No correlation between ras, c-myc and c-jun proto-oncogene expression and prognosis in advanced carcinoma of cervix.

55 patients suffering from stage III or IV carcinoma of cervix were treated with two pulses of neo-adjuvant chemotherapy prior to radical radiotherapy. 51% (26/51) had a partial response. The initial response to chemotherapy is associated with significantly better long-term survival. The 3-year survival of chemotherapy responders is 62% against 21% for non-responders (P = 0.009 log-rank test). To detect possible differences in oncogene expression in biopsy specimens taken from responding and non-responding patients, paraffin-fixed material was immunocytochemically stained for the expression of the protein products of ras, c-myc and c-jun proto-oncogenes. The frequency of oncogene expression was ras 80.4%, c-myc 45.1% and c-jun 39.2%. There was no statistically significant association between oncogene expression, time to local recurrence or development of metastases or survival.

Observer variability in the histopathological reporting of needle biopsy specimens of the prostate.

The Scottish Pathology Consistency Group has in previous studies examined the consistency of histopathological reporting of biopsies from the cervix, bladder, bronchus, and rectum. In the current study, consisting of 100 needle biopsy specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case was circulated in batches of 10 to the 12 pathologists, who filled in a simple proforma. This had two sections: a diagnostic category (benign; suspicious or malignant) along with a standard Gleason score for those regarded as malignant. The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and malignant, 46. The Kappa value for benign cases versus others was 0.86 and for malignant cases versus others was 0.91. Analysis of the data on Gleason scores showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to 10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although not initially part of the design of the study, the majority diagnosis was compared with the original reported diagnosis. In a small subset, examination of further levels, basal cell antibody staining, along with further clinical information, was obtained. With this added information, it appears that there were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The group therefore appeared to perform better than the original reporting pathologists. When compared with the results of our previous studies, this study has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is robust.

Inversion of the gallbladder.

A case of inversion of the gallbladder is described, in which the fundus was inverted into the body of the organ. A localized area of adenomyomatosis (adenomyoma) was present at the apex of the invertum.

Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies.

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

Cor pulmonale due to tumour embolism derived from intrasinusoidal metastatic liver carcinoma.

Two cases of primary breast carcinoma are described, both terminating in acute cardiorespiratory failure due to multiple tumour micro-embolism. In both cases the source of the emboli was extensive metastatic intrasinusoidal carcinomatous infliltration of the liver. The association of these two uncommon conditions has not previously been reported. A brief review of the literature pertaining to diffuse intrasinusoidal metastatic carcinomaof the liver and to carcinomatous pulmonary embolism is included. The latter condition may be commoner and of greater clinical significance than his hitherto been appreciated. Some of the factors which may be responsible for this peculiar type of tumour dissemination are discussed.

A cause of erroneous diagnosis of pigmented villonodular synovitis.

An unusual type of benign vascular hamartoma, which shows a curious papillary organization of thrombus and abundant haemosiderin deposition, is liable to be misdiagnosed histologically as pigmented villonodular synovitis. Nine examples of this type of lesion are briefly presented and the differential diagnosis is discussed.

Adenocarcinoma of the anal glands.

Adenocarcinoma of the anal glands is very rare but it is an important lesion to recognise as with early diagnosis, it has an excellent prognosis. Because it involves the submucosa widely and penetrates the mucosa late, it can be mistaken for metastatic gastrointestinal carcinoma, or tumour arising in sinuses and fistulae. Two cases, in a 44 year old man and a 73 year old woman, which illustrate the typical features are reported, in one of which the diagnosis was missed originally. In situ neoplastic change of the associated anal glands and secretion of mucin lacking O-acetyl groups are useful pointers.

Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry.

AIMS: The diagnosis of malignant mesothelioma in pleural biopsies can be difficult. Survival is short and consequently many of these cases are submitted to necropsy to assist with medicolegal claims. This study compares the histological appearances and immunohistochemical profile of nine biopsy specimens with corresponding postmortem specimens. METHODS: Archival, formalin fixed, paraffin wax embedded material was obtained from nine biopsy and corresponding postmortem cases of malignant mesothelioma. The specimens were examined by light microscopy and stained with an immunohistochemical panel of 12 commercially available antibodies including CAM5.2, HBME-1, and Ber-EP4, and antibodies to thrombomodulin, calretinin, CD44H, WT-1, carcinoembryonic antigen, Leu-M1, epithelial membrane antigen and p53. RESULTS: There was greater variation in the range of histological appearances of mesotheliomas in postmortem specimens compared with biopsy specimens. There was also variability in the immunohistochemical staining pattern for certain antibodies including HBME-1, and Ber-EP4 and antibodies to calretinin, CD44H, WT-1, and p53. CONCLUSIONS: All available information should be taken into account in the histological diagnosis of malignant mesothelioma. Interpretation of the immunohistochemical profile should be regarded with some caution when only postmortem material is available. When reporting a postmortem case of suspected mesothelioma, the pathologist should seek to review all available biopsy material in conjunction with the necropsy.

Effusion cytology of hepatocellular carcinoma with in situ hybridisation for human albumin.

While the cytological features of hepatocellular carcinoma on fine needle aspiration cytology are well described, cases of hepatocellular carcinoma with malignant cells in ascitic fluid and their characteristics are not. A patient is described with cirrhosis resulting from chronic hepatitis B virus infection, ascites, and hepatocellular carcinoma diagnosed by effusion cytology. The malignant cells in the effusion were shown to be positive for alpha fetoprotein using immunocytochemistry, and for human albumin using in situ hybridisation, confirming the diagnosis of hepatocellular carcinoma. Further investigations in a terminally ill patient were thus avoided.

Hepatocellular carcinoma and hepatic cirrhosis in the west of Scotland: a 25-year necropsy review.

A two-fold increase in the incidence of hepatocellular carcinoma in the west of Scotland is reported on the basis of a 25-year retrospective necropsy review (313 cases). This increase is not accompanied by a corresponding increase in the incidence of hepatic cirrhosis. The relationship between hepatocellular carcinoma and hepatic cirrhosis is discussed in the light of these findings.

Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy.

BACKGROUND: Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. AIM: To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. METHODS: The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. RESULTS: The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. CONCLUSIONS: The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control.

Observer variability in histopathological reporting of cervical biopsy specimens.

Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by kappa statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accurately between the lesser grades of CIN. It is recommended that the classification be changed to low grade (present CIN 1 and 2) and high grade (present CIN 3) categories alone. There was very poor agreement in the identification of cellular changes associated with human papilloma virus (HPV) infection.

Observer variability in histopathological reporting of malignant bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to classify lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Eleven histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing lung carcinoma. A single haematoxylin and eosin stained section from each case was circulated and a standard proforma completed. These were analysed using kappa statistics. RESULTS: The histopathologists were excellent at distinguishing between small cell and non-small-cell carcinoma kappa = 0.86), but not so good at subclassifying the non-small cell carcinoma group kappa = 0.25). CONCLUSIONS: The clinically important distinction between small cell and non-small cell carcinoma of the lung is reliably made by competent histopathologists even on limited material.

Observer variability in histopathological reporting of transitional cell carcinoma and epithelial dysplasia in bladders.

Sections from 90 urinary bladder biopsy specimens were examined by 11 consultant histopathologists with varying experience to determine the appropriateness of existing pathology terminology. Analysis with kappa statistics showed fair to good agreement in the grading and staging of transitional cell carcinoma. There was also reasonable agreement in the diagnosis of high grade dysplasia in random biopsy specimens from the urothelium adjacent to the neoplasm, but very poor agreement for lesser degrees of dysplasia. It is concluded that the present classification of bladder carcinomata is reliable and that pathologists can determine stage with a high degree of reproducibility and grade with a fair degree of reproducibility.

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS: To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS: Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS: Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn's disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION: The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.

Observer variability in histopathological reporting of non-small cell lung carcinoma on bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to sub-classify non-small cell lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Twelve histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing non-small cell lung carcinoma. For each case, two sections were circulated, one stained by haematoxylin and eosin and the other by a standard method for mucin (alcian blue/periodic acid Schiff). The participants were allowed to indicate their degree of confidence in their classification of each case. A standard proforma was completed and the results were analysed using kappa statistics. RESULTS: Where the participants were confident in their classification, they were actually quite good at sub-classifying the non-small cell carcinoma sections (kappa = 0.71, standard error = 0.058). Overall, however, the results were only fair (kappa = 0.39, standard error = 0.034). CONCLUSIONS: The majority of non-small cell lung carcinomas can be correctly categorised on adequate bronchial biopsy material. Where a confident diagnosis was made, both squamous carcinoma (kappa = 0.73) and adenocarcinoma (kappa = 0.83) were well recognised.

Coactivation of the antagonist muscle does not covary with steadiness in old adults.

The purpose of the study was to determine the association between steadiness and activation of the agonist and antagonist muscles during isometric and anisometric contractions. Young (n = 14) and old (n = 15) adults used the first dorsal interosseus muscle to perform constant-force and constant-load tasks (2.5, 5, 20, 50, and 75% maximum) with the left index finger. Steadiness was quantified as the coefficient of variation of force and the SD of acceleration normalized to the load lifted. The old adults were less steady at most target forces with isometric contractions (2.5, 5, and 50%) and with most loads during the anisometric contractions (2.5, 5, and 20%). Furthermore, the old adults were less steady when performing lengthening contractions (up to 50%) compared with shortening contractions, whereas there was no difference for young adults. The reduced steadiness exhibited by the old adults during these tasks was not associated with differences in the average level of agonist muscle electromyogram or with coactivation of the antagonist muscle.

Interobserver variability in analysis of asbestos fibres and asbestos bodies in human lung tissue.

Two different methods of quantifying asbestos fibre burden were assessed and the counts obtained were compared with semi-quantitative asbestos body counts in corresponding tissue sections. Comparison of the two methods found significantly different asbestos fibre counts between specimens. Each technique showed wide limits of agreement for reproducibility and interobserver variability as assessed by Bland-Altman plots, such that a repeated count could not necessarily be expected to lie within the same exposure category. Asbestos body counts in tissue sections were reproducible with good correlation between observers. Asbestos body and asbestos fibre counts showed correlation in some samples but not others. Counting of asbestos bodies is a valuable screening technique as the finding of asbestos bodies is accepted as a marker of significant asbestos exposure. When no asbestos bodies are identified asbestos fibres estimations may be useful in proving asbestos exposure. Different techniques are not interchangeable and each laboratory should establish a background range from unexposed individuals.

Primary cardiac leiomyosarcoma with pulmonary metastases: a diagnostic problem.

A case of primary cardiac leiomyosarcoma is reported. Tumour growth into the right ventricular cavity led to multiple pulmonary metastases with haemorrhage. Failure of diagnostic procedures including cardiac catheterisation, angiography and thoracotomy is noted. The incidence and presentation of primary malignant cardiac tumours is briefly discussed.

Haemorrhage from an adhesion-related mesenteric varix in a patient with portal hypertension.

We report a case of profuse gastrointestinal haemorrhage from an ileal varix, in a segment of bowel adherent to the site of a previous incisional hernia repair, in a patient with portal hypertension. This is a rare but recognised complication of portal hypertension. Localisation of the bleeding point was achieved by radionuclide scanning and the segment of abnormal bowel was successfully resected.