A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.

AIMS: The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. METHODS: Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2-4, 5-6, 7 and 8-10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. RESULTS: For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was kappa 0.54 for Gleason score groups 2-4, 5-6, 7, 8-10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, kappa 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2-4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. CONCLUSIONS: Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted.

A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility.

AIMS: To test the effectiveness of a teaching resource (a decision tree with diagnostic criteria based on published literature) in improving the proficiency of Gleason grading of prostatic cancer by general pathologists. METHODS: A decision tree with diagnostic criteria was developed by a panel of urological pathologists during a reproducibility study. Twenty-four general histopathologists tested this teaching resource. Twenty slides were selected to include a range of Gleason score groups 2-4, 5-6, 7 and 8-10. Interobserver agreement was studied before and after a presentation of the decision tree and criteria. The results were compared with those of the panel of urological pathologists. RESULTS: Before the teaching session, 83% of readings agreed within +/- 1 of the panel's consensus scores. Interobserver agreement was low (kappa = 0.33) compared with that for the panel (kappa = 0.62). After the presentation, 90% of readings agreed within +/- 1 of the panel's consensus scores and interobserver agreement amongst the pathologists increased to kappa = 0.41. Most improvement in agreement was seen for the Gleason score group 5-6. CONCLUSIONS: The lower level of agreement among general pathologists highlights the need to improve observer reproducibility. Improvement associated with a single training session is likely to be limited. Additional strategies include external quality assurance and second opinion within cancer networks.

Rare case of primary lymphoma of the prostate: giving the patient the benefit of the doubt.

One third of non-Hodgkin lymphomas are extranodal, however it is uncommon for the lower urinary tract to be involved. We present an unusual case of a low-grade primary lymphoma affecting the prostate, which responded well to radical radiotherapy.

Scleromyxoedema-like changes in four renal dialysis patients.

We describe four renal dialysis patients from our hospital who, over a 6-month period, developed erythematous, thickened, indurated dermal plaques. The plaques were limited to the limbs and in three patients there were associated flexion contractures. The clinical features most resembled scleromyxoedema. All patients had previously received at least one renal transplant. Histopathology of the plaques showed features of scleromyxoedema in two patients, whereas the other two showed a different picture, more suggestive of a morphoea-like process. There are important differences between our patients and classical scleromyxoedema. All four patients had normal immunoglobulins and no paraprotein was detected. Almost all cases of classical scleromyxoedema are associated with an IgGlambda paraproteinaemia. We have not yet identified an underlying cause for this cluster of cases in our hospital. It is possible that the skin changes seen may have been precipitated by an environmental agent, such as in 'toxic oil syndrome' and vinyl chloride-induced scleroderma. We discuss the differences between our patients and those with scleromyxoedema, localized or generalized morphoea and environmentally induced scleroderma. We feel that our patients show a constellation of features similar, but not identical, to scleromyxoedema. There has been only one previous report of similar patients. We believe this to be a new and distinct phenomenon.

Testicular seminoma presenting 22 years after treatment for extra-gonadal germ-cell tumour.

We report an interesting case of testicular seminoma in a 57-year-old man who had received treatment for a pulmonary extra-gonadal seminoma 22 years previously. This case indicates that patients with extra-gonadal germ-cell tumours should either be followed up for life or, if discharged, should be informed of the potential risk of developing testicular tumour in the future and advised of the need for regular self-testicular examination.

Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure.

BACKGROUND AND AIMS: Renal failure occurs in approximately 55% of patients with acute liver failure. We have previously shown that plasma endothelin 1 concentrations are elevated in patients with acute liver failure and the hepatorenal syndrome. There are few reported satisfactory animal models of liver failure together with functional renal failure. In this study, a rat model of acute liver failure induced by galactosamine that also develops renal failure was first characterised. This model was used to investigate the hypothesis that endothelin 1 is an important mediator involved in the pathogenesis of renal impairment that occurs in acute liver failure. METHODS: Acute liver failure was induced in male Sprague-Dawley rats by intraperitoneal injection of galactosamine together with treatment with the endothelin receptor antagonist Bosentan. Twenty four hour urine collections were made using a metabolic cage. Renal blood flow was measured in anaesthetised animals. RESULTS: This model developed renal failure and liver failure in the absence of any significant renal pathology, and with an accompanying fall in renal blood flow. Plasma concentrations of endothelin 1 were increased twofold following the onset of liver and renal failure (p<0.05), and there was significant upregulation of the endothelin receptor A (ET(A)) in the renal cortex (p<0.05). Administration of Bosentan prevented the development of renal failure when given before or 24 hours after the onset of liver injury (p<0.05) but had no effect on liver injury itself, or on renal blood flow. CONCLUSIONS: This study demonstrates that this animal model has many of the features needed to be regarded as a model of renal failure that occurs in acute liver failure. The observation that plasma levels of endothelin 1 and ET(A) receptors are increased and upregulated, and that renal failure is prevented by an endothelin antagonist supports the hypothesis originally put forward that ET(A) is important in the pathogenesis of renal failure that occurs in patients with acute liver failure.

Liver tumours due to endometriosis and endometrial stromal sarcoma.

BACKGROUND: Endometriosis can occur in unusual sites, liver involvement being first described in 1986. Extra-uterine malignant transformation in endometriosis has been reported, occurring mainly in the ovary. Liver involvement with endometrial stromal sarcoma (ESS) has not been previously reported. CASE OUTLINE: Two patients presenting with symptomatic liver masses related to endometriosis, who successfully underwent surgical intervention, are presented. CASE 1: A 31-year-old woman previously had been treated with hysterectomy and bilateral salpingoophorectomy for severe pelvic endometriosis. Six years later, she presented with malaise from bilobar liver involvement with endometrial deposits. She proceeded acutely to hilar obstruction with obstructive jaundice and portal vein thrombosis. CASE 2: A 59-year-old post-menopausal woman had earlier presented acutely from a ruptured mesenteric cyst, which showed features of endometrial stromal sarcoma (ESS). Two years later, she presented with symptoms from a large ESS occupying the right lobe. DISCUSSION: Endometriosis per se, as well as malignant transformation into ESS can involve the liver.These should be considered in women with hepatic space occupying lesions of unknown etiology.

An investigation into the spatial relationship between prostate intraepithelial neoplasia and cancer.

The distribution of high grade prostate intraepithelial neoplasia (PIN) and cancer was analysed in 18 separate areas from 89 radical prostatectomy specimens that had been sectioned and digitally imaged. When the occurrence of each type of pathology was summated a predilection was demonstrated for both pathologies in the apex of the prostate and a linear relationship was found between the frequency of cancer and high grade PIN (r(2)=0.744, P<0.05). This relationship was strongest at the apex (r(2)=0.621, P<0.005), lower in the midgland (r(2)=0.828, P<0.05) and bordered on significance at the base (r(2)=0.621, P<0.063). These results support the theory that cancer could obliterate high grade PIN as it over grows the areas once occupied by PIN.Prostate Cancer and Prostatic Diseases (2001) 4, 97-100

Pure small cell carcinoma of the prostate.

Pure small cell carcinoma of the prostate is a rare anaplastic tumour. This report presents the clinicopathological findings of two patients presenting with this disease. Immunohistochemistry was positive for protein gene product 9.5, neurone specific enolase and calcitonin. Staining was negative for prostate specific antigen and prostate acid phosphatase. androgen ablation has no place in the management of this lesion and patients with this disease should be managed as if they have a neuroendocrine tumour.

Massive colonic haemorrhage from a solitary caecal varix.

A 51 year old lady with chronic active hepatitis presented with massive lower gastrointestinal tract bleeding. Angiography demonstrated a solitary varix in the caecum which was found at laparotomy to be entering the bowel wall at the site of adhesion from a previous appendicectomy. The portal pressure was found to be raised. A right hemicolectomy stopped the blood loss, but she subsequently died of liver failure. Solitary colonic varices associated with adhesions are extremely rare and their optimal management has not been established.

Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis.

Hepatocellular carcinoma arising in a patient with genetic haemachromatosis, without cirrhosis, has only been described once previously. We present a patient with a 15 year history of genetic haemachromatosis who underwent resection of a hepatocellular carcinoma in a liver with normal architecture.