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Biomedical subjects

A R Gibbs

Publications and source records attributed to A R Gibbs.

At least 55 records · Page 3Linked to original sources

A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin.

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesothelioma. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulo-papillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thrombomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.

Antibodies, Monoclonal↗

Observer variation in the histopathological classification of thymoma: correlation with prognosis.

AIMS: To assess the ability of three histopathologists, experienced in thoracic surgical reporting, consistently to classify thymomas as cortical, medullary, or mixed pattern tumours. METHODS: Three histopathologists classified 74 thymomas (none frank carcinomas) as of either cortical, medullary, or mixed pattern, on two separate occasions. Kappa statistics were used to assess inter- and intra-observer agreement. Tumour type was compared with surgical stage as a predictor of biological behaviour. RESULTS: Inter- and intra-observer agreement were only moderate (kappa 0.48 and 0.52, respectively). For only 26 of 74 tumours could a categorisation be consistently agreed on. Follow up information was obtained for 73 cases, with a mean follow up period of five years. The prognoses for those 26 of 74 cases appeared to be at variance from previously reported studies, and showed internal inconsistency, with the mixed pattern category showing a worse survival than the cortical category. For the group as a whole, however, stage at presentation was related to survival, with an overall five year survival of 78% (100% for stage I, 84% for stage II, 27% for stage III and 0% for stage IV). CONCLUSIONS: The classification of thymomas into cortical, medullary, or mixed pattern tumours is difficult to apply. Surgical stage remains a better guide to prognosis.

Adolescent↗

Fuller's earth (montmorillonite) pneumoconiosis.

A fuller's earth worker developed signs of pneumoconiosis. Pathological examination of the lung tissues showed interstitial collections of dust laden macrophages associated with mild fibrosis. Mineralogical analysis showed a high content of montmorillonite. This study shows that a pneumoconiosis can result from prolonged heavy exposure to calcium montmorillonite (fuller's earth) in the absence of quartz. The disease is relatively mild and associated with little clinical disability.

Aged↗

Diffuse pulmonary fibrosis and the Hermansky-Pudlak syndrome: clinical course and postmortem findings.

The Hermansky-Pudlak syndrome consists of albinism, platelet function defect, pigment laden macrophases and, on occasions, pulmonary fibrosis. The clinical course and postmortem findings of a patient with pulmonary fibrosis which mimicked cryptogenic fibrosing alveolitis are reported. Histological examination revealed a chronic inflammatory infiltrate of pigment laden microphages.

Adult↗

Fiber levels and disease in workers from a factory predominantly using amosite.

The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one.

Asbestos, Amosite↗

The diagnostic implications of variable cytokeratin expression in mesotheliomas.

Immunostaining for cytokeratin has a well-established diagnostic application in distinguishing sarcomatous mesotheliomas from sarcomas based on the premise that cytokeratin expression is common in mesotheliomas but very rare in sarcomas. However, the frequency of cytokeratin detection is highly dependent on the choice of antibody. The aim of this study was to examine the distribution of simple cytokeratins and stratified cytokeratins in 45 mesotheliomas of various types and to assess the diagnostic utility of a simple cytokeratin antibody, a stratified cytokeratin antibody, and a broad spectrum cytokeratin antibody with the aim of establishing the superiority of one for routine diagnostic use. Particular attention was paid to the potential utility of these antibodies in biopsy specimens. The broad spectrum cytokeratin antibody performed better than both the simple cytokeratin antibody (paired t-test: P < 0.01) and the stratified cytokeratin antibody (P < 0.01) as a diagnostic marker of mesothelioma and should be used in preference to the other two antibodies, particularly when considering small biopsy specimens.

Antibodies↗

Pulmonary involvement by mycosis fungoides. A case showing angiocentric lesions and granulomas.

We describe an unusual case of pulmonary involvement by mycosis fungoides in a 31-year-old woman. Disseminated disease had developed despite cutaneous irradiation and systemic combination chemotherapy. Microscopy of biopsied tumour deposits in the lung showed a polymorphous, angiocentric lymphoid infiltrate, including atypical cells with convoluted nuclei which displayed a T-cell phenotype. Numerous epithelioid granulomas were also present. These histological appearances represent an unusual pattern of pulmonary involvement by disseminated mycosis fungoides.

Adult↗

The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas.

It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure.

Asbestos↗

An unusual perilobular pattern of pulmonary interstitial fibrosis associated with Crohn's disease.

Pulmonary pathology associated with inflammatory bowel disease is rare, and seldom biopsied. In this report, we describe a case of pulmonary interstitial fibrosis associated with Crohn's disease. Biopsy showed a unique pattern, with cellular fibroblastic proliferation and fibrosis affecting interlobular septa, spreading into the parenchymal interstitium from the periphery, with associated lymphoid aggregates and thickening of arterial adventitia.

Adult↗

How reliable is the diagnosis of lung cancer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party.

BACKGROUND: A study was undertaken to investigate the accuracy of typing of a series of bronchial carcinomas by experienced pathologists with an interest in lung cancer from the examination of bronchoscopic biopsy specimens. METHODS: Eighty bronchial biopsy specimens showing positive results for bronchial carcinoma were circulated to five pathologists, who recorded diagnostic criteria and diagnosis for each. Diagnoses were then compared with the diagnosis agreed from the resection specimen corresponding to each biopsy specimen. A "non-small cell carcinoma, not further specified" classification group was introduced for small biopsy specimens. RESULTS: A diagnostic accuracy of 75% was achieved for squamous cell carcinomas, 66% for small cell carcinomas, and 50% for adenocarcinomas. There was diagnostic confusion between small cell and non-small cell carcinoma in less than 10% of cases. The introduction of a non-specific non-small cell classification improved diagnostic accuracy by 10-15% for each non-small cell tumour group. CONCLUSIONS: There are appreciable inaccuracies in applying the World Health Organisation's 1981 classification of lung cancer to the diagnosis of bronchial carcinoma from small biopsy specimens and these inaccuracies have been measured. They can be diminished by introducing a less specific "non-small cell" category for use with this sort of biopsy material. Care should be taken not to overinterpret small biopsy specimens in lung cancer.

Biopsy↗

Malignant mesothelioma in women.

BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.

Adolescent↗

Percutaneous needle biopsy of the mediastinum: review of 94 procedures.

BACKGROUND: A number of reports of radiologically guided percutaneous biopsy of mediastinal masses have been described but techniques have varied, particularly the type of needle used. In this study mediastinal biopsies with fine aspiration needles and cutting needles have been compared, sometimes in the same patient. The results are reviewed with particular emphasis on the choice of biopsy needle and its influence on pathological diagnosis. METHODS: A retrospective review was undertaken of radiologically guided mediastinal biopsies performed between 1981 and 1991. RESULTS: Sixty fine needle aspiration biopsies (FNA) and 34 Tru-Cut biopsies of mediastinal masses were performed in 75 patients with fluoroscopic or computed tomographic guidance. Overall sensitivity and specificity in terms of diagnosis of malignant disease were 90% and 100% respectively for FNA biopsies, and 96% and 100% for Tru-Cut biopsies. Diagnostic accuracy in terms of precise diagnosis of the malignant or benign nature of a mass and its origin was 77% for FNA biopsies and 94% for Tru-Cut biopsies. For FNA biopsies sensitivity and accuracy were higher for carcinomatous lesions (96% and 88%) than for noncarcinomatous lesions (81% and 69%). The only significant complication encountered was a pneumothorax following a biopsy which required intercostal drainage. CONCLUSIONS: Radiologically guided percutaneous needle biopsy is a safe procedure which provides useful diagnostic information in the majority of cases. Fine needle aspiration techniques usually suffice for carcinomatous lesions but a cutting needle biopsy should be performed whenever possible when lymphoma, thymoma, or neural masses are suspected to obtain larger specimens for more accurate histological diagnosis.

Adolescent↗

'Pleural' and pulmonary carcinosarcomas.

The histological distinction between carcinosarcoma and mesothelioma has received little attention. The object of this study was to describe the histology and immunohistochemistry of two carcinosarcomas presenting as pleural tumours. These were compared with 12 carcinosarcomas from sites within the lung, and with the established features of mesothelioma. Histologically and immunohistochemically, these 'pleural' carcinosarcomas are similar to conventional pulmonary carcinosarcomas but accurate recognition is hindered by their gross appearance and biphasic histology which closely mimic mesothelioma. They may exhibit features such as neutral mucin, expression of carcinoembryonic antigen, squamous differentiation, and neuroendocrine differentiation which, when present, are evidence against mesothelioma. These tumours are rare and have passed unnoticed until now.

Aged↗

p53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections.

The distinction between reactive mesothelium and mesothelioma in pleural biopsy specimens is notoriously difficult, and conventional immunohistochemical markers have provided no relief. The object of this study was to examine the frequency of immunohistochemically detectable p53 overexpression in routinely processed, paraffin-embedded tissue from pleural mesotheliomas and from pleura showing reactive mesothelial hyperplasia, using a polyclonal antibody to formalin-resistant p53 epitopes, and to consider the diagnostic utility of this antibody in the distinction between mesothelioma and reactive mesothelium in pleural biopsy specimens. Immunostaining was enhanced by pepsin predigestion prior to the application of the primary antibody. Positivity occurred in 10/16 epithelial mesotheliomas, 9/19 biphasic mesotheliomas, 2/12 sarcomatous mesotheliomas but in none of 20 reactive pleura. Immunostaining was particularly intense in some of the biopsy specimens, which may be due to the rapidity with which these small pieces of tissue were fixed. In conclusion, this study suggests that p53 immunostaining can help to distinguish epithelial or biphasic mesothelioma from reactive mesothelial hyperplasia in formalin-fixed, paraffin-embedded pleural biopsy specimens.

Adult↗

Immunohistochemical demonstration of chromogranins A and B in neuroendocrine tumors of the lung.

Fifty neuroendocrine tumors of the lung (16 carcinoids, two atypical carcinoids/well-differentiated neuroendocrine carcinomas [WDNCs], 13 neuroendocrine carcinomas of intermediate cell type [SCNCs], and 19 neuroendocrine carcinomas of small cell type [SCNs]) were immunohistochemically investigated with antibodies against chromogranins A and B. All carcinoids and WDNCs were positive for both chromogranins A and B, whereas in cases of ICNC and SCNC both markers were only expressed in six and five cases, respectively. One ICNC was only positive for chromogranin A. In cases of SCNC five tumors were exclusively positive for chromogranin A and six were positive only for chromogranin B. Chromogranins are therefore excellent markers for the immunohistochemical demonstration of carcinoids and WDNCs. It may be speculated that expression of chromogranins in cases of ICNC and SCNC represents a higher degree of differentiation in these tumors.

Carcinoid Tumor↗

Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon.

In this study we examined intermediate filament expression in 45 formalin-fixed mesotheliomas. Immunostaining for cytokeratin was found in 86%, for vimentin in 71%, and for desmin in 4%; none stained for glial fibrillary acidic protein or neurofilament. The two biphasic mesotheliomas which expressed desmin also expressed smooth muscle actin but were negative for myoglobin. This, together with the ultrastructural findings, was taken as unequivocal evidence of a leiomyoid form of mesothelioma which might easily be confused with leiomyosarcoma. Both of these tumours co-expressed cytokeratin, exemplifying the value of cytokeratin immunostaining in the distinction between mesothelioma and sarcoma. Consistent non-expression of glial fibrillary acidic protein in mesotheliomas may help to distinguish them from nerve sheath tumours.

Desmin↗

The histology and immunohistochemistry of small cell mesothelioma.

The object of this study was to describe the histology and immunohistochemistry of 13 small cell mesotheliomas, concentrating on reliable distinctions between them and small cell carcinoma. All 13 tumours showed regions of more typical mesothelioma if multiple blocks were examined. No tumours showed the streams, ribbons, rosettes, or haematoxyphilic blood vessels that are typical of small cell carcinoma. Mitotic figures were relatively scarce and the nuclei had a particularly characteristic open appearance with prominent nucleoli and delicate chromatin. Nuclear moulding was not seen. No tumour produced neutral mucin. Immunohistochemical positivity for neuron-specific enolase (NSE) was found in 11/13, cytokeratin in 9/13 and Leu-7 in 4/13 but none was positive for chromogranin A, carcino-embryonic antigen (CEA) or leucocyte common antigen (LCA). We conclude that the accurate diagnosis of small cell mesothelioma is possible, provided that the clinical presentation is known, the tumour is adequately sampled and the microscopy carefully assessed. In small biopsy specimens, where the diagnosis is less straightforward, immunohistochemistry for CEA, and perhaps LCA and chromogranin A may be helpful. NSE and Leu-7 positivity is common in these tumours and might be misleading if interpreted as reliable evidence of neuroendocrine differentiation.

Aged↗

An assessment of involucrin as a diagnostically useful immunohistochemical marker in lung tumours.

A previous report has described involucrin as a specific immunohistochemical marker of squamous differentiation in lung carcinomas. The aim of our study was to examine the expression of this antigen in a wide variety of lung tumours, with particular attention to its potential value in the typing of biopsy specimens. We found that immunostaining for involucrin was common in squamous carcinomas but was also found in adenocarcinomas, adenosquamous carcinomas, large cell carcinomas and carcinosarcomas. Small cell carcinomas, carcinoid tumours and mesotheliomas were negative. Contrary to previous claims, this marker appears to have little diagnostic utility in the typing of lung tumours.

Biomarkers, Tumor↗