Pathology Commons^™

A Multidisciplinary Approach To Triage Patients With Breast Disease During The Covid-19 Pandemic: Experience From A Tertiary Care Center In The Developing World, Abida K. Sattar, Hania Shahzad, Adnan Abdul Jabbar, Azmina Tajdin Valimohammad, Sadaf Khan, Yasmin Vellani, Romana Idrees, Nasir Ali, Imrana Masroor, Humera Saeed, Gulzar S. Lakhani, Nadia Ayoub, Atif Waqar, Muhammad Zia-Ul Islam, Salman Kirmani, Asad Latif, Ather Enam

Section of General Surgery

Background: The COVID-19 pandemic has created a need to prioritize care because of limitation of resources. Owing to the heterogeneity and high prevalence of breast cancers, the need to prioritize care in this vulnerable population is essential. While various medical societies have published recommendations to manage breast disease during the COVID-19 pandemic, most are focused on the Western world and do not necessarily address the challenges of a resource-limited setting.
Aim: In this article, we describe our institutional approach for prioritizing care for patients presenting with breast disease.
Methods and results: The breast disease management guidelines were developed and approved …

Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …

Direct And Indirect Effect Of 10 Valent Pneumococcal Vaccine On Nasopharyngeal Carriage In Children Under 2 Years Of Age In Matiari, Pakistan, Muhammad Imran Nisar, Sheraz Ahmed, Fyezah Jehan, Shahira Shahid, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Sahrish Munir, Sajid Muhammad, Farah Khalid, Syed Asad Ali, Anita K. M. Zaidi, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Background: Pakistan introduced Ten-valent pneumococcal-conjugate-vaccine PCV10 in 2012 as a 3 + 0 schedule without catch-up.
Methods: Children <2 years old in Matiari, Sindh provided nasopharyngeal swabs between 2014 and 2018, which were cultured for pneumococcus and serotyped through multiplex PCR at the Aga Khan University Hospital. Carriage rates over time for Vaccine-Type (VT) and Non-VT (NVT) serotypes were used to estimate direct, indirect, total and overall effects of vaccination. Regression analysis was used to determine factors associated with VT carriage.
Results: Pneumococcus was detected in 2370/3140 (75%). VT carriage decreased overall, 16.1-9.6% (p-trend <0.001); vaccinated (all 3 doses of PCV10 received) 11.3-8.1% (p-trend 0.031) and unvaccinated (no PCV10 dose received) 17.4-10.3% (p-trend 0.003) with a decline in serotypes 6B, 9V/9A and 19F. Immunization increased from 41.0% to 68.4% (p-trend 0.001). Direct effect of vaccine was 32.8% (95% CI 14.7-47.0%) and indirect effect 44.6%(95% CI 40.6-48.6%). Factors associated with decreased VT colonization were education 1-5 years (aOR 0.7, 95%CI 0.6-1.0), history of difficulty breathing (aOR 0.7, 95%CI 0.5-1.0), exposure to smoke (aOR 0.8, 95% CI 0.6-1.0), child fully immunized (aOR 0.7, 95%CI 0.5-1.0) and enrolled in 3rd (aOR 0.6, 95%CI 0.4-0.8) and 4th (aOR 0.6, 95%CI 0.5-0.9) year of the study whereas history of runny nose (aOR 1.5, 95% CI 1.2-1.9) was positively associated.
Conclusions: Decrease in VT pneumococcal carriage in vaccinated and unvaccinated children indicates herd immunity. Sustained increase in vaccine coverage and close long-term surveillance is warranted.

The Association Of Chest Radiographic Findings And Severity Scoring With Clinical Outcomes In Patients With Covid-19 Presenting To The Emergency Department Of A Tertiary Care Hospital In Pakistan, Raima Kaleemi, Kiran Hilal, Ainan Arshad, Russell S. Martins, Avinash Nankani, Tanveer Ul Haq, Sundas Basharat, Zeeshan Ansar

Department of Radiology

Introduction: While chest x-rays (CXRs) represent a cost-effective imaging modality for developing countries like Pakistan, their utility for the prognostication of COVID-19 has been minimally explored. Thus, we describe the frequency and distribution of CXR findings, and their association with clinical outcomes of patients with COVID-19.
Methods: All adult (≥ 18 years) patients presenting between 28th February-31st May to the emergency department of a tertiary care hospital in Pakistan, who were COVID-19 positive on RT-PCR with CXR done on presentation, were included. A CXR Severity Score (CXR-SS) of 0-8 was used to quantify the extent of pulmonary infection on CXR, …

The Evolution And Future Of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, And Oncolytic Bacteria To The Treatment Of Solid Tumors, Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan, Kaitlin M. Dailey

Journal Articles: Pathology and Microbiology

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap …

Structure And Activity Of A Selective Antibiofilm Peptide Sk-24 Derived From The Nmr Structure Of Human Cathelicidin Ll-37, Yingxia Zhang, Jayaram Lakshmaiah Narayana, Qianhui Wu, Xiangli Dang, Guangshun Wang

Journal Articles: Pathology and Microbiology

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7–10%). These results …

Immunopathogenesis Of Craniotomy Infection And Niche-Specific Immune Responses To Biofilm, Sharon D.B. De Morais, Gunjan Kak, Joseph P. Menousek, Tammy Kielian

Journal Articles: Pathology and Microbiology

Bacterial infections in the central nervous system (CNS) can be life threatening and often impair neurological function. Biofilm infection is a complication following craniotomy, a neurosurgical procedure that involves the removal and replacement of a skull fragment (bone flap) to access the brain for surgical intervention. The incidence of infection following craniotomy ranges from 1% to 3% with approximately half caused by Staphylococcus aureus (S. aureus). These infections present a significant therapeutic challenge due to the antibiotic tolerance of biofilm and unique immune properties of the CNS. Previous studies have revealed a critical role for innate immune responses …

The Mmc Biobank Is A Resource That Supports Biomedical Research, Anne C. Breggia, Sue Lapierre, Christopher Keister, Dawn Charnetzky, Hannah Brown, Joseph Nano, Sydney Robinson, Howard Feller, Susan Nester, Elizabeth Hamir, Heidi Ingersoll, Anthony Sellner, Trevor Jorgensen, Mike Jones

Costas T. Lambrew Research Retreat 2021

Mission: To provide normal and diseased annotated human biospecimens to the research community that supports discoveries leading to improved patient therapies and advances in personalized medicine.

Crosstalk Between Staphylococcus Aureus And Innate Immunity: Focus On Immunometabolism, Christopher M. Horn, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of bacterial infections globally in both healthcare and community settings. The success of this bacterium is the product of an expansive repertoire of virulence factors in combination with acquired antibiotic resistance and propensity for biofilm formation. S. aureus leverages these factors to adapt to and subvert the host immune response. With the burgeoning field of immunometabolism, it has become clear that the metabolic program of leukocytes dictates their inflammatory status and overall effectiveness in clearing an infection. The metabolic flexibility of S. aureus offers an inherent means by which the pathogen could manipulate the …

Association Of Helicobacter Pylori Caga And Vaca Genotypes With Gastric Adenocarcinoma In Kenya, Priscilla Waithira Njenga

Master of Medicine in Anatomic Pathology

Background: Helicobacter pylori infects approximately half of the world’s population. The main virulence factors, CagA and VacA, are associated with chronic gastritis and cancer. Notable geographic and temporal variations in the prevalence and genotypes of H. pylori in relation to gastric pathologies have been observed, however, their significance and trends in African populations is scantly described. The aim of this study was to investigate the association of H. pylori and its respective CagA and VacA genotypes with gastric adenocarcinoma and to describe the trends of H. pylori genotypes over the last 8 years (2012-2019). Materials and Methods: A total of …

Treatment-Resistant Hypercalcemia From Ectopic Pth Hypersecretion Suspected Secondary To Disseminated Ovarian Cancer, Alexander M. Balinski, Neil J. Khatter, Jeffrey M. Gold, Krishna S. Pothugunta, Vamshi K. Garlapaty, Steven M. Rankin, Christopher A. Thornburn, Jamal Abu-Khaled

Articles

Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH suspected secondary to a disseminated mucinous ovarian adenocarcinoma. A 45-year-old female presented with severe hypercalcemia and significant elevations in both PTH and PTHrP two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with numerous metastases. Ectopic PTH secretion was highly suspected …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …

Chronic Pain, Malingering, And The Word Memory Test, Dawn Marie Emmett Bishop

Walden Dissertations and Doctoral Studies

AbstractThe importance of using scientifically grounded strategies to detect malingering has been established in the literature and past research. Many reliable tools have been established for the detection of malingered neurocognition; however, research on how pain may affect these tools is sparse. The purpose of this study was to investigate the effect of pain on cognitive symptom validity testing and to establish the validity of the Word Memory Test (WMT), a cognitive symptom validity test with good sensitivity and specificity, when the test taker is feigning pain (simulating) or remembering pain. The biopsychosocial model and the gate theory of pain …

Developing An Enhanced 7-Color Multiplex Ihc Protocol To Dissect Immune Infiltration In Human Cancers., Zhaoyu Sun, Richard Nyberg, Yaping Wu, Brady Bernard, William L. Redmond

Articles, Abstracts, and Reports

The TSA Opal multiplex immunohistochemistry (mIHC) protocol (PerkinElmer) has been used to characterize immune infiltration in human cancers. This technique allows multiple biomarkers to be simultaneously stained in a single tissue section, which helps to elucidate the spatial relationship among individual cell types. We developed and optimized two improved mIHC protocols for a 7-color panel containing 6 biomarkers (CD3, CD8, CD163, PD-L1, FoxP3, and cytokeratin (CK)) and DAPI. The only difference between these two protocols was the staining sequence of those 6 biomarkers as the first sequence is PD-L1/CD163/CD8/CK/CD3/FoxP3/DAPI and the second sequence is FoxP3/CD163/CD8/CK/CD3/PD-L1/DAPI. By comparing PD-L1/FoxP3 staining in …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …

Malignant Eccrine Adenoma With Sarcomatous (Heterologous) Components: Report Of A Rare Skin Adnexal Neoplasm With Literature Review, Hira Ishtiaq, Muhammad Abdulwaasey, Muhammad Usman Tariq, Saira Fatima

Department of Pathology and Laboratory Medicine

Malignant eccrine spiradenoma (MES) is an exceedingly rare skin adnexal tumor that arises from pre-existing benign eccrine spiradenoma (BES). MES tumors show a wide spectrum of morphological features, posing a diagnostic challenge to the pathologist. Sarcomatous (heterologous) elements are seen in a few of these tumors, further complicating the morphological picture. We herein describe a case of a 66-year-old male who presented with a recently enlarging, ulcerated, nodular skin lesion over the right leg that had been present for the last 25 years. The patient underwent wide local excision of the tumor. Microscopic examination revealed a neoplastic lesion comprising benign …

Newborn Screening For Congenital Hypothyroidism: Improvement In Short-Term Follow-Up By Audit And Monitoring, Hafsa Majid, Sibtain Ahmed, Imran Siddiqui, Khadija N Humayun, Hussain Karimi, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Objective: Newborn screening for congenital hypothyroidism (CH) at our hospital during this study was by measurement of thyroid stimulating hormone (TSH) in serum samples. This audit was conducted over a 2 year period, to determine the compliance of reporting of results greater than the screening cutoffs for serum TSH. Gaps of non-compliance were identified, and re-audit was undertaken after the corrective actions were taken.
Results: The critical limit was defined as serum TSH (≥ 20 µIU/ml) following consultation with a pediatric endocrinologist. All results above this limit were reported urgently to physicians. During the audit period, 27,407 tests were performed, …

Clinicopathological And Immunohistochemical Study Of 29 Cases Of Solid-Pseudopapillary Neoplasms Of The Pancreas In Patients Under 20 Years Of Age Along With Detailed Review Of Literature, Nasir Ud Din, Shabina Rahim, Jamshid Abdul-Ghafar, Arsalan Ahmed, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Background: Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the morphology, differential diagnosis, and prognosis of SPNs in patients under 20 years of age and present a detailed review of literature.
Methods: A total of 29 cases in patients under 20 years of age reported as SPN during the period January 2014 to December 2019, were included in the study. These included 19 resection specimens, 4 incision biopsies and 6 cases received as blocks for second opinion. Hematoxylin and eosin (H&E) slides as well as immunohistochemistry (IHC) …

Does Breast Cancer Subtype Impact Margin Status In Patients Undergoing Partial Mastectomy?, Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-Mcnatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric A. Brown, Amanda Mendiola, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen Mcgowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura L. Walters, Tara Mcpartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar

Conference Presentation Abstracts

BACKGROUND: Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy.

METHODS: Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. …