Masters Degrees (Anatomical Pathology)

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Browsing Masters Degrees (Anatomical Pathology) by Title

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    Fumarate hydratase deficient renal cell carcinoma: a retrospective study performed at NHLS Universitas Academic laboratories, 2001 to 2017
    (University of the Free State, 2021) Du Preez, Michelle; Goedhals, Jacqueline
    Background: Fumarate hydratase deficient renal cell carcinoma (FH deficient RCC) has, in recent years, been described as part of a morphologic spectrum of renal tumours associated with hereditary leiomyomatosis and renal cell carcinoma (HLCRCC) syndrome and is currently recognized as a distinct entity in the 2013 International Society of Urological Pathology (ISUP) Vancouver classification of renal tumours and is included in the 2016 World Health Organization (WHO) classification. FH deficient RCC is an aggressive neoplasm which often presents at a high pathologic stage, with local and distant metastases at the time of diagnosis. FH deficient RCC has a wide variety of morphological patterns, however, the presence of pattern multiplicity, sarcomatoid/rhabdoid morphology and the presence of characteristic nuclear features, i.e. nuclei with prominent viral inclusion-like macronucleoli and perinuclear halos should prompt genetic testing of the tumour. Characteristic immunohistochemical staining patterns, i.e. loss of cytoplasmic expression of fumarate hydratase (FH) and aberrant nuclear expression of S-(2-succino)-cyteine (2SC) have a 100% positive predictive value for identifying FH deficient RCC, however, only FH is available for commercial use. Retention of cytoplasmic staining for FH does not exclude FH deficient RCC since the gene may still be functional in missense variants of the FH gene. To our knowledge, there is presently no published research regarding FH deficient RCC and its association with HLRCC syndrome in Africa. The impact of this disorder in South African patients, is therefore unknown. Aim: The aim of this study was to determine the number and profile of patients with FH deficient RCC seen by the Department of Anatomical Pathology, University of the Free State over a 17-year period, from 1 January 2001 to 31 December 2017. Methods: A retrospective, cross-sectional study was performed. All cases of primary renal cell carcinoma and RCC subtypes diagnosed between 1 January 2001 and 31 December 2017 were included. An immunohistochemical stain for FH was performed on all the cases. All the cases with the typical phenotype for FH deficient RCC were submitted for molecular analysis and genotyping. Results: 172 patients were included in the study. Ninety (52.33%) were male and 82 (47.67%) were female. The mean age at presentation was 54.2 years and most patients presented in the 5th to 6th decades of life. All cases showed retained cytoplasmic staining with FH. One (0.58%) case of FH deficient RCC with the characteristic phenotype and a missense mutation in Exon 7 of the FH gene was identified. The patient was a 53-year-old black female and no information regarding the presence of uterine leiomyomas or family history of RCC was available. Conclusion: All cases of RCC displaying the typical phenotype of FH deficient RCC (whether immunolabeling for FH is retained or lost) should be submitted for molecular testing in order to identify patients with HLRCC syndrome or confirm the diagnosis of sporadic FH deficient RCC to minimize morbidity and mortality in such patients and their families.
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    Genomic analysis of respiratory syncytial virus circulating in the Free State during the COVID-19 pandemic
    (University of the Free State, 2023) Sondlane, Hlengiwe; Nyaga, Martin Munene; Goedhals, Dominique; Bester, Philip Armand
    Respiratory syncytial virus (RSV) is a highly contagious virus that is responsible for most infant hospitalisations in developed nations and accounts for a significant childhood mortality in low- and middle-income countries (LMICs). The RSV has two main subtypes, namely A and B, which co-circulate and exhibit a predominance during different RSV epidemic seasons. This virus exhibits a high degree of genetic diversity, resulting in the emergence of various genotypes. The regulation of viral replication is primarily governed by two major RSV glycoproteins, namely the attachment (G) protein and the fusion (F) protein. These proteins possess potential glycosylation sites, although the variability is more pronounced in the G protein, while the F protein remains relatively conserved across different virus isolates. Following the advent of severe acute respiratory syndrome coronavirus-2 and the onset of the coronavirus disease 2019 (COVID-19) era, a significant decline in RSV activity was observed, aligning with the enforcement of non-pharmaceutical interventions (NPI). Consequently, the COVID-19 pandemic brought about a significant shift in the seasonality and epidemiology of RSV, resulting in an out of season RSV outbreak. Therefore, this study aimed to investigate the genetic diversity of the circulating strains in South Africa before and during the COVID-19 pandemic. In this study, 69 nasopharyngeal swabs were collected from children who presented with respiratory distress (n=50) and severe acute respiratory infection (SARI) (n=19) and required hospital admission in different participating hospitals in the Free State province, Bloemfontein, South Africa. The samples were then subjected to multiplex panels to detect RSV. The viral RNA was extracted from RSV positive samples and overlapping fragments of the RSVA/B genomes were amplified using the Superscript IV One-Step RT-PCR kit. Libraries were prepared with QIAseq-FX single-cell RNA library preparation kit. The RSV whole genome was sequenced using the Illumina MiSeq, platform, and the obtained data was then analysed using Genome Detective and Geneious software. The virus genotypes were identified through phylogenetic analysis utilising a Nextclade typing tool. The phylodynamics of RSV, genetic diversity, and evolutionary patterns were analysed using IQ Tree and BEAST software. The sequence phylogenetic analysis revealed a notable level of genetic diversity among the RSV strains in South Africa. In this study, the analysis showed that all study strains belonged to the GA2.3.5 and GB5.0.5a genotypes, which were predominant during the whole study period. These genotypes have been characterised previously and are circulating globally as the predominating genotypes. The phylogenetic analysis of the G-gene showed that strains responsible for the South African epidemic observed during the COVID-19 resurgence in 2020-2021 formed distinct clusters with contemporary strains from various geographic origins, suggesting continuous minor introduction within South Africa. Furthermore, the estimated mean evolutionary rates for RSV-A and RSV-B were found to be 1.48 × 10⁻³ and 1.92 × 10⁻³ nucleotide substitutions/site/year, respectively. The genetic diversity patterns in GA2.3.5 and GB5.0.5a genotypes were similar according to the Bayesian Skyride plot analysis. Our results suggest that the COVID-19 lockdown in South Africa caused a minor bottleneck suggesting other strains ceased to circulate, then followed by increased diversity as restrictions were lifted, indicating increased circulation of this variants. The relaxation of COVID-19 restrictions in South Africa led to a surge in the off-season RSV epidemic among children. This increase in cases can be attributed to the presence of pre-existing strains, which may have been able to spread in the paediatric population that is immunologically naïve or have waned immunity. Therefore, it is crucial to conduct genomic sequencing to gain insights into the circulation patterns of RSV and the diversity of RSV strains. Given the need to comprehensively understand the RSV evolutionary patterns and its impact on vaccine effectiveness, it is imperative for genomic surveillance strategies to focus on and prioritize the use of whole genome sequencing.
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    NUT midline carcinoma in the state sector of the Free State province, South Africa
    (University of the Free State, 2020-06) Roets, Antoinette Elisabeth; Goedhals, Jacqueline
    Background: NUT midline carcinoma (NMC) is a recently described, rare tumour that can easily be mistaken for a number of other tumours if a NUT immunohistochemical stain is not performed. The tumour is caused by a translocation involving the NUT gene and most cases involve BRD4 - NUT t(15;19) which results in loss of differentiation and uninhibited proliferation. The loss of differentiation is responsible for the monomorphic, primitive morphology of the tumour. The reporting Pathologist should have a high index of suspicion as the tumour shows positively for numerous immunohistochemical markers that vary from case to case. Positivity for CD34, which is unusual in carcinomas, together with positivity for cytokeratins, is a strong diagnostic clue that should prompt testing for the tumour. Previously thought to occur only in midline structures and young patients, recent research has proven the occurrence in a wider age distribution and outside the midline. This tumour is exceptionally aggressive, with only isolated survivors and early identification and aggressive treatment is needed. No research on NMC has been done in South Africa and there is only one case report from the rest of Africa. The incidence of this tumour in South Africa is therefore unknown. Aim: The aim of this study was to determine the number of cases of NMC seen over a twelve year period by the Department of Anatomical Pathology, University of the Free State and National Health Laboratory Service and to describe the demographic features of any patients identified. Methods: A retrospective study was performed. All undifferentiated malignant tumours and tumours with evidence of squamous differentiation from the head, neck and thorax seen between 1 January 2005 and 31 December 2016 were included. A NUT immunohistochemical stain was performed on all cases. The stain was regarded as positive if there was speckled nuclear staining in more than 50% of the tumour cells. Results: Four hundred and ninety eight cases were included in the study of which 424 (85.1%) were male and 74 (14.9%) were female. The mean age was 58.6 years. Only one positive case was identified. The patient was a 30-year-old female with a lung mass and lymph node metastases. Conclusion: This study confirms the rarity of this entity. Additional research is needed in other provinces of South Africa, including the private sector to provide a comprehensive patient profile of NMC in South Africa.
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    Renal cell carcinoma diagnosed by the Department of Anatomical Pathology at the University of the Free State, South Africa: a 10 year histopathological review
    (University of the Free State, 2020) Muller, Louis Johannes; Van der Westhuizen, Gerhard
    Background: Globally, the incidence of renal cell carcinoma varies widely between populations and geographic areas, with the lowest incidence reported in Africa. Very little information is available on the epidemiology or histopathological profile of renal cell carcinoma (RCC) in the South African population, and most studies on RCC in Africa are from Nigeria. The determination of the incidence, demographic and histopathological features of RCC would provide the latest and most up to date information on RCC epidemiology in the state sector in central South Africa and would serve as a foundation for future research. Aim: The purpose of this study was determine the number of cases of RCC seen over a ten year period by the Department of Anatomical Pathology, University of the Free State and National Health Laboratory Service and to describe the demographic profile of the patients identified as well as the histological spectrum. We further aimed to determine the agestandardised incidence rate (ASR) of RCC for state sector patients from the Free State Province. Methods: A retrospective descriptive review with an analytical component was performed. All histologically confirmed cases of RCC identified between 1 January 2005 and 31 December 2014 were included in the study. The pathology reports were reviewed to collect the demographic information for each case and the H&E slides were reviewed to confirm the diagnosis and the specific histological subtype. ASRs were calculated using the population data from the South African census as performed in 2011. ASRs were only calculated for the Free State Province and patients from the North West and Northern Cape Provinces were excluded for these calculations as the department does not receive all the specimens from these two provinces. Results: A total of 105 patients with RCC were diagnosed with a male:female ratio of 1.2:1 and a mean age of 55.1 years. The age standardized incidence rate for the Free State province was 0.4 per 100 000 population. Ten patients (9.5%) were younger than 40 years. The majority of cases were identified in the age group 50 to 59 years (33.3%). The majority of patients (58.1%) were black and they were found to present on average a decade earlier than white patients. The most common histological subtype was clear cell RCC (58.1%). Patients diagnosed with papillary RCC were found to be significantly more likely to be male than female (72.7% vs 27.3%; p=0.03) and were also more likely to be black than white (81.8% vs 13.6%; p<0.01). Patients with chromophobe RCC were more likely to be female (80%) and black (60%). Two cases of a new entity, clear cell RCC with giant cells and emperipolesis were identified. All five patients with MiT family translocation RCC were diagnosed in black females. Conclusion: To our knowledge this is the most comprehensive study on RCC performed in our region. Our study demonstrated that the incidence of RCC in our population is lower than reported in the rest of the world. The age distribution correlates closely with other African studies, with black patients presenting a decade earlier than white patients. In addition, our findings identified distinct age, sex and racial differences for the various RCC subtypes, which warrants further research.