Pathology Commons^™

Labrad : Vol 47, Issue 1 - June 2022, Aga Khan University, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• From the Editor’s Desk
• LABRAD Star Contributors for the Year 2021
• Clinical Relevance of Measuring Thyroid Stimulating Hormone Receptor Antibodies in Pregnancy and Newborns
• Aromatic l-amino Acid Decarboxylase (AADC) Deficiency- An Ultra-rare and Underdiagnosed Neurometabolic Disorder
• Role of Flowcytometry & Kleihauer - Betke Test in Detection and Quantification of Fetomaternal Hemorrhage
• Gestational Trophoblastic Diseases: An Overview
• Acrania-Exencephaly-Anencephaly Sequence/ Spectrum: Radiological Features on Antenatal Screening
• Minimally Invasive Tissue Sampling (MITS) A New Way to Investigate Cause of Death In Resource-constrained Countries
• Laboratory Guideline for Detection, Interpretation and Reporting of Maternal Cell Contamination (MCC) in Prenatal Analysis
• Molecular Analysis of Alpha Thalassemia …

Comparison Of Two Immunoassays For Detection Of Anti-Sars Cov-2 Antibodies Among Healthcare Workers At A Tertiary Referral Hospital In Nairobi, Kenya, Patrick Muriuki Mugaine

Master of Medicine in Clinical Pathology

Background: Tests for antibodies against severe acute respiratory syndrome coronavirus 2, the aetiologic agent of coronavirus disease 2019, provide evidence of past infection or immunization. At the individual level, they are useful as markers of protection against severe disease and in cases where the diagnosis by nucleic acid amplification is inconclusive. At the population level, they are an indirect measure of exposure and may be useful in monitoring changes in viral infection or uptake of immunization over time. The interpretation and optimal use of antibody assays on populations requires an appreciation of the wide variability in individual antibody responses, the …

Validation Of A Whole Genome Methylation Profiling Classifier For Central Nervous System Tumors, Lucas Santana-Santos, Kwok Ling Kam, David Dittman, Stephanie De Vito, Matthew Mccord, Pouya Jamshidi, Hailie Fowler, Xinkun Wang, Alan Aalsburg, Daniel Brat, Craig Horbinski, Lawrence Jennings

Conference Presentation Abstracts

Whole genome methylation profiling is proving to be an incredibly powerful tool to diagnose tumors that are otherwise difficult to classify by histopathology and sequencing. The reference library of tumor DNA methylation data, using a machine learning-based tumor classifier, was developed by the German Cancer Research Network (DKFZ), and is available publicly on a research basis. However, medical institutions desiring to implement that classifier for routine clinical care need to import, adapt, and validate the classifier internally. We did this for our own DNA methylation-based classifier of central nervous system (CNS) tumors, using the same training and validation datasets as …

Retained Lens Fragment Presenting 32 Years After Cataract Extraction, Thomas Tien, Marcos A Crespo, Tatyana Milman, Zeba Syed

Wills Eye Hospital Papers

Purpose: To report a patient with retained lens material presenting over three decades after initial cataract extraction with fluctuating corneal edema and intraocular inflammation.

Observations: A 66-year-old man presented with a first episode of decreased vision and photophobia 32 years after cataract extraction without intraocular lens implantation in the right eye. Slit lamp examination revealed a tan-colored oblong mass in the inferior angle, in addition to corneal edema and an anterior chamber reaction. The patient was aphakic with traumatic mydriasis, and accordingly it was noted that the mass shifted location between anterior and posterior chambers over subsequent evaluations. The anterior …

The 5th Edition Of The World Health Organization Classification Of Haematolymphoid Tumours: Lymphoid Neoplasms, Rita Alaggio, Catalina Amador, Ioannis Anagnostopoulos, Ayoma D. Attygalle, Iguaracyra Barreto De Oliveira Araujo, Emilio Berti, Govind Bhagat, Anita Maria Borges, Daniel Boyer, Shahin Sayed

Pathology, East Africa

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as …

A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation …

A Rare Case Of Segmental Arterial Mediolysis, Ashbina Pokharel, Lauren Reinhold, Ashbita Pokharel, Judith Bateman

Conference Presentation Abstracts

Segmental arterial mediolysis (SAM) is a rare vasculopathy of unknown etiology characterized by disruption of the arterial layer, which can result in vessel dissection, hemorrhage and ischemia. Literature review has demonstrated a varied presentation ranging from benign abdominal pain to life threatening hemorrhage. We report a case of 58 year old female with past medical history of deep vein thrombosis/pulmonary embolism secondary to Protein C and S deficiency on Coumadin who presented with right flank pain for 3 days. Complete blood count and complete metabolic panel were within normal limits. CT scan of abdomen and MRI showed ischemia of segment …

Complications Of Fitz-Hugh-Curtis Syndrome In A Teenage Female: A Case Presentation, Marina Cugliari, Trupti Pandit

Rowan-Virtua Research Day

Fitz-Hugh-Curtis Syndrome is a manifestation of Pelvic Inflammatory Disease (PID) associated with Chlamydia trachomatis infections and less frequently with Neisseria gonorrhea.

PID affects sexually active women (15-30 years old) and accounts for 750,000 cases each year.

The case presented illustrates a female who presented with a small bowel obstruction and appendicitis, who was incidentally found to have Fitz-Hugh-Curtis Syndrome on laparoscopic exam.

Foci Of Idc In Phyllodes Tumors: Should We Be Worried?: A Systematic Review Of The Literature, Kathryn Eckert, Victoria Tiedemann, Linda Szczurek

Rowan-Virtua Research Day

Phyllodes tumors are rare, fast growing fibroepithelial tumors of the breast that account for less than 1% of all breast tumors globally. They were first characterized by Johannes Muller in 1838 and most often present in the 5th decade of life. Phyllodes tumors are histologically composed of a stromal component and an epithelial component. The stromal component has a widely accepted malignant potential in up to 30% of cases. Grading of the stromal malignant potential of phyllodes tumors has been defined by the World Health Organization (WHO) as benign, borderline, or malignant based on the presence and degree of stromal …

Characterization Of The Clinical Impact Of A Celiac Disease Algorithm On Diagnostic Workup Of Patients At Beaumont Hospital Royal Oak, Omid Vadpey, Gabriel N. Maine

Posters

INTRODUCTION
Advancements in medical technology and laboratory testing have prompted room for more accurate diagnostic procedures that can aid in diagnostic efficiency, reducing time to diagnosis, unnecessary test ordering, and costs. Celiac Disease is a complex gastrointestinal autoimmune disorder characterized by symptoms that mimic other bowel diseases, such as diarrhea, steatorrhea, and malnutrition. The primary goal of this pilot study is to determine if the implementation of a diagnostic serologic algorithm differs from the current standard of practice for patients that are suspected of celiac disease at Beaumont Health-Royal Oak (BH-RO).

Csf Flow Cytometry In Patients With Leukemia And Lymphoma, Patricia Rusli, James Huang

Posters

INTRODUCTION
The use of flow cytometric testing in analyzing bodily fluid for hematologic neoplasms is not novel. Flow cytometric immunophenotyping of cerebrospinal fluid (CSF) has previously been demonstrated to have high sensitivity and specificity for the detection of lymphoma and leukemia. They are able to determine definitive diagnostic information from even very low cellularity samples. In this study, we reviewed the experience of our clinical flow cytometry laboratory in evaluating CSF specimens in order to find the disease distribution of positive CSF samples.

Characterization Of Cd57+ T-Cell Subset In Blood, Bone Marrow, And Lymphoid Tissue, Michelle Ka Yan Wu, Xia Chen, James Huang

Posters

INTRODUCTION
A CD57+ T-cell subset has shown to have diagnostic and prognostic significances in some cancers. However, its specific distributions in tissues and specific variations among different diseases are yet to be further defined. This Embark project aims to examine the distributions and antigen expression profiles in the CD57+ T-cell subset in peripheral blood (PB), bone marrow (BM), and lymph node (LN).

Identification Of Aggressive Variants Of Mantle Cell Lymphoma Based On Flow Cytometry, Alan Nguyen, Alia Gupta, Marc Smith, James Huang

Posters

INTRODUCTION
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma characterized by a (1,14) translocation resulting in overexpression of cyclin D1.1 MCL variants and a heterogenous disease presentation make this a challenging diagnosis with a highly variable outcome. Pleomorphic and blastic variants have an aggressive clinical course and shorter survival than the classical type.2 The pleomorphic variant shows a marked variation in nuclear size, shape, and mitotic index.3 The blastic variant appears small and immature with fine chromatin mimicking acute leukemia.3 The aim of our study is to explore if flow cytometry analysis can help with the …

Comparison Of Maldi-Tof Ms And 16s Rrna Sequencing For Identification Of A Collection Of Clinical Isolates Of Nonntuberculous Mycobacteria In Kenya And Describing Their Antimicrobial Susceptibilities, David Enoch Kawalya

Master of Medicine in Clinical Pathology

Study background: non-tuberculous mycobacteria (NTM) are members of the genus Mycobacteria that are ubiquitous in the environment. They are increasingly documented to cause multi-drug resistant human and animal infections in immunocompromised as well as immunocompetent hosts and thus, they are a huge burden on public health resources. Diagnosis and treatment of these infections is particularly challenging due to their variable clinical presentation and the lack of easily accessible identification methods. MALDI-TOF MS is a proteomic method that has gained traction in the identification of microbial organisms in clinical practice due to its fast turn-around time, high resolution, and cost-effectiveness but …

Anti-Nmda-Receptor Encephalitis In A Patient With Ovarian Teratoma, Harboring Brain Histology Of Varying Developmental Stages, Seyedalireza Fatemi, Joseph Fullmer

Conference Presentation Abstracts

Anti-NMDA-receptor encephalitis is a subacute, autoimmune disorder thought to be caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor. Although NMDAR encephalitis is a familiar entity to psychiatrists and neurologists, it is less commonly reported in the pathology literature. Clinical symptoms of anti-NMDAR encephalitis may mimic schizophrenia and psychotic spectrum disorders or substance-induced psychosis. Although initially described in association with ovarian teratomas in women, anti-NMDAR encephalitis has been reported in individuals without paraneoplastic association, as well as in males. Previous literature has suggested NMDA receptor expressing teratoma neurons are densely aggregated and are smaller in size. Ki-67 index can be …

Linear Cutaneous Lupus Erythematosus Following Blaschko’S Lines On The Scalp: Additional Cases And Review Of The Literature, Heather Reagin, Daniel A. Nguyen, Marc R. Lewin, Gregory A. Hosler, Eric Weisberg, Stephen E. Weis

HCA Healthcare Journal of Medicine

Alopecia of the scalp has various causes and presentations. However, linear alopecia is unusual and lupus erythematosus presenting as linear alopecia is exceedingly rare. To date, there have been 16 documented cases of linear alopecia diagnosed as chronic cutaneous lupus erythematosus occurring in a linear configuration following Blaschko's lines. We report 2 additional cases and review the clinical and histologic features along with treatment. This Blaschkoid linear variant of cutaneous lupus erythematosus has distinct clinical and histologic characteristics that set it apart from other causes of alopecia and from classic forms of cutaneous lupus. These distinct features include a linear …

Indispensable Role Of Immunophenotyping In Diagnosing Leukemic Phase Of Blastic Plasmacytoid Dendritic Cell Neoplasm Without Cutaneous Manifestation, Hareem Alam, Nabiha Saeed, Anila Rashid

Department of Pathology and Laboratory Medicine

Blastic plasmacytoid dendritic cell neoplasm usually presents as skin lesions. Diagnostic error occurs when it primarily presents in leukemic phase without skin involvement. Triad of CD4, CD56 and CD123 immunophenotype expression is essential to avoid misdiagnosis of this rare hematological malignancy. Here we describe a patient who presented in overt leukemic phase of BPDCN highlighting diagnostic challenges encountered that resulted in delayed diagnosis and poor outcome

Concurrent P53 Mutation In Egfr Mutant Non-Small Cell Lung Cancer Is Associated With Resistance To First And Second Generation Egfr Tyrosine Kinase Inhibitors, A Meta-Analysis, Marissa Viola, Adam Kolatorowicz, Jun Wang

Research Day

Epidermal growth factor receptor (EGFR) mutant lung cancers tend to respond well to EGFR tyrosine kinase inhibitors (TKIs). However, resistance has been described. Molecular studies have revealed that concurrent mutations of tumor driver genes are associated with TKI resistance. To delineate the role of concurrent mutation of tumor suppressor gene p53 in TKI resistance, a meta-analysis was performed using published observations of EGFR mutant lung cancer patients treated with first or second generation TKIs. 31 studies are included in the analysis following a search of PubMed. Probability of TKI resistance and progress free survival (PFS) were compared in patients with …

Reduced Er-Mitochondria Connectivity Promotes Neuroblastoma Multidrug Resistance., Jorida Çoku, David M. Booth, Jan Skoda, Madison C Pedrotty, Jennifer Vogel, Kangning Liu, Annette Vu, Erica L Carpenter, Jamie C Ye, Michelle A Chen, Peter Dunbar, Elizabeth Scadden, Taekyung D Yun, Eiko Nakamaru-Ogiso, Estela Area-Gomez, Yimei Li, Kelly C Goldsmith, C Patrick Reynolds, György Hajnóczky, Michael D Hogarty

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive …

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …