Implications of Observer Variation in Gleason Scoring of Prostate Cancer on Clinical Management: A Collaborative Audit.

BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in men. Histological tumour grade is a strong predictor of outcome and helps determine what treatment options are offered. There are numerous studies on Inter-observer agreement/variability on prostate cancer grading. In this study, we were looking to establish if disconcordance between pathologists when grading prostate cancer, could affect treatment options offered to men. METHODS: In Greater Manchester West Cancer Sector, all prostate cancer biopsies undergo a central review by three pathologists with a special interest in urological pathology prior to referral for treatment at specialist centres. 96 prostate biopsies (from 48 patients) from a District General Hospital were reviewed during a 6-month period (March 2014-September 2014). The original Gleason Score assigned was compared with the uropathologists consensus diagnosis established at the central review meeting. Any changes in patient risk and treatment plans were subsequently reviewed. RESULTS: Of the 96 biopsies discussed at central review meeting, 24 (25%) biopsies from 19 patients underwent a change in Gleason grade and a subsequent change in risk for 13 (68%). Of the 19 patients, management plans could be affected for 9 patients (47%) and treatment options could potentially be affected for 5 (26%). CONCLUSION: This study shows that where disconcordance between pathologists is present, there is the potential to affect patient management. A central review process can help to minimize the effect over or undergrading can have on the patient and should be considered a necessary step in the management of prostate cancer.

Interobserver variability amongst gastrointestinal pathologists in assessing prognostic parameters of malignant colorectal polyps: a cause for concern.

BACKGROUND: Malignant colorectal polyps (MCRP) have become a major challenge in the field of coloproctology from diagnosis to full treatment. One important facet of the challenge is the histopathological staging of the lesion and identifying various prognostic parameters. The primary aim of this study was to find the interobserver variation amongst 4 experienced gastrointestinal pathologists when assessing important parameters and staging systems (Haggitt, Kikuchi and Ueno) in MCRPs. METHODS: Four experienced gastrointestinal pathologists independently assessed 56 cases of MCRP, and each pathologist completed a pro forma for each case. The results were collated and statistically analysed. RESULTS: There was a significant variation in the assessments using the various published staging systems agreed upon on important prognostic parameters. CONCLUSIONS: None of the staging systems used is suitable for all polyp types or has good reproducibility. There is an urgent need to make pathologists' assessment of MCRPs easier and more reproducible.

Prostate biopsy handling: special tiss1ue embedding technique with sponges affects the yield of prostatic tissue available for microscopic examination.

Prostate cancer is considered as the second most frequently diagnosed malignancy and the sixth leading cause of cancer death in males. The quality of the prostate biopsy and its processing techniques may influence the outcome of the histopathological assessment which is the gold standard for cancer diagnosis. An audit of 240 prostate biopsies from 20 patients was conducted to compare the quality and length of tissue before and after the implementation of sponge embedding technique. The average length of prostatic biopsy before the procedure was 5.8 mm (range 1-15 mm) and the average length after implementation of the procedure was 9.5 mm (range 2-17 mm). This equates to a total of 60% increase in tissue volume after implementation of sponge embedding. A simple modification in the embedding of prostate biopsy in the laboratory resulted in higher quality biopsies available for histopathological examination.

Histological grading of tumour regression and radiation colitis in locally advanced rectal cancer following neoadjuvant therapy: a critical appraisal.

AIM: Locally advanced rectal cancer is commonly treated by neoadjuvant therapy and the resultant tumour response can be quantified histologically. This therapy may also induce radiation colitis, which also can be graded. The aim of this study was to assess the grading of tumour regression and of radiation colitis and their relationship to other prognostic parameters. METHOD: Between 2000 and 2006, 75 patients (23 women; median duration of follow up, 58 months) with rectal cancer were evaluated. Sixty-three had short-course radiotherapy and 12 had long-course radiotherapy. Tumour regression was graded histologically using the three-point Ryan system: patients with grades 1 and 2 were considered as responders and patients with grade 3 were considered as nonresponders. Radiation colitis was graded histologically as mild, moderate or severe, as described previously (J Pathol 2006; 210: P25). RESULTS: Twenty-nine patients were classified as responders and 46 as nonresponders. The former were less likely to be lymph node positive compared with the latter (P=0.001). Tumour response did not correlate with local recurrence. Responders showed a disease-free survival (not overall survival) advantage at 2 and 5 years over nonresponders. Responders showed a higher rate of postoperative abdominal complications. Histological evidence of regression was demonstrated in patients treated with short-course radiotherapy. There was no relationship between radiation colitis grade and abdominal complications. CONCLUSION: Radiation colitis grade does not correlate with postoperative complications. More abdominal complications occurred in patients receiving long-course radiotherapy.

Radiation bowel disease and its clinical implication.

Pre-operative radiotherapy may induce radiation colitis and tumour regression. Histological evaluation of radiation colitis needs to be reproducible to assess disease progression. The severity of radiation colitis can be assessed and graded according to its histological features. Increased severity of disease appears to be associated with a higher degree of cellular atypia and a lesser eosinophilic infiltrate. The severity of histological changes does not appear to be associated with post-operative complications. Tumour regression is an interesting phenomenon, the histological grading of which is of prognostic importance. Patients treated with long course radiotherapoy appear to have more incidences of postoperative complications. However, these are though to be related to the degree of tumour regression rather than to the type of radiotherapy.

Inflammatory bowel disease: the problems of dysplasia and surveillance.

Patients with ulcerative colitis and colonic Crohn's disease are at an increased risk of developing colorectal malignancy. The reporting of such cases in the literature has led to the identification of a number of risk factors for the development of mucosal dysplasia and cancer. The diagnosis of dysplasia and the subsequent management, however, are not without controversy, as is the practice of surveillance colonoscopy that is commonly performed in an attempt to reduce the risk of cancer.

METH-2 silencing and promoter hypermethylation in NSCLC.

The antiangiogenic factor METH-2 (ADAMTS-8) was identified in a previous dual-channel cDNA microarray analysis to be at least two-fold under-represented in 85% (28 out of 33) of primary non-small-cell lung carcinomas (NSCLCs). This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed. Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs. DNA methylation analysis of the proximal promoter region of this gene revealed abnormal hypermethylation in 67% of the adenocarcinomas and 50% of squamous cell carcinomas, indicating that epigenetic mechanisms are involved in silencing this gene in NSCLC. No homozygous deletions of METH-2 were found in lung cancer cell lines. Allelic imbalance in METH-2 was assessed by an intronic single nucleotide polymorphism (SNP) assay and observed in 44% of informative primary samples. In conclusion, the downregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease.

Aneursymal bone cyst of the proximal phalanx of the thumb in a child.

Aneursymal Bone Cysts (ABCs) involving the hand are a rare occurrence. We report a case of an ABC of the proximal phalanx of the thumb in a boy which was treated successfully with curettage and autologous bone grafting. When the diagnosis of ABC of the small bones of the hand is entertained, prompt therapeutic intervention is indicated because of the potential for aggressive local behaviour. In the paediatric patient, simple surgery to preserve the growth plate is recommended.

Ruptured abdominal aortic aneurysm in a 12-month-old boy.

A rare case of abdominal aortic aneurysm in a 12-month-old boy is reported. The clinical presentation was one of acute catastrophic rupture. The morphologic and histologic findings suggested an idiopathic etiology.

Spontaneous coronary artery dissection in a healthy postmenopausal woman.

Spontaneous coronary artery dissection (SCAD) is rare and when it occurs is most commonly seen in young females following childbirth. We report a case of a 55-year-old female who was found dead at her home. She had no history of cardiovascular disease. She smoked approximately 10 cigarettes per day. She complained of mild chest discomfort the night before her death, lasting for 10 minutes, for which no medical attention was sought. She had been seen and appeared well 15 minutes before death. At autopsy, the only abnormality was in the left anterior descending coronary artery, which showed a two cm segment with periluminal blood in the wall of the vessel compressing the lumen. Histologically, a dissection was seen between the media and the external elastic lamina of the affected artery. There was a mixed inflammatory infiltrate including eosinophils and very occasional giant cells. Alcian blue staining was negative. The appearances were those of a localised dissection. The remaining coronary arteries were free of atheroma. SCAD should be suspected in young females in their postpartum period presenting with chest pain since emergency treatment can greatly increase survival.

Mortality in epilepsy in the west of Ireland: a 10-year review.

BACKGROUND: Sudden and unexpected death is not an uncommon event in otherwise healthy epileptics. AIMS: To study the autopsied cases of sudden death in known epileptic patients in the West of Ireland. METHODS: A retrospective study was carried out which involved the review of 3,103 autopsy reports over a 10-year period in Galway University Hospital. RESULTS: Twenty-two cases were classified as sudden, unexpected death in epilepsy (SUDEP). Forty-five per cent had been found dead in bed. The mean age was 38 years and 68% were males. Of 16 cases with data about antiepileptic drug (AED) levels, 68% had absent or low levels at postmortem. Eighty-eight per cent of the cases had a past history of a generalised seizure. Pulmonary oedema was present in 86% of cases at postmortem. CONCLUSIONS: Compliance with treatment and frequent nightly observations to those at high risk of sudden death may help to minimise its incidence. The patients and their families should be aware of this potential outcome.