Masters Degrees (Anatomical Pathology)

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    Prevalence of ERG overexpression in prostate cancer on prostate biopsies at a tertiary public hospital in the Western Cape, South Africa
    (Stellenbosch : Stellenbosch University, 2023-12) McCree, Kevin; Van Wyk, Abrie; Fernandez, Pedro; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Division of Anatomical Pathology.
    ENGLISH ABSTRACT: Background: Prostate cancer is the most diagnosed non-cutaneous malignancy in men in South Africa across all race groups with 10495 new cases reported in 2019. The TMPRSS2-ERG fusion gene and resultant overexpression of ERG is estimated to occur at a rate of 30-50% within prostate cancer. The fusion gene is specific to prostate cancer and high grade prostatic intraepithelial neoplasia and has not been reported in other malignant neoplasms. The TMPRSS2-ERG fusion gene, and by implication the overexpression of ERG, may serve as a diagnostic, prognostic or therapeutic biomarker. The prevalence of the TMPRSS2-ERG fusion gene in prostate carcinoma in South Africa has not been investigated previously. We sought to determine the prevalence of the TMPRSS2-ERG gene fusion among men undergoing prostate biopsies at Tygerberg Hospital, Cape Town, South Africa and to determine whether there is an association between prostate cancer grade and ethnicity/race. Methods: This is a retrospective descriptive laboratory study where we analysed 362 prostate biopsies, diagnosed with prostate cancer, between January 2010 and December 2017. All 362 cases were reviewed, and the diagnosis was confirmed. 336 cases were stained with ERG (Cell Marque, clone EP111) an adequate surrogate marker for the TMPRSS2-ERG fusion gene. The prevalence was calculated and compared with Gleason grade group and ethnicity/race to determine if there is an association. Results: ERG overexpression was detected in 34% of cases. Our study showed an association with a lower Gleason score and ERG overexpression. There is a higher prevalence of TMPRSS2-ERG amongst the coloured population in this cohort, at 34%. Conclusions: This is the first study to characterise the prevalence of ERG overexpression in prostate cancer in patients who underwent prostate biopsies in South Africa. Our results show that this gene rearrangement is common in the study population and that the prevalence of 34% is within the range reported in international literature.
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    Placental syphilis: a comprehensive review of routine histomorphology, HIV co-infection, penicillin treatment, immunohistochemistry, and polymerase chain reaction.
    (Stellenbosch : Stellenbosch University, 2023-04) Marais, Yolandi Anne; Mason, Deidré; Barnard, Annelize; Saaiman, Chestley Rashaell; Els, Hester Christine; Kluge, Judith; Glass, Allison Joy; Wright, Colleen Anne; Schubert, Pawel Tomasz; Schubert, Pawel Tomasz; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Division of Anatomical Pathology.
    ENGLISH ABSTRACT: Introduction: Placental examination is useful to diagnose congenital syphilis. The classical histological diagnostic triad is, however, an infrequent finding. Additional morphological clues, special investigations, and knowledge of potential alterations by HIV co-infection and penicillin treatment can aid in making the diagnosis. Materials and methods: Placental specimens diagnosed with treponemal infection were reviewed. Morphological findings, IHC and qPCR results were assessed. Results: Two-hundred and twenty-two placentas were recruited. Villitis (93.2%), acute chorioamnionitis (91%) and villous immaturity (64%) were the most common abnormalities. HIV co-infection and penicillin treatment demonstrated alterations that may hamper diagnosis. Treponema IHC and q-PCR had a sensitivity of 74.4% and 25.81%, respectively and confirmed an additional 41 cases with negative or unknown serology. Conclusion: Villitis, acute chorioamnionitis and villous immaturity are the most common microscopic abnormalities in placental syphilis. HIV co-infection and penicillin treatment may alter morphology. Treponema IHC and q-PCR are useful adjuncts when serology is negative.
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    Correlating p16INK4a /Ki-67 co-expression and gene methylation with HIV infection and high-risk HPV in abnormal cervical squamous intraepithelial cells
    (Stellenbosch : Stellenbosch University, 2023-03) Louw, Meagan; Sanderson-November, Micheline; Neethling, Greta; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Anatomical Pathology.
    ENGLISH SUMMARY: Globally, cervical cancer is the fourth most common cancer amongst women. Persistent infection with high-risk human papillomavirus (HPV) is shown as the causal factor in cervical cancer development. Women living with HIV is six times more prone to cervical cancer development. The aim of this study was to identify the HR-HPV types, investigate the simultaneous expression of p16INK4a and Ki-67 and evaluate the methylation status of CADM1, MAL and miR124-2 genes in cytology samples from HIV-positive and HIV-negative women with LSIL, HSIL, ASC-US, and ASC-H Pap smear results. Study participants were women between the ages of 21 years to 60 years referred to the Colposcopy clinic at Tygerberg Academic Hospital. Exfoliated cervical intraepithelial cells were collected in Surepath medium and HR-HPV types were determined using the Hybrispot HPV direct flow chip kit, whereas the co- expression of p16INK4a/Ki-67 proteins was evaluated with the CINtec® Plus cytology immunocytochemistry kit. For methylation assays, DNA was isolated from the left-over exfoliated cells followed by the assessment of quantity and purity of isolated DNA using fluorometry and spectrophotometry, respectively. Isolated DNA was bisulfite converted and the methylation assays for the CADM 1, MAL and miR-124-2 genes were done using the respective EpiMelt assays. HPV DNA detection results were associated with cytological diagnosis as well as HIV status. In our study group 74 % (51/69; 95% CI: 62,1%-83%) of woman tested positive for HPV of which 70.6% (36/51) were of WLWH and 29.4% (15/51) of HIV negative women. Our results showed that p16INK4a /Ki-67 dual-staining was detected in 43.8% (25/57) of the samples with the HSIL cytology showing the highest p16INK4a /Ki-67 co-expression rate of 64% (16/25) compared to the other cytology groups. The proportion of the LSIL group with p16INK4a /Ki- 67 dual staining was 33,3% (4/12), whereas that of the ASC-US and ASC-H groups were 25% (2/8) and 23% (3/13) ASC-H, respectively. CADM1 methylation was detected in 12.3% (7/57) of samples, while MAL and the miR-124-2 genes showed methylation in 14% (8/57) and 12.3% (7/57)of the samples, respectively. HPV infection was detected in 28.1% (16/57) of the samples with methylated CADM1, MAL and miR-124-2 genes. A significant relationship was found between HR-HPV and miR-124-2 methylation. The logistic regression model analysis employing predictors such HR-HPV, p16INK4a and Ki- 67 co-expression, as well as the methylation status of the CADM1, MAL, and miR-124-2 genes, for LSIL cytology showed low sensitivity and high specificity, contrasting to that of the HSIL model with high sensitivity and low specificity. Therefore, we conclude that a larger study is warranted, with removing or adding predictors for model improvement.
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    Treatment of lentigo maligna of the head and neck with staged excision in South Africa : assessing surgical excision margins with Melan A, SOX10 and PRAME immunohistochemistry
    (Stellenbosch : Stellenbosch University, 2022-11) de Wet, Johann; Schneider, Johann Wilhelm; du Plessis, Pieter; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Anatomical Pathology.
    ENGLISH SUMMARY: Lentigo Maligna (LM) is a subtype of melanoma in situ that occurs on sun-damaged skin, typically on the head and neck area of older individuals. LM is associated with significant subclinical extension beyond the visible clinical margins and therefore recommended surgical excision margins may be inadequate for complete surgical clearance of the tumour. Staged Excision (SE) has emerged as the treatment of choice for LM of the head and neck. It allows for complete margin control, superior clearance, and lower recurrence rates compared to conventional wide local excision (WLE). Differentiating between actinic melanocyte hyperplasia (AMH) and LM at the peripheral margin complicates the assessment of completeness of excision when using this technique. Objectives: The study aimed to describe the patient demographics, tumour characteristics, and histological findings of LM cases on the head and neck treated with SE. Secondary objectives included: (1) To determine if standard recommended surgical excision margins for LM of the head and neck are adequate to achieve a 97% clearance rate and if any patient or tumour characteristics warranted wider margins, (2) To determine whether immunohistochemical (IHC) staining with SOX10 and PRAME aids in diagnosing LM on excision margins compared to conventional Hematoxylin and Eosin (H&E) and Melan A IHC staining. Methodology: The study involved a retrospective chart review of all patients diagnosed with LM of the head and neck and treated with SE at the Skinmatters Mohs Micrographic Surgery and Reconstructive Unit. Tissue sections of LM cases with LM reported to be present at margins were immunohistochemically stained with SOX10 and PRAME and reviewed by a Mohs surgeon and a pathologist with expertise in melanoma pathology. Results: The first component of the study showed that 6mm, 9mm, and 12mm surgical excision margins obtained complete excision in 60.94%, 71.88%, and 90.64% of the LM cases, respectively. A surgical excision margin of 18mm correlated with complete excision in 96.7% of tumors, while complete excision in 100% of LM cases required a 21mm margin. Recurrent tumors (p-value = 0.01) and tumour size larger than 20mm were associated with wider surgical excision margins (pvalue= 0.154). The second study component evaluated IHC stains and consisted of 35 sections. Based on H&E and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 cases consistent with a diagnosis of LM and 9 revealing actinic melanocyte hyperplasia (AMH). PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of AMH (p=0.009). The presence of melanocyte nests (p=0.29) and pagetoid spread (p = 0.003) were the most reliable histological findings for distinguishing LM from its mimics. Conclusion: This study of LM in a South African population corroborates that the standard surgical excision margins recommended by international melanoma guidelines for LM are inadequate to achieve a 97% clearance rate. Recurrent LM cases and tumours larger than 20mm may require wider margins. The study further concluded that SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared to Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.
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    Determining the suitability of bio-specimens obtained by fine needle aspiration biopsy at a tertiary hospital in Malawi for immunocytochemical assessment
    (Stellenbosch : Stellenbosch University, 2022-04) Mulenga, Maurice; Schneider, Johann Werner; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology.
    ENGLISH SUMMARY: Fine-needle aspiration biopsy (FNAB) is a quick, economical, least invasive and easy to perform a minor surgical procedure. In resource-limited settings, FNAB is of utmost importance in providing a rapid diagnosis that facilitates timely and correct institution of treatment. The FNAB smear preparation provides an opportunity for either rapid on-site evaluation or routine diagnosis if ancillary tests are necessary to establish a specific diagnosis. Cell blocks (CB) prepared from FNAB specimens improve the diagnostic yield, increase the sensitivity and reduce false-positive interpretations of detecting a malignant neoplasm. In addition, CB allow for additional morphological evaluation with a better architectural pattern, enable the performance of numerous ancillary diagnostic studies, including immunocytochemistry and molecular studies and offer the storage of material that can be used for future research studies. Delays in fixing the cell block have been challenges in various cell block preparatory techniques. However, a special alcohol-based fixative, commercially available solution called CytoRich Red® (CRR) has been described to be comparative to liquid-based cytology due to its effectiveness in lysing red blood cells, reducing background material, and improving staining qualities of the nucleus and cytoplasm in routine preparations of non-gynaecological material in suspension or fluids. Despite this breakthrough, there is a paucity of data on the suitability of CRR cell blocks for immunocytochemical and DNA assessment from FNAB material obtained from solid tumours. This study aimed to establish and confirm the suitability of CytoRich Red® Cell Blocks and FNAB biospecimens obtained and prepared at Kamuzu Central Hospital, Lilongwe, Malawi, for cytomorphological and immunocytochemical assessment. This study analysed 144 cell blocks and 128 FNAB smears. It is one of the first within sub-Saharan Africa to describe diagnostic efficacy from FNAB specimens obtained from various superficial and deep masses fixed in CRR. It describes the advantage of using an alcohol-based fixative immediately to reduce pre-fixation time lag. This study showed that CRR-fixed cell blocks improve sensitivity and architectural preservation, and immunocytochemical staining characteristics of the aspirate compared to routine FNAB smears. It is envisioned that CRR-fixed cell blocks will be a source of extractable, stable and usable DNA that supports research in biorepositories and biobanks.