Search PubMed⌕ Search

Biomedical subjects

A R Gibbs

Publications and source records attributed to A R Gibbs.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms.

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Biomarkers, Tumor↗
PubMed2000

The separation of benign and malignant mesothelial proliferations.

The separation of benign from malignant mesothelial proliferations has emerged as a major problem in the pathology of the serosal membranes. For both epithelial and spindle cell mesothelial processes, true stromal invasion is the most accurate indicator of malignancy, but stromal invasion is often difficult to assess, especially in small biopsies. In the pleural cavity, deep penetration of a thickened and fibrotic pleura or penetration of mesothelial cells into the fat of the chest wall are good indicators of malignancy; however, superficial entrapment of mesothelial cells and glands by organizing effusions is common in benign reactions and needs to be distinguished from invasion. In the peritoneal cavity, invasion of fat or of organ walls is again the most reliable indicator of malignancy, but entrapment of benign cells in organizing granulation tissue or between fat lobules is frequent and confusing. Proliferations confined to the pleural or peritoneal space, particularly linear arrays of atypical mesothelial cells on the free surface, should not be called malignant in the absence of unequivocal invasion. Cytologic atypia is often not helpful in separating benign from malignant reactions, because benign processes are commonly atypical and mesotheliomas are often deceptively monotonous. Densely packed mesothelial cells within the pleural space are frequent in benign reactions, but densely packed mesothelial cells within the stroma favor a diagnosis of malignancy. Organizing effusions (fibrous pleurisy) typically show zonation with high cellularity and cytologic atypia toward the pleural space and increasing fibrosis with decreasing cellularity and lesser atypia toward the chest wall, whereas sarcomatous (including desmoplastic) mesotheliomas do not demonstrate this type of zonation. Elongated capillaries perpendicular to the pleural surface are seen in organizing effusions but are not a feature of sarcomatous mesotheliomas. The combination of a paucicellular storiform pattern, plus invasion of the stroma (including fat and adjacent tissues), or bland necrosis, overtly sarcomatous foci, or distant metastases, is required for the diagnosis of desmoplastic mesothelioma. Necrosis is usually a sign of malignancy but is occasionally seen in benign mesothelial reactions. Keratin staining is useful in indicating the distribution of mesothelial cells, and particularly in demonstrating penetration of mesothelial cells into the stroma or adjacent structures, but is of no help in separating benign and malignant proliferations because both are keratin-positive. Although both p53 and EMA staining have been proposed as markers of mesothelial malignancy, in our experience they are not helpful for the individual case.

Diagnosis, Differential↗
PubMed2000

acp. Best practice no 161. Examination of lung specimens.

This article gives guidance for the handling and examination of various types of lung tissue specimens to provide: (1) accurate diagnosis and assessment of severity of disease; (2) sufficient information for the accurate staging of tumours; and (3) an assessment of the contribution of various occupational disorders to the cause of death.

Biopsy, Needle↗
PubMed2000

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.

Adult↗
PubMed1998

Pulmonary giant cell carcinoma: pathological entity or morphological phenotype?

AIMS: To evaluate the morphological spectrum and clinical significance of giant cell carcinoma and to assess the frequency of tumour giant cell production in a consecutive series of primary (non-giant cell) lung tumours. METHODS AND RESULTS: Forty-six cases of giant cell carcinoma of the lung were collated from two centres over a 12-year period. Giant cell carcinoma was found to be associated with areas of clear cell carcinoma, spindle cell carcinoma and showed trophoblastic differentiation (syncytiotrophoblastic giant cells and beta-human chorionic gonadotrophin immunopositivity) in 57%, 34% and 26% cases, respectively. 'Pure' giant cell carcinoma was identified in five (11%) cases. Eleven of the tumours contained diastase-resistant periodic acid-Schiff positive material and were separately designated as giant cell adenocarcinomas. Areas of squamous cell and neuroendocrine differentiation (as determined by chromogranin A and Leu-7 immunopositivity) were not found. The median survival for giant cell carcinoma (excluding the giant cell adenocarcinomas) was 18 months. Median survival was not adversely affected by the extent of tumour giant cell formation or by the presence of trophoblastic differentiation. Of 200 consecutive non-small cell lung carcinomas, tumour giant cells constituting < 10% of the tumour were identified in 32% of adenocarcinomas and 26% of squamous cell carcinomas. CONCLUSIONS: The presence of tumour giant cells in lung carcinoma does not, in itself, indicate a more aggressive tumour type, Giant cell carcinoma of the lung does not appear to be a distinct entity but a morphological phenotype expressed by a heterogenous group of tumours. We support and advocate the use of an encompassing term such as 'pleomorphic' or 'anaplastic' carcinoma for those tumours showing no specific differentiation pattern but which express diverse morphological features such as giant cell formation, clear or spindle cell change.

Adenocarcinoma↗
PubMed1998

SV40 DNA sequences in mesotheliomas.

To investigate the presence of SV40 DNA sequences in human British mesotheliomas, PCR analysis using PYV and SV primers which amplify a 172 bp fragment of SV40LTAg and a 105 bp fragment unique to the SV40LTAg respectively was performed on archival and frozen tissues. Nine pleural mesotheliomas, nine adenocarcinomas metastatic to the pleura and three inflammatory disorders of the pleura were studied. PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma with concordance between paraffin embedded and frozen tissues. Positivity with the PYV primer set was observed in six mesotheliomas, two adenocarcinomas and one of the reactive pleurae. This study indicates that SV40 DNA sequences are present in a substantial proportion of British mesotheliomas.

Adenocarcinoma↗
PubMed1997

Characterization of highly radiosensitive cell lines from a human ovarian small-cell cancer.

Cells were obtained at paracentesis from a patient with a rapidly growing ovarian tumor. A monolayer cell line (V7S), a xenograft tumor line (V7), and subsequently a xenograft-derived monolayer cell line (V7M) were established. Histological and immunohistochemical studies of the original tumor, xenograft, and cell lines provided a diagnosis of small-cell carcinoma of the ovary-which is consistent with the clinical course of the patient. V7S and V7M had a predominantly hypodiploid karyotype with a small tetraploid population. The V7M, which has been in long-term culture, also showed a nonrandom translocation involving chromosomes 1 and 14 and monosomy of X. Radiobiologically, V7S, V7, and V7M showed marked radiosensitivity with surviving fractions at 2 Gy, measured by clonogenic assay, of between 0.022 and 0.147. Split-dose experiments provided evidence that this radiosensitivity was not due to an inability in cellular repair. In vivo data from the xenograft (V7) revealed a highly radiosensitive tumor, corroborating the in vitro studies.

Carcinoma, Small Cell↗
PubMed1997

Pathology of malignant mesothelioma.

The diagnosis of malignant mesothelioma can pose several problems to the surgical pathologist. First, the morphological appearances of the tumour are known to be diverse with mimicry of a range of both reactive and neoplastic conditions. Second, due to the relative inaccessibility of the serosa, biopsy material is often scanty and fragmentary, producing a plethora of interpretive ambiguities. Third, adjunct techniques such as mucin histochemistry and immunohistochemistry, whilst useful in excluding malignant mesothelioma have little role in confirming the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is important for two reasons: (1) In relation to prognosis as it has an almost invariable fatal outcome, which contrasts with the other mesothelial neoplasms such as the benign adenomatoid tumour and the borderline malignant tumours, namely the well-differentiated papillary mesothelioma and multicystic mesothelioma; (2) In relation to occupational-related compensation claims following asbestos exposure. This review summarizes the aetiology of asbestos-induced neoplasia, possible mechanisms of tumour development and highlights potential diagnostic pitfalls.

Asbestos↗
PubMed1997

CD44H expression in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma.

Malignant mesotheliomas are known to produce hyaluronic acid, in contrast to most pulmonary adenocarcinomas which produce neutral mucin. CD44H is the major cell surface receptor for hyaluronic acid. The aim of this study was to investigate immunohistochemically the expression of this antigen in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma and to assess its diagnostic utility in distinguishing the two tumours. Diffuse and intense membranous CD44H immunoreactivity was seen in 15 of 20 (75%) mesotheliomas and in all 20 biopsies of reactive mesothelium. In contrast, focal (< 10% tumour) expression of CD44H was seen in only three of 20 (15%) pulmonary adenocarcinomas. We advocate the use of CD44H as a positive mesothelial marker for incorporation alongside other established immunohistochemical markers used to distinguish mesothelioma from adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Primary sarcomas of the lung: a clinicopathological and immunohistochemical study of 14 cases.

The clinicopathological features and immunohistochemical findings in 14 primary sarcomas of the lung collected over a 30-year-period are presented. This represents one sarcoma per 550 bronchogenic carcinomas undergoing resection in this centre. The study group comprised six leiomyosarcomas, five malignant peripheral nerve sheath tumours, two haemangiopericytomas and one epithelioid haemangioendothelioma. The majority of cases occurred in men (nine males: five females), with mean age at presentation of 54 years for men and 47 years for women. All leiomyosarcomas were seen in men, whereas malignant peripheral nerve sheath tumours showed no particular sex preponderance. Leiomyosarcomas were larger tumours than malignant peripheral nerve sheath tumours, mean tumour diameter 15 cm (range 10-25 cm) compared to 9.5 cm (7-15 cm), respectively. All leiomyosarcomas were situated intraparenchymally whereas two of the five malignant peripheral nerve sheath tumours were endobronchial in site. Extrathoracic metastates were seen at death in two of the six leiomyosarcomas but not in any of the malignant peripheral nerve sheath tumours. Overall survival was 28 months although for the leiomyosarcoma/malignant peripheral nerve sheath tumour group alone survival was 8 months. Tumour grading appeared to be a more useful prognostic factor than tumour site (endobronchial/parenchymal) or tumour size. Haemangiopericytoma and epithelioid haemangioendothelioma were associated with a more favourable prognosis.

Adult↗
PubMed1996

Examination of cytological smears and clot sections prepared from pleural fluids: a comparative study.

Between January 1989 and May 1990, the Department of Cytology of Llandough Hospital examined 784 pleural fluid cytological preparations, 99 of which were also examined as paraffin wax sections of clots that had formed. To assess whether this practice yields worthwhile information, we reviewed the cytology and clot sections of 99 patients with pleural effusions and correlated the results with subsequent histology and review of clinical case notes. The specificities of each method separately and when combined was high: 92% clot section, 85% smear cytology and 85% combined. The sensitivity using clot section alone was 49%, smear cytology alone 46% and in combination, 54%. Analysis showed no significant difference between sensitivities. When pleural fluid clot formation occurs, we recommend the continued examination of clot sections, since it yields an increase in positive diagnoses, albeit not statistically significant.

Cytodiagnosis↗
PubMed1996

Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma.

The aim of this study was to examine the expression of three putative mesothelioma-binding antibodies, thrombomodulin, OV 632 and HBME-1 in 42 malignant mesotheliomas (27 pleural and 15 peritoneal) and 32 pulmonary adenocarcinomas. Evaluation of their use in differentiating between the mesotheliomas and pulmonary adenocarcinomas was assessed. Thrombomodulin was expressed by 22 of 42 (52%) mesotheliomas but was seen in eight of 12 pure epithelial-type mesotheliomas of the pleura and in all four papillary epithelial peritoneal mesotheliomas. For pure epithelial mesotheliomas thrombomodulin was 75% sensitive. Only two of 32 pulmonary adenocarcinomas were immunoreactive yielding a 94% specificity for thrombomodulin. In comparison, OV 632 and HBME-1 showed 67% and 62% antibody sensitivity, respectively, for malignant mesothelioma but this was accompanied by low specificity (OV 632, 37%; HBME-1, 28%). Both OV 632 and HBME-1 are considered unsuitable for use in differentiating between mesotheliomas and pulmonary adenocarcinomas. We advocate the use of thrombomodulin as a mesothelioma-binding antibody in the standard panel of antibodies used in the evaluation of malignant mesothelioma.

Adenocarcinoma↗
PubMed1996

Mesothelioma in a community in the north of England.

OBJECTIVES: To find the numbers of mesotheliomas in Calderdale over the period 1966-94 and determine their relation to asbestos exposure, pathology, and mineral fibre burden within the lungs of affected subjects. METHODS: Cases were entered into the study if the subject has been diagnosed with mesothelioma after postmortem and histopathological examinations. Occupational data were obtained mainly from the case records of the Cape Asbestos medical officer, hospital, and medical practitioner and from death certificates. Analyses of the mineral fibres were performed with transmission electron microscopy and energy dispersive x ray spectrometry. RESULTS: 73 mesotheliomas were diagnosed from 1966 to 1994. Forty four were associated with exposure at the Acre Mill factory, which manufactured asbestos products. Concentrations of amphibole asbestos fibres were found to be raised above controls in 31 out of 32 cases associated with Acre Mill exposure, in 10 out of 12 other cases exposed to asbestos and eight out of 17 cases not exposed to asbestos. CONCLUSIONS: There was a high number of mesotheliomas in Calderdale. More than half of the cases were associated with occupation at the Acre Mill factory and were associated with exposure to amphibole asbestos, predominantly crocidolite. No cases associated with neighbourhood exposure to asbestos were identified.

Adult↗
PubMed1996

Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue.

BACKGROUND: DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period. METHODS: DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively. RESULTS: PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other. CONCLUSIONS: Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.

Adult↗
PubMed1996

Analysis and interpretation of inorganic mineral particles in "lung" tissues.

Mineral analysis of tissue specimens has provided very useful information in pathological conditions associated with occupational exposures to mineral particles, particularly when combined with epidemiological information. Most of the data have been related to exposures to fibrous particles such as asbestos. More investigations of this nature are required in diseases associated with exposure to non-fibrous particles. In the future it is likely that these types of investigation will be extended into the effects of pollutants.

Bronchoalveolar Lavage Fluid↗