B. Corrin

High resolution computed tomography as a predictor of lung histology in systemic sclerosis.

BACKGROUND: The relative proportions of fibrosis and inflammation seen by open lung biopsy examination is a predictor of disease outcome in fibrosing alveolitis. This study was designed to assess the ability of high resolution computed tomography to predict the histological appearance of open lung biopsy specimens from patients with systemic sclerosis. METHODS: Twenty abnormal biopsy specimens from 12 patients were assessed; abnormalities were categorised as fibrotic (fibrosis exceeding inflammation) or inflammatory (inflammation equal to or exceeding fibrosis). Computed tomography appearances were scored for the lobe from which the biopsy specimen was taken; scans were graded from parenchymal opacification alone through to a reticular pattern alone. RESULTS: Two lobar appearances were identified on computed tomograms: amorphous parenchymal opacification equal in extent to reticulation (grade 3) and a predominantly reticular pattern (grade 4). There was a significant association between a fibrotic histological appearance and a grade 4 computed tomogram, and between an inflammatory histological appearance and a grade 3 computed tomogram. Computed tomography grade 4 was associated with a fibrotic histological appearance in 12 out of 13 lobes, and grade 3 with an inflammatory histological appearance in four out of seven lobes. CONCLUSION: Computed tomography discriminated between biopsy specimens that were predominantly fibrotic and a smaller group with a larger amount of inflammation.

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 hyperpiasia 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.

Localization of β2-adrenoceptor messenger RNA in human and rat lung using in situ hybridization: correlation with receptor autoradiography

We have used in situ hybridization to study the localization of mRNA encoding the beta 2-adrenoceptor in tissue sections of the human and rat lung and compared this with the distribution of beta 2-receptor binding sites using receptor autoradiography. To localize beta 2-receptor mRNA, a [32P]labeled antisense RNA probe (riboprobe) was generated from human or rat beta 2-receptor cDNA. A similar distribution of beta 2-receptor mRNA was identified in both species. The highest intensity of beta 2-receptor mRNA was detected in smooth muscle of small airways, airway epithelium and pulmonary blood vessels. Lower intensity of beta 2-receptor mRNA was identified in smooth muscle of large airways, and alveolar epithelium (presumably type I and type II pneumocytes). No significant hybridization signal was detected in interstitial tissue. The specificity of the hybridization signal was confirmed with a sense probe (having identical sequence to the mRNA) and preincubation with RNase A, and by Northern blot analysis which revealed a single band of mRNA of 2.2 kb. There was a correspondence between mRNA localization and the distribution of beta 2-receptors visualized by [125I]iodocyanopindolol autoradiographically in the presence of CGP 20712 (a beta 1-selective antagonist). However, alveolar walls that showed a high beta 2-receptor density had relatively low levels of mRNA. This cellular heterogeneity may reflect differences in RNA stability or transcription rate in different lung cells. This approach opens up new options in the investigation of the regulation of pulmonary beta 2-receptor gene expression in health and disease.

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.

Fibrosing alveolitis in systemic sclerosis: increase in memory T-cells in lung interstitium

Despite the large numbers of T-cells present in the lungs in fibrosing alveolitis, their pathogenetic role is poorly understood. If these cells are involved in pathogenesis, they are more likely to express the CD45RO+ memory phenotype. To test this hypothesis, open lung biopsies from patients with fibrosing alveolitis associated with systemic sclerosis (FASSc) were compared with grossly normal lung taken from the periphery of lobes resected for lung cancer. Biopsies from eight patients with FASSc were compared with tissue from seven cancer controls. Paraffin sections were stained with a polyclonal anti-CD3 antibody for T-lymphocytes, monoclonal anti-CD45 antibody for leucocyte common antigen, and monoclonal anti-CD45RO antibody for primed T-lymphocytes. Staining was assessed quantitatively by computerized image analysis: in each case, the number of immunopositive cells was related to alveolar wall area and alveolar wall length. Mean alveolar wall thickness was increased in patients with FASSc (60.7 +/- 24.0 microns) compared with cancer controls (15.7 +/- 5.3 microns). Patients with FASSc had greater numbers of CD45+, CD3+ and CD45RO+ cells.mm-1 alveolar wall length compared with the controls. CD45RO+ cells made up 77% (median) of the CD3+ cells in FASSc, and their numbers per unit alveolar wall length were positively associated with alveolar wall thickness (r = 0.61). In conclusion, in fibrosing alveolitis of systemic sclerosis, most interstitial T-lymphocytes express the phenotype of memory cells; these cells are likely to be involved in the persistent inflammatory process.

Pathogenesis of Idiopathic Interstitial Pulmonary Fibrosis

The histopathology and ultrastructure of idiopathic interstitial pulmonary fibrosis is described and illustrated. There is evidence that proliferating type II pneumocytes in regenerating alveolar epithelium are implicated in the pathogenesis of this disorder.

Epithelioid Hemangioendothelioma of the Lung

Light and electron microscopic features of an epithelioid hemangioendothelioma of the lung in a 43-year-old woman are reported. The tumor cells stained for factor VIII-related antigen. A mass excised from the thigh 10 years earlier showed identical appearances.