Medicine and Health Sciences Commons^™

Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali

Department of Pathology and Laboratory Medicine

Introduction: von Willebrand disease is the most common inherited bleeding disorder. It is classified into 3 main types, type I and III are quantitative defects whereas type II is qualitative defect which is further sub-classified in to II-A, II-B, II-M, II-N. The aim of the present study is to see frequency and types of von Willebrand disease in a tertiary care hospital of Karachi, Pakistan.
Materials and methods: This retrospective cross-sectional study was conducted in the section of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, the Aga Khan University hospital, Karachi, from May 2020 to April 2021 …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar

Department of Pathology and Laboratory Medicine

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster …

Reporting Of Mycetoma Cases From Skin And Soft Tissue Biopsies Over A Period Of Ten Years: A Single Center Report And Literature Review From Pakistan, Mohammad Zeeshan, Saira Fatima, Joveria Farooqi, Kauser Jabeen, Arsalan Ahmed, Afreen Haq, Muhammad Omer Arif, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma cases have frequently been diagnosed in histopathology and microbiology laboratories. However, there is scarcity of published data from this country. Therefore, the objectives of this study were to evaluate the frequency and type of mycetoma reported in skin and soft tissue biopsies from a single center over 10 years and review of published literature from Pakistan.
Method: This descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory, Karachi, Pakistan. Laboratory data from 2009-2018 …

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

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 = …

Paratesticular Solitary Fibrous Tumour Mimicking Cellular Angiofibroma: An Unusual Morphology And Rare Site, Madiha Bilal Qureshi, Muhammad Usman, Qurratulain Chundriger, Nasir Uddin

Department of Pathology and Laboratory Medicine

Solitary fibrous tumour (SFT) is a ubiquitous benign mesenchymal tumour of fibroblastic origin, which occurs most often in middle-aged adults. It usually presents as lung mass originating from pleura, but extrapleural occurrence is also common. Tumour is characterised by hypo- and hyper-cellular areas of spindle-shaped cells, arranged in haphazard manner with dispersed staghorn-shaped vessels. Surgical excision is the curative treatment. SFTs of the primary testicular or paratesticular region are extremely rare, but they exhibit histologic findings similar to SFTs originating at other body sites. Here, we report the case of a paratesticular SFT in a 37-year male, who presented with …

A Streptococcus Pneumoniae Lineage Usually Associated With Pneumococcal Conjugate Vaccine (Pcv) Serotypes Is The Most Common Cause Of Serotype 35b Invasive Disease In South Africa, Following Routine Use Of Pcv, Kedibone M. Ndlangisa, Mignon Du Plessis, Stephani Lo, Linda De Gouveia, Chrispin Chaguza, Martin Antonio, Brenda Kwambana-Adams, Jennifer Cornick, Dean B. Everett, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in …

Chloroquine-Susceptible And -Resistant Plasmodium Falciparum Strains Survive High Chloroquine Concentrations By Becoming Dormant But Are Eliminated By Prolonged Exposure, Johan Ursing, Rasmus Johns, Berit Aydin-Schmidt, Carla Calçada, Poul-Erik Kofoed, Najia Karim Ghanchi, Maria Isabel Veiga, Lars Rombo

Department of Pathology and Laboratory Medicine

Background: Plasmodium falciparum strains that are resistant to standard-dose chloroquine can be treated by higher chloroquine concentrations maintained for a longer time in vivo.
Objectives: To determine the relative importance of chloroquine concentrations versus exposure time for elimination of chloroquine-susceptible and -resistant P. falciparum in vitro.
Methods: Chloroquine-susceptible (3D7) and -resistant (FCR3) strains were exposed in vitro to 1, 2, 4, 8, 16 or 32 times their respective 90% inhibitory chloroquine concentrations for 3, 5, 7 or 14 days and then followed until recrudescence, or not, by 42 days after the end of exposure.
Results: Exposure to chloroquine appeared to …

Development And Validation Of Standard And Real Patient Gallstone Library Using Fourier Transform Infra-Red Spectroscopy, Lena Jafri, Muhammad Abbas Abid, Humera Asif, Syed Bilal Hashmi, Hafsa Majid, Farooq Ghani, Sibtain Ahmed, Imran Siddiqui, Aysha Habib

Department of Pathology and Laboratory Medicine

Background: Analysis of the constituents of gallstones using various spectroscopic techniques assists in identification of the pathogenesis of gallstones. In the current study, using Fourier Transform Infra-Red (FTIR) Spectroscopy, a Gallstone Standard Library (GSL) and a Gallstone Real Patients' Library (GRPL) were developed and validated for gallstone composition analysis.
Methods: The study was conducted at the Department of Pathology & Laboratory Medicine, Aga Khan University, Pakistan. Pure standards (cholesterol, calcium carbonate, bilirubin and bile salts) and gallstone specimens were analyzed using FTIR Nicolet iS-5 Spectrometer from Thermo Fisher Scientific, USA. Thermo Scientific™ QCheck™ algorithm, embedded within the OMNIC™ software, was …

Perspective On Newborn Screening (Nbs): Evidence Sharing On Conditions To Be Included In Nbs In Pakistan, Hafsa Majid, Lena Jafri, Sibtain Ahmed, Khadija Humayun, Salman Kirmani, Natasha Bahadur Ali, Bushra Moiz, Aysha Habib, Bushra Afroze

Department of Pathology and Laboratory Medicine

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one …

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas

Looks Can Be Deceiving: Adrenal Teratoma Causing Diagnostic Difficulty, Nadeem M, Ather M. H, Sulaiman M. N, Shahid Pervez

Department of Pathology and Laboratory Medicine

Teratomas are unusual tumours that derived from totipotent cells with their origin from more than one or usually all three germ cells. Here authors are presenting a case of primary retroperitoneal tumour that is a rare clinical entity. A 19-year-old male presented with right lumbar pain and was found to have complex cyst with large calcification in right adrenal gland on imaging. Intraoperatively, he was found to have a solid mass with areas of soft consistency, which was excised en bloc. On gross examination, the cyst contained pieces of bone, few teeth, and hairs entangled in mucinous material. On histological …

Ethnic Disparity In 21-Hydroxylase Gene Mutations Identified In Pakistani Congenital Adrenal Hyperplasia Patient, Aysha Habib Khan, Muniba Aban, Jamal Raza, Naeem Ul Haq, Abdul Jabbar, Tariq Moatter

Department of Pathology and Laboratory Medicine

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH.

Methods: A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.

Results: Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females …

Infiltrating Ductal Carcinoma Breast With Central Necrosis Closely Mimicking Ductal Carcinoma In Situ (Comedo Type): A Case Series, Shahid Pervez, Hassan Khan

Department of Pathology and Laboratory Medicine

Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial …

Prostate Cancer: Some Clinical And Scientific Dilemmas., Paul D. Abel, El-Nasir Lalani

Department of Pathology and Laboratory Medicine

No abstract provided.

Soft Tissue Sarcomas: Pattern Diagnosis Or Entity, Naasha Talati, Shahid Pervez

Department of Pathology and Laboratory Medicine

Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub- categorization is based purely on histomorphological grounds, but as new techniques evolve, a more, conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry(IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991 …

Efficient Immortalization Of Luminal Epithelial Cells From Human Mammary Gland By Introduction Of Simian Virus 40 Large Tumor Antigen With A Recombinant Retrovirus, Bartek J, Bartkova J, Kyprianou N, El-Nasir Lalani, Staskova Z, Shearer M, Chang S, Taylor Papadimitriou J

Department of Pathology and Laboratory Medicine

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining …