Pathology Commons^™

Localizing An Occult Insulinoma By Selective Calcium Arterial Stimulation Test: First Ever Experience And A New Dimension To Diagnosis In Pakistan, Muhammad Owais Rashid, Sumerah Jabeen, Zareen Kiran,, Khurram Minhas, Muhammad Azeemuddin, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Insulinomas are rare, usually benign, solitary tumours accounting for 60% of islet cell tumours. These tumours can be difficult to localize preoperatively due to their small size. We present a challenging case of a 40 year old male with frequent hypoglycaemic spells and endogenous hypoglycaemia who presented as a diagnostic dilemma. Patient had an occult insulinoma with inconclusive CT Abdomen, MRI Abdomen and Octreotide scan. The final localization of the tumour was made by selective arterial calcium stimulation testing (SCAT), done for the first time in Pakistan at Aga Khan University Hospital. This was followed by successful distal pancreatectomy as …

Machine Learning Can Identify Abnormal Chromosomes To Facilitate Initial Screening In The Cytogenomics Laboratory, Mark Micale, Zhenhong Qu, Blake Martin

Conference Presentation Abstracts

Context: Artificial intelligence/machine learning (AI-ML) has made great strides in recent years with applications in diagnostic medicine. We tested the hypothesis that AI-ML can permit initial screening for structural chromosome abnormalities at various band levels of resolution. Such technology could markedly reduce the downstream laboratory workload and increase turnaround time in cases positive for a clinically significant chromosome abnormality.

Design: We utilized partial karyotypes of normal chromosomes 4, 5, 7, 9, 13, 21, and 22 and abnormal derivative chromosomes 9 and 22 from the t(9;22)(q34;q11.2) associated with chronic myeloid leukemia to train our AI-ML system to identify normal from abnormal …

Regulation Of Microrna-497-Targeting Akt2 Influences Tumor Growth And Chemoresistance To Cisplatin In Lung Cancer., Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Jian-Ge Qiu, Feng-Mei Zhou, Wen-Jing Liu, Di-Di Wan, Marie Chai-Mi Lin, Ling-Zhi Liu, Jian-Ying Zhang, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear.

Methods: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was …

Quantification Of Lactoyl-Coa (Lactyl-Coa) By Liquid Chromatography Mass Spectrometry In Mammalian Cells And Tissues., Erika L Varner, Sophie Trefely, David Bartee, Eliana Von Krusenstiern, Luke Izzo, Carmen Bekeova, Roddy S O'Connor, Erin L Seifert, Kathryn E Wellen, Jordan L Meier, Nathaniel W Snyder

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Lysine lactoylation is a recently described protein post-translational modification (PTM). However, the biochemical pathways responsible for this acylation remain unclear. Two metabolite-dependent mechanisms have been proposed: enzymatic histone lysine lactoylation derived from lactoyl-coenzyme A (lactoyl-CoA, also termed lactyl-CoA), and non-enzymatic lysine lactoylation resulting from acyl-transfer via lactoyl-glutathione. While the former has precedent in the form of enzyme-catalysed lysine acylation, the lactoyl-CoA metabolite has not been previously quantified in mammalian systems. Here, we use liquid chromatography-high-resolution mass spectrometry (LC-HRMS) together with a synthetic standard to detect and validate the presence of lactoyl-CoA in cell and tissue samples. Conducting a retrospective analysis …

Mast Cells As A Surrogate Marker For Diagnosis Of Persistent Eosinophilic Esophagitis., Subhashree Mallika Krishnan, Ping Zhang, Zhenhong Qu

Articles

Context: Histologically, the hallmark of active eosinophilic esophagitis (EoE) is the presence of intraepithelial eosinophils (iEos). Recently, studies have evaluated the etiologic role of intraepithelial mast cells (iMCs) in pathogenesis of EoE and residual disease. We aimed to evaluate diagnostic and prognostic value of iMCs in EoE by its prevalence in esophageal biopsy cases in association with presence of iEos and/or lymphocytes. Design: Esophageal biopsy cases were prospectively reviewed for presence of iEos, lymphocytes, and/or iMCs. An experienced gastroenterology pathologist at our institution quantitated the number of inflammatory cells. Immunohistochemistry (CD117) was used to highlight iMCs. Unpaired Student t test …

Whole Genome Sequencing Reveals Virulence Potentials Of Helicobacter Pylori Strain Ke21 Isolated From A Kenyan Patient With Gastric Signet Ring Cell Carcinoma, Catherine Mwangi, Stephen Njoroge, Evariste Tshibangu-Kabamba, Zahir Moloo, Allan Rajula, Smita Devani, Takashi Matsumoto, Kimang’A Nyerere, Samuel Kariuki, Gunturu Revathi, Yoshio Yamaoka

Pathology, East Africa

Helicobacter pylori (H.pylori) infection is etiologically associated with severe diseases including gastric cancer; but its pathogenicity is deeply shaped by the exceptional genomic diversification and geographic variation of the species. The clinical relevance of strains colonizing Africa is still debated. This study aimed to explore genomic features and virulence potentials of H. pylori KE21, a typical African strain isolated from a native Kenyan patient diagnosed with a gastric cancer. A high-quality circular genome assembly of 1,648,327 bp (1590 genes) obtained as a hybrid of Illumina Miseq short reads and Oxford Nanopore MinION long reads, clustered within hpAfrica1 population. This genome …

Folic Acid Supplementation In Patients With Elevated Homocysteine Levels, Alan D. Kaye, George M. Jeha, Alex D. Pham, Mitchell C. Fuller, Zachary I. Lerner, Gerald T. Sibley, Elyse M. Cornett, Ivan Urits, Omar Viswanath, Christopher G. Kevil

School of Medicine Faculty Publications

Introduction: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods: A literature review of …

Frequency Of Translocation T(11;22)(Q24;Q12) Using Fluorescence In Situ Hybridization (Fish) In Histologically And Immunohistochemically Diagnosed Cases Of Ewing's Sarcoma, Muhammad Rizwan Bashir, Shahid Pervez, Atif Ali Hashmi, Muhammad Irfan

Department of Pathology and Laboratory Medicine

Introduction: Ewing sarcoma (ES) family of tumors is one of the most common groups of malignancies arising in children, adolescents, and young adults. Although characteristic histology with immunohistochemical expression of CD99 and FLI1 after exclusion of other small round blue cell tumors is considered diagnostic of ES, frequency of typical ES translocation, i.e., t(11;22)(q24;q12) is not known in our population. Therefore, in this study, we aimed to evaluate the frequency of this translocation in histologically and immunohistochemically diagnosed cases of ES along with its association with other pathological parameters.
Methods: A total of 43 morphologically and immunohistochemically diagnosed cases of …

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …

Oral Cancer: Clinicopathological Features And Associated Risk Factors In A High Risk Population Presenting To A Major Tertiary Care Center In Pakistan, Namrah Anwar, Shahid Pervez, Qurratulain Chundriger, Mohammad Sohail Awan, Tariq Moatter, Tazeen Saeed Ali

Department of Pathology and Laboratory Medicine

Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features …

Cutaneous Carcinosarcoma: A Small Case Series And Review Of The Literature Of A Rare Skin Tumor., Ethan Y Song, Sean J. Wallace Md, Hina A. Sheikh, Randolph Wojcik Md, Chetan Nayak

Department of Surgery

Carcinosarcomas are composed of epithelial and mesenchymal elements and primarily present within visceral organs. Despite being potentially aggressive, they are a rare diagnosis in the skin, and few manifestations have been reported to date. In this report, we describe two separate cases of carcinosarcoma presenting as nonhealing scalp wounds. Patient A: a 57-year-old male with a nonhealing skin lesion of ten years successfully treated with wide-local excision and local ortichochea flap reconstruction. Patient B: a 75-year-old female that presented with a painless, slow-growing hemorrhagic mass of 7 years invading the skull and dura ultimately requiring craniectomy and free-tissue transfer with …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Snail Fever Of The Bladder In A Non-Endemic Area, Romana Idress, Zehra Jamil, Muhammad Areeb Ashfaq, Daniya Umer, Romana Idress, Hammad Ather

Department of Pathology and Laboratory Medicine

Schistosomiasis is rarely seen in Pakistan and is generally not very high on the list of differential diagnoses. However, it is an important cause of haematuria in certain endemic areas. It can affect multiple organs including the bladder, liver and lungs. We present a case of a young Pakistani male, travelling to and from Africa, who presented with complains of haematuria and suprapubic discomfort. Final pathologic diagnosis was urinary schistosomiasis (hematobium species). This case is particularly notable for the characteristic sago nodules identified on cystoscopy. It is important to consider schistosomiasis in the differential of haematuria in such scenarios as …

Implementing Parasite Genotyping Into National Surveillance Frameworks: Feedback From Control Programmes And Researchers In The Asia-Pacific Region, Rintis Noviyanti, Olivo Miotto, Alyssa Barry, Jutta Marfurt, Sasha Siegel, Nguyen Thuy-Nhien, Huynh Hong Quang, Nancy Dian Anggraeni, Ferdinand Laihad, Najia Karim Ghanchi

Department of Pathology and Laboratory Medicine

The Asia-Pacific region faces formidable challenges in achieving malaria elimination by the proposed target in 2030. Molecular surveillance of Plasmodium parasites can provide important information on malaria transmission and adaptation, which can inform national malaria control programmes (NMCPs) in decision-making processes. In November 2019 a parasite genotyping workshop was held in Jakarta, Indonesia, to review molecular approaches for parasite surveillance and explore ways in which these tools can be integrated into public health systems and inform policy. The meeting was attended by 70 participants from 8 malaria-endemic countries and partners of the Asia Pacific Malaria Elimination Network. The participants acknowledged …

Invasive Pulmonary Infection By Syncephalastrum Species: Two Case Reports And Review Of Literature, Memoona Irshad, Nosheen Nasir, Urooj Haider Hashmi, Joveria Farooqi, Syed Faisal Mahmood

Section of Internal Medicine

Background: Syncephalastrum species belong to the class Zygomycetes and order Mucorale. These are found in the environment and tropical soil, usually presenting as colonizers and rarely cause human infection. Syncephalastrum racemosum is a species of the genus Syncephalastrum and is the most commonly identified pathogen. Most cases are reported in immunocompromised individuals, such as patients on long term steroids, poorly controlled diabetes, or patients with malignancy.
Case presentation: We are describing two cases of rare fungal infection by Syncephalastrum species causing invasive pulmonary manifestation. Both patients had compromised immune status and presented with worsening dyspnea to the emergency room. Both …

Impact Of Covid-19 On Laboratory Professionals-A Descriptive Cross Sectional Survey At A Clinical Chemistry Laboratory In A Developing Country, Lena Jafri, Sibtain Ahmed, Imran Siddiqui

Department of Pathology and Laboratory Medicine

Background: The lab professionals at one end are at increased risk of contracting the infection while on the other end have to deal with the various challenges during the Coronavirus Disease 2019 (COVID-19) outbreak. This survey was undertaken to analyze the lab professionals' perspectives, in terms of the challenges, financial implications, fears, motivation and satisfaction from organizational processes and policies adopted, amid the COVID-19 crisis.
Material & methods: The study utilized a cross-sectional survey design. The survey was administered online via the google docs survey tool from medical laboratory professionals (n = 64) serving at the section of Clinical Chemistry, …

A Rare Case Of Constrictive Pericarditis As Initial Manifestation Of Paediatric Anaplastic Large Cell Lymphoma Requiring Urgent Pericardiectomy, Sara Iqbal, Abdul Ahad Sohail, Narmeen Asif, Muhammad Rahil Khan, Sabeehuddin Siddique, Saulat Fatimi

Section of Cardiothoracic Surgery

Constrictive pericarditis (CP) is a rare end stage inflammatory disorder affecting both parietal and visceral pericardium leading to a right heart failure. Malignancy is the least common cause of CP. Anaplastic large cell lymphoma (ALCL) accounts for 10-15% of all Non-Hodgkin lymphomas in children. Very few case reports have reported ALCL that is involving the heart and only two have been published involving pericardium but all were managed medically. We present an interesting case of an 11 year old child who presented with an effusive CP that required urgent Pericardiectomy for managing right heart failure. His histopathology was positive for …

Determination Of Reference Intervals For Common Chemistry And Immunoassay Tests For Kenyan Adults Based On An Internationally Harmonized Protocol And Up-To-Date Statistical Methods, Geoffrey Omuse, Kiyoshi Ichihara, Daniel Maina, Mariza Hoffman, Elizabeth Kagotho, Alice Kanyua, Jane Mwangi, Caroline Wambua, Angela Amayo, Peter Ojwang, Zul Premji, Rajiv Erasmus

Pathology, East Africa

Background: Due to a lack of reliable reference intervals (RIs) for Kenya, we set out to determine RIs for 40 common chemistry and immunoassay tests as part of the IFCC global RI project.

Methods: Apparently healthy adults aged 18–65 years were recruited according to a harmonized protocol and samples analyzed using Beckman-Coulter analyzers. Value assigned serum panels were measured to standardize chemistry results. The need for partitioning reference values by sex and age was based on between-subgroup differences expressed as standard deviation ratio (SDR) or bias in lower or upper limits (LLs and ULs) of the RI. RIs …

Bilateral Gonadoblastoma With Dysgerminoma In A Phenotypically Normal Female With 46xx Karyotype: Report Of A Rare Case And Literature Review, Muhammad Abdur Raafey, Muhammad Abdulwaasey, Syeda Samia Fatima, Zeeshan Uddin, Muhammad Usman Tariq

Department of Pathology and Laboratory Medicine

Gonadoblastoma is a rare ovarian neoplasm which belongs to "germ cell-sex cord-stromal tumor" category. This tumor is frequently associated with invasive germ cell malignancy. It commonly arises in dysgenetic gonads of young individuals who are phenotypically females but possess 46XY karyotype. It has been rarely reported in females with normal phenotype and genotype. We herein describe a case of 10-year-old female who presented with abdominal pain, abdominal distention and fever. CT scan of the abdomen and pelvis revealed bilateral ovarian masses, ascites and pelvic and para-aortic lymphadenopathy. Serum lactate dehydrogenase levels were also elevated. She underwent left salpingo-oophorectomy, right ovarian …

Neuroendocrine Tumor Of The Gallbladder, A Rare Incidental Finding, Alvaro Frometa, Yasna Chaudhary, Omar Ansari, Nigel Jagoo, Iqbal Kapadia

HCA Healthcare Journal of Medicine

Background: Neuroendocrine tumors are a rare finding in the gallbladder. The incidence of this entity in the gallbladder is roughly 1.13 cases per 100,000 in the US, with a steady increase in the last decade. Gallbladder neuroendocrine tumors are generally asymptomatic; the majority of cases have been reported as incidental findings in specimens, resected due to secondary symptomatology, such as chronic cholecystitis. Treatment strategies are limited, in part due to the often advanced stage in which this disease presents. Furthermore, there is a restricted utility of diagnostic tools for early detection; these factors contribute to the poor prognosis of this …