Search PubMed⌕ Search

Biomedical subjects

R Chetty

Publications and source records attributed to R Chetty.

At least 55 records · Page 3Linked to original sources

Gastric adenocarcinoma--a perspective from Durban, KwaZulu-Natal.

KwaZulu-Natal is not a recognised 'hot-spot' for gastric cancer. The purpose of this paper was to ascertain the clinicopathological features of a cohort of cases encountered in the province. Data for 124 cases were collected and analysed for age, gender, race, tumour size, histological type, lymph node status and Helicobacter pylori status. The majority of cancers occurred in the 6th and 7th decades, irrespective of sex and race. More cases were encountered in males than females. The average tumour size was 4.5 cm, two-thirds of cases presented with lymph node metastases, and the vast majority of cases were of the intestinal histological subtype. Only 50 of the 124 cases contained microscopically demonstrable H. pylori organisms. While not as common as in the Western Cape and Japan, gastric cancer in KwaZulu-Natal has similar clinicopathological features to those found in these two high-risk areas.

Adenocarcinoma↗

Follicular thyroid carcinoma with rhabdoid phenotype.

The aim of this paper is to highlight the occurrence of an unusual histological variant of follicular carcinoma of the thyroid. Three cases are presented: each of the tumours contained a significant population of rhabdoid cells (accounting for 30-40% of the total tumour content). They were all found in female patients aged 65, 43 and 56 years, who presented with enlarged thyroid glands and were subjected to lobectomies. The tumours contained foci of well-differentiated follicular carcinoma, with areas of capsular and vascular invasion, and an accompanying rhabdoid cell component that merged with the neoplastic follicles. Immunohistochemically, the follicular component was positive with thyroglobulin, but the rhabdoid cells were negative in all three cases. The cytoplasmic aggregates in the rhabdoid cells were strongly positive for epithelial markers and vimentin. Two tumours pursued an aggressive biological course similar to other composite extrarenal rhabdoid tumours. A rhabdoid component accompanying thyroid follicular carcinomas is an adverse prognostic factor.

Adenocarcinoma, Follicular↗

Loss of retinoblastoma protein expression is frequent in small cell neuroendocrine carcinoma of the cervix and is unrelated to HPV type.

We have previously identified an inverse relationship between p53 and retinoblastoma protein (pRb) immunoreactivity in non-small cell carcinoma of the cervix. Because pRb is infrequently expressed in small cell carcinoma of the lung, we analyzed 25 small cell neuroendocrine carcinomas of the cervix to test the hypotheses that 1) lack of pRb expression is associated with the neuroendocrine phenotype in human papillomavirus (HPV)-associated cervical carcinoma and 2) the inverse relationship between p53 and pRb immunoreactivity also occurs in these tumors. HPV type was analyzed by PCR, HPV distribution by in situ hybridization and expression of p53 and pRb by immunohistochemistry. All of the tumors contained HPV sequences, with 13 tumors HPV 16 positive, 11 HPV 18 positive, and 1 HPV 45 positive. In situ hybridization showed large intranuclear dot-like signals in all positive tumors, suggesting viral integration. No multiple infections were identified. Expression of retinoblastoma protein was not detectable in 23 tumors (92%), the remaining two showing only weak, focal expression. Expression of p53 protein was variable in distribution and intensity. It did not correlate with HPV type, and there was no relationship with pRb immunoreactivity. These data indicate that, although there is no reciprocal relationship between p53 and pRb immunoreactivity in these tumors, retinoblastoma protein is infrequently expressed in HPV-containing small cell neuroendocrine carcinoma of the cervix, irrespective of infecting HPV type. This is consistent with the reported findings in small cell carcinoma of the lung and suggests that the small cell neuroendocrine phenotype may be related to the abrogation of retinoblastoma protein function.

Carcinoma, Neuroendocrine↗

Arterial aneurysms in patients infected with human immunodeficiency virus: a distinct clinicopathology entity?

Arterial aneurysms have only recently been associated with the human immunodeficiency virus (HIV). The clinical and pathological features of 10 HIV-positive patients with arterial aneurysms were retrospectively evaluated. These aneurysms were unusual in that they affected young black patients, occurred in atypical sites, and tended toward multiplicity. Surgery was performed in eight patients. Acute and chronic inflammatory changes were revealed by means of histologic examination of the aneurysm walls, with occlusion of the vasa vasora by inflammatory infiltrate or edema being a prominent feature. Culture of the aneurysm wall or thrombus yielded positive results in two patients. The association between HIV and aneurysms may be coincidental, caused by direct viral action or by bacterial infection resulting from immunosuppression. Implications for therapy are discussed, and the need for further study is highlighted.

Adolescent↗

Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis.

Cytokines such as tumour necrosis factor-alpha and interferon gamma are associated with active pulmonary inflammation in sarcoidosis and they upregulate inducible nitric oxide synthase (iNOS). The objectives of this study were to examine iNOS upregulation in sarcoidosis by showing raised exhaled nitric oxide and increased iNOS activity in lung biopsy specimens of these patients utilizing immunohistochemistry. Exhaled NO was measured by a chemiluminescence analyser in 12 patients with newly diagnosed biopsy-proven sarcoidosis before and after 6 weeks of corticosteroid therapy. Lung biopsy specimens from these patients were subjected to immunohistochemical staining with a specific iNOS antibody. Exhaled NO was raised in newly diagnosed sarcoidosis (mean+/-SEM): 9.8+/-0.4 versus 4.1+/-0.2 parts per billion (ppb) in 21 healthy controls, p<0.001; and fell significantly after 6 weeks treatment with corticosteroids to 5.9+/-1.4 ppb; p<0.01. There was no correlation between exhaled NO and other markers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoidosis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosis and may be a result of inducible nitric oxide synthase upregulation. The fall in exhaled nitric oxide following corticosteroid therapy may reflect inhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.

Adult↗

Pacinian collagenoma.

An unusual histological variant of collagenoma is described. A 36-year-old woman presented with a lump in the left hypothenar eminence. Histological examination revealed a well-delineated lesion composed of paucicellular collagen fibres arranged in concentric lamellations giving rise to an onion skin appearance. The overlying epidermis was thin and the lateral borders were demarcated by an epidermal collarette. Inflammation and xanthoma cells were absent and occasional capillaries were present. The lesion was positive for collagen stains, reticulin and CD34. This lesion represents an uncommon histological form of collagenoma or fibroma. It can be distinguished from histological look-alikes on the basis of the characteristic morphology and immunophenotype.

Adult↗

Bcl-2 and p53 immunoprofile in Kaposi's sarcoma.

Seventy three cases of Kaposi's sarcoma (KS) from the 3 histological subtypes (patch, plaque and nodular) were assessed for bcl-2 and p53 protein expression. The aim was to determine the level of expression of these proteins in KS and in the different subtypes. Commercially available antibodies to bcl-2 and p53 were applied after both microwave and pressure cooking antigen retrieval. Bcl-2 immunoexpression increased from the patch stage (36%) to the plaque stage (45%) to the nodular stage (70.83%). Better immunostaining for bcl-2 was obtained after pressure cooking. p53 on the other hand, was not expressed in the patch or plaque stages, but 54.16% of cases in the nodular stage were immunopositive. These results show a progression of immunoexpression of both bcl-2 and p53 from the early histological stages to the late tumor stage, implying that these proteins are upregulated late in the evolution of KS.

Acquired Immunodeficiency Syndrome↗

p53 and cyclin A protein expression in squamous carcinoma of the oesophagus.

The aim of this study was to explore the relationship between p53 and cyclin A immunostaining in squamous carcinomas of the oesophagus. It has been shown that both these proteins are overexpressed in poorly differentiated endometrial carcinomas. Fifty oesophagectomy specimens were analysed for p53 and cyclin A immunoexpression. This was correlated with patient age and gender and tumor stage and grade. Forty-two percent of cases were p53 positive, while 94% of the squamous cancers expressed cyclin A protein. Neither protein showed any statistically significant correlation with clinicopathological parameters. This study has demonstrated that only 42% of oesophageal squamous carcinomas from South Africa express p53 protein, while the vast majority (94%) express cyclin A protein. Neither of these proteins showed any relationship to each other or any clinical feature or the tumor grade or stage.

Adult↗

Epstein-Barr virus status and the histopathological changes of parotid gland lymphoid infiltrates in HIV-positive children.

This study examined the EBV status and the morphology in parotid glands of a large cohort of HIV-positive pediatric patients. Nineteen children with vertically acquired HIV infection, ranging in age from three months to seven years and two months, were analyzed. Seventeen patients were assessed for serological evidence of EBV infection; nine showed evidence of past infection, one each re-activation and current infection and six did not have serological evidence of EBV. Immunohistochemistry and in situ hybridization for EBER 1 and 2 were performed on formalin-fixed, paraffin-embedded tissue. Fourteen of the 19 cases were classified as severe or established myoepithelial sialadenitis (MESA) and five were regarded as having mild MESA. The majority of intraepithelial lymphocytes were of B-cell lineage, while the pericystic infiltrate contained CD8-positive T-lymphocytes. p24 immunohistochemistry for HIV showed positive follicular dendritic cells, lymphoid cells and macrophages. Ten of 14 cases were positive for EBER 1 and 2. These included cases that were serologically negative for EBV. This study confirms that the morphology and immunophenotype of pediatric HIV-associated parotid lesions are similar to those seen in adults. Ten of 14 cases with evidence of EBV within the lymphoid infiltrate showed the same morphology and immunophenotype as cases in which EBV was not detected either by serology or by in situ hybridization. These findings indicate that EBV is not uniformly found in either the tissue or serum of these patients, and may not have a pathogenetic role in HIV-associated lymphoepithelial lesions in the pediatric age group.

Child↗

Heterotopic pancreas, periampullary somatostatinoma and type I neurofibromatosis: a pathogenetic proposal.

This case documents the association of ectopic pancreatic tissue with a duodenal somatostatinoma in a patient with type I neurofibromatosis. Pancreatic ducts have been noted within the centres of somatostatinomas, but little significance has been attached to this finding. Here we describe a patient in whom a separate proliferation of somatostatin cells occurred in association with the ectopic pancreatic ductular epithelium. This lesion bore a striking resemblance to the ductulo-insular or ductulo-endocrine complexes that are seen in nesidioblastosis in the pancreas. We therefore postulate that the ducts, which are sequestered within somatostatinomas, are of pathogenetic significance. The somatostatin-producing cells arise from these ducts, very much in the fashion of ductulo-endocrine complexes in nesidioblastosis.

Adult↗

Cyclin E in human cancers.

Regulators of the cell cycle such as cyclin E play an important part in neoplasia. The cyclin E protein forms a partnership with a specific protein kinase. This complex phosphorylates key substrates to initiate DNA synthesis. Cyclin-dependent kinase inhibitors (CKIs) are able to suppress the activity of cyclin E. Various substances (including proteins produced by oncogenic viruses) affect cyclin E directly or indirectly through an interaction with CKIs. These interactions are important in elucidating the mechanisms of neoplasia. They may also provide prognostic information in a wide range of common cancers. Cyclin E may even be a target for treatment of cancers in the future.

Breast Neoplasms↗

Cytomegalovirus-induced syringosquamous metaplasia.

An unusual case of syringosquamous metaplasia of the eccrine ducts caused by cytomegalovirus (CMV) is presented. The patient was HIV positive and had extensive excoriation of the perineum and vulva. Biopsy revealed the presence of herpes simplex virus (HSV) inclusions in the necrotic exudate, a CMV vasculitis and extensive involvement of the eccrine ducts. In addition to containing typical CMV inclusions, the eccrine ducts showed proliferation and squamous metaplasia. Inclusions of HSV were not seen within the eccrine ducts by light microscopy or immunohistochemistry. The extensive proliferation with accompanying squamous metaplasia superficially can resemble an infiltrating squamous carcinoma, but this was not evident to a great extent in this case. To the best of our knowledge, our case represents the first of syringosquamous metaplasia of eccrine ducts caused by CMV infection.

AIDS-Related Opportunistic Infections↗

Allelic imbalance and microsatellite instability in chromosomes 2p, 3p, 5q, and 18q in esophageal squamous carcinoma in patients from South Africa.

Microsatellite polymerase chain reaction (PCR) and fluorescent DNA technology was used to assess allelic imbalance (AI) or loss of heterozygosity (LOH) and microsatellite instability (MSI) in chromosomes 2p, 3p, 5q, and 18q in esophagectomy specimens from 39 patients who had squamous carcinoma and who lived in a high-incidence geographic location in South Africa. The squamous carcinomas were graded by conventional light microscopy and staged using the tumor-node-metastasis (TNM)-Union Internationale Contre Le Cancer (UICC) criteria. The DNA was isolated using proteinase K digestion and standard phenol-chloroform extraction procedure. Microsatellite PCR was performed using fluorescent, CY5-labeled primers for the following markers: D2S123 (2p), D3S659 (3p), D3S1255 (3p), D5S346 (5q), DCC (18q), D18S34 (18q), and D18S58 (18q). These markers were chosen because they are the most frequently used and most informative markers for these particular gene loci. Results were analyzed using software attached to an automated DNA sequencer. Molecular changes obtained were correlated with clinicopathologic parameters. Molecular analysis did not correlate with clinicopathologic features, such as tumor grade, stage, or lymph node status. No correlation with patient outcome was seen, though only limited follow-ups were obtained. Rates of MSI and LOH on 3p and 18q in these specimens are similar to the range seen in studies from other geographic areas. However, a striking point of departure is the high LOH (30% of informative cases) seen on 2p.

Adult↗

Vasculitis-induced membranous fat necrosis.

Membranous fat necrosis (MFN) a distinct degenerative process of adipose tissue, is characterised by the presence of membranocystic lesions (MCLs) superimposed on a background of typical traumatic-type fat necrosis. MCLs are cysts, of varying size and shape, that are lined by an eosinophilic, crenulated membrane, having the staining properties of ceroid. Although MFN has been documented in varying systemic adipose tissue sites and in tumours, the pathogenesis of this pathological curiosity is unknown. To date, an ischemic basis for MFN has been the most proximate, and atherosclerosis and venous insufficiency, due to large and medium vessel disease, have been the most popular underlying clinical disorders. Although systemic vasculitis has been quoted as the underlying ischemic disorder in some patients, vasculitis has not been commented on nor demonstrated in tissue sections in association with MFN. In,reporting vasculitis-induced MFN, we document the occurrence of MFN in association with uncommon causes of vasculitis, namely: 1) Granulomatous vasculitis in a post-herpetic zosteriform scar; 2) Cytomegalovirus-induced vasculitis in the clinical setting of systemic lupus erythematosus; and 3) Lymphocytic vasculitis in a tetanus toxoid immunization site reaction.

Adolescent↗

Coexistent gastric MALT lymphoma and Kaposi sarcoma in an HIV positive patient.

A 47 year old HIV positive male presented with haematemesis and epigastric pain. A gastrectomy was performed for intractable bleeding. The cause of the haematemesis proved to be a Kaposi sarcoma of the stomach which had resulted in mucosal ulceration. Several other smaller foci of Kaposi sarcoma were also present. Coexistent with the Kaposi sarcoma was a dense lymphoid infiltrate with lymphoid follicles and reactive germinal centres. Centrocyte-like cells caused marked effacement and destruction of gastric glands with the formation of lymphoepithelial lesions, typical of a MALT lymphoma. These cells were of B cell lineage and some expressed the HIV antigen, p24. Follicular dendritic cells and macrophages within germinal centres were also p24 positive. Immunohistochemistry and in situ hybridisation did not detect Epstein-Barr virus. Although Helicobacter pylori was not identified by light microscopy in the sections sampled, this does not preclude its possible role, with other cofactors such as HIV, in the causation of the MALT lymphoma.

Gastrectomy↗

DNA repair gene status in oesophageal cancer.

DNA repair genes and microsatellite instability (MSI) are relatively recently described molecular events that have been associated particularly with colorectal cancers in the setting of hereditary non-polyposis colorectal cancer or the Lynch syndromes. Several other gastrointestinal (and other) malignancies have been analysed for abnormalities in DNA repair genes and MSI. Dietary and environmental factors have been implicated strongly in the aetiology of oesophageal cancer. However, the effect of this on the genetic profile, especially the DNA repair system and resultant MSI, is largely unknown. The purpose of this review is to provide a brief background of the dietary and environmental factors in oesophageal carcinogenesis and to discuss the role of the repair genes and MSI in the molecular pathogenesis of this malignancy. Several studies indicate that MSI (range, 3-40%) and loss of heterozygosity (LOH) (range, 3-64%) in the DNA repair genes are uncommon in carcinogenesis of the oesophagus. Most data are at the lower end of the ranges and this, together with the lack of uniform criteria for the assessment of MSI, accounts for the higher figures obtained in some studies. The rates of detection of MSI do not approach that of other gastrointestinal malignancies, such as gastric (up to 23%) and colorectal (up to 31%) carcinomas.

DNA Repair↗

Gastro-intestinal Kaposi's sarcoma, with special reference to the appendix.

Kaposi's sarcoma (KS) of the gastro-intestinal tract is a common disease in the AIDS setting, although it is often asymptomatic. In this paper we wish to highlight the occurrence of gastro-intestinal KS with appendiceal involvement. Two of the patients presented with features of acute appendicitis, and KS of the appendix was not suspected at the time of surgery. In the remaining patient KS of the appendix was part of generalised gastro-intestinal involvement. It is important to remember that KS can cause appendicitis by producing a submucosal nodule that abuts into the lumen and thereby causes obstruction. KS of the gastro-intestinal tract may therefore masquerade as 'simple' appendicitis, or indeed remain asymptomatic.

Acquired Immunodeficiency Syndrome↗