Pathology Commons^™

Association Of Body Composition With Odds Of Breast Cancer By Molecular Subtype: Analysis Of The Mechanisms For Established And Novel Risk Factors For Breast Cancer In Nigerian Women (Mend) Study, Tomi Akinyemiju, Kelley Jones, Anjali Gupta, Taofik Oyekunle, Veeral Saraiya, April Deveaux, Omolola Salako, Allison Hall, Olusegun Alatise, Gabriel Ogun, Adewale Adeniyi, Omobolaji Ayandipo, Thomas Olajide, Olalekan Olasehinde, Olukayode Arowolo, Adewale Adisa, Oludolapo Afuwape, Aralola Olusanya, Aderemi Adegoke, Trygve O. Tollefsbol, Donna K. Arnett, H3 Africa Kidney Research Network, Adetola Daramola

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women.

METHODS: We estimated odds ratios (ORs) and 95% confidence intervals …

A Case Report Of Metastatic Castration-Resistant Prostate Cancer Harboring A Pten Loss, Zin W. Myint, Derek B. Allison, Carleton S. Ellis

Internal Medicine Faculty Publications

The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has dramatically improved over the last decade; however, patients with visceral metastases are still faced with poor outcomes. Phosphatase and tensin homolog (PTEN) loss is observed in 40%–60% of mCRPC patients and is also associated with a poor prognosis. Several PI3K/AKT/mTOR pathway inhibitors have been studied, with disappointing anti-tumor activity. Here, we present a case of a patient with heavily treated mCRPC who had a modest tumor response to concurrent carboplatin, abiraterone acetate/prednisone, and liver-directed radiation therapy. We discuss the potential rationale supporting the use of this combination therapy …

Super-Enhancer-Based Identification Of A Batf3/Il-2r-Module Reveals Vulnerabilities In Anaplastic Large Cell Lymphoma, Huan-Chang Liang, Mariantonia Costanza, Nicole Prutsch, Mark W. Zimmerman, Elisabeth Gurnhofer, Ivonne A. Montes-Mojarro, Brian J. Abraham, Nina Prokoph, Stefan Stoiber, Shahid Pervez

Department of Pathology and Laboratory Medicine

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and …

Rapid 3d Reconstruction Guided Embolization For Catastrophic Bleeding Following Vacuum Assisted Breast Biopsy; A Case Report And Review Of The Literature, Martin Halicek, Chenghao Qian, Driss Raissi, Xiaoqin Wang, Yevgen Chornenkyy, William B. Bates, Michael Winkler

Radiology Faculty Publications

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.

Nsg-Pro Mouse Model For Uncovering Resistance Mechanisms And Unique Vulnerabilities In Human Luminal Breast Cancers, Yunguang Sun, Ning Yang, Fransiscus E Utama, Sameer S Udhane, Junling Zhang, Amy R Peck, Alicia Yanac, Katherine Duffey, John F Langenheim, Vindhya Udhane, Guanjun Xia, Jess F Peterson, Julie M Jorns, Marja T Nevalainen, Romain Rouet, Peter Schofield, Daniel Christ, Christopher J Ormandy, Anne Rosenberg, I Chervoneva, Shirng-Wern Tsaih, Michael J Flister, Serge Y Fuchs, Kay-Uwe Wagner, Hallgeir Rui

Department of Surgery Faculty Papers

Most breast cancer deaths are caused by estrogen receptor-α-positive (ER+) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER+ tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER+ breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed a prolactin-humanized Nod-SCID-IL2Rγ (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naïve, estrogen-dependent PDX tumors that progress to lethal metastatic disease. Preclinical trials provide first-in-mouse efficacy of pharmacological hPRL suppression on residual ER+ human breast cancer …

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with …

Concomitant Bilateral Mandibular Cemento-Ossifying Fibroma And Cementoblastoma: Case Report Of An Extremely Rare Occurrence, Madiha Bilal Qureshi, Muhammad Usman Tariq, Jamshid Abdul Ghafar, Muhammad Raza, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Background: Cemento-ossifying fibroma (COF) and cementoblastoma (CB) are rare benign odontogenic tumors with a predilection for the mandible. Cemento-ossifying fibroma is a fibro-osseous lesion that originates in the tooth bearing areas of jaw and shows cementum-like tissue in a fibrotic stroma. Cementoblastoma is classically related to roots of teeth with the presence of calcified cementum-like material. To date, only a single case of concomitant unilateral COF and CB has been reported in the literature.
Case presentation: We present an unusual case of a 37-year-old female who presented with two discrete bilateral swellings in the right and left mandible for 10 …

Editorial: Vitamin D Deficiency And Sufficiency In Reproduction And Bone Metabolism, Rehana Rehman, Faiza Alam, Mukhtiar Baig, Aysha Habib Khan, Naseer Ahmed

Department of Biological & Biomedical Sciences

No abstract provided.

Comparative Analysis Of N95 Respirators Fit Testing With Commercially Available And In House Reagent, Erum Khan, Joveria Farooqi, Humaira Shafaq, Kaleem Ullah Khushik, Syed Shamim Raza, Sara Khan, Zohra Rafiq, Bushra Ahmed, Shazia Chisti, Kehkashan Imtiaz, Hasnain Zafar, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Due to COVID-19, thousands of healthcare workers have been affected and have lost their lives in the line of duty. For the protection of healthcare workers, WHO and CDC have made standard guidelines and requirements for PPE use. N95 masks are amongst the most readily used PPE by healthcare professionals and it is highly recommended by OSHA that every make and model of N95 should go through a fit test at least once in a year.
Method: A total of 30 randomly selected healthcare professionals (who were a regular user of N95 respiratory masks) were subjected to assess in-house …

Diagnosis And Management Of Diffuse Large B-Cell Lymphoma: Society Of Medical Oncology, Pakistan Society Of Hematology, And Pakistan Society Of Clinical Oncology Joint Clinical Practice Guideline, Raheel Iftikhar, Muhammad Ayaz Mir, Munira Moosajee, Kamran Rashid, Syed Waqas Bokhari, Ahmed Nadeem Abbasi, Tahir Sultan Shamsi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil

Section of Haematology/Oncology

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the …

Whole-Genome Sequence-Informed Maldi-Tof Ms Diagnostics Reveal Importance Of Klebsiella Oxytoca Group In Invasive Infections: A Retrospective Clinical Study, Aline Cuénod, Daniel Wüthrich, Helena M. B. Seth-Smith, Chantal Ott, Christian Gehringer, Frédéric Foucault, Roxanne Mouchet, Ali Kassim, Gunturu Revathi, Deborah R. Vogt

Pathology, East Africa

Background: Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence.

Methods: We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. …

Primary Osteoarthritis Early Joint Degeneration Induced By Endoplasmic Reticulum Stress Is Mitigated By Resveratrol, Jacqueline T Hecht, Alka C Veerisetty, Juliana Wu, Francoise Coustry, Mohammad G Hossain, Frankie Chiu, Francis H Gannon, Karen L Posey

Faculty, Staff and Student Publications

Increasing numbers of people are living with osteoarthritis (OA) due to aging and obesity, creating an urgent need for effective treatment and preventions. Two top risk factors for OA, age and obesity, are associated with endoplasmic reticulum (ER) stress. The I-ERS mouse, an ER stress-driven model of primary OA, was developed to study the role of ER stress in primary OA susceptibility. The I-ERS mouse has the unique ability to induce ER stress in healthy adult articular chondrocytes and cartilage, driving joint degeneration that mimics early primary OA. In this study, ER stress-induced damage occurred gradually and stimulated joint degeneration …

How Much Time Do General Surgical Pathologists Spend On Diagnostic Data Entry?, Zhenhong Qu, Lanjin Zhang, Xianzhong Ding, Kausar Jabbar

Conference Presentation Abstracts

Context: As many pathology institutions have eliminated transcription service by office assistants, pathologists assume the task of diagnostic data entry (DDE) into pathology reports in the laboratory information system. This is not a trivial undertaking, yet tangible data are lacking on how much DDE adds to the workload of pathologists. Without such data, it is very difficult to assess the financial benefit of such a task shift and establish benchmarks. Design: Four practicing pathologists covering a general surgical pathology service in 3 institutions with different laboratory information systems were selected for their dominant DDE method (speech recognition, pre-text, or manual …

Ossifying Fibromyxoid Tumor: A Rare Subcutaneous Tumor, Karla C. Guerra, Luke Godwin, Chad Johnston, Maggie Noland, David Rowe

HCA Healthcare Journal of Medicine

The following case study demonstrates a 26-year-old male that presented to the dermatology clinic with an enlarging, raised skin nodule located on the left inferior lateral lower back. The patient reported it had persisted for two years, and he had not received prior treatment. He noted a family history of nonmelanoma skin cancer but had no other dermatological issues in the past. Physical examination revealed a pink, firm and well-circumscribed subcutaneous mass with a prominent follicular pore. It was assumed the lesion was an epidermal inclusion cyst, and surgical excision was performed. Histopathology revealed lobules of epithelioid cells with indistinct …

Higher Entropy Observed In Sars-Cov-2 Genomes From The First Covid-19 Wave In Pakistan, Najia Karim Ghanchi, Asghar Nasir, Kiran I. Masood, Syed Hani Abidi, Syed Faisal Mahmood, Akber Kanji, Safina Abdul Razzak, Waqasuddin Khan, Saba Shahid, Maliha Yameen, Ali Raza, Javaria Ashraf, Zeeshan Ansar Ahmed, Mohammad Buksh Dharejo, Nazneen Islam, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials and methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.
Results: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The …

Use Of Immunohistochemistry To Determine Expression Of Rab5 Subfamily Of Gtpases In Mature And Developmental Brains, Kwok Ling Kam, Paige Parrack, Marcellus Banworth, Sheeja Aravindan, Guangpu Li, Kar Ming Fung

Books and Book Chapters

Rab GTPases are essentially molecular switches. They serve as master regulators in intracellular membrane trafficking from the formation and transport of vesicles at the originating organelle to its fusion to the membrane at the target organelle. Their functions are diversified and each has their specific subcellular location. Their expression may vary significantly in the same cell when the level of protein production is significantly different in different physiologic status. One of the best examples is the transition from fetal to mature status of cells. Expression and localization of Rab GTPases in mature and developing brains have not been well studied. …

Acute Generalized Exanthematous Pustulosis Induced By Cetuximab, Sadia Masood, Mohammad Rizwan, Saira Fatima, Palwasha Jalil

Department of Medicine

A wide variety of diseases and drugs can cause cutaneous pustular eruptions. Acute generalized exanthematous pustulosis (AGEP) is a unique drug-induced dermatosis clinically presented as erythematous papular and pustular eruption, usually caused by certain systemic drugs. We are presenting a very rare association of AGEP with a biological agent, cetuximab. A male aged 66 years, who was recently diagnosed with a case of squamous cell carcinoma of glottis, presented in the dermatology clinic with a recent onset of fever and widespread pustular eruption over the face, trunk, and limbs. The eruption was noted after the injection of cetuximab given for …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Discrepancy Between Pcr Based Sars-Cov-2 Tests Suggests The Need To Re-Evaluate Diagnostic Assays, Zain Mushtaq, Sadia Shakoor, Akber Kanji, Najma Shaheen, Asghar Nasir, Zeeshan Ansar Ahmed, Imran Ahmed, Syed Faisal Mahmood, Rumina Hasan, Zahra Hasan

Section of Internal Medicine

Objective: We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays.
Results: Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was …