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A G Nicholson

Publications and source records attributed to A G Nicholson.

At least 73 records · Page 4Linked to original sources
PubMed2000

The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa.

Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non-immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P < 0.05) in the number of bacteria adhering to ECM after preincubation of bacteria with fibronectin and after preincubation of the tissue with M. avium FAP in a concentration-dependant manner. The number of bacteria adhering to fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.

Adenoids↗
PubMed2000

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.

Aged↗
PubMed2000

Nonspecific interstitial pneumonia: variable appearance at high-resolution chest CT.

PURPOSE: To describe the computed tomographic (CT) findings in patients with nonspecific interstitial pneumonia (NSIP) and to compare these with the CT findings of other chronic infiltrative lung diseases. MATERIALS AND METHODS: Findings in 50 patients with biopsy-proved NSIP and a CT scan were reviewed by two thoracic radiologists in consensus. After the findings were described, the observers judged whether the findings were compatible with previously published descriptions of NSIP or whether the findings would support the diagnosis of a different chronic infiltrative lung disease. RESULTS: Eleven (22%) of the 50 patients had CT findings that were compatible with previous descriptions of NSIP. Sixteen (32%) patients had CT findings that were more compatible with usual interstitial pneumonia. The other 23 (46%) patients had findings that were nondiagnostic or most compatible with the diagnosis of another chronic infiltrative lung disease. CONCLUSION: Contrary to previously published articles, there are a wide variety of CT findings in cases of NSIP.

Adult↗
PubMed2000

The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis.

Lone cryptogenic fibrosing alveolitis (CFA) is a progressive interstitial lung disease, with a median survival of 3 to 6 yr from the onset of dyspnea. CFA can be subdivided into prognostically significant histopathologic patterns, including nonspecific interstitial pneumonia (NSIP). We reviewed 78 patients with a clinicopathologic diagnosis of CFA, biopsied between 1978 and 1989, to evaluate the prevalence and prognostic significance of these histopathologic patterns, in particular NSIP. Biopsy appearances were reclassified by two pulmonary histopathologists as usual interstitial pneumonia (UIP) (47%), NSIP (36%), or desquamative interstitial pneumonia (DIP)/respiratory bronchiolitis-associated interstitial lung disease (RBILD) (17%). The kappa coefficient of agreement between pathologists was 0.49. In 67 cases, follow-up was complete to death or 10 yr after biopsy, with 50 deaths during a median follow-up of 42 mo (UIP, 89%; NSIP, 61%, DIP/RBILD, 0%). Survival was highest in DIP/RBILD and higher in NSIP than UIP, p < 0.0005. When analysis was confined to patients with UIP or NSIP, the mortality of UIP remained higher, p < 0.01, but the 5-yr survival in patients with fibrotic NSIP was only 45%, indicating that this histologic appearance is often associated with a poor outcome. A response to treatment was more frequent in DIP/RBILD than in NSIP (p < 0.01) or UIP (p < 0.0005). This study confirms the prognostic value of subclassifying patients with CFA according to histopathologic pattern. However, in patients with clinically typical CFA, a histologic diagnosis of fibrotic NSIP needs to be interpreted with caution and does not necessarily denote a good outcome.

Biopsy↗
PubMed2000

Diagnostic accuracy of thin-section CT and chest radiography of pediatric interstitial lung disease.

OBJECTIVE: We assessed the accuracy of thin-section CT and chest radiography to diagnose pediatric interstitial lung disease. MATERIALS AND METHODS: We identified 20 infants, boys, and girls (age range, 1 month to 14 years) with histopathologic confirmation of interstitial lung disease. Six boys and girls without interstitial lung disease were also included. Two observers independently assessed chest radiograph and CT images. The observers stated the most likely diagnosis and a differential diagnosis. We evaluated individual CT features and their distribution. RESULTS: Observers' diagnoses on CT images were correct (first choice or differential) in 66% of observations versus 45% on chest radiographs (p < 0.025). Correct diagnoses were made on first choice in 61% of CT observations versus 34% on chest radiographs (p < 0.005). Observers were confident (versus uncertain) in 42% of the CT observations versus 18% on chest radiographs; of the confident diagnoses made on CT, 91% were correct. CT interpretations were most accurate in the diagnosis of pulmonary alveolar proteinosis, congenital lymphangiectasia, and idiopathic pulmonary hemosiderosis. All healthy patients examined with CT were correctly identified as such. We noted a distinctive CT pattern in three patients with nonspecific interstitial pneumonitis and one patient with desquamative interstitial pneumonitis; the CT pattern consisted of upper zone predominant honeycombing on a background of ground-glass attenuation. CONCLUSION: A higher proportion of pediatric interstitial lung diseases can be diagnosed on thin-section CT than on chest radiographs. In our study, confident and correct diagnoses were made more frequently with CT than with chest radiographs.

Adolescent↗
PubMed1999

The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis.

Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.

Biomarkers, Tumor↗
PubMed1999

Open lung biopsy for diffuse interstitial lung disease in children.

The aim of the study was to investigate the contribution that open lung biopsy makes to the management of children with diffuse interstitial lung disease and to review the procedure-related morbidity in comparison with published literature on other biopsy techniques. The authors reviewed the case notes and histology of patients under 18 yrs who had had an open lung biopsy in 1991-1998 for investigation of diffuse interstitial lung disease. The majority of patients returned from theatre breathing spontaneously and without an intercostal drain. Three out of 27 suffered a complication related to the biopsy that required intervention. A clear histological diagnosis was reached in 25/27 patients resulting in a change of management in 15/27. The most common histological patterns were nonspecific interstitial pneumonitis which generally had a favourable prognosis and follicular bronchiolitis/lymphocytic interstitial pneumonitis where prognosis was largely dependent on that of an underlying systemic disorder. It is concluded that open lung biopsy makes a substantial contribution to the management of diffuse interstitial lung disease in children and considering both diagnostic yield and safety, remains the biopsy technique of choice.

Adolescent↗
PubMed1999

Malignant myxoid endobronchial tumour: a report of two cases with a unique histological pattern.

AIMS: To present two cases of malignant endobronchial myxoid tumours with a highly distinctive sarcomatoid pattern not previously described at this site, and discuss their histogenesis in relation to previously documented endobronchial neoplasms. METHODS AND RESULTS: Both tumours presented in young adult females and were purely sarcomatoid with interweaving cords of small uniform, rounded or slightly elongated cells lying within a myxoid stroma. The stroma was alcian blue positive, but sensitive to hyaluronidase in both cases. The tumour cells contained a small volume of periodic acid-Schiff-positive eosinophilic cytoplasm and stained positively for vimentin only, but there also was a prominent background population of CD68-positive dendritic cells. Ultrastructural studies showed that the tumour cells contained an excess of rough endoplasmic reticulum, with some of the cisternae appearing dilated, and scalloping of the cell surfaces, although no intracisternal tubules were identified. CONCLUSIONS: Although the histological pattern was most reminiscent of extraskeletal myxoid chondrosarcoma, the sensitivity of the stroma to pretreatment with hyaluronidase precluded the diagnosis. However, there were similarities with the sarcomatoid component of malignant salivary gland-type mixed tumours of the lung and this tumour possibly represents a variant of a bronchial gland tumour. Despite this uncertainty over origin, this pattern should be recognized as part of the differential diagnosis of myxoid tumours in the lung, as an apparently indolent type of malignant endobronchial neoplasm.

Adult↗
PubMed1999

Interstitial pneumonitis following mitozantrone, chlorambucil and prednisolone (MCP) chemotherapy.

We describe two cases of interstitial lung disease in patients with non-Hodgkin's lymphoma who were treated with combination chemotherapy including mitozantrone. In both we had radiological and histological evidence of interstitial lung disease, with patterns of organizing pneumonia and hypersensitivity without a clear aetiological agent. Clinical resolution occurred on withdrawal of chemotherapy. One patient required a course of corticosteroid treatment. To date, both patients are well and in remission, and there has been no recurrence of their respiratory disease. We postulate that these observations are hitherto undescribed pulmonary abnormalities secondary to mitozantrone therapy.

Aged↗
PubMed1999

Spontaneous regression of large-cell carcinoma of the lung--a rare observation in clinical practice.

Spontaneous regression of non-small-cell lung carcinoma is extremely rare and there are few documented cases. We report a 59-year-old man with a right upper lobe tumour which showed progressive regression while hilar adenopathy appeared 2 months after the initial tumour detection. At operation, only scar tissue was found in the lung but a hilar lymph node contained large-cell undifferentiated carcinoma. This report indicates that a decrease in size of a pulmonary mass does not exclude the diagnosis of carcinoma and that metastatic disease can occur even if the primary tumour regresses.

Bronchoscopy↗
PubMed1999

Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease.

BACKGROUND: Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking. METHODS: Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10 remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians. RESULTS: Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated. CONCLUSIONS: This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD and DIP and their strong association with smoking, the term "smoking related interstitial lung disease" is suggested for those patients who are smokers.

Adult↗
PubMed1999

Follicular bronchiolitis: thin-section CT and histologic findings.

PURPOSE: To evaluate the thin-section computed tomographic (CT) findings of follicular bronchiolitis and compare them with the histologic findings. MATERIALS AND METHODS: Thin-section CT scans obtained in 12 patients (age range, 24-77 years; mean age, 47 years) with follicular bronchiolitis proved at open lung biopsy were reviewed by two observers. Underlying conditions included rheumatoid arthritis (n = 8), mixed collagen vascular disorders (n = 2), autoimmune disorder (n = 1), and acquired immunodeficiency syndrome (n = 1). All patients had thin-section CT scans (1.0-1.5-mm collimation, 11 patients; 3.0-mm collimation, one patient; high-spatial-frequency reconstruction algorithm) obtained at 10-mm intervals through the chest. RESULTS: The main CT findings included bilateral centrilobular (n = 12) and peribronchial (n = 5) nodules. All 12 patients had nodules smaller than 3 mm in diameter; six patients also had nodules 3-12 mm in diameter. Areas of ground-glass opacity were present in nine (75%) patients. Histologically, all patients had lymphoid hyperplasia along the bronchioles; eight had peribronchiolar lymphocytic infiltration. CONCLUSION: The cardinal CT feature of follicular bronchiolitis consists of small centrilobular nodules variably associated with peribronchial nodules and areas of ground-glass opacity.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis.

This study aimed to investigate whether there was a difference in outcome related to histologic pattern in cryptogenic fibrosing alveolitis (CFA) and to see whether there were correlations between clinical and radiologic findings and histology. One hundred thirteen lung biopsies from consecutive patients taken for the diagnosis of diffuse lung disease were reviewed and reclassified using the Katzenstein and Myers criteria for interstitial pneumonias. Patients lacking full investigational data at presentation and those with conditions predisposing to lung fibrosis were excluded, leaving 15 patients diagnosed with nonspecific interstitial pneumonia (NSIP) and 15 with usual interstitial pneumonia (UIP). Clinical and radiologic findings at presentation and serial lung function information and survival status in November 1998 were compared for the two groups. Survival was found to be significantly greater in the NSIP group compared with the UIP group (p < 0.001). This could not be explained by differences in treatment. Patients with UIP showed a progressive deterioration in lung function whereas those with NSIP remained stable. CT scans of patients with UIP showed more fibrosis than those of patients with NSIP (p < 0.011). A histologic diagnosis of NSIP is associated with a better prognosis than UIP. This subclassification of CFA is clinically useful.

Adult↗
PubMed1998

Thoracic metastasectomy for germ cell tumours: long term survival and prognostic factors.

BACKGROUND: This study evaluated the results of thoracic metastasectomy for germ cell tumours to assess long term survival and identify prognostic factors. PATIENTS AND METHODS: A series of 141 consecutive patients who underwent resection of thoracic metastases at Royal Brompton Hospital were retrospectively reviewed. Kaplan-Meier estimates of survival were calculated for clinical variables related to primary tumour and thoracic metastases, using the Cox model for multivariate analysis. RESULTS: Complete resection was achieved in 123 cases (87%); pathology showed viable malignant elements in 46 (32%), necrosis or fibrosis in 32, differentiated teratoma in 63. The overall survival was 77% at five years and 65% at 15 years, being significantly shorter in patients with malignant teratomatous elements (51% at five years, P = 0.0001) or incomplete resection (64% at five years, P = 0.019). At multivariate analysis these factors retained their prognostic value, with a relative risk of death of 5.7 for malignant teratomatous elements and 4.0 for incomplete resection. In addition, the Cox model revealed a 3.2 times higher risk of relapse in patients with malignant teratomatuos elements at the time of thoracic metastasectomy. CONCLUSIONS: These data confirm the value of thoracic metastasectomy to asses pathological response and achieve permanent cure of chemoresistant disease.

Adult↗
PubMed1998

Multiple synchronous lung cancers and atypical adenomatous hyperplasia in Li-Fraumeni syndrome.

AIM: We report a patient with Li-Fraumeni syndrome who developed multiple synchronous primary lung cancers together with atypical adenomatous hyperplasia, and discuss the pathogenesis of the lesions. CASE DETAILS: A 57-year-old woman with Li-Fraumeni syndrome and a history of smoking was diagnosed as having multiple synchronous primary lung tumours, all of which were treated by surgical excision. Histological examination showed three separate well-differentiated adenocarcinomas and a single focus of atypical adenomatous hyperplasia. A constitutional mutation of the p53 gene had been identified, both in this patient and other members of her family. CONCLUSION: Multiple synchronous primary lung tumours have not been reported before in association with this syndrome. With both smoking and Li-Fraumeni syndrome known to be associated with mutations in the p53 gene, a cumulative effect is suggested in this patient.

Adenocarcinoma↗
PubMed1998

The value of classifying interstitial pneumonitis in childhood according to defined histological patterns.

AIMS: Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term 'chronic pneumonitis of infancy' has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile. METHODS AND RESULTS: Twenty-five of 38 open lung biopsies showed an overlapping spectrum of interstitial pneumonitis, including three cases that fulfilled the histological criteria for chronic pneumonitis of infancy. There were 11 cases of reactive pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or follicular bronchiolitis), five of which were associated with abnormalities of the immune system. Four cases were classified as desquamative interstitial pneumonitis and the remaining seven cases were classified as nonspecific interstitial pneumonitis. There were no cases with the histological features of usual interstitial pneumonitis. Most patients responded to steroids but tended to have a residual deficit in lung function. Mortality appeared to be associated with presentation at a young age. CONCLUSION: Classification of interstitial pneumonitis according to their adult counterparts is appropriate for this younger age group and can provide valuable information for the clinician. The term 'chronic pneumonitis of infancy' refers to a specific histological pattern, but whether it represents a separate disease or a reflection of pulmonary immaturity remains to be proven.

Adolescent↗
PubMed1998

Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases.

AIMS: Synovial sarcomas are rare tumours occasionally arising in the pleural cavity, a site where their histological characteristics may be mistaken for those of malignant mesothelioma. We examined three cases of primary pleural synovial sarcoma in order to look for clinicopathological features that may help in distinguishing them from both mesotheliomas and other sarcomas that may arise in the pleura. METHODS AND RESULTS: All three patients were male, aged 42, 28 and 42, respectively, and had no known exposure to asbestos. One biphasic tumour contained neutral mucin in focal epithelial elements that also stained positively for BerEP4 and AUA1. All three tumours showed focal positivity for either keratin or EMA in the sarcomatous elements, and they also stained positively for bcl-2 protein and MIC2 gene product (CD99). CONCLUSIONS: Our results emphasize the importance of being aware of synovial sarcoma as a possible primary pleural malignancy, especially in a young patient with a localized mass. In addition, the presence of bcl-2 protein perhaps represents a useful marker in distinguishing synovial sarcoma, especially monophasic variants, from mesothelioma within a panel of antibodies.

Adult↗