Pathology Commons^™

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 …

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 …

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 …

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 …

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 …

A New Pipeline For Clinico-Pathological And Molecular Placental Research Utilizing Ffpe Tissues., Jiaqi J O'Reilly, Stephanie Barak, Anna A Penn

Pathology Faculty Publications

The placenta is at the core of many pregnancy pathologies, but we have limited knowledge about placental function because of two key research barriers: 1) lack of guidelines for sample collection and pathologic diagnosis; and 2) limited tools are available for molecular analysis of stored placental samples. We aimed to create a searchable, population-based placental database of pathologic diagnoses, and to validate molecular methods for gene expression studies of matching formalin fixed paraffin embedded (FFPE) placental blocks. Our database has over 1000 pregnancies coded for clinical diagnosis with corresponding FFPE blocks that are available for gene expression studies. RNA harvested …

Segmental Absence Of Intestinal Musculature In A Child With Type Iv Ehlers-Danlos Syndrome, Nicole Zeky, Celia Short, Brent Keith, Randall Craver, Jessica A. Zagory

School of Medicine Faculty Publications

Patients with vascular Ehlers-Danlos syndrome (vEDS) have a defect in the formation of type III collagen. This defect puts patients at risk of vascular rupture, uterine rupture, and bowel perforations. The segmental absence of intestinal musculature is a rare histopathologic finding, wherein there is a lack of a muscularis propria layer in the intestinal wall. Although typically documented in the literature in neonates or adults, it can be seen in children of other ages. This is a case report of a patient who exhibits both rare entities, which has not been described in the literature to date.

Our Experience Of Treating Adult Bone Lymphoma, A Retrospective Cross-Sectional Study In A Tertiary Care Center, Aga Khan University Hospital, Karachi, Masood Umer, Muhammad Younus Khan Durrani, Javeria Saeed, Nasir Ud Din

Section of Orthopaedic Surgery

Objective: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone.
Methodology: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study.
Results: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours …

Orofacial Manifestations Of Lyme Disease: A Systematic Review, Brenda Bradshaw, Kelsey M. Jones, Joleen M. Westerdale-Mcinnis, Holly Gaff

Dental Hygiene Faculty Publications

Purpose: Orofacial manifestations of Lyme disease can affect head and neck anatomical structures that are frequently examined by dental professionals. The purpose of this systematic review was to examine the literature for types and frequencies of orofacial manifestations documented in populations in the United States (US) with Lyme disease.

Methods: Four electronic databases (Dentistry and Oral Sciences, PubMed, Cinahl Plus, and Medline) were systematically searched during the summer of 2019 using keywords and MeSH terms to identify relevant studies. Search term alterations and synonyms were cross-checked using the US National Library of Medicine Unified Medical Language System Metathesaurus. Full-text, English …

Prevalence And Determinants Of Inappropriate Antibiotic Dispensing At Private Drug Retail Outlets In Urban And Rural Areas Of Indonesia: A Mixed Methods Study, Luh Putu Lila Wulandari, Mishal Khan, Marco Liverani, Astri Ferdiana, Yusuf Ari Mashuri, Ari Probandari, Tri Wibawa, Neha Batura, Gill Schierhout, John Kaldor

Department of Pathology and Laboratory Medicine

Introduction: The aim of this mixed-method study was to determine the extent and determinants of inappropriate dispensing of antibiotics by licensed private drug retail outlets in Indonesia.
Methods: Standardised patients (SPs) made a total of 495 visits to 166 drug outlets (community pharmacies and drug stores) between July and August 2019. The SPs presented three clinical cases to drug outlet staff: parent of a child at home with diarrhoea; an adult with presumptive tuberculosis (TB); and an adult with upper respiratory tract infection (URTI). The primary outcome was the dispensing of an antibiotic without prescription, with or without the client …

Synchronous Primary Diffuse Large B-Cell Lymphoma And Papillary Thyroid Carcinoma: A Case Report Highlighting "Lymphoma First Approach", Rahim Dhanani, Ambreen Abdullah Unar, Muhammad Hassan Danish, Hamdan Ahmed Pasha, Ummiya Tahir, Mubasher Ikram

Section of Otolaryngology, Head & Neck Surgery

Papillary thyroid carcinoma (PTC) is the most common type of all thyroid carcinomas and accounts for up to 90% of all thyroid malignancies. It is the most indolent form of the disease and has an excellent prognosis. On the other hand, Primary thyroid lymphoma (PTL) is a rare entity accounting for only about 1% to 5% of all thyroid malignancies and only 2% of extranodal lymphomas. Synchronous PTC and PTL is a very rare condition and only a few cases have been reported in the literature up till now. We report one such case in a 52-year-old lady who was …