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A G Nicholson

Publications and source records attributed to A G Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma.

AIMS: The differentiation of benign pleural conditions from malignant mesothelioma may be difficult, especially with a small biopsy. We have tested the hypothesis that assessment of the cell cycle status is of value in the histopathological diagnosis of such biopsies, by comparing 33 malignant mesotheliomas with 36 cases of reactive mesothelial hyperplasia and reactive pleural fibrosis. METHODS AND RESULTS: Biopsies were investigated for proliferative status by immunostaining for a novel antibody, MCM2, all of which showed nuclear expression of MCM2 at higher frequency than Ki67 (P < 0.0001). Counts in areas of maximum tumour staining showed significantly higher labelling indices (LIMax) in epithelioid and sarcomatoid mesotheliomas compared with reactive mesothelial hyperplasia and reactive pleural fibrosis (P < 0.0001 for both). Average counts (LIAve) revealed a significant increase in epithelioid mesothelioma compared with reactive mesothelial hyperplasia (P < 0.0001). CONCLUSION: We consider MCM2 to be a useful adjunct in the differential diagnosis of malignant mesothelioma.

Biomarkers, Tumor↗
PubMed2003

Cystic fibrohistiocytic tumours presenting in the lung: primary or metastatic disease?

AIMS: Cystic fibrohistiocytic tumour of the lung is a rare proliferative process. Its histogenesis is uncertain, but evidence suggests that some cases represent metastatic disease from apparently indolent skin lesions, namely cellular fibrous histiocytomas. This study presents four cases and reviews the literature concerning this pattern of disease and its aetiology. METHODS AND RESULTS: All patients were male (age range 35-54 years). Two presented with recurrent haemoptysis. Two cases had histories of cutaneous fibrohistiocytic lesions in the chest wall, excised 10 and 23 years prior to presentation with lung disease. Imaging data showed multiple bilateral cystic lung lesions in all four patients with nodular cavitating opacities seen on high-resolution computed tomography scans. Microscopy showed variably dilated thin-walled cystic airspaces lined by cuboidal epithelium and an underlying layer of mildly pleomorphic spindle cells with slightly wavy morphology and storiform architecture, admixed with inflammatory cells. Tumour cells stained for CD68 in three of four cases. All cases were negative for CD34. All patients were alive with disease, although one required pneumonectomy for intractable haemoptysis. CONCLUSION: This study and a review of published cases show that the majority of cystic fibrohistiocytic tumours of the lung probably represent metastases from cellular fibrous histiocytomas. However, rare cases may be either primary in origin or the primary site remains occult; the term cystic fibrohistiocytic tumour remains appropriate for such cases.

Adult↗
PubMed2003

Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone.

Erdheim-Chester disease is a rare multisystem histiocytic disorder in which death most commonly results from pulmonary or cardiac involvement. We report the case history of a 55 year old man with this condition with extensive and progressive pulmonary disease. He had no response to prednisolone alone, but treatment with prednisolone plus cyclophosphamide was associated with a rapid improvement in symptoms, lung function, and the chest radiographic appearance. He subsequently showed a symptomatic, functional, and radiological deterioration, followed by a marked slowing in the rate of decline. He currently remains stable 41 months after treatment was initiated. This is the first report of pulmonary Erdheim-Chester disease showing improvement in both lung function and symptoms with any form of treatment.

Anti-Inflammatory Agents↗
PubMed2003

The safety and quality of endobronchial biopsy in children under five years old.

BACKGROUND: Little is known about the airway pathology of wheezing disorders in infants and preschool children, partly owing to the difficulty of undertaking invasive studies in this age group. The safety of endobronchial biopsy and the quality of biopsies obtained were reviewed in infants and preschool children. METHODS: Case notes of children under five years of age who underwent bronchoscopy and endobronchial biopsy were reviewed. The safety of the procedure was compared in a control group matched for weight and age, undergoing bronchoscopy without endobronchial biopsy. A consultant histopathologist assessed biopsy quality. RESULTS: 33 patients (mean age 31 months, range 4 to 59) underwent bronchoscopy and endobronchial biopsy, and were matched with 33 controls (mean age 28 months, range 3 to 52). There was no significant difference between groups in the number, type, or severity of complications occurring during or after the procedure. Biopsies from 30 of the 33 subjects could be assessed. Reticular basement membrane was identified in all 30; inflammation could be assessed in 26; areas of smooth muscle were present in 23. CONCLUSIONS: In a group of preschool children undergoing bronchoscopy under general anaesthetic, performance of endobronchial biopsy carried no extra risk. The quality of biopsies obtained was usually sufficient to allow an assessment of remodelling and inflammation.

Biopsy↗
PubMed2003

Investigation of mycobacterial colonisation and invasion of the respiratory mucosa.

BACKGROUND: The pathogenesis of Mycobacterium avium complex and Mycobacterium tuberculosis in the respiratory tract is poorly understood, as are the reasons for their differing virulence. We have previously shown that their initial adherence to the mucosa is identical. METHODS: The interaction of M avium complex, M tuberculosis, and M smegmatis with human respiratory tissue was investigated in an organ culture model with an air interface. Tissue was infected for intervals up to 14 days and assessed by scanning electron microscopy for adherent bacteria or cultured for recoverable bacteria. RESULTS: The mean number of adherent bacteria/mm(2) (and the viable count of macerated tissue, cfu/ml) at 15 minutes, 3 and 24 hours, 7 and 14 days were: M avium complex 168 (153), 209 (136), 289 (344), 193 (313), 14140 (16544); M tuberculosis 30 (37), 39 (23), 48 (53), 1 (760), 76 (2186); M smegmatis 108 (176), 49 (133), 97 (81), 114 (427), 34 (58), (n=6). There was no significant change in morphology between infected and uninfected tissue or tissue infected with the different species over 14 days. The number of M avium complex on the mucosa and recovered from tissue increased over time (p=0.03). M tuberculosis decreased on the surface, but recoverable bacteria increased (p=0.01). M smegmatis numbers on the mucosa and recovered from tissue decreased. Sectioned tissue showed M avium complex and M tuberculosis in submucosal mucus glands and M tuberculosis penetrating epithelial cells in one experiment. CONCLUSIONS: The initial adherence to the mucosa of the three species was similar, but after 14 days they varied in their interaction with the tissue in a manner compatible with their pathogenicity.

Bacterial Adhesion↗
PubMed2003

Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is associated with altered plasma and lung iron chemistry. Iron can promote microbial virulence and catalyse pro-oxidant reactions, thereby contributing to the oxidative stress that characterises the syndrome. Therefore, the expression of ferritin and transferrin receptors (TfR) were sought in the lungs and hearts of rodents treated with lipopolysaccharide (LPS), and measurements of TfR and ferritin protein expression were taken from lung biopsy specimens from patients with ARDS and appropriate controls. TfR messenger ribonucleic acid (mRNA) was significantly upregulated in the lungs and significantly downregulated in the hearts of rats 4 h after LPS. Ferritin mRNA levels (light and heavy chains) remained unaltered. Protein TfR levels were significantly upregulated in lungs and downregulated in hearts 4 h post-LPS. Ferritin protein levels were significantly downregulated in lungs compared to baseline values but were unaltered in hearts. Nonhaem iron levels were increased in lungs and decreased in hearts, and iron-regulatory-protein activity increased in hearts but not lungs. TfR protein levels were significantly increased in lung biopsies from patients with ARDS compared to controls. Transferrin receptors are upregulated in rodent lungs during inflammation but are downregulated in the heart. Transferrin receptor protein levels were significantly increased in the lungs in clinical acute respiratory distress syndrome. These findings have implications for the pathogenesis of acute respiratory distress syndrome, especially in relation to the role of iron as a mediator of oxidative stress.

Adult↗
PubMed2003

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

Bronchoalveolar Lavage↗
PubMed2002

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas.

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

Robotic telepathology: efficacy and usability in pulmonary pathology.

Robotic telepathology is well established in the USA as a method of case referral, but is less frequently used in the UK. Using cases covering a broad spectrum of pulmonary pathology, this study assessed its application in primary diagnosis and its functionality in terms of accuracy of diagnosis and time per case, for both small biopsies and open lung biopsies/resections. Forty cases (20 bronchoscopic and 20 surgical lung biopsy/resection specimens) were reviewed in blinded fashion by a single pathologist using robotic telepathology. Connection between the John Radcliffe and Royal Brompton Hospitals was via 10 Mb/s LAN to the Internet (supported by the Joint Academic Network). The cases were then randomized and reviewed a second time with conventional light microscopy. Diagnosis, initial time to reach diagnosis, and overall time per case were recorded. In two bronchoscopic biopsy cases, there were clinically significant differences between telepathology and conventional light microscopy, one probably attributable to user inexperience and the other to either speed of image capture or digital image quality. In the surgical lung biopsies and resections, there was one variation of opinion: with telepathology a case was considered to be probably mesothelioma, whereas this was thought less likely on light microscopy. In both instances, immunohistochemistry was requested prior to clinical management. Telepathology was 14 times slower than conventional light microscopy when examining bronchoscopic biopsies. The average time spent per slide was 7 min 21 s, compared with 32 s per slide with conventional light microscopy. When assessing open lung biopsies and resections, telepathology was five times slower, at 6 min 13 s compared with 1 min 10 s with conventional light microscopy. This study showed that robotic telepathology is accurate for primary diagnosis in pulmonary histopathology, but modifications in both laboratory protocols and telepathology hardware are needed to decrease the time difference between telepathology and conventional light microscopy, for telepathology to be usable within the framework of a busy referral practice.

Biopsy↗
PubMed2002

Inflammatory endobronchial polyps in childhood: clinical spectrum and possible link to mechanical ventilation.

Inflammatory polyps of the airways are now regarded as histopathologically distinct nonneoplastic endobronchial lesions, which in adults are associated with a variety of chronic inflammatory insults. However, their clinical presentation in the pediatric population is extremely rare, with the etiology of such polyps poorly defined. The clinical and histopathological data from four pediatric patients, identified in the histopathology files of the Royal Brompton Hospital, were retrospectively reviewed. Three out of 4 patients had a history of mechanical ventilation in the neonatal period. In these 3 patients, the polyps were all situated in the proximal airways on the right side. These 3 patients presented at 6 weeks, 7 weeks, and 2 years, respectively, and were successfully treated by polypectomy at rigid bronchoscopy, with subsequent return to normality. One patient, presenting at 12 years of age without history of iatrogenic intervention, underwent a left lower lobectomy for a polyp sited in a segmental bronchus. Presentation in 3 of the 4 patients was with lobar collapse. The fourth patient presented with hyperinflation. We conclude that inflammatory endobronchial polyps may be associated with a history of mechanical ventilation in the neonatal period, polyp formation perhaps being secondary to airway trauma. The small caliber of the main airways in neonates may also be a contributory factor in presentation.

Bronchial Neoplasms↗
PubMed2002

Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms.

AIMS: The histopathological features of some thymic neoplasms overlap with those of pulmonary squamous and large-cell undifferentiated carcinomas, and identification of the primary site may be difficult on routine staining. We have assessed a panel of antibodies that may help to distinguish between neoplasms from these two sites. METHODS AND RESULTS: Antibodies identifying cytokeratin 7 (CK7), CD5, CD10, CD1a and thyroid transcription factor-1 (TTF-1) were applied to a series of 20 thymic neoplasms (thymic carcinomas, atypical thymomas and thymomas), 10 primary squamous cell carcinomas of the lung and 10 large-cell undifferentiated carcinomas of the lung. Staining for TTF-1 was positive in 3/10 large-cell undifferentiated carcinomas, but negative in all other tumours. CD5 showed strong membranous staining in 3/6 thymic carcinomas and 1/14 thymomas, but only focal staining in 1/20 pulmonary carcinomas. CD1a was consistently positive in thymic lymphocytes in both typical and atypical thymomas, but only focally in 1/6 thymic carcinomas. CD1a stained dendritic cells in 7/20 pulmonary carcinomas, but did not stain lymphocytes. Staining for CK7 and CD10 did not aid in differentiating between a pulmonary or thymic origin of the tumour. CONCLUSION: Staining for TTF-1, CD5 and CD1a have potential use in distinguishing between pulmonary and thymic neoplasms.

Antigens, CD1↗
PubMed2002

Expression of respiratory mucins in fatal status asthmaticus and mild asthma.

AIMS: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel-forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. METHODS AND RESULTS: Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. CONCLUSIONS: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.

Asthma↗
PubMed2002

Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup.

Since Liebow and Carrington's original classification of idiopathic interstitial pneumonias, there have been controversies over which histological patterns should be included and how they relate to clinicopathological diseases such as cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis (CFA/IPF). Because of these differences and the wealth of overlapping terminology, a consensus classification system has been proposed, devised by a group of clinicians, radiologists and pathologists. Seven histological patterns are recognized: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), organizing pneumonia (OP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis (RB) and lymphocytic interstitial pneumonia (LIP), each with a clinicopathological counterpart, the most well defined being UIP and CFA/IPF. The system is applicable both in terms of the pathologist identifying histological patterns in isolation and in terms of the pathologist's role in contributing to the final clinicopathological diagnosis. It will probably provide greater consistency in diagnosis, early studies suggesting that the system is reproducible, and also identify purer cohorts for studies investigating causation. It also highlights the fact that the 'gold standard for diagnosis' is no longer a surgical lung biopsy in isolation but more the clinicopathological conference, when clinical, imaging and histological data are jointly discussed to produce the final clinicopathological diagnosis.

Consensus↗
PubMed2002

Unusual sclerosing haemangiomas and sclerosing haemangioma-like lesions, and the value of TTF-1 in making the diagnosis.

AIMS: Sclerosing haemangiomas typically comprise a mixture of four architectural patterns (papillary, sclerotic, solid and haemorrhagic) and two cell types, eosinophilic cuboidal epithelial lining cells and sheets of rounded cells with either eosinophilic or clear cytoplasm. In most instances, recognition of these architectural and cytological features provides sufficient evidence for diagnosis. This study presents and discusses the histogenesis of four cases where difficulties in diagnosis were encountered, and reports the value of the antibody TTF-1 in making the diagnosis. METHODS AND RESULTS: Four cases with focal areas reminiscent of sclerosing haemangioma were reviewed and immunostained with an antibody panel including antibodies to TTF-1 and surfactant apoprotein A. Of these, one case was classified as sclerosing haemangioma combined with typical carcinoid, in which there was a mediastinal lymph node metastasis solely comprising the solid component of sclerosing haemangioma. The second was classified as an alveolar adenoma with sclerosing haemangioma-like areas. In the remaining two cases, diagnosis was confounded by presentation with predominantly cystic masses, the largest 70 mm in diameter. Immunohistochemically, TTF-1 was of greater value than surfactant apoprotein, in particular in identifying the solid component of sclerosing haemangioma when this was solely present. CONCLUSION: Sclerosing haemangiomas should be considered in the differential diagnosis of cystic pulmonary masses. They may also present histologically as combined tumours and metastasize to mediastinal nodes, indicating an, albeit low, malignant potential. TTF-1 is a valuable antibody in identifying the presence of a sclerosing haemangioma when typical features are absent.

Aged↗
PubMed2002

The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas.

AIMS: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies. METHODS AND RESULTS: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin. CONCLUSION: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.

Antibodies, Neoplasm↗
PubMed2002

Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung.

Hypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells. MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia.

Bronchi↗
PubMed2002

Interaction of Mycobacterium tuberculosis with human respiratory mucosa.

OBJECTIVE: Endobronchial infection is associated with pulmonary tuberculosis in the majority of cases. We have investigated the adherence of Mycobacterium tuberculosis to the human respiratory mucosa. DESIGN: Organ cultures constructed with human tissue were infected with M. tuberculosis in the presence or absence of mycobacterial fibronectin attachment cell surface proteins and examined by scanning electron microscopy. RESULTS: M. tuberculosis adhered mainly to extracellular matrix (ECM) in areas of mucosal damage, but not to ciliated mucosa, intact extruded cells, basement membrane or collagen fibres. Bacteria also adhered to fibrous but not globular mucus and occasionally to healthy unciliated mucosa, open tight junctions and to extruded cells that had degenerated, exposing their contents. There was a significant reduction (p<0.05) in the number of bacteria adhering to ECM after pre-incubation of bacteria with fibronectin and after pre-incubation of the tissue with M. avium fibronectin attachment protein (FAP) and M. bovis antigen 85B protein, in a concentration dependent manner. The combined effect of FAP and antigen 85B protein was significantly greater than either protein alone. Bacterial adherence to fibrous mucus was not influenced by fibronectin. CONCLUSION: We conclude that M. tuberculosis adheres to ECM in areas of mucosal damage at least in part via FAP and antigen 85B protein.

Acyltransferases↗