Browsing by Author "Benediktsson, Hallgrímur"

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    Phospholipase A2 Receptor and α-enolase in the Immunodiagnosis of membranous nephropathy
    (2015-02-02) Zhang, Ying; Benediktsson, Hallgrímur
    M-type phospholipase A2 receptor (PLA2R) and α-enolase are two recently identified autoantigens in adult idiopathic membranous nephropathy (IMN). To identify their diagnostic value and the potential roles in the pathogenesis of MN, renal biopsies and sera from 23 patients with MN were investigated. In 19 IMN cases, the positivity for glomerular PLA2R and circulating anti-PLA2R antibodies was 47% and 26% respectively, while only 5% glomeruli showed positive α-enolase staining. IgG4 was often codominant with either IgG1 or IgG3 in PLA2R-positive glomeruli which also showed more prevalent and stronger C3 staining as compared with PLA2R-negative glomeruli. A positive correlation between IgG1 with complement C3C expression in glomeruli was observed. Circulating anti-PLA2R autoantibody titers and PLA2R expression in renal biopsies were associated with clinical outcomes (follow up proteinuria). The results indicate that in PLA2R related MN, autoantibody –antigen interaction activates complement C3 directly or indirectly, resulting in podocyte injury and proteinuria.
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    Tailoring Ovarian Cancer Strategies to a Sub-Saharan Region: Testing the Developed Country Experience
    (2018-08-16) Rambau, Peter Fabian; Köbel, Martin; Manyama, Mange J.; Benediktsson, Hallgrímur; Hallgrímsson, Benedikt; Lukowiak, Ken D.; Quan, May Lynn
    Ovarian carcinoma is a spectrum of different histotypes which differ in risk factors, precursor lesions, molecular alterations and prognosis. Most of the research focused on high grade serous carcinoma which constitutes the majority of ovarian carcinoma. Endometrioid carcinoma (EC) constitutes 11% of ovarian carcinoma. Studies on EC have been limited by lack of sufficient number of cases for a meaningful conclusion. Seromucinous carcinoma, a newly introduced histotype shows resemblance to EC with no studies on its diagnostic reproducibility and molecular alterations. In developing countries, few studies have addressed the tumor types and histotype distribution of ovarian cancer, which could be useful in resource allocation, in addition the diagnostic accuracy of histotyping is not known. This study utilized immunohistochemical markers in a cohort of EC to study the diagnostic and prognostic biomarkers, as well as histotyping of ovarian cancers from Tanzania to establish diagnostic accuracy. Morphological studies and targeted deep sequencing was applied to seromucinous carcinoma to detect recurrent mutations known to occur in ovarian carcinoma, to justify whether it deserves a separate classification. This study found that, a defect in mismatch repair proteins was restricted to EC, and therefore screening for Lynch syndrome should be restricted to endometrioid histotype. This study also validated the association of hormone receptor (estrogen and progesterone) expression with ovarian cancer specific survival, with limited clinical utility. For seromucinous carcinoma, this study shows that the morphological diagnosis of seromucinous carcinomas is not very reliable. It did not show a distinct immunophenotype or genotype, and molecular features overlaps with endometrioid and low-grade serous carcinomas. Therefore, seromucinous carcinoma can be assigned to one of the major histotypes by ancillary molecular tests. Ovarian cancer in Tanzania shows relatively few cases compared to the Alberta population, with poor diagnostic agreement by using the current WHO criteria and immunohistochemistry. Improvement of H&E staining and adoption of current WHO classification can achieve a reasonable correct histotyping of ovarian carcinoma which can be meaningful in this area where the resource are scarce.
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    The impact of the ISN/RPS classification of glomerulonephritis in systemic lupus erythematosus on the histological diagnosis of focal and diffuse lupus nephritis
    (2013-07-17) Beeby, Melike; Edworthy, Steven; Benediktsson, Hallgrímur
    Different frequencies for each class of LN have been reported when the biopsies were classified according to WHO and ISN/RPS classification systems.The purpose of this study was to investigate the reason for the observed differences in frequencies of LN, when the biopsies are classified under different classifications. The inclusion of sclerotic glomeruli in the count of total glomeruli affected by LN, in the ISN/RPS 2003 classification, might be a possible reason for the differences in diagnoses. We reclassified 172 renal biopsies with LN class III and IV using two different classification systems.Our results indicate the importance of the change in handling the sclerotic glomeruli, which resulted in class-switching in some of the cases. This is important because depending on the approach of the clinician, it may lead to an increased immunosuppression for the same lesion when diagnosed under the ISN/RPS classification compared to the 1995 WHO classification system.
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    The Terry Rapid Razor Section Method for Intraoperative Diagnosis: Revival for Contemporary Application
    (2016) Duchesne, Stéphan R.; Wright, James Jr; Naugler, Christopher; Matyas, John; Brundler, Marie-Anne; Benediktsson, Hallgrímur; Wright, James Jr; Naugler, Christopher; Armstrong, Glen
    During and after World War I, Unna’s polychrome methylene blue, a supravital stain critical to the Mayo Clinic’s frozen section technique, became unavailable. Benjamin Taylor Terry (1876-1955) developed a replacement stain, and an intraoperative diagnostic method (rapid razor sections) that was arguably better, faster, and inexpensive compared with frozen sections. However, Terry’s contributions to the history of surgical pathology are largely unknown. But his efforts helped solidify the role of hospital-based pathology practice in North America. He played critical roles in stain development, popularization of intraoperative diagnostic techniques, and the institutionalization of hospital-based pathology. After thoroughly studying Terry’s life and the evolution of his methodology, his method was revived and adapted to a contemporary environment. Using a new sectioning device and modifications to his methodology, tissue sections were produced, stained, examined microscopically, and critiqued. Further research in perfecting diagnostic-worthy sections could provide a benefit to pathology laboratories in resource-limited countries.