Browsing by Author "Pillay, Komala"

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    Open Access
    Beware of 'normal' creatine kinase levels in HIV-associated polmyositis
    (2010) Heckmann, Janine; Pillay, Komala; Kenyon, Christopher R
    Generalised weakness may be a common complaint of persons infected with HIV, but the development of significant proximal weakness requires specific attention. Polymyositis may occur in HIV infection and is readily treatable with prednisone. Elevated creatine kinase (CK) levels have been regarded as an important criterion for diagnosing polymyositis. A study of HIV-associated polymyositis reported similarly elevated CK levels to those observed in non-HIV settings.1 However, muscle inflammation can be associated with normal or near-normal CK levels. We report 4 cases of HIV-associated polymyositis in which the diagnosis was almost missed owing to the absence of raised CK levels.
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    Biliary atresia at Red Cross War Memorial Children's Hospital: A retrospective descriptive study reviewing the age of presentation, clinical course and outcome of infants presenting to RCWMCH with biliary atresia
    (2016) Levin, Lindsey Nicola; Goddard, Elizabeth; De Lacy, Ronalda; Pillay, Komala
    Background: Biliary atresia (BA) is a progressive obstructive cholangiopathy of unknown aetiology, occurring during the perinatal period. If left untreated it rapidly progresses to hepatic fibrosis and cirrhosis, with death occurring within 2 years. It is the leading cause of end-stage liver disease in the paediatric population and remains the most common indication for paediatric liver transplantation in South Africa. Objectives: Despite a wealth of information from developed countries, very little information is available in Africa and other developing nations. This study aimed to describe the age of presentation, clinical course and outcome of infants presenting to Red Cross War Memorial Children's Hospital (RCWMCH) with BA. Methods: A retrospective folder review was conducted on all patients with BA presenting to RCWMCH between January 2003 and December 2013. The main outcomes assessed were median time to presentation to tertiary services, clearance of jaundice post Kasai procedure (bilirubin <20μmol/L) and 2- and 5-year overall survival (OS) and survival with native liver (SNL). Results: The median age at presentation in the 80 cases reviewed was 70 days. Kasai procedure (KP) was performed in 62 (77.5%) patients at a median age of 68 days. 18 patients who presented late did not undergo KP. Clearance of jaundice was achieved in 39% of KPs. 13 patients underwent KP beyond 90 days with a success rate of 38%. 2- and 5-year SNL rates were 41% and 37.5% respectively with OS of 59% at 2-years and 56% at 5-years. Liver transplant was only performed in 12 of the 54 patients who showed progression to require transplantation. Conclusions: Jaundice clearance post KP and SNL compared favourably with international figures, however, lower overall survival rates reflected lack of access to transplantation. Age at KP was not a predictor of poor outcome.
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    Cytohistologic correlation of suspected Cervicofacial Head & Neck Extra-Pulmonary Tuberculosis in children: A retrospective case series
    (2023) Jackson, Christopher; Pillay, Komala; Peer Shazia
    Background Tuberculosis (TB), especially extrapulmonary TB, is a difficult diagnosis to make in children due to the paucibacillary nature of paediatric disease and difficulty in obtaining sputum and tissue samples for microbiology confirmation. Lymphadenopathy in children with suspected cervicofacial TB are amenable to FNA or surgery for further cytological and histological assessment. It is therefore important to understand how well the morphologic features (from cytology and histology) correlate with defined reference standards (TB culture and molecular evidence of MTb) for the diagnosis of TB and the reliability of these features. Aim The aim of the study is to determine how well the cytology and histology-made TB diagnoses in children with suspected cervicofacial EPTB correlates with TB culture and MTb PCR results. Materials and methods This is a descriptive retrospective study that involved a re-appraisal of all patients with suspected cervicofacial EPTB who had histology and cytology performed at Red Cross Children's Hospital identified from the National Health Laboratory Service (NHLS) Trakcare system over a 5 year period (2012-2017). Following identification of histopathology accession numbers, histopathology reports and slides were retrieved from the archive of the Division of Anatomical Pathology/ National Health Laboratory Service, Red Cross Children's Hospital, Cape Town for evaluation. In addition, results for Genexpert testing and TB culture were identified using the National Health Laboratory Service (NHLS) Trakcare system. In patients that did not have either of the above, MTb PCR testing was performed. Results Data from the reports of 76 children with suspected cervicofacial TB were included in this study. More biopsies were submitted for histology (48) than for cytology (22). Six children had biopsies for both cytology and histology done. Most children had suspected and confirmed TB involvement of the cervical lymph nodes. On histology, the feature that correlated the best with proven TB was necrotising granulomatous inflammation (79.5% of cases had confirmed TB). On cytology, necrotising inflammation, necrotising granulomatous and non-necrotising granulomatous inflammation correlated well with proven TB. The sensitivity of cytology was 77.3% against TB culture and 81.8% against GXP for TB diagnosis. Whilst for histology the sensitivity was 82.5% against TB culture and 90.3% against GXP as reference standards for TB diagnosis. Conclusion FNA for cytology is a safer procedure with less complications than biopsy for histology. Also, the use of cytology together with a GXP renders a rapid and accurate diagnosis of TB and our findings are supportive for the combined use of these modalities as first line investigations. However, every attempt should still be made to obtain a sample for TB culture (as the WHO recommended gold standard for TB confirmation).
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    Identifying Children with Constitutional Mismatch Repair Deficiency (CMMR-D) Syndrome in the Expanding Lynch Syndrome population in Cape Town
    (2021) Tu, Sindy Jen-Yi; Pillay, Komala; Ramesar, R; Wessels, A
    INTRODUCTION: Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome is a rare tumour predisposition and polyposis syndrome that presents in childhood. It is caused by mutations in mismatch repair (MMR) genes that result in a tumour spectrum including colorectal cancers, high-grade gliomas, non-Hodgkin T-cell lymphomas and leukaemias. It is characterized by biallelic germline mutation of one of four possible MMR genes resulting in loss of protein expression that can be identified by applying immunohistochemistry to formalin fixed paraffin embedded tissue sections. Use of MMR immunohistochemistry is established in the setting of Lynch syndrome (LS); however, the pattern of loss of staining in the background, non-tumour tissue is unique to CMMR-D syndrome. CMMR-D syndrome is seen in LS families and occurs as a result of consanguinity or founder effect. The South African population has LS families concentrated in the Western Cape and Northern Cape Provinces and the mixed ancestry population shows a unique MLH1 c1528C>T mutation which may have implications on the incidence, penetrance and severity of CMMR-D syndrome seen in our population. The diagnosis of CMMR-D syndrome includes clinical findings outlined in the European Consortium's Care of CMMRD document and confirmation of the biallelic mutation in one of the MMR genes. MMR immunohistochemistry can be used in the diagnosis of CMMR-D syndrome by identifying cases for targeted molecular genetic tests. However, MMR immunohistochemical staining patterns are not usually described in detail, particularly the loss of staining of the affected gene in the background, non-tumour tissue, the key feature of CMMR-D syndrome. METHODS: We performed a retrospective analysis of archival formalin fixed paraffin embedded tissue of children attending Red Cross Children's Hospital with tumours that form part of the CMMR-D spectrum, outlined by the Care for CMMRD criteria. We used the criteria of high-grade gliomas (WHO Grade III or IV) occurring before 25 years of age, cutaneous lesions suggestive of CMMR-D syndrome and patients with a first or second degree relative diagnosed with LS. MMR immunohistochemistry was applied, and the staining pattern was documented in terms of proportion of tumour staining and intensity of staining using a modified Allred Scoring system. Specific attention was given to the characterization of the staining pattern of the background normal tissue. RESULTS: 21 samples taken from 18 patients were evaluated. 16 samples represented brain tumours, predominantly high-grade gliomas. Three samples were excluded due to suboptimal staining despite positive external controls. 12 samples showed intact staining of all four MMR stains. Two samples showed staining of unknown significance. Four samples from 3 different patients showed staining patterns compatible with MMR deficiency. This included two patients, each with a biopsy showing high-grade glioma and two samples of the same patient taken at a 1-year interval of a Burkitt lymphoma. Of these four samples, three samples showed loss of staining in background non-tumour tissue with positive external control, the unique staining pattern for CMMR-D syndrome. These cases will be referred for confirmatory testing by molecular genetic techniques. CONCLUSION: MMR immunohistochemistry can be used in the evaluation of CMMR-D syndrome, but care is needed in evaluating adequacy of staining, the pattern and scoring of staining of both the tumour and the background non-tumour tissue. Endothelial cells are easy to identify and evaluate as background tissue which is useful in extra-intestinal tumours. Neurons and choroid plexus can also be evaluated as background tissue in brain tumour samples. Selection bias in this study resulted in the underrepresentation of lymphomas and colorectal carcinomas. Improved characterization and search for Non-Hodgkin T-cell lymphomas and inclusion of samples of colorectal carcinomas of adolescents and adults would be needed to include these tumours. Use of MMR immunohistochemistry in postmortem tissue samples is not recommended because of suboptimal staining, even with a short post-mortem interval of 1 day. The diagnosis of CMMR-D syndrome depends on clinical application of Care for CMMRD criteria, MMR immunohistochemistry in conjunction with molecular genetic testing. It is important to identify cases of CMMR-D syndrome and offer cancer screening to prevent development of other cancers in the index patient. It also provides an opportunity for genetic counselling and testing of the parents and at-risk siblings.
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    Juvenile pilocytic astrocytomas: A search for prognostic markers
    (2022) Osman, Naeem; Pillay, Komala
    Introduction: Juvenile pilocytic astrocytomas are one of the most frequent central nervous system tumours occurring in children. While they are classified as WHO Grade I tumours, their natural progression is difficult to predict with some patients suffering significant morbidity and mortality despite showing similar light microscopic features. Activation of the MAPK pathway of cell proliferation is a consistent finding in these tumours. Studies of these tumours are largely aimed at components of this pathway in an effort to establish reliable prognostic and predictive markers. Aims and objectives: Our study was aimed at reviewing the light microscopic features and also evaluating the BRAF, p16 and protein kinase ERK components of the MAPK pathway. The findings thereof were correlated with the clinical picture to establish if these markers have any prognostic or predictive value. Materials and methods: The total number of cases retrieved was 62. The light microscopic findings were evaluated. The cases were analysed for overexpression of BRAF by fluorescence in-situ hybridisation and p16 and pERK by immunohistochemistry. Our findings were considered statistically significant if P < 0.05. Results: There were no specific light microscopic findings present in those cases associated with disease progression and recurrence. BRAF overexpression was associated with better clinical outcomes (P=0.03). There was no statistically significant correlation between p16 and pERK expression and patient outcomes. Conclusion: Overexpression of BRAF in juvenile pilocytic astrocytomas is associated with better clinical outcomes. BRAF may still serve as a therapeutic target and reduce risks associated with surgery, especially in tumours that are not surgically accessible. Further evaluation of p16, pERK and other components of the MAPK pathway of cellular proliferation will undoubtedly be useful in identifying therapeutic targets for those patients who experience disease recurrence and progression.
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    Morphological classification of childhood medulloblastomas with β-catenin immunohistochemistry and mycn fluorescent in situ hybridization
    (2015) Okiro, Patricia Opon; Pillay, Komala
    Medulloblastoma is the most frequently occurring childhood malignant brain tumour, affecting 1 of 5 children presenting with a brain tumour, between the ages of 0 and 9 years. The basic prognostic stratification that relies on clinical and histological findings alone has proven unsatisfactory as an outcome predictor. Distinct molecular genetic profiles have been described, with four molecular variants of medulloblastoma with specific demographic and prognostic features. These are the WNT subgroup, SHH subgroup, Group 3 and Group 4 tumours. The aim of this study was to describe the expression status of β-catenin, and MYCN, using IHC and FISH respectively, and to correlate these findings with clinico-pathological and demographic characteristics and clinical outcome. Materials and Methods This study was a nested retrospective analytical study, reviewing 54 cases of childhood medulloblastoma diagnosed between 1988 and 2014. Results Classic histology accounted for 40.7% of cases, LCA 37%, ND 16.7% and 5.6% MBEN). Based on β-catenin IHC, the WNT subgroup accounted for 16.7% of cases. This group had no mortalities or recurrences. Seven patients showed amplification of MYCN gene. The SHH group, defined by ND/MBEN histology and/or MYCN amplification, accounted for 27.7% of patients. Non-WNT/non-SHH tumours 30 patients (55.6%) showed a male predilection, and accounted for 37.5% recurrences and 50%. mortalities also falling in this group. Conclusions Nuclear β-catenin identifies WNT tumours. Nodular desmoplastic morphology is useful in identifying some, but not all cases of SHH group medulloblastomas. MYCN positive tumours also showed classical, and LCA morphology.. Patients of all the beta-catenin positive cases were free of recurrence and alive at last follow up. Patients with MYCN amplification and non-ND histology (LC/A or classic) had poorer outcomes than patients with ND histology. One patient showed both MYCN amplification and nuclear β-catenin translocation, and had good clinical outcome. This finding requires validation with other molecular techniques.
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    A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma
    (BioMed Central Ltd, 2011) Pillay, Komala; McCleod, Heather; Chetty, Runjan; Hall, Pauline
    BACKGROUND: Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma. METHODS: Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology. RESULTS: There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup. CONCLUSION: This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.
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    A study to investigate the role of P27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma
    (2006) Pillay, Komala; Govender, Dhiren
    Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. To investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma. Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submtted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions peformed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.
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    A ten year retrospective study of the aetiology and outcome of crescentic glomerulonephritis in children presenting to the Red Cross Children's Hospital, Cape Town, South Africa
    (2017) Mwaba, Chisambo; Gajjar, Priya; Nourse, Peter; Pillay, Komala
    Background: Crescentic glomerulonephritis represents the extreme end on the spectrum of glomerular injury. It can result from a wide range of disease conditions and clinically is marked by a rapid deterioration in renal function over days, weeks or months. Although rare, crescentic glomerulonephritis is an important entity to recognize because prompt treatment can improve patient outcomes significantly. Literature on the prevalence, clinical presentation, aetiology and outcome of histologically proven crescentic glomerulonephritis among children, in Africa, is scanty. Most of what is known about this entity is extrapolated from adult studies and from paediatric studies that have for the most part been conducted outside the African continent. Objective: This study was conducted in order to determine the incidence, clinical presentation, aetiology and outcome of histologically proven crescentic glomerulonephritis in children presenting to the Red Cross Children's Hospital, Cape Town, South Africa. Methods: This was a retrospective folder review in which the renal biopsy records of children less than 18 years old who had had native kidney biopsies performed between 2004 and July 2015 at the Red Cross Children's Hospital were reviewed. The clinical notes of patients found to have been diagnosed with crescentic glomerulonephritis were traced so as to extract demographic and clinical information which was then recorded onto the study data sheet. No attempt to contact patients or their families was made. Data analysis with regard to the incidence, the clinical features and the outcome of crescentic glomerulonephritis was done using SPSS version 22. Results: A total of 470 native kidney biopsies were performed in the period under review. Of these, 24 had crescentic glomerulonephritis, accounting for an incidence of 5.1 %. The sub-types of crescentic glomerulonephritis were immune-complex in 19 (80%), Pauci-immune in 2 (8 %), unspecified type in 3 (12 %) and no child had the anti-glomerular basement membrane subtype. The underlying aetiology of the immune complex sub-type was post-infectious in 11(57.9%), idiopathic in 4(21%), HSP/IgA nephropathy in 2 (10.5%), SLE in 1 (5.3%) and mesangiocapillary glomerulonephritis in 1(5.3%). Fourteen of the subjects were male thus giving a male to female ratio of 1.4 while the mean age of the children was 8.3 [range- 1 to 14 years]. The commonest clinical features were hypertension (90%), nephrotic range proteinuria (80%), macroscopic haematuria (57%), oedema (94%) and anaemia (88%). None of these had a statistically significant association to the renal outcome. Ten (77%) out of the 13 children with crescentic glomerulonephritis who were followed up for more than a year were found to have either died, had residual renal dysfunction or been transplanted at the last clinical contact. Conclusion: Crescentic glomerulonephritis was diagnosed in 5.1% of paediatric native renal biopsies which is consistent with what has been reported elsewhere. Unlike reports from other geographical areas the vast majority (80%) of the cases had immune-complex glomerulonephritis with a suspected post-infectious aetiology in over half of these. Similar to earlier reports from South Africa the outcome was poor in most (77%) of the patients. Further research is required to characterise the factors that make post-infectious glomerulonephritis particularly severe in this population.
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    The prevalence of different human papillomavirus genotypes in lesions of the uterine cervix as a method in risk assessment of cervical cancer
    (2025) Dittrich, Corneli; Pillay, Komala; Ikumi, Nadia
    Cervical cancer carries significant morbidity and mortality worldwide and presents a global health challenge. Despite longstanding screening programmes for precursor lesions, there remains a high incidence and prevalence of disease. Cervical cancer is caused by persistent infection with Human Papillomavirus (HPV), a sexually transmitted, oncogenic virus. There are more than 100 different HPV genotypes. Of these, studies have largely shown that the high- risk types 16 and 18 account for most cancers. However, with improved screening methods, other genotypes in particular HPV 31, are also emerging as significant. It is therefore important that there is an increase in National health education drives, opportunistic cervical screening and management programmes, particularly in low-income and middle-income countries (LMICs) where the bulk of cervical cancer cases and cancer-related deaths occur. The South African health system is disparate in that most women do not have access to adequate screening and that a small percentage of women with access to private healthcare are prone to over-screening. There is access to prophylactic vaccination, however, the only formal program available exists in the public setting, with vaccination against two oncogenic HPV genotypes, types 16 and 18. Given that other genotypes are emerging as significant causes of cancer across other settings globally, there is need for data on the prevalence of the different high-risk HPV genotypes in the South African population. Adequate data regarding prevalence of specific High-risk genotypes will also guide vaccination choices. Aim: To establish the prevalence of the different high-risk Human Papillomavirus genotypes in precursor and malignant lesions of the uterine cervix within a South African cohort. To compare our results to published data on prevalence of different HPV genotypes to South African statistics, Sub-Saharan African statistics and global statistics. Method: This was a cross-sectional, retrospective study using data from a pre-existing anonymised database that was created during the validation of the BD Viper as a new platform. There are two main arms to the study: Cytopathology and Histopathology. In both, the prevalence of the different high risk HPV genotypes will be established in different cohorts. The former in different screening groups and the latter on confirmed cases of malignancy. HPV genotyping is available on different platforms with different assays. For this study the focus is on PCR-based tests. Other methodologies such as linear array will be included in the literature review. Available PCR tests include the Cepheid Test on the GeneXpert platform, the Roche assay on the Cobas® platform and the BD OnclarityTM assay on the Viper system. The former two tests report HPV 16, 18 and a pool of ‘other' high risk genotypes on LBC samples. The latter offers extended genotyping, beyond 16 and 18 on LBC and formalin fixed paraffin embedded tissue samples (FFPE). This study therefore aims to report on the results from screening of the routine LBC samples for diagnostic co-tests performed on Roche Cobas® 6000 HPV Test used as a validation benchmark for the BD OnclarityTM HPV Assay. In addition, the study will include the analysis of the findings on the performance of the BD OnclarityTM HPV Assay on the genotyping of formalin fixed paraffin embedded tissue samples of proven cervical squamous cell carcinoma and adenocarcinoma for validation purposes of FFPE testing. Results: In the first group in the cytology arm of the study (NILM, ASCUS and LSIL) the three most prevalent high-risk genotypes for all LBC samples were HPV P2 (HPV types 56, 59 and 66) at 23%, P3 (HPV types 35, 39 and 68) accounting for 18% and type 31 at 14%. Among high-grade precursor lesions (HSIL and AGC) on cytology HPV 16 was the most frequently detected genotype, accounting for 33% of the total genotypes identified, followed by HPV P3 (HPV types 35/39/68) [17%], HPV 52 (11%), and HPV P1 (HPV types 33/58) [9%]. V The other high-risk genotypes in precursor lesions are HPV P3 (HPV types 35/39/68), HPV 52 and HPV P1 (HPV types 33/58), and in invasive carcinoma are HPV 18, HPV P3 (HPV types 35/39/68) and HPV 45. There were neither squamous cell carcinomas nor adenocarcinomas diagnosed on LBC and therefore no genotype analysis was performed. On the histopathology samples of squamous cell carcinoma HPV 16 was the most frequently detected genotype, accounting for approximately half (49%) of the genotypes identified, followed by HPV 18 (13%), HPV P3 (HPV types 35/39/68) [9%], and HPV 45 (9%). In cervical adenocarcinoma HPV 18 was the most frequently detected genotype, accounting for 50% of the total genotypes identified, followed by HPV 16 (23%), HPV 45 (14%), and HPV P3 (9%). An interesting finding was that of multiple HPV oncotypes detected in single cases. Conclusion: HPV 16 is the most common genotype in high-grade precursor lesions and invasive squamous cell carcinoma. HPV 18 is the most common genotype in invasive adenocarcinoma of the uterine cervix. The other high-risk genotypes in high-grade precursor lesions are HPV P3 (35/39/68), HPV 52 and HPV P1 (33/58), and in invasive carcinoma are HPV 18, HPV P3 (35/39/68) and HPV 45. For better comparison assays should match, as our pooled group results does not distinguish between individual oncotypes. Further studies and a South African meta-analysis are needed. We recommend that for adequate vaccine prevention of carcinoma of the cervix, in addition to HPV 16 and HPV 18 more genotypes should be included i.e. vaccination with the nano valent vaccine which offers protection against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58. As an added benefit vaccination with this vaccine also protects against genital warts (condyloma acuminata) caused by HPV types 6 and 11.
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    The relationship between BRAF genetic alterations and the risk of tumour recurrence in Pilocytic Astrocytomas in children diagnosed at Red Cross Children's Hospital over a 33-year period
    (2024) Viljoen, Nandi; Pillay, Komala; Ramburan Amsha; Singh, Shivhani; Ikumi, Nadia
    Introduction: Pilocytic astrocytomas (PAs), glial-derived neoplasms, are the most common central nervous system (CNS) tumours reported in the paediatric population. 1 PAs are circumscribed astrocytic gliomas associated with a favourable overall survival and thus regarded as low grade by the World Health Organisation (WHO), with a reported five-year survival rate between 75% to 100%. 2,3 Optimal treatment of partially resected, deep anatomic location and recurrent tumours are challenging. Over the past decades, PAs have been the object of an increasing number of molecular studies which tried to identify favourable and unfavourable prognostic factors. Essentially all PAs harbour genetic aberrations resulting in the deregulation of the MAPK signalling pathway, with BRAF gene mutations being the most frequent. 4 However, reports on the impact of specific mutations on patient prognosis are controversial. 5–8 Advances in molecular techniques have opened the door for further studies to determine the relationship between these BRAF alterations (point mutations and gene fusions) and the risk of tumour recurrence. Purpose: The overall aim of this study was to determine if BRAF genetic alterations impact patient prognosis. This was done by evaluating the expression of BRAF using immunohistochemistry (IHC), fluorescence-in-situ hybridisation (FISH) and polymerase chain reaction (PCR) and comparing it to tumour recurrence. The results will also be compared to clinicopathological findings. Methods: Study design: A retrospective cohort laboratory-based study included all cases diagnosed with PAs that presented to Red Cross Children's Hospital (RCC) from January 1984 to December 2016. Patient selection and data collection: Convenient sampling was done by searching the electronic laboratory information database (Disa and NHLS TrakCare) of the Division of Anatomical Pathology for all cases diagnosed with PAs. Data collection included: age at diagnosis, tumour site, management and recurrence. Laboratory methods: Archived stained slides of all the cases were reviewed, the diagnosis was confirmed on histology, and tissue blocks were retrieved. The presence of BRAF genetic aberrations were examined using immunohistochemistry, FISH and PCR. Results: Sixty-nine paediatric patients with PAs were identified over the study period with a median age of 6 years. This included 33 females and 21 males (in 15 cases the gender was not documented). Most tumours (62.32%) were located in the cerebellum, followed by the cerebral hemisphere (18.84%). The tumour recurred in 21 individuals, of which 3 had incomplete surgical resections. 46.16% of supratentorial tumours recurred compared to a recurrence risk of only 20.93% in infratentorial tumours. BRAF immunohistochemistry was negative in all the cases, and FISH studies did not show BRAF rearrangements. Conclusion: The findings of this study were broadly consistent with published literature in terms of age at presentation, location of the tumour and tumour location concerning the risk of recurrence. While most studies revealed an equal or slight male predominance, this study showed that the tumour developed slightly more frequently in females. Our study did not find a correlation between the risk of recurrence and BRAF genetic aberrations.