Search

Pathological specimens from columnar-lined oesophagus ( CLO) comprise a considerable proportion of the workload of gastrointestinal pathologists in Western countries. There remain controversies concerning the diagnostic role of pathology. More recently, in the UK at least, the diagnosis has been regarded as primarily an endoscopic endeavour, with pathology being corroborative and only diagnostic when endoscopic features are equivocal or when there are additional features that make the endoscopic diagnosis unclear. There is also recognition that demonstration of intestinalisation or 'goblet cells' is not paramount, and should not be required for the diagnosis. There have been notable changes in the management of CLO neoplasia: pathologists are centrally involved in its management. Pathological assessment of endoscopic mucosal resection ( EMR) specimens provides the most useful means of determining the management of early neoplasia and of determining indications for surgery. This represents an extraordinarily rapid change in management, in that, <10 years ago, laborious Seattle-type biopsy protocols were recommended, and high grade dysplasia was an indication for resectional surgery. Now, individual patient management is paramount: multi-professional meetings determine management after biopsy and EMR assessment. One significant change is that major resections are undertaken less often, in Western countries, for CLO neoplasia. [ABSTRACT FROM AUTHOR]

Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression analysis to identify potential pathways in serrated adenomas. An initial panel of 9 sessile serrated adenomas (SSA) and one TSA were analysed using Illumina Goldengate HumanLinkage panel arrays to ascertain regions of loss of heterozygosity. This was verified via molecular inversion probe analysis and microsatellite analysis of a further 32 samples. Methylation analysis of genes of interest was carried out using methylation specific PCR (verified by pyrosequencing) and immunohistochemistry used to correlate loss of expression of genes of interest. All experiments used adenoma samples and normal tissue samples as control. SSA samples were found on whole-genome analysis to have consistent loss of heterozygosity at 4p15.1–4p15.31, which was not found in the sole TSA, adenomas, or normal tissues. Genes of interest in this region were PDCH7 and SLIT2, and combined MSP/IHC analysis of these genes revealed significant loss of SLIT2 expression associated with promoter methylation of SLIT2. Loss of expression of SLIT2 by promoter hypermethylation and loss of heterozygosity events is significantly associated with serrated adenoma development, and SLIT2 may represent a epimutated tumour suppressor gene according to the Knudson “two hit” hypothesis. [ABSTRACT FROM AUTHOR]

Shetty S, Anjarwalla S M, Gupta J, Foy C J W, Shaw I S, Valori R M & Shepherd N A (2011) Histopathology 59, 850-856 Focal active colitis: a prospective study of clinicopathological correlations in 90 patients Aims: Considerable controversy exists about the clinical implication of a diagnosis of focal active colitis (FAC). The aim of this study was to assess clinicopathological correlations of FAC in 90 adults, representing the largest and only prospective series of FAC. Methods and results: Patients were assessed by comprehensive clinical follow-up and questionnaires. Fifteen histopathological features were scored and correlated with clinical outcome. In 24% of patients drugs, especially NSAIDs, were implicated. Infection was a probable cause in 19%. In 14 patients (15.6%), predominantly women, a diagnosis of chronic inflammatory bowel disease was ultimately made. Most were Crohn's disease, but this is the first study in which FAC has presaged an ultimate diagnosis of ulcerative colitis in adults (in two patients). A specific subtype of FAC, termed basal FAC, was significantly associated with drugs. These excepted, this study has found no histopathological parameters of FAC, such as amount, location and/or distribution, to correlate with clinical outcome or allowed selection of those patients more likely to show subsequent evidence of chronic inflammatory bowel disease. Conclusion: This study has provided powerful information on the implication of a diagnosis of FAC. In a small but not inconsiderable case number, the ultimate diagnosis will be chronic inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Objective. In the USA, detection of intestinal metaplasia is a requirement for enrolment in surveillance programmes for dysplasia or adenocarcinoma in columnar-lined oesophagus. In the UK, it is believed that failure to detect intestinal metaplasia at index endoscopy does not imply its absence within the columnarized segment or that the tissue is not at risk of neoplastic transformation. The aim of this study was to investigate the factors predicting the probability of detection of intestinal metaplasia in the columnarized segment. Material and methods. Demonstration of intestinal metaplasia was analysed in 3568 biopsies of non-dysplastic columnar-lined oesophagus from 1751 patients from 7 centres in the UK. Development of dysplasia and adenocarcinoma was analysed in 322 patients without intestinal metaplasia and compared with that in 612 patients with intestinal metaplasia. Results. Intestinal metaplasia was more commonly detected in males than in females (odds ratio 1.244), longer segment length (10.3% increase per centimetre) and increasing number of biopsies taken (24% increase per unit increase). After 5 years of follow-up, 54.8% of patients without intestinal metaplasia at index endoscopy demonstrated intestinal metaplasia, and 90.8% after 10 years. There was no significant difference in the rate of development of dysplasia or adenocarcinoma between patients with or without intestinal metaplasia detection at index endoscopy. Conclusions. Detection of intestinal metaplasia is subject to significant sampling error. It increases with segment length and number of biopsies taken. In the majority of patients, if sufficient biopsies are taken over time, intestinal metaplasia will be demonstrated. The decision to offer surveillance should not be based upon the presence or absence of intestinal metaplasia at index endoscopy as the risk of dysplasia and adenocarcinoma is similar in both groups. [ABSTRACT FROM AUTHOR]