serum Tests For Donor-Derived Cell-Free Dna Are Well Correlated With Renal Transplant Rejection In Renal Biopsies: Our Preliminary Experience Of New Surveillance For Monitoring Rejection, Reenal Patel, Brandon Metcalf, Dilip Samarapungavan, Hassan D. Kanaan, Wei Li, Sarah T. Suliman, Atul Singh, Ping L. Zhang

Conference Presentation Abstracts

Context: Noninvasive serum test for donor-derived cell-free DNA (dd-cfDNA) has been found useful for monitoring acute cellular rejection (ACR) and antibody-mediated rejection (AMR) since 2018, and the accepted threshold to indicate rejection is 1%. The goal of this pilot study was to determine if this test can correlate with renal biopsy results during a 1-year period when the dd-cfDNA test was initiated in our medical center.

Design: Renal transplant biopsies were evaluated for various rejection and nonrejection etiologies. Their corresponding dd-cfDNA percentages were identified. The biopsy data and dd-cfDNA results were correlated.

Results: During a year, we noticed a trend …

Unexpected Drug-Induced Liver Injury Associated With Menofit: A Synbiotic Menopause Supplement, Apaar Dadlani, Azubuogu Anudu, E Celia Marginean

Faculty, Staff and Students Publications

MenoFit is a widely available over-the-counter synbiotic supplement, which is marketed for use in relieving menopausal symptoms. So far, there is no published data on liver injury because of its use. We present the first reported case of MenoFit-induced liver injury in a patient who presented with 1 week of jaundice and abnormal liver biochemical tests in the absence of other risk factors and negative comprehensive workup for known etiologies of liver disease.

Renal Cell Carcinoma With Fibromyomatous Stroma Has A Distinctive Staining Pattern With Gata3 And Cd133 From Clear Cell Rcc And Clear Cell Papillary Rcc (Ccp-Rcc), Brandon Metcalf, Jining Feng, Leilei Chen, Vaishali Pansare, Ping L. Zhang

Conference Presentation Abstracts

Context: Renal cell carcinoma with fibromyomatous stroma (RCC-FMS) is a provisional entity of renal cell neoplasm that can be difficult to distinguish from low-grade clear cell RCC and clear cell papillary renal cell carcinoma (CCP-RCC) owing to its fibromyomatous stroma, low-grade nuclei, and clear cell cytoplasm.

Design: In this pilot study, we evaluated the utility of GATA3 and CD133 (a stem cell marker) as immunostain markers for the standard panel of cytokeratin 7 (CK7), CD10, and CAIX in distinguishing RCC-FMS from clear cell RCC and CCP-RCC. We stained 6 RCC-FMSs, 5 clear cell RCCs, and 5 CCP-RCC samples for all …

Igm-Dominant Immune Complex-Mediated Glomerulonephritis Should Be Classified As Membranoproliferative Glomerulonephritis, Igm Subtype, Sarang Khan, Brandon Metcalf, Wei Li, Hassan Kanaan, Ping L. Zhang

Conference Presentation Abstracts

Context: Immunoglobulin M (IgM) glomerulopathy usually presents as drug-resistant nephrotic syndrome and is characterized by diffuse effacement of foot processes and scattered mesangial IgM deposits, which is considered within the spectrum of minimal change disease and primary focal segmental glomerulosclerosis. However, IgM-dominant immune complex–mediated glomerulonephritis (IgM-ICMGN) is a rare renal entity and usually characterized by a membranoproliferative pattern with light microscopy; dominant IgM staining by immunofluorescent staining; and subendothelial, mesangial, and occasional subepithelial deposits by electron microscopy.

Design: We report our experience of 5 IgM-ICMGN cases with their pathologic phenotypes and clinical scenarios.

Results: Patient ages ranged from 47 to …

Monoclonal Immunoglobulin-Associated Glomerulopathy: Single Health Center Experience With 16 Cases, Brandon Metcalf, Yazan A. Al-Othman, James Huang, Wei Li, Hassan D. Kanaan, Ping L. Zhang

Conference Presentation Abstracts

Context: In addition to monoclonal cryoglobulinemic glomerulopathy, nonorganized monoclonal immunoglobulin (Ig) can deposit in glomeruli, causing either proliferative glomerulonephritis or membranous glomerulopathy. We present our experience related to this phenomenon.

Design: Sixteen cases of monoclonal immunoglobulin-associated glomerulopathy (MIAGN) from 14 patients were identified during the past 13 years and their pathologic and clinical features were collected and presented.

Results: One case of membranous glomerulopathy with monoclonal immunoglobulin deposits (MGNMID) (also called membranous glomerulopathy with light-chain–restricted deposits) was found. The patient was a 71-year-old woman with serum creatinine at 0.7 mg/dL and nephrotic syndrome (urine protein to creatinine ratio at 5.41), …

Malignant Tumors Arising From Adult Polycystic Kidney Disease, Yazan Al-Othman, Mai Elzieny, Christopher Thorburn, John D. Schwartz, Susan I. Daraiseh, Hassan D. Kanaan, Zhenhong H. Qu, Ping L. Zhang

Conference Presentation Abstracts

Context: The prevalence of renal tumors arising from adult polycystic kidney disease (APKD) has been rarely reported in the pathology literature. We report our findings of various renal tumors in APKD nephrectomy specimens.

Design: We searched our database for APKD during the past 11 years and identified various primary malignant tumors within the kidneys of APKD.

Results: Forty-eight nephrectomies with APKD were evaluated. Ten malignant tumors were identified in the APKD kidneys, indicating a prevalence of 20.8% (10/48; Table). These included 4 clear cell (CC) renal cell carcinomas (RCCs) ranging from 1 mm to 6.7 cm, 3 papillary RCCs …

Combined Smad4 And Imp3 Immunohistochemical Stains To Increase The Probability Of Diagnosing Pancreatic Adenocarcinomas In Fine-Needle Biopsies, Reenal Patel, Ashbita Pokharel, Ping L. Zhang, Zhenhong H. Qu

Conference Presentation Abstracts

Context: SMAD4 and IMP3 are useful stains in diagnosing pancreatic cancer but not perfect to reach that goal individually. We attempted to determine if using both SMAD4 and IMP3 can increase the diagnostic specificity of fine-needle biopsies (FNBs) for pancreatic adenocarcinomas, as FNBs often showed limited tissue for the morphologic evaluation.

Design: Fifteen FNBs with or without prior cytology were evaluated with both SMAD4 and IMP3 stains. Nuclear loss of SMAD4 was graded as 0 (no loss), 1–2+ (partial loss), and 3+ (total loss), whereas IMP3 was graded 0–3+ by staining intensity. Staining results were correlated with morphologic changes for …

Doac Therapy Associated With Macroscopic Hematuria: Investigation Of The Underlying Urologic Etiologies, Catherine Xie, Mary Wyrzykowski, Subhash Edupuganti, Ming Xie

Conference Presentation Abstracts

Context: Direct oral anticoagulants (DOACs) have gained wide use in prevention and treatment of thromboembolic diseases. Both major and nonmajor bleeding events have been reported. Hematuria is a common bleeding complication in patients receiving DOACs.

Design: This study retrospectively investigates the underlying urologic etiologies responsible for DOAC therapy–related macroscopic hematuria. During a 1-year period, hospitalized patients with prolonged PTT and DOAC therapy–related hemorrhage were identified. Medical chart review focused on urology consult and related laboratory and imaging findings.

Results: Among 93 patients with DOAC therapy–related hemorrhage, 15 had macroscopic hematuria (16%), including 11 men and 4 women with a median …

Using An Artificial Intelligence (Ai) Tool (Chatgpt) To Identify The Main Indications And Side Effects Of Drugs In Patient Medical Records, Mai Elzieny, Zhenhong Qu

Conference Presentation Abstracts

Context: Drug history is important clinical information for the correct histologic diagnosis of a wide variety of nonneoplastic diseases, such as hepatitis, gastritis, and colitis. As pathologists, however, keeping a strong knowledge of all drugs (and variations of drug names) can be challenging. Using online databases to find relevant drug information one at a time is very time-consuming.

Design: Sixty-seven drugs were collected from the medical records of 5 randomly selected patients. ChatGPT (https://chat.openai.com/chat) was instructed to identify (1) the main clinical indications, and (2) the major side effects of each drug, using the prompt “List the major indications and …

Evaluation Of A Novel Lupus Anticoagulant Assay Designed To Reduce False Positive Results Due To Anticoagulation: A Retrospective Study At A Single Health System, Jessica D. Anderson, Tamara Sabih, Yuying Xing, Lili Zhao, Marc D. Smith

Conference Presentation Abstracts

Introduction: Lupus anticoagulants (LA) are antibodies directed against phospholipids/phospholipid-protein complexes involved in coagulation and are associated with thrombotic events and recurrent fetal loss. There is no gold standard test for LA, therefore at least two LA-specific tests are recommended before excluding LA. Potential testing methods involve dilute Russell viper venom time (dRVVT) and hexagonal phase phospholipid assays (HPPA); however, many of these tests are susceptible to interference with anticoagulant therapy which can lead to false positive results. In this study, we compared the performance of our current HPPA, StaClot LA (SCLA), with a novel assay reported to have relatively minimal …

Stratification Of Pediatric Covid-19 Cases Using Inflammatory Biomarker Profiling And Machine Learning., Devika Subramanian, Aadith Vittala, Xinpu Chen, Christopher Julien, Sebastian Acosta, Craig Rusin, Carl Allen, Nicholas Rider, Zbigniew Starosolski, Ananth Annapragada, Sridevi Devaraj

Faculty, Staff and Students Publications

While pediatric COVID-19 is rarely severe, a small fraction of children infected with SARS-CoV-2 go on to develop multisystem inflammatory syndrome (MIS-C), with substantial morbidity. An objective method with high specificity and high sensitivity to identify current or imminent MIS-C in children infected with SARS-CoV-2 is highly desirable. The aim was to learn about an interpretable novel cytokine/chemokine assay panel providing such an objective classification. This retrospective study was conducted on four groups of pediatric patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of …

A Defective Mechanosensing Pathway Affects Fibroblast-To-Myofibroblast Transition In The Old Male Mouse Heart, Aude Angelini, Joann Trial, Alexander B Saltzman, Anna Malovannaya, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The cardiac fibroblast interacts with an extracellular matrix (ECM), enabling myofibroblast maturation via a process called mechanosensing. Although in the aging male heart, ECM is stiffer than in the young mouse, myofibroblast development is impaired, as demonstrated in 2-D and 3-D experiments. In old male cardiac fibroblasts, we found a decrease in actin polymerization, α-smooth muscle actin (α-SMA), and Kindlin-2 expressions, the latter an effector of the mechanosensing. When Kindlin-2 levels were manipulated via siRNA interference, young fibroblasts developed an old-like fibroblast phenotype, whereas Kindlin-2 overexpression in old fibroblasts reversed the defective phenotype. Finally, inhibition of overactivated extracellular regulated kinases …

The Rise Of Degrader Drugs, Mingxing Teng, Nathanael S Gray

Faculty, Staff and Students Publications

The cancer genomics revolution has served up a plethora of promising and challenging targets for the drug discovery community. The field of targeted protein degradation (TPD) uses small molecules to reprogram the protein homeostasis system to destroy desired target proteins. In the last decade, remarkable progress has enabled the rational development of degraders for a large number of target proteins, with over 20 molecules targeting more than 12 proteins entering clinical development. While TPD has been fully credentialed by the prior development of immunomodulatory drug (IMiD) class for the treatment of multiple myeloma, the field is poised for a "Gleevec …

The Combination Of Platelet Rich Plasma And Corticosteroids In Musculoskeletal And Musculotendinous Pathologies, Mikayla Stoudt

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

- 126 million Americans reported to have a musculoskeletal or musculotendinous pathology in 2012¹

- Combined direct and indirect cost of these injuries in 2015 was $874 billion¹

- Corticosteroid injections have been the mainstay of invasive management after conservative methods fail
Long-term effects of corticosteroids

• Intra-articular injections for knee osteoarthritis resulted in cartilage volume loss¹⁰
• Harm to flexor tendons, neurovascular structures, and compromised integrity^{7, 11}

- Platelet Rich Plasma

• Sample patient blood --> Centrifuge --> Separate plasma and platelets from other blood products --> Reconcentrate the platelets into the plasma
• Platelets release growth factor …

Persistent Foci Of Infection: A Case Of Two Mycotic Aneurysms Separated In Time In A Patient With Infective E. Faecalis Endocarditis, Julia C. Stone, Joel Thompson, Joseph Hatem, Evan Basha

Advances in Clinical Medical Research and Healthcare Delivery

This is a case report of a patient who presented with mycotic aneurysms of two different blood vessels at separate hospital visits following a diagnosis of infective endocarditis.

Identification Of Immune Biomarkers In Thyroid Cancer, Anupam Kotwal

Theses & Dissertations

Thyroid cancer is the most common endocrine malignancy, estimated to be the second most common cancer in women by 2030. The frequency of differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, is higher in patients with autoimmune thyroid disease but the influence of the immune milieu on thyroid carcinogenesis remains unclear. To address this gap in knowledge, we performed clinical and translational experiments to identify immune biomarkers for the occurrence and prognosis of DTC. Multiparameter flow cytometry of peripheral blood from 32 adults found advanced thyroid cancer either at presentation or during the disease-course to be associated …

Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron

School of Medicine Faculty Publications

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the “first wave” of the pandemic with alpha …

Pitfalls In Machine Learning-Based Assessment Of Tumor-Infiltrating Lymphocytes In Breast Cancer: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Jeppe Thagaard, Glenn Broeckx, Chowdhury Arif Jahangir, Sara Verbandt, Rajarsi Gupta, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Shahin Sayed

Pathology, East Africa

Abstract: The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL …

Spatial Analyses Of Immune Cell Infiltration In Cancer: Current Methods And Future Directions: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, David Page, Chowdhury Jahangir, Sara Verbandt, Rajarsi Gupta, Jeppe Thagaard, Reena Khiroya, Zuzana Kos, Khalid Abduljabbar, Sunil Badve, Shahin Sayed

Pathology, East Africa

Abstract: Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described …

Prame And Lef1 In Combined Deep Penetrating Nevus And Combined Blue Nevus: Utility And Pitfall, Kaitlin Vanderbeck, Aimi T Rothrock, Woo Cheal Cho, Priyadharsini Nagarajan, Phyu P Aung, Courtney Hudgens, Roland L Bassett, Doina Ivan, Victor G Prieto, Jonathan L Curry, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME …