No abstract

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.

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-biotinperoxidase 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.

The clinical, morphological and immunohistochemical features of 15 cases of pulmonary lymphoproliferative disease are described. The diagnosis of primary pulmonary lymphoma was based in 13 cases on the demonstration of light chain restriction and in two cases on morphological characteristics. Many patients had a prolonged clinical course without significant clinical or radiographic deterioration, a feature associated with malignant lymphomas of mucosa-associated lymphoid tissue in other sites. Lymphoepithelial lesions were characteristic and malignant cells had the features of centrocyte-like cells, similar to those described in gastric and salivary gland lymphomas. Germinal centres were present in three cases: some were partially overgrown by centrocyte-like cells but residual polyclonal follicle centre cells and dendritic reticulum cells were still detectable. It is suggested that primary pulmonary lymphoma arises from centrocyte-like cells normally present in bronchus-associated lymphoid tissue. In addition to the malignant population, reactive follicles and polytypic plasma cells are frequently present and may prejudice interpretation of immunohistochemical features. In the light of these findings, cases previously diagnosed as pseudolymphoma or lymphoid interstitial pneumonia require careful assessment and the majority are, in reality, examples of primary pulmonary lymphomas.

No abstract