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Biomedical subjects

A G Nicholson

Publications and source records attributed to A G Nicholson.

At least 91 records · Page 5Linked to original sources

Detection of SV40 sequences in human mesothelioma.

The presence of SV40 DNA sequences in British cases of mesothelioma was investigated using previously reported PCR assays. Three different SV40 primer sets were used which gave positive detection rates of 100% (SV.for3/SV.rev), 42% (PYV.for/rev) and 15% (SV.for2/SV.rev). When 26 mesothelioma biopsies were tested. Negative samples included 22 semen samples from AIDS patients, 10 blood donor DNAs and the human mesothelioma cell line H-MESO-1. The problems encountered with these assays and the interpretation of the results are discussed.

Base Sequence↗

Full thickness eosinophilia in oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis. A common allergic inflammatory profile?

Oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis are both extremely rare. The former is a diffuse proliferation of smooth muscle in the muscularis propria, whilst the latter is an idiopathic inflammatory condition, thought to be associated with background atopy and characterized by an infiltrate of eosinophils throughout the full thickness of the oesophagus. However, two recent cases of oesophageal leiomyomatosis showed similar full thickness infiltration of the oesophageal wall by eosinophils and this inflammatory cell infiltrate was investigated in conjunction with one case of idiopathic eosinophilic oesophagitis. All three had a similar allergic profile characterized by CD45RO-positive primed T-lymphocytes, EG2-positive (i.e., activated) eosinophils, and tryptasepositive mast cells, together with gene expression for interleukin 4. Previous descriptions of leiomyomatosis describe an association with systemic mastocytosis and urticaria and the possibility that there is a common underlying allergic component to both disorders is raised.

Adult↗

Primary epithelioid angiosarcoma of the lung presenting as pulmonary hemorrhage.

Pulmonary angiosarcomas are usually secondary tumors, and only a few primary cases have been described. We report a unique case of epithelioid angiosarcoma arising in the lungs as a bilateral multinodular infiltrate and presenting as pulmonary hemorrhage. Because of its epithelioid histology, this tumor may resemble a carcinoma, also staining positively for keratin markers. Therefore, unless the diagnosis of epithelioid angiosarcoma is considered and endothelial markers used, the diagnosis of epithelioid angiosarcoma may be overlooked at this site.

Aged↗

Does the use of immunohistochemistry to identify micrometastases provide useful information in the staging of node-negative non-small cell lung carcinomas?

Immunohistochemical studies using epithelial markers have recently been published which identified micrometastases in lymph nodes that had not been found on routine pathological assessment, therefore increasing the accuracy of staging of non-small cell lung cancers. The presence of these micrometastases was associated with reduced survival. We have therefore performed a retrospective immunohistochemical study on all the lymphoid tissue from five lymph node stations (2 hilar, 3 mediastinal) from 49 patients with T1-2, N0 disease. Before immunohistochemistry was undertaken, all slides were reviewed, with the lymph nodes confirmed as negative. In total, 1447 lymph node slices (average 30 per case, 5.9 per lymph node station) were examined, these figures reflecting sectioning of lymph nodes at approximately 3 mm intervals before processing. MNF116, a broad spectrum anti-keratin antibody was then used to look for occult metastases, with adjacent serial sections being examined to ensure that any positively staining cells were detected solely by immunohistochemistry and not through deeper sectioning. In five cases, lymph nodes contained positively staining cells. Two cases proved to be false positives, further immunohistochemistry identifying the cells as benign mesothelial inclusions. In the remaining three cases, positive staining correlated with tumour cells in the adjacent serial sections. Follow-up on 46 of 49 patients revealed recurrence in 27% (actual survival 68%); however all three cases containing tumour cells on immunohistochemistry were free from recurrence. These results suggest that the use of immunohistochemistry adds little useful information above that of thorough routine examination of lymph nodes. They also document that benign mesothelial inclusions within lymph nodes are more frequent than previously reported.

Antibodies↗

Synovial sarcoma of the heart.

Primary synovial sarcomas of the heart are exceptionally rare tumours, only five being previously documented. We report a sixth case and review published data. Ages ranged from 13-53 (mean 40.8) years. There were four men and two women who characteristically presented with syncope or dyspnoea. Most of the tumours arose in the right atrium where they formed pedunculated or polypoid masses. In the previously documented cases, all patients died within 9 months. However in our case, local excision was felt to have been complete and the patient remains disease free at 10 months.

Adolescent↗

Cryptogenic fibrosing alveolitis: lack of association with Epstein-Barr virus infection.

BACKGROUND: Cryptogenic fibrosing alveolitis (CFA) is a well defined clinical entity of unknown aetiology. An association between CFA and the presence of protein indicating Epstein-Barr virus (EBV) replication within epithelial cells of the respiratory tract has recently been suggested, leading to speculation for a role for EBV in the pathogenesis of CFA. METHODS: Lung tissue was obtained from patients in three groups: those with cryptogenic fibrosing alveolitis, either lone or associated with systemic sclerosis; patients with other pulmonary disorders; and patients with normal lung. Paraffin blocks were stained using three antibodies raised against well defined EBV antigens. In addition, EBER-1 and EBER-2 anti-sense nucleotide probes were used in an attempt to identify EBV RNA. DNA was also extracted from the tissue sections and evaluated for evidence of EBV DNA using the polymerase chain reaction. RESULTS: Immunohistochemistry showed inconsistent focal positive staining with anti-EBV antibodies in all three groups, but there was no evidence of EBV RNA using in situ hybridisation. None of the samples from patients with pulmonary fibrotic disorders was found to contain EBV DNA following gene amplification. CONCLUSION: Contrary to an earlier report, these results do not support the hypothesis that EBV has a role in the pathogenesis of CFA.

DNA, Viral↗

Lymphomatoid granulomatosis: evidence that some cases represent Epstein-Barr virus-associated B-cell lymphoma.

Lymphomatoid granulomatosis is currently classified as part of a spectrum of angiocentric immunoproliferative lesions. These were initially thought to be of T-cell phenotype, but recent papers have shown that some cases are B-cell proliferations, sometimes associated with Epstein-Barr virus infection. We reviewed the clinicopathological features of 16 patients with pulmonary lymphomatoid granulomatosis, using immunohistochemistry to assess the phenotype of the infiltrate, the polymerase chain reaction to look for immunoglobulin heavy chain and T-cell receptor gene rearrangements, and in-situ-hybridization to look for Epstein-Barr virus infection. In seven of seven cases the atypical lymphoid population was of B-cell phenotype, with four cases showing evidence of either monoclonality or oligoclonality. All seven cases, including those that lacked unequivocal proof of malignancy, behaved aggressively. Epstein-Barr virus RNA was detected in four cases. We conclude that some cases of lymphomatoid granulomatosis are B-cell lymphomas, sometimes associated with Epstein-Barr virus infection.

Adult↗

Pulmonary B-cell non-Hodgkin's lymphoma associated with autoimmune disorders: a clinicopathological review of six cases.

Because pulmonary B-cell non-Hodgkin's lymphomas are now thought to arise in bronchial mucosa-associated lymphoid tissue (MALT), 45 patients with pulmonary B-cell lymphomas were reviewed to look for aetiological factors in the lung. It was found that six of the 45 lymphomas arose in patients with systemic autoimmune disease, which in three patients involved the lung. These three patients all had cryptogenic fibrosing alveolitis treated with long-term immunosuppressive therapy. Five of the six lymphomas were high grade and one was low grade. The association of pulmonary lymphomas with autoimmune interstitial lung disease is consistent with associations between autoimmune diseases and lymphomas presenting at other mucosal sites, and lends weight to the hypothesis that formation of bronchial mucosa-associated lymphoid tissue precedes the development of lymphoma.

Adult↗

Pulmonary B-cell non-Hodgkin's lymphomas. The value of immunohistochemistry and gene analysis in diagnosis.

We reviewed 45 pulmonary B-cell non-Hodgkin's lymphomas to determine whether their morphology and immunohistochemical features were those of lymphomas arising from mucosa-associated lymphoid tissue (MALT), as described in other sites. The polymerase chain reaction was used to provide further information on clonality. We found that these lymphomas infiltrate the pulmonary interstitium along bronchovascular bundles and interlobular septa, subsequently spilling out into airspaces and finally destroying the alveolar architecture of the lung. Central hyaline sclerosis and vascular infiltration were common features. All lymphomas stained CD20 positive and were accompanied by variable numbers of reactive CD3 positive T-cells. Cytokeratin staining with CAM 5.2 was useful in identifying lymphoepithelial lesions. CD21 staining of follicular dendritic cells revealed germinal centres where they were not recognizable on H & E staining. The polymerase chain reaction was performed on paraffin tissue from 28 patients. Twenty were low grade, of which 12 showed a clonal band and eight showed a polyclonal smear pattern. Eight were high grade, of which one revealed a clonal band. Three produced polyclonal smear patterns and four cases were inadequate samples. In one patient who had lymphoma at a second extranodal site, identical bands were identified, evidence for 'homing' of lymphoid cells towards mucosal epithelium.

Base Sequence↗

Reactive pulmonary lymphoid disorders.

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperplasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Adolescent↗

The value of PE-10, a monoclonal antibody against pulmonary surfactant, in distinguishing primary and metastatic lung tumours.

A new monoclonal antibody (PE-10) raised against components of pulmonary surfactant has been assessed for its ability to distinguish primary from secondary carcinomas in the lung. We applied this antibody to a series of 107 primary lung carcinomas, 40 adenocarcinomas of other sites, and 26 cases of adenocarcinoma metastatic to lung and pleura. Of the primary lung carcinomas, all the non-mucinous bronchiolo-alveolar carcinomas were positive whereas all the mucinous cases were negative; 60% of other types of adenocarcinoma were positive and 10% of large cell undifferentiated carcinomas, 20% of small cell carcinomas and 40% of atypical carcinoids also showed focal positivity. Squamous cell carcinomas were all negative. Adenocarcinomas of the breast, kidney, large bowel and ovaries were all negative, as were all 26 cases of adenocarcinoma metastatic to the lung and pleura. We conclude that this antibody is highly specific and moderately sensitive for primary tumours of the lung.

Adenocarcinoma↗

Dieulafoy's disease of the bronchus.

Dieulafoy's vascular malformation has not been described outside the gastrointestinal tract. Two cases are reported in which this vascular abnormality arose in right lower lobe bronchi, both of which presented with massive haemoptysis.

Adult↗