Pathology Commons^™

Not All That Hurts Is Malignant: A Painful Case Of Focal Nodular Hyperplasia, Zamanali Khakhar, Abdullahi Abdigafar Yunis, Dayib Buthul, Khadija Warfa, Soraiya Manji, Rajiv Patel, Sayed Ali Raza Bukhari

Imaging & Diagnostic Radiology, East Africa

Focal nodular hyperplasia (FNH) is a benign hepatic lesion most often detected incidentally during imaging studies. While typically asymptomatic, a small subset of patients may present with abdominal pain or discomfort. Clinically and radiologically, FNH can mimic malignant liver tumors, occasionally resulting in unnecessary invasive procedures. This case report describes a 45-year-old woman with symptomatic FNH who was placed on routine imaging surveillance and managed conservatively. This case underscores the importance of accurately distinguishing this benign condition from hepatic malignancies. It further highlights the diagnostic challenges associated with achieving a definitive diagnosis.

Challenges And Opportunities With Providing Genetic Testing And Counseling For Mucopolysaccharidosis Type Ii In Kenya, Lucy Mungai, Charles Njeru, Allan Njoroge, Michuki Maina, Syokau Ilovi, Dalton Wamalwa, Ruth Nduati, Beatrice Odongkara, Danny Miller

Pathology, East Africa

Background Limited or absent genetic counseling and testing resources in low- and medium-income countries lead to missed or late diagnoses for treatable metabolic conditions with irreversible complications. In some communities, misunderstanding about the etiology of a genetic condition may lead women whose children are affected to be viewed as a bad omen and become stigmatized or ostracized from their community. Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal storage disorder in which deficiency or inactivity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans throughout the body. The diagnosis can be made through clinical assessment, enzyme activity …

Single-Cell-Driven Design Of Logic-Gated Car Circuits For Enhanced Solid Tumor Immunotherapy, Sanna Madan, Tian-Gen Chang, Alexandra Harris, Huaitian Liu, Andrew Martinez, Saugato Dhruba, Binbin Wang, Padma Rajagopal, Sanju Sinha, Shahin Sayed

Pathology, East Africa

Background Chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer immunotherapy for hematological malignancies but faces critical barriers in solid tumors due to tumor antigen heterogeneity and on-target, off-tumor toxicities. Logic-gated multi-antigen targeting using Boolean operators (AND, OR, NOT) represents an emerging precision immunotherapy engineering approach to overcome these challenges.

Methods We developed LogiCAR designer, a genetic algorithm-based computational framework that systematically identifies optimal logic-gated antigen combinations (i.e., ‘circuits’) from single-cell transcriptomics data. The algorithm identifies CAR circuits consisting of 1-5 antigens from 2,758 cell surface proteins, optimizing tumor-targeting efficacy while maintaining stringent safety requirements in normal tissues. …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Shahin Sayed

Pathology, East Africa

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: ‘Tumours of the nail unit’ and ‘Metastases to skin’, along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective Of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience, Gabriela Llaurador, Matthew Willis, Michele S Redell, M Monica Gramatges, Andrea N Marcogliese, Swati Naik, Robert Krance, Erin Doherty, Alexandra M Stevens

Faculty, Staff and Students Publications

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1).

Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort.

Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children's Hospital from 2000 to 2022 was conducted.

Results: Twenty-nine …

Prevalence And Clinical Impact Of Pseudohypercalcemia In Paraproteinemia: A Case And Cohort Study, Usman Sunusi, Li Chen, Nianyi Li, Jason K Y Lee, Irmeen Siddiqui, Erin Goodhue, Rongrong Huang, Jieli Li

Faculty, Staff and Students Publications

Background: Hypercalcemia is a common and serious complication of malignancy, often contributing to morbidity and mortality. In patients with paraproteinemia, elevated total calcium with normal ionized calcium, termed pseudohypercalcemia, can complicate diagnosis and lead to inappropriate treatment. While this phenomenon has been described in case reports, its prevalence and clinical impact in routine practice remain poorly defined.

Methods: We report a case of pseudohypercalcemia in a patient with IgG κ multiple myeloma and conducted a retrospective review of de-identified data to assess the prevalence and biochemical associations of pseudohypercalcemia in paraproteinemia. Available data included serum protein electrophoresis (SPEP), …

The Roles Of Sirt1 In Breast And Gynecologic Malignancies, Jianmin Ding, Matthew T Ye, Songlin Zhang

Faculty, Staff and Students Publications

Sirtuin 1 (SIRT1), an NAD+-dependent histone deacetylase, exerts complex and context-dependent effects in breast and gynecological cancers. By deacetylating histone and non-histone proteins such as p53, FOXO, and NF-κB, SIRT1 regulates essential processes including DNA repair, apoptosis, metabolism, and stress response. In breast cancer, SIRT1 may act as a tumor suppressor in early stages by maintaining genomic stability but promotes epithelial–mesenchymal transition, metastasis, and chemoresistance in aggressive subtypes such as triple-negative breast cancer. Similarly, in gynecological cancers, SIRT1 displays dual roles: promoting proliferation via estrogen signaling and p53/FOXO1 inhibition in Type I endometrial cancer yet potentially supporting DNA repair in …

Perceived Gaps In Preparation For Pathology Residency And Opportunities For Improvement, Barbara Knollmann-Ritschel, Julie Karp, Stephanie Barak, John Childs, Kristen Johnson, Amanda Lofgreen, Mary Berg, Satyapal Chahar, Hailey Gosnell, Cindy Mccloskey, Balaram Puligandla, Kristie White, Bronwyn Bryant

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The transition from medical school to residency is both a transformative and a challenging process. International literature suggests that there are known or perceived gaps in preparation for residency training in many areas of medicine. However, in the current published literature, there is no discussion of perceived gaps existing in pathology residency preparation. This study surveyed both pathology residency program directors and first-year pathology residents about the knowledge of pathology and basic medical skills residents received in medical school, perceptions about readiness for pathology residency, and perceived gaps in preparation for pathology residency that could be addressed. This survey found …

Role Of M6a Mrna Methylation In Plant Defense, Rakesh Srivastava, Niraj Lodhi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

N6-methyladenosine (m⁶A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m⁶A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m⁶A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m⁶A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host–pathogen arms race. …

Mechanistic Study Of Pexidartinib-Induced Toxicity In Human Hepatic Cells, Si Chen, Yuxi Li, Xilin Li, Nan Mei, Xiaobo He, Matthew S Bryant, Xuan Qin, Feng Li, Lei Guo

Faculty, Staff and Students Publications

Pexidartinib, a tyrosine kinase inhibitor, was approved by the U.S. Food and Drug Administration in 2019 for treating adult patients with symptomatic tenosynovial giant cell tumors. Because of its hepatotoxicity risks, pexidartinib received a boxed warning; however, mechanistic studies on this hepatotoxicity remain limited. In this study, we demonstrate that pexidartinib decreases cell viability in primary human hepatocytes and hepatic HepG2 cells. A 24-h treatment with pexidartinib led to apoptosis in HepG2 cells, as evidenced by increased caspase 3/7 activity and the induction of cleaved PARP and γ-H2A.X. Pexidartinib-induced endoplasmic reticulum (ER) stress was observed at early time points of …

Dual Membrane Receptor Degradation Via Folate Receptor Targeting Chimera, Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei

School of Medicine Faculty Publications

Cancer drug resistance poses a significant challenge in oncology, often driven by intricate cross-talk among membrane-bound receptors that compromise mono-targeted therapies. We develop a dual membrane receptor degradation strategy leveraging Folate Receptor α (FRα) to address this issue. Folate Receptor α Targeting Chimeras-dual (FolTAC-dual) are engineered degraders designed to selectively and simultaneously degrade distinct receptor pairs: (1) EGFR/HER2 and (2) PD-L1/VISTA. Through modular optimization of modality configurations and geometries, we identify the “string” format as the most effective construct. Mechanistic studies demonstrate an ~85% increase in EGFR-binding affinity compared to the conventional knob-into-hole design, likely contributing to the improved efficiency …

Decorin Evokes A Pro-Lysosomal Pathway In Lymphatic Endothelial Cells, Gabriel J. Pascal, Dipon K. Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal …

Nonexposed Endoscopic Full Thickness Resection Of Residual Disease After Definitive Chemoradiation For Locally Advanced Gastric Cancer, Brennan W Gioe, Bryan C Luu, Michael M Ittmann, George Chen, Yvonne H Sada, Wasseem Skef

Faculty, Staff and Students Publications

Salvage endoscopic resection of residual esophageal neoplasia for patients that prefer to avoid surgery or are poor surgical candidates has been reported. We report a case of gastric signet ring cell carcinoma with residual disease after definitive chemoradiotherapy, that was treated with nonexposed endoscopic full thickness resection. This endoscopic resection achieved negative margins, with postresection surveillance endoscopy and imaging showing no evidence of disease. This case highlights the potential use of salvage endoscopic resection as a therapy for residual gastric cancer after chemoradiation in patients where surgery is not an option.

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Protein Kinase Rock1 Activates Mitochondrial Fission Linking To Oxidative Stress And Muscle Atrophy, Meijun Si, Jihong Chen, Rizhen Yu, Hongchun Lin, Feng Li, Sungyun Jung, Sandhya S Thomas, Farhard R Danesh, Yanlin Wang, Hui Peng, Zhaoyong Hu

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is associated with protein-energy wasting, characterized by a reduction in muscle mass and strength. Although mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of muscle wasting, underlying mechanisms remain unclear.

Methods: Here, we used transcriptomic analysis, metabolomics analyses, and mouse gene manipulation to investigate the effects of mitochondrial plasticity and oxidative stress on muscle wasting the subtotal nephrectomy mouse models of CKD. The mice with CKD were age- and sex-matched to sham-operated controls.

Results: Through these approaches, Rho-associated kinase ROCK1 emerged as a key molecule responsible for the observed mitochondrial fission and oxidative …

Fructose And Glucose From Sugary Drinks Enhance Colorectal Cancer Metastasis Via Sord, Tianshi Feng, Qin Luo, Yanlin Liu, Zeyu Jin, David Skwarchuk, Rumi Lee, Miso Nam, John M Asara, Daya R Adye, Philip L Lorenzi, Lin Tan, Guangsheng Pei, Zhongming Zhao, Neda Zarrin-Khameh, Adriana Paulucci-Holthauzen, Brian W Simons, Ju-Seog Lee, Scott Kopetz, Jihye Yun

Faculty, Staff and Students Publications

The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC). However, the effects of SSB consumption on advanced stages of disease progression, including metastasis, remain poorly understood. Here we show that exposure of CRC cells to a glucose and fructose formulation-reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs-enhances cellular motility and metastatic potential compared to glucose alone. Given that CRC cells grow poorly in fructose alone, and cells in vivo are not physiologically exposed to fructose without …

Changes In Antiviral Prescribing For Children With Influenza In Us Emergency Departments., Tess Stopczynski, Olla Hamdan, Justin Z. Amarin, James W. Antoon, Laura S. Stewart, Haya Hayek, James Chappell, Andrew J. Spieker, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, John V. Williams, Marian G. Michaels, Julie A. Boom, Leila C. Sahni, Mary Allen Staat, Elizabeth P. Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Ayzsa Tannis, Heidi L. Moline, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low.

OBJECTIVE: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control …

Fifth Edition Who Classification: Mature B-Cell Neoplasms, Kikkeri Naresh, Kennosuke Karube, Anita Borges, Wah Cheuk, Sumeet Gujral, Shahin Sayed, Aliyah Sohani, Stefano Lazzi, German Ott, Ming-Qing Du

Pathology, East Africa

We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into ‘essential’ and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma …

Decorin Evokes A Pro-Lysosomal Pathway In Lymphatic Endothelial Cells, Gabriel J. Pascal, Dipon K. Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones, is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …