Pathology Commons^™

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …

The Top 10 Things To Know About Transfusion Medicine Before Intern Year: An Evidence-Based Course For Graduating Medical Students., Alexis R. Peedin, Irina Perjar, Marshall A. Mazepa, Marian A. Rollins-Raval, Yara A. Park, Jay S. Raval

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Transfusion medicine (TM) knowledge varies widely among physician trainees. In addition, there have been few instances in which curricular changes have been meaningfully assessed for TM education in medical school.

Methods: We created and presented a novel lecture to improve TM knowledge for graduating medical students using eight objectives designed to reinforce critical information about blood management. Each objective was coded according to unique color schemes, fonts, and graphics to create visual associations while quickly and clearly presenting complex concepts. The validated BEST Collaborative exam was used to measure changes in student TM knowledge, while a survey was conducted …

Blood Film Says It All! Rare Case Of Congenital Ttp Misdiagnosed As Itp, Ayesha Majeed Memon, Natasha Ali

Department of Pathology and Laboratory Medicine

We report a case of a 16-year-old female who presented with bleeding diathesis. Peripheral blood film examination was consistent with microangiopathic hemolytic anemia with 7% fragmented red blood cells. The ADAMTS13 level was 40 ng/ml (reference range: 630-850 ng/ml). She responded to plasma exchange therapy and methylprednisolone and was discharged in a stable condition.

Mutational Landscape Of Head And Neck Squamous Cell Carcinomas In A South Asian Population, Kulsoom Ghias, Sadiq S. Rehmani, Safina Abdul Razzak, Sarosh Madani, M Kamran Azim, Rashida Ahmed, Mumtaz J Khan

Department of Biological & Biomedical Sciences

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is anmong the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel …

Chimeric Antigen T Cell Receptor Treatment In Hematological Malignancies, Natasha Ali

Department of Pathology and Laboratory Medicine

No abstract provided.

Safety And Efficacy Of Bendamustine In The Conditioning Regimen For Autologous Stem Cell Transplantation In Patients With Relapsed/Refractory Lymphoma, Munira Moosajee, Samad Jehangir, Sobia Sawani, Tariq Muhammed, N. Ali, Usman Shaikh, Salman Adil

Section of Haematology/Oncology

Background: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas.
Methods: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT.
Results: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's …

Second-Harmonic Generation Microscopy Analysis Reveals Proteoglycan Decorin Is Necessary For Proper Collagen Organization In Prostate., Kirby R. Campbell, Rajeev Chaudhary, Monica Montano, Renato V. Iozzo, Wade A. Bushman, Paul J. Campagnola

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn  -    /    -  ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to …

Lymphocytic Lobulitis Presenting In An Adolescent Female: A Case Report, Kevin Meilak Md

Research Days

No abstract provided.

Perceptions Of Parents And Religious Leaders Regarding Minimal Invasive Tissue Sampling To Identify The Cause Of Death In Stillbirths And Neonates: Results From A Qualitative Study, Anam Shahil Feroz, Mohsina Noor Ibrahim, Elizabeth M. Mcclure, Anum Shiraz Ali, Shiyam Sunder Tikmani, Sayyeda Reza, Zahid Abbasi, Jamal Raza, Haleema Yasmin, Khadija Bano, Afia Zafar, Sameen Siddiqi, Robert L. Goldenberg, Sarah Saleem

Community Health Sciences

Background: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS.
Methods: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan. Focus group discussions (FGDs) …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Diffuse Large B-Cell Lymphoma In Kenya: Myc, Bcl2, And The Cell Of Origin, Jonathan Wawire, Shahin Sayed, Zahir Moloo, Aliyah R. Sohani

Pathology, East Africa

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed non-Hodgkin lymphoma in adults in Kenya. Cell of origin (COO) and double expression of MYC and BCL2 are two important prognostic factors for DLBCL. A small subset (5% to 10%) of DLBCL cases show positivity for CD5 and are associated with poor prognosis, whereas CD30 antigen, seen in up to 10% of cases, may be a useful target for therapy. We sought to determine the prevalence of MYC/BCL2 double expression, COO, and proportion of Epstein-Barr virus positivity among patients with DLBCL diagnosed at a tertiary referral laboratory in Kenya. …

Is There An Association Between Placental Inflammatory Lesions And Vaginal Microbiota In Preterm Labour? A Case Control Study, David Ogechi Atandi

Master of Medicine in Anatomic Pathology

Background: Preterm birth continues to be a significant contributor to neonatal mortality and morbidity despite diverse unique interventional strategies. There is need for better understanding of differences and influences of the now characterized vaginal microbiome on terminal inflammatory effects in the uterine microenvironment in term and preterm labour to improve on current strategies. How the existence of a postulated placenta microbiome also affects this understanding should be considered. Objectives: The aim of this study was to explore the association between the maternal vaginal microbiota and placental inflammatory lesions in preterm labour and to determine the presence of a placenta microbiome …

The Predictive Value Of Urine Dipstick Glucose Test In The Screening For Gestational Diabetes Mellitus In A Tertiary Private Hospital In Kenya, Janet Maranga

Master of Medicine in Clinical Pathology

Background: Worldwide, there is no consensus on the best approach to diagnose gestational diabetes mellitus (GDM) and though oral glucose tolerance testing (OGTT) is considered the gold standard, practices in the administration and interpretation of the test differ depending on the guidelines in use. Previous studies have questioned the utility of glycosuria as a screening test for GDM. Since the studies were conducted, there have been diagnostic threshold changes that might impact its utility. Justification: Diagnostic cut-offs of OGTT used in GDM diagnosis have evolved over time necessitating re-evaluation of glycosuria. The study was aimed at re-assessing the utility of …

Neuroblastoma In Adolescents And Children Older Than 10 Years: Unusual Clinicopathologic And Biologic Features, Laura Mccarthy, Katherine Chastain, Terrie Flatt, Eugenio Taboada, Robert E. Garola, John Herriges, Linda D. Cooley, Atif Ahmed

Posters

This poster describes four cases of neuroblastoma diagnosed since 2008 in children greater than 10 years and presents their clinical, histologic and biologic features, emphasizing unusual clinicopathologic characteristics and the role of DNA microarray analysis and Next Generation Sequencing in their management.

Diagnostic Accuracy Of Diffusion Weighted Mri In Differentiating Benign And Malignant Meningiomas, Din Muhammad Sohu, Saba Sohail, Rehana Shaikh

Department of Radiology

Objective: To determine the diagnostic accuracy of DWI in differentiating benign and malignant meningiomas keeping histopathology as gold standard.
Methods: This was a descriptive analytical study conducted at Radiology Department, DUHS/Dr. Ruth K. M. Pfau Civil Hospital Karachi, from August 2016 to March 2018.It included152 patients clinically suspected of meningioma on conventional neuroimaging. Imaging features of DWI were compared with histopathology findings. The diagnostic accuracy of DWI was calculated in terms of sensitivity, specificity, accuracy, PPV and NPV using histopathology as gold standard.
Results: There were 59 male and 93 female patients with mean age of 55.38±9.8 years. Mean duration …

Are Serum Leptin Levels Predicted By Lipoproteins, Vitamin D And Body Composition?, Aysha Habib Khan, Syeda Sadia Fatima, Ahmed Raheem, Lena Jafri

Department of Pathology and Laboratory Medicine

BACKGROUND: Both obesity and vitamin D deficiency are important health issues in Pakistan. The connection between body composition, Vitamin D and leptin in young adults is important to be studied as body composition may affect bone health and therefore the possibility of osteoporosis in later life. Few studies have attempted to investigate the effect of body composition and leptin with vitamin D in adolescence. AIM: To investigate the association of serum leptin with body composition, lipids and 25-hydroxyvitamin D (25OHD) in adults. METHODS: This cross-sectional study was conducted on 167 apparently healthy adults. Demographics were recorded, bioelectrical impedance analysis was …

Orthokeratinized Odontogenic Cyst (Ooc): Clinicopathological And Radiological Features Of A Series Of 10 Cases, Nasir Ud Din, Maha Zubair, Jamshid Abdul-Ghafar, Zia Ullah Khan, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Background: Orthokeratinized Odontogenic Cyst (OOC) is a rare, developmental odontogenic cyst which was considered in the past to be a variant of Odontogenic keratocyst (OKC) later renamed as keratocystic odontogenic tumor (KCOT). The treatment of OOC is by enucleation and the prognosis, following enucleation is excellent with a recurrence rate of less than 2%. On the other hand, OKC has a recurrence rate between 8 and 25% after enucleation. Thus it is important to differentiate between the two entities.
Methods: All cases reported in our section as OOC during the period 2013 to 2018 were retrieved from the surgical pathology …

Assessing The Criteria For Definition Of Perimembranous Ventricular Septal Defects In Light Of The Search For Consensus, Justin T. Tretter, Vi-Hue Tran, Seth Gray, Hieu Ta, Rohit S. Loomba, William O'Connor, Diane E. Spicer, Andrew C. Cook, Robert H. Anderson

Pathology and Laboratory Medicine Faculty Publications

Background: Discussions continue as to whether ventricular septal defects are best categorized according to their right ventricular geography or their borders. This is especially true when considering the perimembranous defect. Our aim, therefore, was to establish the phenotypic feature of the perimembranous defect, and to establish the ease of distinguishing its geographical variants.

Methods and results: We assessed unrepaired isolated perimembranous ventricular defects from six historic archives, subcategorizing them using the ICD-11 coding system. We identified 365 defects, of which 94 (26%) were deemed to open centrally, 168 (46%) to open to the outlet, and 84 (23%) to the inlet …

Raised Levels Of Ifn-Gamma And Il-13 Are Associated With Pre-Diabetes Amongst Newly Diagnosed Patients With Tuberculosis, Zahra Hasan, Muhammad Irfan, Qamar Masood, Owais Ahmed, Shoaib Rao, Umme Salama Moosajee, Naseem Salahuddin

Department of Pathology and Laboratory Medicine

Objective: To investigate pre-diabetes and diabetes in newly-diagnosed tuberculosis patients and to assess the association of serum cytokine levels with diabetes status.
Methods: The cross-sectional study was conducted at Indus Hospital and The Aga Khan University Hospital, Karachi from May to November 2015, and included patients of either gender aged 18 years or more with a confirmed diagnosis of tuberculosis who were either newly diagnosed or had received up to 1 month of anti-tuberculosis therapy were included. Patients were enrolled from among those presenting to the clinics at Indus Hospital, Karachi, and the Department of Medicine, Aga Khan University Hospital …