Pathology Commons^™

C1q Is Elevated During Chronic Staphylococcus Epidermidis Central Nervous System Catheter Infection, Matthew K. Beaver, Lara Bergdolt, Anna Dunaevsky, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

INTRODUCTION: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

METHODS: We examined complement activation throughout

RESULTS: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and …

Antimicrobial Activity Of Gallium(Iii) Compounds: Pathogen-Dependent Targeting Of Multiple Iron/Heme-Dependent Biological Processes, Seoung-Ryoung Choi, Mohammed A. Hassan, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth …

Aconitate Decarboxylase 1 Mediates The Acute Airway Inflammatory Response To Environmental Exposures, Aaron Schwab, Amy J. Nelson, Angela Gleason, Oliver Schanze, Todd A. Wyatt, Dhananjay Shinde, Peng Xiao, Vinai Chittezham Thomas, Chittibabu Guda, Kristina L. Bailey, Tammy Kielian, Geoffrey M. Thiele, Jill A. Poole

Journal Articles: Pathology and Microbiology

Background: Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline)exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 inenvironmentalexposure-induced lung inflammation.

Methods: Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 …

A Rare Case Of A Giant Cell Tumor Of The Peroneal Tendon Sheath, Francois M. Lokenye Dpm, Breana Marine Dpm, Orlexia Thomas Dpm, Mariam Kamil Bs

Posters

This case report discusses a 31-year-old male with TGCT in the peroneal tendon sheath, detailing clinical and radiological features.

his study explores the surgical interventions, diagnostic challenges, treatment options, and outcomes of TGCT, emphasizing its consideration in the differential diagnoses of painful foot and ankle masses.

Bacterial Single-Cell Rna Sequencing Captures Biofilm Transcriptional Heterogeneity And Differential Responses To Immune Pressure, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display metabolic and transcriptional diversity along with recalcitrance to antibiotics and host immune defenses. Here, we present an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. BaSSSh-seq captures extensive transcriptional heterogeneity during biofilm compared to planktonic growth. We quantify and visualize transcriptional regulatory networks across heterogeneous biofilm subpopulations and identify gene sets that are associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq …

Metabolic Diversity Of Human Macrophages: Potential Influence On Staphylococcus Aureus Intracellular Survival, Blake P. Bertrand, Dhananjay Shinde, Vinai C. Thomas, Marvin Whiteley, Carolyn B. Ibberson, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of medical device-associated biofilm infections. This is influenced by the ability of S. aureus biofilm to evade the host immune response, which is partially driven by the anti-inflammatory cytokine interleukin-10 (IL-10). Here, we show that treatment of human monocyte-derived macrophages (HMDMs) with IL-10 enhanced biofilm formation, suggesting that macrophage anti-inflammatory programming likely plays an important role during the transition from planktonic to biofilm growth. To identify S. aureus genes that were important for intracellular survival in HMDMs and how this was affected by IL-10, transposon sequencing was performed. The size of the S. aureus …

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Tetracycline And Oxacillin Act Synergistically On Biofilms And Display Increased Efficacy In Vivo Against Staphylococcus Aureus, Amy K. Tooke, Rebecca E. Hodges, Josie F. Pyrah, Kenneth W. Bayles, Stephen A. Renshaw, Simon J. Foster

Journal Articles: Pathology and Microbiology

Oxacillin (bactericidal) and tetracycline (bacteriostatic) are clinically relevant antibiotics that are routinely prescribed to treat Staphylococcus aureus infections but not conventionally used in combination. There is an urgent need for treatment regimens that can act upon biofilms during infection, associated with chronic infections on indwelling devices, as well as acute planktonic (systemic) infection. Here we show that in an in vitro model oxacillin and tetracycline act synergistically against S. aureus UAMS-1 biofilms, reducing the concentration of both antibiotics necessary to eradicate an established biofilm. Using an in vivo zebrafish larval infection model with S. aureus NewHG, they display improved bacterial …

Disseminated Peritoneal Leiomyomatosis Mimicking Carcinomatosis, Matthew Lee, Gabriella Morey, Susana Ferra

East Florida Division GME Research Day 2024

No abstract provided.

Potential Prognostic Determinants For Fet::Creb Fusion-Positive Intracranial Mesenchymal Tumor, Frank M. Mezzacappa, Frankie K. Smith, Weiwei Zhang, Andrew Gard, Fatmagul Kusku Cabuk, Ignancio Gonzalez-Gomez, Hector L. Monforte, Jiancong Liang, Omkar Singh, Martha M. Quezado, Kenneth D. Aldape, Murat Gokden, Julia A. Bridge, Jie Chen

Journal Articles: Pathology and Microbiology

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and …

A Challenging Diagnosis: A Rare Variant Of Primary Lung Adenocarcinoma With Desquamative Interstitial Pneumonia-Like Morphology, Laura Luu, Maritess Dejesus, Christina Kovacs, Renu Khode

West Florida Division GME Research Day 2024

No abstract provided.

Ominous Mediastinal Mass Revealing Ectopic Thyroid, Cameron Summers, Gabriella Morey, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: This report describes an asymptomatic 63-year-old female with a right paratracheal mass compressing and displacing the trachea to the left. Additionally, the epidemiology, clinical manifestation, diagnosis, and management of mediastinal ectopic thyroids are discussed.

Case Summary: A 63 y/o female with history of hypertension, myasthenia gravis and Type 2 diabetes mellitus had a hospitalization for pneumonia and was incidentally found via chest CT scan with a right paratracheal soft tissue mass with few coarse calcifications measuring 7.5 cm displacing the trachea to the left without compromise of the lumen. She was referred to a local cardiothoracic surgeon and underwent …

A Case Of Chronic Appendiceal Intussusception Secondary To Unsuspected Endometriosis, Matthew Lee, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: Intussusception of the appendix is an exceedingly rare pathology with an incidence of 0.01%.

Case Summary: Patient is a 55 y/o female with appendiceal intussusception on CT and endoscopy. She was admitted for elective laparoscopic appendectomy, a distorted area involving the cecum and terminal ileum was identified. Procedure was converted to an open ileocolic resection due to the unclear anatomy and concern for possible malignancy. An intraoperative consultation revealed an inverted appendix.

Results: Gross examination of the specimen showed a structure protruding into the cecum lumen with an intact mucosal surface. Microscopic examination revealed a central fibromuscular core with …

Primary Squamous Cell Carcinoma (Scc) Of The Sigmoid Colon: A Rare Location & Histological Subtype Of Colorectal Carcinoma (Crc), Astrid Sacasa, Stachyse Stanis, Mohtashim Naeem

East Florida Division GME Research Day 2024

Introduction. Primary squamous cell carcinoma (SCC) of the colon is a rare histological subtype of CRC with poor prognosis. It most frequently occurs in the right colon, and least commonly in the sigmoid colon. Similar CRC symptoms no matter the subtype can range from asymptomatic to rectal bleeding, abdominal pain, change in bowel habits, and weight loss. Here, we describe a case of primary basaloid SCC of the sigmoid colon.

Case description. A 71-year-old female with no significant past medical history presented with guaiac-positive stools, underwent a colonoscopy revealing an ulcerated mass in the left colon. Histopathology and immunohistochemical results …

Spinal Pilomyxoid Astrocytoma In A 17-Month-Old Twin, Gul Emek Wymer, Chamyan Gabriel, Robert Bender, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: A pilomyxoid astrocytoma is a rare type of brain tumor that primarily affects young children, typically arising in the hypothalamic-suprasellar region of the brain. Unlike pilocytic astrocytoma, PMA is characterized by a more aggressive clinical course and distinct histopathological features, including a monomorphic cell population, angiocentric arrangement, and a myxoid background.

Case presentation: A 17 months old patient with a history of twin to twin transfusion was brought to the hospital with a complaint of motor regression, compared to his twin. The CT and MRI images revealed an intradural intramedullary spinal mass. The mass tissue biopsy was sent to …

Standardization Of Operating Room (Or) Formalin Fixation Time Reporting In Breast Cancer Cases. An Institutional Experience., Cameron Summers, Astrid Sacasa, Nicole Sant Elia, Susana Ferra

East Florida Division GME Research Day 2024

Background: The current guidelines of the American society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) regarding laboratory testing of estrogen receptor (ER), progesterone receptor (PR) and HER-2 in breast cancer have been in place since 2010. Optimal tissue handling requires a cold ischemic time of less than 1 hour and a formalin fixation time between 6 and 72 hours. In July 2023 HCA Westside hospital implemented a new Formalin Fixation Time documentation protocol. The data is presented quarterly at the Cancer Committee meeting.

Goal: To standardized the cold ischemic time and formalin fixation time reporting and measure …

Single-Cell Profiling Reveals A Conserved Role For Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Lee E. Korshoj, Joseph P. Menousek, Cortney E. Heim, Rachel W. Fallet, James Campbell, Carol Reynolds Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, Walter S. Campbell, William Thorell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The …

The Protective And Pathological Role Of The Spleen In Malaria, Julie Hwang, Md, Amy Dechet

Books, Presentations, Posters, Etc.

Case Presentation: • Background: There were 241 million cases of malaria globally. Compared to 2,000 cases in the U.S. Splenomegaly has previously been used to determine the severity of malaria. This is a rare case of hyper reactive malarial splenomegaly (HMS) due to chronic plasmodium ovale • 23 year-old female with gradually worsening left upper quadrant abdominal pain of 1 month. Pain sharp and stabbing in quality, no alleviating or aggravating factors. Associated with subjective early satiety and 10 Ibs weight loss, generalized weakness, shortness of breath • PMH: Schistosomiasis 2008,unclear if treated • Soc: Born in Congo and immigrated …

Non-Coding Rnas Involved In The Molecular Pathology Of Alzheimer’S Disease: A Systematic Review, Reynand Jay Canoy, Jenica Clarisse Sy, Christian Deo Deguit, Caitlin Bridgette Castro, Lyoneil James Dimaapi, Beatrice Gabrielle Panlaqui, Wenzel Perian, Justine Yu, John Mark Velasco, Jesus Emmanuel Sevilleja, Anna Gibson

Ateneo School of Medicine and Public Health Publications

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass …

Ossifying Fibroma And Central Giant Cell Granuloma, A Hybrid Tumor In The Maxilla, Jason Phung, Robert Bender, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: Ossifying fibromas (OF) and central giant cell granulomas (CGCG) are benign lesions of the jaw. The presence of a hybrid lesion consisting of OF and CGCG is exceedingly rare.

Case summary: A 28-year-old male presented with complaints of nasal congestion and loud snoring worsening over six months. CT scan revealed a 2.2 x 1.5 x 1.2 cm radiolucent lesion involving the right maxillary sinus. During endoscopic sinus excision, a friable light tan and hemorrhagic lesion was seen occupying the right maxillary sinus with underlying bone destruction. Intraoperative pathology evaluation revealed no malignancy.

Results: Histologic examination revealed a biphasic …

Solitary Fibrous Tumor, Not Always The Pleura, Not Always Benign, Robert Bender, Susana Ferra

East Florida Division GME Research Day 2024

Introduction: Solitary Fibrous Tumor (SFT) is rare, especially in locations outside the pleura, and it can mimic benign mesenchymal tumors. Misdiagnosis, leading to inadequate treatment, can increase the risk of metastasis and recurrence. Dedifferentiated SFT (DD-SFT), is the most aggressive subtype.

Case Summary: A 45-year-old male presented with a rapidly growing, non-painful, palpable, exophytic right thigh mass. CT revealed an 8 x 7.4 x 7.0 cm heterogenous mass abutting the underlying muscle. His care team made a presumptive diagnosis of sarcoma, and referred him to a local oncologic surgeon who performed a radical excision and submitted the tumor to Pathology. …

The First Reported Case Of Relapsing Polychondritis Presenting With Invasive Squamous Cell Carcinoma, Navpreet Uppal, Lili Janasky, Maha Abdulla, Mohamad Saad

East Florida Division GME Research Day 2024

No abstract provided.

Cystic Neutrophilic Granulomatous Mastitis With Corynebacterium And Pseudomonas Species: A Comparison, Astrid Sacasa, Mohtashim Naeem, Susana Ferra

East Florida Division GME Research Day 2024

Introduction. Cystic neutrophilic granulomatous mastitis (CNGM) is an uncommon subtype of granulomatous mastitis (GM) affecting young to middle-aged parous women. Although there is no universally accepted diagnostic criteria, CNGM has a highly distinct histological pattern characterized by suppurative lipogranulomas composed of central lipid vacuoles rimmed by neutrophils with an outer cuff of epithelioid histiocytes.

Case 1: 42-year-old recently pregnant woman with a history of left breast mastitis and abscess treated with incision and drainage (I&D) six months prior, presented with contralateral right breast mastitis with abscess without improvement on oral antibiotics. Histologic examination revealed CNGM, with Corynebacterium identified on Gram …

Extending The Gift—Utilizing Residual Human Anatomical Materials For Training Pathologists' Assistants In Surgical Pathology Techniques, Kerwin M. Kolheffer, Lauren Yoho, Matthew Myers, Ismail El Moudden

Department of Pathology & Anatomy Faculty Publications

This study investigates the effectiveness of using residual human anatomical materials, obtained from a gross anatomy course, for training Pathologists' Assistant (PathA) students in surgical pathology techniques. We utilized two surveys to assess the perceived efficacy of this approach: one survey targeted PathA students to evaluate their training experiences with both human and animal tissues, while the other assessed the impact of specimen collection on the educational experiences of gross anatomy course students.

The Role Of Dystrophic Microglia In Aging And Disease, Ryan K. Shahidehpour

Theses and Dissertations--Neuroscience

Microglia are the primary immune cells of the central nervous system and are crucial in maintaining homeostasis and defense from disease and injury in the brain. Recent genome-wide association studies (GWAS) have also highlighted microglia as a central player in Alzheimer’s disease (AD). However, the mechanisms of microglia’s influence are poorly understood. Traditionally, microglial subtypes characterized physiologically as “reactive” or “activated” have been linked with disease and injury in the brain. However, morphologically, a recently described microglia category known as “dystrophic,” characterized structurally by fragmented processes and cytoplasmic decay is believed to be more strongly associated with aging and neurodegeneration. …

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Comparison Between Acute Leukaemia Screening Tube And Lineage Specific Panels For The Diagnosis Of Acute Leukaemia At The Aga Khan University Hospital, Nairobi, Douglas Irimu Munga

Master of Medicine in Clinical Pathology

Introduction; Acute leukaemia is a heterogeneous group of haematological malignancies. It is categorized depending on the immature cells that proliferate and replace the normal tissue in the bone marrow. The broad categories are acute myeloid leukaemia if the immature cells are myeloblasts and acute lymphoid leukaemia if lymphoblasts. Other rare categories are blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute leukaemias of ambiguous lineage which include acute undifferentiated leukaemia and mixed phenotype acute leukaemias (MPALs). The classification is important as the treatment and management differ hence a timely and accurate diagnosis is paramount. Multiparameter comparison of the immunophenotype is possible …

A Rare Case Of Breast Carcinoma Metastasis Into A Meningioma In A 64-Year-Old Female Patient, Edwin Mogere, Miriam Mutebi, Allan Njau, Manel Haj Mansour

General Surgery, East Africa

This report discusses the occurrence of tumor-to-tumor metastasis—an atypical phenomenon in oncology where a secondary malignancy develops within an existing primary tumor. The case of a 64-year-old woman is presented, who, with a history of stage II invasive ductal carcinoma of the breast treated with mastectomy and chemoradiotherapy, developed neurological symptoms indicative of a secondary brain tumor. MRI and subsequent histopathological analysis post-craniotomy confirmed a meningioma with a metastatic breast carcinoma, demonstrating the clinical importance of considering tumor-to-tumor metastasis in similar patient histories.

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications. A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer., Shahin Sayed, Chowdhury Arif Jahangir, David Page, Glenn Broeckx, Claudia Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge Reis-Filho, Amy Ly, Paul Harms

Pathology, East Africa

Recent advances in thefield of immuno-oncology have brought transformative changes in the management ofcancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis andtreatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged aspotent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, therebyexpanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing thephenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinicallyrelevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential toguide appropriate treatment …

Improving Neuropathological Analysis With Aβgan: Addressing Morphology Imbalance For Efficient Alzheimer's Disease Diagnosis, Sujatha Alla, Prasanthi Chidipudi, Nagesh Bheesetty, Vedvikash Reddy Velur, Joshit Mohanty, Puneeth Bheesetty, Marisha Jmukhadze, Narendra Lakshmana Gowda, Sai Gireesh Komaragiri

Engineering Management & Systems Engineering Faculty Publications

Histopathologists are experiencing a digital revolution in their field thanks to the digitization of Whole Slide Images (WSIs), which are microscope slides of tissue that can measure gigapixels in size. With so much high resolution data at their disposal, computer vision techniques can now be used to automate laboratory processes, create visual standards, and increase analysis throughput, all of which reduce the workload of pathologists [1]. The "gold" standard in neuropathology, particularly for Alzheimer's Disease- is pathological diagnosis made by looking at White Matter Inclusions (WSIs) in brain tissue. Semi-quantitative scoring in accordance with the standards established by the Consortium …