Masters Degrees (Anatomical Pathology)
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Item A morphologic and immunohistochemical appraisal of invasive breast carcinomas with neuroendocrine differentiation.(2021) Naicker, Nimallen.; Nhlonzi, Gamalenkosi Bonginkosi.; Mwazha, Absalom.Background: Invasive breast carcinomas with neuroendocrine differentiation (IBCNED) are a heterogenous group of tumours first recognised, as a distinct entity, by the World Health Organisation (WHO) in 2003. The classification of these tumours has undergone significant changes since they were first described, and the diagnostic criteria has been inconsistent amongst reporting authors. IBCNED have not been studied in the South African context, and this study aims to review the incidence, demographic profile, histopathology and immunohistochemical profile of IBCNED. Materials and Methods: A three-month retrospective study of cases with the diagnosis of invasive breast carcinomas was undertaken to determine the clinicopathologic profile of IBCNED. Results: The mean age of female patients with IBCNED was 55 years. Thirty-five (35/91, 38%) cases were positive for synaptophysin and/or chromogranin A. The tumours showed a histomorphology comparable with invasive breast carcinoma of no special type and were predominantly (33/35, 94%) moderately to poorly differentiated. The predominant molecular subtype, with 91% (33/35), was luminal B . Conclusion: IBCNED show a diverse range of histomorphologic features, similar to those seen in conventional breast carcinomas of no special type, however they do have distinct cytomorphological characteristics and show a predilection for luminal B molecular subtype. A larger cohort is necessary to confirm these findings and to expand knowledge and treatment options.Item Gastrointestinal tract plasmablastic lymphoma in HIV infected adults: a histopathological audit.(2020) Mwazha, Absalom.; Nhlonzi, Gamalenkosi Bonginkosi.Background: Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma that is characterised by the expression of plasma cell antigens and loss of pan B-cell antigens. The neoplasm is extensively reported in the oral cavity and anorectal region but rarely in the gastrointestinal tract where only isolated case reports and small case series exist. In the current study, morphologic, immunohistochemical and molecular features of 17 cases of gastrointestinal tract PBL were reviewed. Materials and Methods: Ten-year retrospective study that reappraised the histomorphological and immunophenotypic features of HIV-associated PBLs in the gastrointestinal tract that were diagnosed and coded as ‘plasmablastic lymphoma’. Results: The average age of the study patients was 41 years with a 3:1 ratio of males to females. The most frequent site of involvement was the small intestine (42%). Majority of the cases showed a predominant diffuse (82%) growth pattern. Immunoblasts and plasmablasts were observed in all cases. Sixty-five percent (65%) of the cases exhibited scattered centroblasts and one case demonstrated predominance of centroblasts. Other features observed include pseudo-alveolar growth pattern, plasmacytic differentiation, scattered multinucleated giant cells, focal clear cell change, high mitotic activity with high proliferative indices (Ki-67 >90%), apoptotic bodies and necrosis. Immunohistochemistry revealed absence of pan B-cell antigens and expression of plasma cell antigens. Epstein-Barr virus-encoded RNA was expressed in 53% of the cases. Conclusion: This study highlights the spectrum of histopathological features of gastrointestinal tract PBLs. Additional observations not previously described or emphasised in literature includes pseudo-alveolar growth pattern, centroblast-predominance, multinucleated giant cells and clear cell change. Awareness of this entity in the gastrointestinal tract and its histopathological features and immunohistochemical profile is essential for making an accurate diagnosis and avoiding potential diagnostic errors. Keywords: Plasmablastic lymphoma; HIV-related lymphoma; AIDS-related lymphoma; gastrointestinal tract; stomach; small intestine; colon.Item Progesterone related cellular change in the uterine cervix with particular reference to progesterone-only contraceptives.(1993) McCallum, Shan Merrell.; Chrystal, V.This study examines the effect of progesterone-only injectable contraceptives, and medroxyprogesterone acetate (Depo-Provera) in particular, on the cells of the uterine cervix. Cervical and vaginal smears were taken before commencement of therapy and at 3 and 6 month intervals thereafter on 79 asymptomatic women attending a family planning clinic. Results of hormonal and cellular measurements before and after therapy were compared. menstrual cycling was also studied. The effect on Methods used were hormonal maturation indices, image analysis measurements and microscopic observation of cellular . features. The latter included anisocytosis, anisokaryosis, karyomegaly , plaque formation, cytoplasmic wrinkling, nuclear grooving, hypertrophy, atrophy, cytoplasmic moulding and density, retarded maturation and nuclear protrusions. Squamous, endocervical and metaplastic cells were examined. Analysis of the results showed that progesterone-only contraceptives produce all of the above to a greater or lesser degree resulting in an increased relative nuclear area which may be confused with intraepithelial neoplasia. This is due to the production of a folate deficiency at target organ level which interferes with cell division and slows the maturation process. This effect enabled further observations to be made leading to the establishment of the origin and content of the nipple-like protrusions which occur in endocervical cells in response to hormonal activity. Physiological effects included amenorrhoea and irregular menstrual cycling. Most women showed evidence of interference with normal cycling to a varying degree. The documented cellular changes were shown to modify the expression of common inflammatory and neoplastic conditions of the uterine cervix. These included trichomoniasis, herpesvirus cervicitis, human papillomavirus infection, folate deficiency, cervical intraepithelial neoplasia and invasive carcinoma as well as multiple pathologies. The potential for diagnostic error was examined. New diagnostic criteria were formulated based on the comparison of cellular features found in the presence of the contraceptive with those found under normal conditions. It is anticipated that these criteria will facilitate the cytological diagnosis of pathological conditions of the uterine cervix in users of depo-medroxyprogesterone acetate (DMPA), leading to increased accuracy and improved and better directed patient management.Item A histopathological and immunohistochemical evaluation of scar basal cell carcinomas.(2006) Sydney, Clive.; Ramdial, Pratistadevi K.; Madaree, Anil.Infiltrative morphological mimicry at sites of biopsy-proven nodular basal cell carcinoma has been described. The immunoprofile of scar BCCs (scar BCCs,SBCCs) has not been documented. The aim of this study was to assess the histopathological spectrum, stromal (fibronectin, laminin, actin, desmin and vimentin) response and proliferation (bcl-2, MIB1 and p53) status of SBCCs. Twenty nine BCCs occurring in scars, unrelated to previous malignancy (de novo scar BCCS, DN-SBCCs), 27 BCCs that were incompletely excised and regrew at the same site (regrowth scar BCCs, RG-SBCCs) and 25 BCCs that were completely excised with tumour free margins, but recurred at the same site (recurrent scar BCCs, R-SBCCs) were accessed from the files of the Department of Pathology and Plastic and Reconstructive Surgery of the Faculty of Medicine, University of KwaZulu Natal, and formed the basis of this study. The morphological features of DN-SBCCs was pure (3%), predominantly nodular (79%), micronodular (7%) and infiltrative (11 %). RG-SBCCs were predominantly nodular (82%), micronodular (7%) and infiltrative (11%). RSBCCs were predominantly nodular (80%), micronodular (4%) and infiltrative (16%). The majority of DN-SBCCs, RG-SBCCs and R-SBCCs showed intact basement membrane laminin staining, while two (7%) DN-SBCCs showed 1 + and 2+ loss of basement membrane laminin staining. Three (11 %) and two (8%) RG-SBCCs and R-SBCCs,respectively, showed 2+ or 3+ basement membrane laminin discontinuity. The majority of DN-SBCCs (83%), RGSBCCs (75%) and R-SBCCs (88%) were actin negative. No desmin immunopositivity was demonstrated in the epithelial or stromal components of DN-SBCCs, RG-SBCCs and R-SBCCs. All BCC groups showed high 3+ or 4+ vimentin immunopositivity. The majority (>50%) of the SBCCs showed low (2+) bcl-2 immunopositivity. There was no significant difference in p53 immunopositivity in all SBCCs. SBCCs demonstrate phenotypic and immunophenotypic heterogeneity. That DN-SBCCs with the infiltrative and micronodular patterns have not recurred implies that the histomorphology is a pseudo-aggressive pattern. A similar view could pertain to RG-SBCCs, but because the scar did not cicatrise the incompletely excised BCC implies that the histomorphology of RG-BCC may be a potentially more aggressive phenotype. The recurrence of a completely excised basal cell carcinoma may be viewed as a feature of an aggressive tumour, especially when the recurrent BCC contains micronodular and infiltrative components. However, as most R-SBCCs occurred at head and neck sites that are exposed to ultraviolet light, it is also possible that these are simply new BCCs occurring within scars in head and neck sites prone to BCCs. Furthermore, these R-SBCCs were not destructive tumours. CONCLUSION: None of the infiltrative foci of DN-SBCCs demonstrated laminin loss. Three of 5 with intra-epithelial actin immunopositivity also demonstrated low bcl-2 and high p53 staining, immunoprofiling these with an aggressive infiltrative component. Of 11 RG-SBCCs with high p53 staining, 4 had high p53 staining in the infiltrative component, but only one had a low bcl-2 composite score and low bcl-2 score in the infiltrative focus. In addition, these infiltrative foci demonstrated intraepithelial MSA positivity and a "VA" immunophenotype of the stromal cells, indicating one RG-SBCC with an established, aggressive immunophenotype. Those positive with one or more, but not all, aggressive immunostains, are hypothesised to be RG-SBCCs evolving/developing an aggressive immunophenotype. Only one R-SBCC, with a predominantly infiltrative pattern, had a "full-house" of aggressive immunostaining in the infiltrative foci: low bcl-2, high p53, 2+ laminin discontinuity and intra-epithelial and stromal MSA positivity. Of significance is that 7 with a predominant nodular pattern had a high p53 score. Of these, 5 had high bcl-2 scores. Hence, while high p53 may be a feature of aggressive growth, it is important that this staining be complemented with that of bcl-2, laminin and MSA.Item A clinico-pathological and biochemical study of the toxicity of callilepis laureola (impila)(1983) Bhoola, Keshavlal Daya Narotam.; Leary, W. P. P.This study was undertaken as a result of the occurrence of a large number of deaths among the local Black population from the use of herbal medicines prepared from the rootstock of Callilepis laureola known to the Zulus as impila. The salient clinico-pathological features in these cases were hypoglycaemia, centrilobular zonal liver necrosis and acute renal tubular necrosis. The purpose of this study was to investigate fully the clinical, biochemical and pathological aspects of the toxicity produced by Callilepis laureola (impila). The first part of the investigation consisted of an assessment of all cases of death due to acute liver necrosis diagnosed by necropsy at King Edward VIII Hospital, Durban. A review of clinical and necropsy records of 21687 consecutive post-mortems performed on Black patients during a 20 year period showed that acute liver necrosis was the major contributing cause of death in 447 patients. In 263 cases the hepatic lesion was centri lobular zonal necrosis with associated acute tubular necrosis (Group A); while in 184 cases the I iver necrosis was of the massive or submassive type (Group B). A comparative assessment of these two groups as regards necropsy prevalence, age and sex distribution and the clinical, biochemical and pathological findings was undertaken. This study shows that the combination of hypoglycaemia, centri lobular zonal liver necrosis and acute renal tubular necrosis due to Callilepis laureola (impila) poisoning is a distinct clinico-pathological entity and differentiates this group from cases of acute massive and submassive liver necrosis resulting in most cases from fulminant viral hepatitis. In the search for the toxic components of the root of Callilepsis laureola several compounds were isolated. These were atractyloside, carboxyatractyloside, two thymol related oils and a carbohydrate. The thymol related oils as well as the carbohydrate were found to be non-toxic in laboratory rats. The crude methanol extract of the root of Callilepsis laureola, when injected intraperitoneally into laboratory rats, produced centrilobular zonal liver necrosis and acute renal tubular necrosis, the lesions identical to those seen in patients who had died after intake of impila prescribed by witchdoctors and other dispensers of herbal medicines. On the other hand intraperitoneal injections of the purified compound atractyloside caused acute renal tubular necrosis and hypoglycaemia in laboratory rats but failed to produce liver necrosis. Carboxyatractyloside also failed to cause liver necrosis. This indicated that there may be at least two toxins contained in the rootstock of Callilepsis laureola, one causing the liver lesion and the other (atractyloside) causing nephrotoxicity and hypoglycaemia. Repeated attempts at isolating the hepatotoxin have failed; the liver toxin or toxins being lost during the process of extraction and purification. Identification of the hepatotoxin awaits further investigation. It is possible that the liver necrosis may be caused by a metabolite or that it may be a synergistic effect of two or more compounds.