Inter-observer variation between pathologists in diffuse parenchymal lung disease.

BACKGROUND: There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study. METHODS: A method for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed. RESULTS: The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia. CONCLUSION: These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.

Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies.

AIM: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required. METHODS: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin-biotin-peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue. RESULTS: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1. CONCLUSION: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma.

Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behçet disease.

Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.

The distribution and density of airway vasoactive intestinal polypeptide (VIP) binding sites in cystic fibrosis and asthma.

The densities of airway binding sites for Vasoactive intestinal polypeptide (VIP) were determined using 125I-labelled VIP (IVIP) and the technique of autoradiography applied to cryostat sections. Tissue studied included: grossly normal airway tissue taken from lungs resected for bronchial carcinoma (Ca; n = 11) and lungs removed at transplant from patients with cystic fibrosis (CF; n = 7). Lung tissue obtained at post-mortem in cases of fatal asthma (n = 3) or lobes resected for bronchiectasis (n = 3) were taken as further disease controls. In the Ca controls there was dense IVIP labelling, of alveolar wall, blood vessels, airway epithelium, submucosal glands, and bronchial smooth muscle: labelling of bronchiolar smooth muscle was sparse. In comparison with the Ca controls, IVIP labelling of all tissue structures in CF, with the exception of bronchial smooth muscle, was reduced (P <0.01). The most striking reductions were associated with airway epithelium and alveolar wall. These reductions showed a similar trend in bronchiectasis but did not achieve statistical significance. There was no such change in lung tissue obtained from the cases of fatal asthma where labelling of bronchial smooth muscle and all other structures was similar to that of the Ca controls. It is likely that the reduction of VIP binding sites in CF is secondary to infection and inflammation.

Interstitial pneumonia in simian immunodeficiency virus infection.

Interstitial pneumonia unrelated to Pneumocystis carinii or other infections was observed histopathologically in 5 of 25 rhesus monkeys infected with simian immunodeficiency virus (SIV). The predominant lesion was lymphocytic infiltration of interalveolar septa and hyperplasia of peribronchial and perivascular lymphoid tissue. Immunohistochemical staining using a panel of antibodies against human T and B lymphocytes, macrophages, and immunoglobulins showed that peribronchial aggregates and interstitial infiltrates were predominantly B cells, whereas perivascular masses consisted mainly of T cells. One animal with a primary B-cell lymphoma of the spinal cord had secondary plasmacytoid lymphomatous nodules throughout the lung which were accompanied locally by reactive B-cell lymphoid follicles. Another animal also had large areas of diffuse alveolar fibrosis and epithelial metaplasia to a bronchiolar type. In two monkeys, branches of the pulmonary arteries showed intimal proliferation and organizing occlusive thrombi, some of which were mineralized.

Long-term survival of a patient with malignant lymphoma of bone.

Malignant lymphoma of bone is an uncommon tumour. A number of studies have outlined the clinicopathological findings and overall favourable prognosis in adults. We report on a woman whose tumour was originally diagnosed as a secondary carcinoma of the upper femur. Twenty-three years later following proximal femoral replacement, the original histology was reviewed using immunohistochemical techniques and revised to B-cell malignant lymphoma of bone.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus. A thymic lymphoma mimicking myoepithelial sialadenitis.

We describe two cases of primary low-grade B-cell lymphoma of the thymus that showed histological features of low-grade B-cell lymphoma arising in mucosa-associated lymphoid tissue (MALT). The appearances most closely resembled MALT lymphoma arising in myoepithelial sialadenitis (MESA). In both cases, the tumor was excised. In one case, there has been no recurrence in 4 years of follow-up without further treatment; in the second case, the tumor has involved an axillary lymph node. Immunohistochemistry showed light-chain restriction in both cases, and the B-cell phenotype was similar to that previously described in MALT lymphomas. The occurrence of MALT lymphoma in the thymus is consistent with the presence of mucosal structures (Hassall's corpuscles) and with recent descriptions of a native B-cell population in this organ. The relationship of this previously undescribed thymic low-grade B-cell MALT lymphoma arising in the thymus has not yet been clarified.

Histopathology of the pleura.

This review attempts to provide up to date information on structure/function relationships of the pleura and on the pathology of pleural effusions, pneumothorax, pleural repair, pleural infections, pleural involvement in systemic connective tissue disorders, non-malignant asbestos-induced pleural disease, mesothelioma and other pleural tumours.

Changes in vein interstitium following distension for aortocoronary bypass.

Some patients who undergo aortocoronary bypass develop lesions in the graft and recurrence of symptoms. Hydraulic distension is used for preparation of veins. We have studied properties of vein interstitium, before and after peroperative distension, in 30 consecutive unselected patients. Segments of vein were studied for water content, swelling behaviour, tracer distribution, and uronic acid content. Initial water content was the same in distended and undistended vein; initial uronic acid content was slightly lower in distended veins, 8.7 (SD = 2.3) micrograms/m, n = 4 vs 10.5 (SD = 5.1) micrograms/mg dry weight, n = 6, not significant. The initial ratio, uronate/hydroxyproline was less in distended veins, 0.14 (SD = 0.05) n = 4 vs 0.19 (SD = 0.07), n = 6 in controls, not significant. Distended veins swelled less during incubation in saline. Average weight gain/initial weight was 0.65 (SD = 0.45), n = 27, and 1.1 (SD = 0.66), n = 25 in controls (p less than 0.01); change in water content/dry weight was 1.2 (SD = 1.1), n = 22, and 1.7 (SD = 1), n = 23 (p less than 0.02), in controls. Distended veins desorbed less uronic acid into the bath; 0.40 (SD = 0.2) microgram/mg wet tissue, n = 26 and 0.59 (SD = 0.3), n = 25 in controls (p less than 0.01). The pattern of uptake of two tracers 125I Serum albumin and 51Cr EDTA, was similar in both groups. These findings suggest alteration of the interstitial matrix of veins during distension. Histologic examination of glutaraldehyde-fixed tissue by light and electron microscopy revealed mural thinning and endothelial cell damage in distended veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of the embryonal neural cell adhesion molecule N-CAM in lung carcinoma. Diagnostic usefulness of monoclonal antibody 735 for the distinction between small cell lung cancer and non-small cell lung cancer.

Paraffin sections of 19 surgically resected small cell lung carcinomas (SCLC), 33 non-small cell lung carcinomas (NSCLC) of various types, and four bronchial carcinoids were immunostained with monoclonal antibodies (MoAbs) 735 and anti-Leu 7, both recognizing some sugar epitopes present on the neural cell adhesion molecule N-CAM. With MoAb 735, all SCLC were stained focally or diffusely, and one carcinoid was stained focally. Only three of the 33 NSCLC were faintly and focally positive with MoAb 735; these three tumours showed relatively small tumour cells and small, oval nuclei. Anti-Leu 7 stained all the carcinoids, only eight SCLC, sometimes focally, and eight NSCLC. MoAb 735 was thus superior to anti-Leu 7 in distinguishing between SCLC and NSCLE. Since MoAb 735 stained all SCLC strongly and is applicable on paraffin sections, it provides a well-needed addition to the immunomarkers used in the diagnostic distinction of SCLC and NSCLC.

Pulmonary involvement in systemic sclerosis: the detection of early changes by thin section CT scan, bronchoalveolar lavage and 99mTc-DTPA clearance.

Systemic sclerosis is frequently complicated by fibrosing alveolitis although clinical and radiological abnormalities are not usually apparent until the lung disease is well established. The aim of this study was to investigate pulmonary involvement in systemic sclerosis by thin section CT scan, bronchoalveolar lavage (BAL) and 99mTc-DTPA clearance studies, and assess the value of these tests in defining pulmonary abnormalities in patients with a normal chest radiograph. Patients were divided into those with an abnormal chest radiograph (Group I, n = 14) and those with a normal chest radiograph (Group II, n = 16). CT scans were abnormal in all patients in Group I and 7 of 16 (44%) in Group II. BAL inflammatory cell counts were raised in all 12 (100%) patients studied in Group I and 11 of 15 (73%) in Group II. There was no difference in the type of inflammatory cells observed between the two groups. 99mTc-DTPA clearance was faster than normal controls in ten of 14 patients (71%) in Group I and seven of 15 (47%) in Group II and correlated with carbon monoxide transfer factor (P less than 0.05). Lung biopsies were performed on nine patients in Group I and three in Group II all of whom had abnormal CT scans. Fibrosing alveolitis was confirmed in every case. Group II biopsies could not be distinguished from Group I biopsies; both showed fibrosis as well as inflammation suggesting that pulmonary fibrosis is an early abnormality in systemic sclerosis. Our results indicate that CT scans, BAL and 99mTc-DTPA are frequently abnormal in asymptomatic patients with systemic sclerosis who have normal chest radiographs. When the CT scan is normal abnormalities of BAL and/or 99mTc-DTPA (99mTechnetium diethylenetriamine pentacetate) clearance may indicate lung disease at a still earlier stage. This observation requires further investigation.

Peripheral T-cell lymphoma presenting with angioedema and diffuse pulmonary infiltrates.

Peripheral T-cell lymphoma is becoming increasingly recognized as a clinical entity despite its protean clinical manifestations and morphological features. Pulmonary involvement is evident in 20% of patients at initial diagnosis and develops in a further 20% during the course of their disease. Angioedema resulting from immune-mediated complement depletion is a rare complication of B-cell tumors. It has not been reported in T-cell lymphoma. We describe a patient with peripheral T-cell lymphoma who presented with angioedema and diffuse pulmonary infiltrates. Normal serum complement levels suggest that this patient developed angioedema independent of abnormalities in the complement cascade.