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A detailed pathological study was made in 10 patients dying up to 13 months after aortocoronary saphenous vein bypass grafting for coronary atherosclerosis. The coronary arteries and vein grafts were investigated by injection with a radio-opaque mass, radiography, dissection, and histology. The report is to some extent historical since the patients died during a period when the operation was first being introduced into two cardiothoracic hospitals. About 80 operations were performed during the time the 10 deaths occurred, a mortality of 12-5 per cent (including cases followed up to 13 months after operation). Seven of the patients were operated on for intractable angina and 3 with a view to aneurysmectomy. All the patients selected for operation were severely disabled despite medical treatment. The main cause of death was extremely severe coronary artery disease and its effects on the left ventricle; in one case, over two-thirds of the left ventricle had been destroyed by infarction before operation. Other causes or contributing causes of death were pulmonary embolism, myocardial infarction complicating angiography (ostial stenosis), and cerebral damage. Ten of the 14 vein grafts (71%) were patent at necropsy. A free flow of injection medium usually occurred between patent grafts and coronary arteries. Thrombosis of a graft was thought to have contributed to death in 3 patients, but not in a fourth who died of pulmonary embolism. Since thrombosis of grafts was usually secondary to poor run-off blood into severely atheromatous coronary arteries, this was also an indirect effect of the advanced coronary arterial disease. In one case, thrombosis followed severe chronic intimal thickening of a graft in place for 13 months. The study of these deaths emphasizes that in some patients the pathological changes in the coronary arteries and left ventricle are too severe for them to benefit from surgery. Vein grafts cannot be expected to distribute blood effectively through grossly narrowed coronary arteries. In addition, when a large part of the left ventricle is infarcted or scarred, it is almost certain that improving the blood supply by grafting will not result in significant regeneration of cardiac muscle. Since the time when this study was made, there have been few deaths among the many vein graft operations subsequently carried out in the hospitals involved. The two most important factors thought responsible for the improvement are the selection of cases more suitable for surgery by continued improvement of diagnostic techniques, and also the employment of more radical surgical procedures in the form of coronary endarterectomy and the insertion of more grafts per patient. [ABSTRACT FROM PUBLISHER]

The accuracy of diagnosis in 656 patients with the four common histopathological types of primary lung cancer has been assessed by comparing the cell type diagnosis made on cytological and histological investigation with that determined by examination of the surgically resected or necroscopy specimen. The accuracy of diagnosis achieved by cytological examination of sputum and bronchial aspirate, and by bronchial biopsy histology was over 85%. The least accurate diagnostic procedure was percutaneous needle biopsy (62%). Squamous and small cell tumours were accurately diagnosed by all four investigations but errors were made in the diagnosis of large cell and adenocarcinomas. Nearly half the number of patients (43%) with large cell carcinoma were later reclassified as having squamous carcinoma and of the patients with adenocarcinoma 32% had been predicted to be squamous and 18% large cell carcinoma. We consider such quality control of pretreatment diagnosis mandatory in management of individual patients and before enrollment in clinical trials. [ABSTRACT FROM PUBLISHER]

Sarcoidosis is best defined in histopathological terms as 'a disease characterised by the presence in all of several affected organs and tissues of non-caseating epithelioid-cell granulomas, proceeding either to resolution or to conversion into hyaline connective tissue'. Although the defining characteristics are thus histopathological, diagnosis during life depends largely upon clinical, radiological, and immunological findings. The amount of support required from histology varies greatly from case to case. Though histology from one site cannot in itself establish the diagnosis of sarcoidosis, a generalised disease, detailed histological study of biopsy tissue makes an important and often essential contribution. In many instances, complete lack of necrosis, an intact reticulin pattern, and failure to demonstrate infective agents permit an unequivocal statement of compatibility with this diagnosis; however, a compatible clinical picture and absence of evidence of known causes of local granulomatous reactions or of other generalised granulomatous diseases are required for definitive diagnosis. In some, the histological pattern deviates in some particular from the accepted 'typical' pattern; there may be a little necrosis, the follicular pattern of the granuloma may be less than perfect, and exclusion of known infective agents can never be absolute. In such instances, subsequent surveillance, including possible response to treatment, may show a clinical course justifying a diagnosis of sarcoidosis, and necropsy may establish it; but it must be recognised that in a few cases, particularly those in which the clinical evidence of disease is confined to one organ, diagnosis is likely to remain in doubt for long periods. Reports on the histology of the Kveim test should be made without knowledge of clinical findings and in terms of the presence and quality of granulomatous response. A granulomatous reaction to a validated test suspension makes a contribution to diagnosis similar to the finding of granulomas in an additional organ or tissue. [ABSTRACT FROM PUBLISHER]

The differing clinical behaviour of malignant mesothelioma of different cell types was studied in 115 cases of pleural mesothelioma, classified histologically into epithelial (60), sarcomatous (25), and mixed (30). Epithelial mesotheliomas were associated with clinical features characteristic of carcinomas rather than sarcomas, including spread of tumour by direct extension, large pleural effusions, contralateral pleural effusions, ascites, metastases in regional lymph nodes, and occasional response to radiotherapy. Sarcomatous mesotheliomas were associated with clinical features more characteristic of sarcomas, with more frequent distant metastases, little or no effusion, and shorter survival. Mixed tumours had features of both, large pleural effusions occurring as frequently as with epithelial tumours, but survival being almost as poor as in sarcomatous cases. Despite these differences there is evidence from published reports that epithelial, sarcomatous, and mixed mesotheliomas have a common origin from mesothelial cells or their precursor cells. [ABSTRACT FROM AUTHOR]

Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract. [ABSTRACT FROM AUTHOR]

A man aged 57 years who had lived most of his life in London, suffered from asthma which had begun during army service in Burma 37 years previously. Latterly he was treated with increasing doses of corticosteroids but his symptoms continued to worsen and he died of asthma. Necropsy revealed a heavy opportunistic infection of the bronchi and lungs by the nematode Strongyloides stercoralis which he had presumably acquired while on service abroad. The case illustrates the need, even in non-endemic areas, to suspect opportunistic pulmonary strongyloidiasis when a patient's asthma worsens despite treatment with increasing doses of corticosteroids. Although it is a potentially lethal iatrogenic opportunistic infection, it is amenable to treatment with anthelminthic agents if recognized in time. [ABSTRACT FROM PUBLISHER]

Diaphragms were dissected out intact from 29 male and 9 female cadavers at necropsy. Fifteen of the males and eight of the females were grouped as controls, having no history of chest disease. Fourteen of the males and one female gave a history of chronic bronchitis. Point-counting and other methods were employed to measure the mean area, thickness, and volume of the diaphragmatic muscle, excluding the central tendon. The results showed that the diaphragm was reduced in area, thickness, and volume in the chronic bronchitics, the figures being 350 cm, 0·29 cm, and 99·7 cm respectively in male controls, and 295 cm, 0·23 cm, and 68·7 cm in the bronchitics. In the female controls, the values were significantly lower than in the male controls. The one female bronchitic had a muscle volume of only 40 cm. The male controls were similar in height to the bronchitics, but their mean weight was higher, being 69·4 kg against 56·0 kg in male bronchitics. It is concluded that the diaphragm is smaller in chronic bronchitics than in controls at necropsy and that while a major factor in causation is an associated low body weight, other factors such as the mechanical consequences of flattening of the diaphragm, longstanding reduction in physical activity, and other diseases such as cancer may also play a part. No histological changes by non-quantitative methods were found in the diaphragm in the chronic bronchitics, but muscle fibre shrinkage was suspected. By contrast, a few cases of asthma examined to date have shown no evidence of reduction in diaphragm size. The mechanical implications are discussed. [ABSTRACT FROM PUBLISHER]

The course of cryptogenic fibrosing alveolitis (CFA) in 96 patients is described. The mean survival from the onset of the first symptom until death was 47·4 months in all the 59 fatal cases, 49·6 months in those dying from CFA only, and 48·4 months in those dying from CFA in whom the course of the illness was not influenced by corticosteroids. There was a wide variation in the natural course of the disorder, varying from death within a year of the onset of symptoms in five patients to prolonged survival with slow or arrested progress in four patients not treated with corticosteroids. Most patients died from CFA but five developed bronchial carcinoma and two died after lung biopsy. The main factor influencing the prognosis was the effectiveness of corticosteroid drugs. Only 16% of the treated patients had a worthwhile (grade 2) response to these drugs and the five-year survival of this group was 67%. In those patients in whom the course of the illness was uninfluenced by corticosteroids the five-year survival rate was only 20%. The histological appearances on lung biopsy gave a rough guide to the likely effect of corticosteroid therapy. Other factors influencing the prognosis were the degree of dyspnoea on presentation, the vital capacity, and the presence of arterial hypoxaemia. Patients who had had symptoms for more than four years before the first hospital attendance had a relatively good prognosis. By contrast, neither the extent of radiographic abnormality nor the presence of circulating rheumatoid and antinuclear factors influenced subsequent survival. [ABSTRACT FROM PUBLISHER]

Histological changes attributable to busulphan were found at necropsy in the lungs of six out of 14 cases of chronic granulocytic leukaemia. The alveoli contained persistent fibrinous oedema converting to fibrous tissue, and also atypical cells. Only one out of seven controls with leukaemia showed fibrinous oedema, and atypical cells were absent. In the lungs from rare cases of fatal pulmonary fibrosis due to busulphan, the histological changes were similar but more severe. It is concluded that busulphan commonly causes fibrinous oedema in chronic granulocytic leukaemia and on rare occasions it becomes severe or persistent enough to cause fatal fibrosis of the lungs. The name busulphan lung is suggested for any of these changes. The term `intra-alveolar fibrosis' should be used instead of `interstitial fibrosis', as it had been called by most previous authors. Despite these findings we consider that this valuable drug should be discontinued only in those very rare instances when intra-alveolar fibrosis shows signs of becoming disabling. [ABSTRACT FROM PUBLISHER]

In a group of 23 patients with histologically confirmed malignant mesothelioma of the pleura who could not recall exposure to asbestos dust, survival was significantly longer than in a group of 83 patients with known exposure. Asbestos bodies were found by a quantitative method significantly less frequently in the unexposed than in the exposed group. The longer survival of patients without known exposure could not be correlated with any significant difference in the histological cell types of the tumours from those of exposed patients. In the 83 patients with known exposure survival did not relate to duration of exposure. Consequently, although the tumours of patients unable to recall exposure may be caused by unrecognised environmental contamination with asbestos dust, the longer survival of these patients would suggest a different aetiology. [ABSTRACT FROM AUTHOR]

The perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (-19.6, 25.1); P = 0.65). The PPAF range overall was 3.8-94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung. The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung.

Structural heterogeneity of mast cells in human bronchial mucosa was investigated by examining 100 cells by electron microscopy and morphometry. Differential counts of secretory granules allowed subdivision of mast cells into three groups: (1) 49 cells with greater than 65% mixed granules; (2) 30 cells with greater than 30% scrolled granules; (3) 12 cells with greater than 30% particulate granules. Nine cells showed borderline characteristics. Records of depths of cells in the mucosa showed that most mixed-granule cells occupied middle levels, whereas most scrolled granule cells lay higher up, near the basement membrane. This raised the possibility that scrolled-granule cells may represent partly degranulated mixed-granule cells. Nineteen mast cells were filled with very dense mixed granules, and appeared to correspond to those staining with safranin in paraffin sections. However, morphometry did not produce any criteria for distinguishing these cells sharply from paler mixed-granule cells, which were therefore regarded as degranulating forms of the same type of cell. Evidence was found of a gradient of mast cell degranulation which appeared to increase in magnitude upward from deep submucosa to superficial mucosa. This evidence included finding a significant upward reduction in total granule area per cell, total granule numbers, numbers of mixed granules, and numbers of dense-cored granules. It was concluded that although bronchial mucosal mast cells could be subdivided ultrastructurally into three apparently heterogeneous groups, degranulation was found to produce a wide range of different cell appearances, and could, conceivably, even be responsible for the above grouping, rather than intrinsic mast cell heterogeneity.

An infant with congenital left upper lobe emphysema presenting with respiratory distress and failure to thrive, which necessitated lobectomy, is described. Careful pathological examination revealed two defects in association with the emphysema: bronchial atresia and defective bronchial cartilage in the affected lobe. Whilst congenital lobar emphysema is the term usually employed to describe this clinical presentation of respiratory distress in infancy, 'panlobular emphysema of infancy' would be a more accurate description. Congenital defects in the airways may account for the development of emphysema, but there may be a more fundamental congenital tissue abnormality at alveolar level.

Eight patients with histological intra-alveolar organization, but no evidence of an infective or other aetiological agent, are reported. They characteristically presented with a short history of severe dyspnoea, cough, malaise, weight loss, bilateral radiographic shadowing and a raised ESR. There was a dramatic response clinically and radiologically to prednisolone but relapse occurred quickly as the dose was reduced. Control was re-established with an increased dose of prednisolone. In order to avoid confusion with post-infective organizing pneumonia the term cryptogenic organizing pneumonitis is suggested.

The role of changes in the relative amounts of types I and III collagen in cryptogenic fibrosing alveolitis was investigated using a biochemical method adapted for small amounts of human lung tissue. Measurements were performed in 18 biopsy and seven post-mortem lung samples from patients with cryptogenic fibrosing alveolitis and the results were compared with clinical, physiological, radiological and histological data. The mean percentage type III collagen, compared with type I collagen, was significantly lower in post-mortem lung samples from patients with cryptogenic fibrosing alveolitis who died from the disease compared with the biopsy lung samples (p less than 0.01) and with the control lung samples (p less than 0.05). There was a positive correlation between the percentage of type III collagen and response to treatment at six months as shown by the improvement in the percentage predicted Kco (p less than 0.005) and FVC (p less than 0.01) and with the radiological changes (p less than 0.05). These changes remained significant at one year (p less than 0.05 in all cases). These results suggest that patients with a higher proportion of type III collagen have earlier disease and show a better response to treatment than those with a lower proportion of type III collagen. The potential advantages of measuring collagen types for staging cryptogenic fibrosing alveolitis are discussed.

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.