Pathology Commons^™

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 …

Potassium Channel Subfamily T Member 1(Kcnt1) Pathological Variant Causing Epilepsy Of Infancy With Migrating Focal Seizures: A Case Report, Prem Chand, Meher Angez, Ayesha Nasir Hameed, Salman Kirmani

Department of Paediatrics and Child Health

Pathological mutation of potassium channel subfamily T member 1 (KCNT1) gene causes an autosomal dominant disorder characterised by secondarily generalised seizures/migratory focal seizure, cyanosis, and dysmorphic features. We report the case of a five-month old male with pathological KCNT1 variant who presented with focal clonic seizures, Mongol spots, and grade two systolic murmur at the left lower sternal border and loud P2. The seizures were refractory to most anti-epileptic drugs but showed some response to Valproic acid. This case demonstrated that EIMFS is a grave infantile epileptic encephalopathy which is refractory to anti epileptic drugs and can present with a …

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 …

Development, Roll-Out And Implementation Of An Antimicrobial Resistance Training Curriculum Harmonizes Delivery Of In-Service Training To Healthcare Workers In Kenya, Josiah Njeru, Joshua Odero, Sheilla Chebore, Mungai Ndung’U, Emmanuel Tanui, Evelyn Wesangula, Romona Ndanyi, Susan Githii, R Gunturu, Willy Mwangi

Pathology, East Africa

Background: Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.

Methods: An initial stakeholders’ forum was convened to …

Primary Adrenal Angiosarcoma: A Case Report And Review Of The Literature, Zunaira Naeem, Joon Yau Leong, Arianna Morton, Alaa Hrizat, Eric Shiffrin, Andrew Gomella, Peter Mccue, Mark Mann, Li Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Primary adrenal angiosarcoma is an extremely rare malignant tumor with challenging diagnosis. A 66-year-old woman had a 4.3 cm right adrenal mass suspicious for adrenal cortical carcinoma. Pathological examination demonstrated a hemorrhagic adrenal cyst with numerous irregularly shaped anastomosing vascular channels lined by atypical endothelial cells that had frequent atypical mitotic figures (12/10 HPF, Ki67 10%). The tumor cells were positive for CD31, ERG, and FLI-1, but negative for adrenal and other tumor lineage markers by immunohistochemistry. NGS fusion gene testing ruled out epithelioid hemangioendothelioma. Accurate diagnosis and differential inclusion are important for appropriate treatment of this rare tumor.

Ifit2 Restricts Murine Coronavirus Spread To The Spinal Cord White Matter And Its Associated Myelin Pathology, Madhav Sharma, Debanjana Chakravarty, Afaq Hussain, Ajay Zalavadia, Amy Burrows, Patricia Rayman, Nikhil Sharma, Lawrence C. Kenyon, Cornelia Bergmann, Ganes C. Sen, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-β-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 …

The Association Between Higher Expression Of Talin-1 And The Reduced Survival Rate In Ovarian Serous Carcinoma Patients, Mina Sharbatoghli, Leili Saeednejad Zanjani, Fahimeh Fattahi, Elham Kalantari, Zohre Habibi Shams, Mahshid Panahi, Medhi Totonchi, Mohsen Asadi-Lari, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients.

Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. …

Fibrosis-The Tale Of H3k27 Histone Methyltransferases And Demethylases, Morgan D. Basta, Svetlana Petruk, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 …

Labrad : Vol 48, Issue 1 - July 2023, Aga Khan University Hospital, Karachi

LABRAD

• Editorial
• Articles
• Toxicology In Public Health: Mitigating Risk, Fostering Well-Being
• Predictive And Prognostic Biomarkers in Histopathology
• Cancer Registry and Public Health Surveillance - Role of Pathologists
• Diagnosis of Celiac Disease DQA1*02,05; DQB1*02,03:02 (DQ2&DQ8) in patients
• Magnifying The Clinical Value of Expert Review and Reassessment
• Urine Cytology: A Screening and Surveillance Test
• An Overview of Convalescent Plasma for The Treatment of COVID-19
• Role of Imaging in Public Health Care
• Microsatellite Instability (MSI) Testing
• MRI Liver with Hepatocyte-Specific Contrast Agent
• Basics and Role of Cytopathology
• Bone Tumors: From Timely Diagnosis to Improved Patient Outcome
• Differentiating Between Dengue Fever and Malaria Using The …

Oropharyngeal Teratoma: Five-Month-Old Presenting With Failure To Thrive And Severe Obstructive Sleep Apnea., Anna Lawrence, Melissa Gener, Shao Jiang, Jill M. Arganbright

Manuscripts, Articles, Book Chapters and Other Papers

Oropharyngeal teratomas are an extremely rare congenital tumor. They are often diagnosed prenatally and can cause significant airway obstruction and feeding difficulties at birth. We present a five-month-old female that was diagnosed with a palatal teratoma that presented with failure to thrive, difficulty feeding, and eventually with severe obstructive sleep apnea. We present a five-month-old term, otherwise healthy female who became stridulous after an episode of the respiratory syncytial virus at one month old. At three months old, an otolaryngologist diagnosed mild laryngomalacia with no mass identified, and no surgical intervention was recommended. Due to continued poor weight gain, at …

Resolved Peristomal Erosive Papulonodular Dermatitis Mimicking Nevoid Hyperkeratosis Of The Nipple And Areola, Christa M. Tomc, Daniel A. Nguyen, Joseph S. Susa, Stephen E. Weis

HCA Healthcare Journal of Medicine

Introduction

Nevoid hyperkeratosis of the nipple and areola (NHKNA) is a rare cutaneous entity with a distinct clinical and histological presentation. The type II form of this condition can result from various dermatoses, such as irritant contact dermatitis. Erosive papulonodular dermatitis is a chronic irritant dermatitis that often occurs in areas of occlusion and maceration, such as peristomal skin. Pseudoverrucous papules and nodules are a variant of erosive papulonodular dermatitis and have a non-specific histologic pattern of reactive hyperplasia.

Case Presentation

We present a case of a patient with resolved peristomal erosive papulonodular dermatitis who presented status-post ileostomy reversal with …

Immune Cells Localize To Sites Of Corneal Erosions In C57bl/6 Mice., Phuong M. Le, Sonali Pal-Ghosh, A. Menko, Mary Ann Stepp

Computational Medicine Center Faculty Papers

Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the …

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett

School of Medicine Faculty Publications

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells …

June 2023: 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

Radiologic And Histologic Findings Of Locally Advanced Mucoepidermoid Carcinoma Managed With Total Surgical Excision, Christopher R. Huber, Don Truong, Joseph Hatem, Joel Thompson, Bryan Scott

Advances in Clinical Medical Research and Healthcare Delivery

The present case report provides images from computed tomography and histology of a patient with a salivary gland neoplasm consistent with mucoepidermoid carcinoma.

57 Yo Man With High Grade Astrocytoma With Piloid Features And 2 Other Cns Lesions, Joseph Fullmer

Conference Presentation Abstracts

Patient is a 57 yo man who presented with periodic headaches and lower back pain, initially attributed to lifting heavy weights but symptoms persisted. Eventual imaging was performed and revealed a 4 cm heterogeneously enhancing left cerebellar mass, 1 cm enhancing lateral right frontal subcortical lesion, and enhancing T12-L1 spinal cord lesion and multiple smaller spinal cord lesions suggestive of drop metastasis. The cerebellar lesion was first resected and final results, including methylome profiling, were consistent with high grade astrocytoma with piloid features (HGAP). The T12-L1 spinal lesion was later resected and had somewhat distinct histology although intraoperatively surgeon felt …

Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of patients worldwide. Many therapeutics are available for treating PD symptoms but there is no disease-modifying therapeutic that has been unequivocally shown to slow or stop the progression of the disease. There are several factors contributing to the failure of many putative disease-modifying agents in clinical trials and these include the choice of patients and clinical trial designs for disease modification trials. Perhaps more important, however, is the choice of therapeutic, which for the most part, has not taken into account the multiple and complex pathogenic mechanisms and processes involved …

Rare Autoimmune Disease Caused By Not-So Rare Virus, Tiffany Marchewka, Acho Bernard, Molly Kempa, Kathryn Heal, Joseph M. Fullmer

Conference Presentation Abstracts

No abstract provided.

A Cadaveric Case Study On Lung Cancer Pathology, Anna Beth Boyette, Sarah Kate Boyette, Haley Garrett, Janai Groves, Perry Chandler Mullis, Sofia Sirocchi, Shiv Dhiman, Savita Arya

Research Day

INTRODUCTION: Lung cancer is the most commonly diagnosed cancer amongst both genders, currently accounting for about 18% of all cancer deaths.

OBJECTIVES: The overall purpose of this study was to evaluate the pathology associated with the patient’s cause of death, cardiorespiratory failure and lung cancer. The secondary aims of this study were to confirm the presence of malignant neoplasms within a human cadaver, determine the type of cancer present, and take specimens for histological examination to evaluate the patient’s cause of death.

METHODS: This is a case report from one of the cadavers in the Gross Anatomy laboratory at the …

Oral Manifestations Of Acute Lymphocytic Leukemia, Angela Yepes Dds, Ms, Mba, Juan Yepes Dds, Md, Mph, Ms, Drph, James E. Jones Dmd, Msd, Edd, Phd

The Journal of the Michigan Dental Association

Leukemia is the most prevalent malignancy of leukocytes and can occur in children and adults. Oral manifestations are part of the complexity of signs and symptoms in patients with leukemia and, in some patients, oral manifestations precede systemic manifestations. Oral signs of leukemia include spontaneous bleeding, gingival enlargement, and whiteness of the oral mucosa. Head and neck lymphadenopathy is common in patients with leukemia. Oral manifestations are the result of the direct invasion of immature cells in the oral cavity tissues or indirectly caused by the replacement of the normal blood cells for immature cells causing anemia, leucopenia, and thrombocytopenia. …

Immunophenotypic Expression Profile Of Multiple Myeloma Cases At A Tertiary Hospital In Nairobi Kenya, Isabella Mengich, Sheerien Rajput, Riyat Malkit, Zahir Moloo, Elizabeth Kagotho, El-Nasir Lalani, Anne Mwirigi

Pathology, East Africa

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously.

Methods: A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM …

Neonatal Reference Intervals For Thyroid Stimulating Hormone And Free Thyroxine Assayed On A Siemens Atellica® Im Analyzer: A Cross Sectional Study, Geoffrey Omuse, David Kawalya, Patrick Mugaine, Assumpta Chege, Daniel Maina

Pathology, East Africa

Background Deriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya. …

Effects Of Comorbidities And Choice Of Treatment On Overall Survival: A Beaumont Experience, Bilal M. Ali, Emma Herrman, James Huang Huang, Mohammad Muhsin Chisti

Posters

First line therapy for Acute Myeloid Leukemia (AML) is 7+3 regimen. It often cannot be used in elderly patients due to intensity. Venetoclax + hypomethylating agent (HMA) is approved for AML treatment in these patients. We investigate the efficacy of this treatment in a community setting where patients do not have the same resources available to them as a large academic center. Primary outcome was survival of patients greater than 60 years of age with a diagnosis of AML who received 7+3 therapy versus those who received venetoclax + HMA. Secondary outcomes included characteristics of those who received the two …

Monitoring Concordance In The Management Of Transfusing Blood Components In Cirrhotic Patients For Paracentesis With Evidence-Based Guidelines, Joseph Kim, Gregory Moses

North Texas Research Forum 2023

Initiative to decrease unnecessary hemostatic agent transfusion in cirrhotic patients undergoing paracentesis: a resident-led approach quality improvement project to prevent transfusion overuse. Currently, there is no official guideline placed in the hospital for the administration of a hemostatic agent such as fresh frozen plasma in the setting of an elevated international normalized ratio, which paradoxically is an anticipated finding in cirrhotic patients. This process leads to unnecessarily prolonging the duration of the hospital course due to delays in performing the interventional procedures and interruptions in scheduling. The goal of this project is to educate and provide physicians with the most …

An Exceedingly Rare Case Of Bilateral Synchronous Germ Cell Testicular Tumors Of Different Histological Types, Joseph Kim, Ray Page, Gregory Moses, Rod Carlo Columbres

North Texas Research Forum 2023

It is exceedingly rare to find a case of bilateral synchronous germ cell testicular tumors of different histological types, and there have been only a handful of cases because of a lack of connections through lymphatic or vascular pathways between the testes. Here we present a unique case of a 43-year-old man who initially presented to the primary care physician for increasing right testicular swelling. He had a testicular sonogram that showed a large right testicular mass as well as a 1.7 cm left testicular mass suspicious of malignancy. Pre-surgical laboratories showed PSA 0.97, alpha-fetoprotein 1875, quantitative hCG 2508, and …

Lesion Size Inclusion On Dermatopathology Requisition Forms: A Quality Improvement Project, Christopher M. Wong, Henry Lim, Christian Scheufele, Daniel A. Nguyen, Ashleigh E. Hermann, Michael Carletti, Stephen Weis

North Texas Research Forum 2023

Introduction: Dermatopathology requisition forms (RFs) are a critical communication tool between dermatologists and dermatopathologists. Including detailed information on RFs improves the diagnostic accuracy of the consulting dermatopathologist. However, the diameter of the biopsied lesion is often omitted on RFs. This study aimed to increase the rate of reporting lesion diameters on RFs from an academic outpatient dermatology clinic to greater than 65% through education, reinforcement, and evaluation. Methods: This quality improvement project retrospectively and prospectively analyzed the inclusion rate of lesion diameters on dermatopathology RFs from a single institution. In Phase 1, data was collected from all skin biopsies performed …

Head And Neck Tumor Histopathological Image Representation With Pre- Trained Convolutional Neural Network And Vision Transformer, Ranny Rahaningrum Herdiantoputri, Daisuke Komura, Tohru Ikeda, Shumpei Ishikawa

Journal of Dentistry Indonesia

Image representation via machine learning is an approach to quantitatively represent histopathological images of head and neck tumors for future applications of artificial intelligence-assisted pathological diagnosis systems. Objective: This study compares image representations produced by a pre-trained convolutional neural network (VGG16) to those produced by a vision transformer (ViT-L/14) in terms of the classification performance of head and neck tumors. Methods: W hole-slide images of five oral t umor categories (n = 319 cases) were analyzed. Image patches were created from manually annotated regions at 4096, 2048, and 1024 pixels and rescaled to 256 pixels. Image representations were …

Educational Case: Ovarian Neoplasms: A Series Of Educational Cases To Review Malignancies Of Epithelial, Stromal, And Germ Cell Origin, Jordyn B. Tumas, Joanna Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M. Holloman, Mary P. Berg, Bronwyn Bryant, Lisa Ross Dixson, Melissa R. George, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B. Mccloskey

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Medical student interest and pursuit of a career in pathology have been steadily declining since 2015. We conducted three separate surveys of medical students to better understand these trends. In our first survey, we focused on assessing U.S. allopathic medical students understanding and perceptions of pathology. We later surveyed U.S. osteopathic medical students as a companion to the allopathic medical student survey, in which many similarities were discovered with some key differences. In our final survey, we specifically looked at curriculum differences between the U.S. allopathic medical schools that graduate the most students who enter pathology training programs (Group 1) …

How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students’ Selecting Pathology As A Specialty?, Cindy B. Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R. George, Ashley M. Holloman, Bronwyn Bryant, Mary P. Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, Robert D. Hoffman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences …