Sarcoidosis complicating treatment with natalizumab for Crohn's disease.

Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.

Accuracy of cell typing in nonsmall cell lung cancer by EBUS/EUS-FNA cytological samples.

Endoscopic ultrasound-guided transbronchial or transoesophageal lymph node aspiration is increasingly used as a method of diagnosing nonsmall cell carcinoma. Data validating the accuracy of cell typing of nonsmall cell carcinoma using these cytological samples has not been assessed. 23 samples were identified in Edinburgh, UK and a further 25 in Cambridge, UK, with matching histological samples. The morphological cell type, as assessed on the cytological preparations and cell blocks, was recorded and immunohistochemical staining was performed, where possible, as an adjunct. The final cell type, as assessed by morphology with or without immunohistochemistry, was correlated with that reported in the paired histological samples. Cell blocks with tumour were available in 39 out of 48 cases. The accuracy of cell typing when no cell block was available was four out of nine cases. This increased to 25 out of 39 when a cell block was available, increasing to 33 out of 39 with the addition of immunohistochemistry. The overall accuracy of classification was 37 out of 48 cases. Accurate cell typing of nonsmall cell carcinomas can be performed using endoscopically derived fine-needle aspirates. The importance of obtaining sufficient material for the production of cell blocks is critical in allowing optimal assessment.

Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology.

BACKGROUND: Optimal management of patients with lung cancer requires accurate cell typing of tumours and staging at the time of diagnosis. Endobronchial ultrasound-guided lymph node aspiration as a method of diagnosing and staging lung cancer is a relatively new technique. AIM: To report the use of liquid-based-thin-layer cytology for the processing and reporting of these specimens. METHODS: The specimens obtained from 80 patients were processed using the ThinPrep system, with the remainder of the samples being processed as a cell block. RESULTS: 40 of the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small-cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The cell blocks were found to contain sufficient material to allow the immunohistochemical characterisation of tumour cells with a range of antibodies. CONCLUSION: The use of liquid-based-thin-layer cytological techniques provides high-quality specimens for diagnostic purposes. When used in conjunction with cell blocks, sufficient material may be obtained to allow immunohistochemical studies to confirm the tumour cell type. Given the current move towards centralisation of pathology services, this approach gives the pathologist high-quality specimens without the need for direct onsite support at the time of the procedure.

Focal neuroendocrine differentiation in non-small cell carcinoma is not predicted by pre-operative routine investigation.

AIMS: Between 10 and 35% of resected non-small cell carcinomas of the lung show focal neuroendocrine differentiation. The significance of this is uncertain but recent studies have suggested that these tumours may be more responsive to chemotherapeutic agents than other non-small cell carcinomas. This study was undertaken to determine if focal neuroendocrine differentiation in surgically resected non-small cell carcinomas could be predicted in patients who had undergone traditional routine pre-operative diagnostic investigations. METHODS: Sixty-six consecutive resections for non-small cell carcinoma were reviewed for the presence of focal neuroendocrine morphology or positive immunohistochemical staining with neuroendocrine markers. Pre-operative biopsy and cytology samples from these patients were then sought for similar assessment. RESULTS: Ten of the 66 cases showed either morphological or immunohistochemical evidence of neuroendocrine differentiation. All 10 patients had undergone pre-operative investigation including bronchoscopy but in only four were pre-operative diagnostic samples obtained (two cytology and two biopsies). None of these specimens showed features to suggest the presence of neuroendocrine differentiation within the resected tumours. CONCLUSION: The presence of focal neuroendocrine features in an unselected series of resected non-small cell carcinomas was not predicted by traditional pre-operative diagnostic investigations This indicates that focal neuroendocrine differentiation in patients with unresectable non-small carcinoma cannot be reliably identified for inclusion in clinical trials using traditional investigate approaches.

Diagnosis and staging of lung and pleural malignancy - an overview of tissue sampling techniques and the implications for pathological assessment.

Malignant diseases of the lungs and pleura are common causes of morbidity and mortality throughout the developed world. Determining the appropriate treatment strategies for an individual patient requires a multidisciplinary approach integrating input from many disciplines including pathology. In this overview, we discuss diagnosis of lung and pleural malignancy from the pathologist's perspective, placing particular emphasis on methods available to obtain material for pathological assessment, and their implications for diagnosis and provision of information to guide patient management.

Non-small-cell lung cancer dimensions: CT-pathological correlation and interobserver variation.

The aim of the study was to identify the most accurate CT window level setting for the measurement of non-small-cell lung cancer to optimise CT planning for radiotherapy treatment. 27 patients who underwent resection for non-small-cell lung cancer in a single institution were studied. The maximal superior-inferior, anteroposterior and mediolateral dimensions of the resected tumours were measured by a consultant pathologist. Two radiologists made corresponding measurements using pre-operative CT scans independently of each other and of the pathologist's findings. The measurements were obtained using four different CT window settings. The mean pathological size of the superior-inferior tumours, the anteroposterior tumours and the mediolateral tumours was 32 mm, 28 mm and 25 mm, respectively. A total of 648 CT measurements were taken, of which 321 were within +/-5 mm of the pathological size (49.5%). There was significant interobserver variability between the two radiologists. There was poor correlation between the pathological and radiological measurements of tumour size. Significant interobserver variability was noted between the two radiologists and no window setting could be identified as being superior in accurately assessing the tumour size.

Gene therapy for chronic obstructive pulmonary disease: twilight or triumph?

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome presenting as progressive airflow limitation that is poorly reversible as a result of bronchitis and emphysema. The prevalence of COPD is alarming and even more so its current and projected impact on morbidity and mortality. To date, there are no effective treatments for emphysema, nor are there efficient clinical management strategies. Existing and prospective therapies, although promising, have yet to demonstrate their efficacy to slow, halt or reverse the disease. Novel approaches using gene therapy and stem cell technologies may offer new opportunities. However, this will remain almost entirely dependent on a more thorough understanding of the pathogenesis of COPD. This review is not aimed at highlighting the vast effort of studying COPD, but rather describing the state of the field in an abstract fashion to expose the focus of research efforts to date, which has primarily been limited to predisposing factors and inflammation. We would like to draw attention to other elements of the disease, such as the alveolar remodelling that characterises emphysema. Although the main cause may prove to be elusive, carefully designed clinical treatment and management may deliver the required therapeutic outcome.

Emphysema: the challenge of the remodelled lung.

Emphysema is recognized as the component of chronic obstructive airways disease that is responsible for airways obstruction. Different patterns of emphysema are, however, recognized, suggesting possible different pathogenetic processes within the lung. This, coupled with the associated idea of susceptibility factors to the development of emphysema, has led to studies of genes that may be involved in the defence of the lung from proteolytic and oxidative damage. These studies have been driven by the goal of finding a treatment for emphysema, but appear to have lost sight of the fundamental remodelling of the lung that has occurred in patients with emphysema and the fact that it is not a single morphological entity.

Transplant histopathology for the general histopathologist.

The number of patients undergoing solid organ transplants and surviving long-term has increased enormously in the last 10 years. This means that pathologists in non-specialist transplant centres are increasingly involved in the interpretation of biopsy and autopsy material from allograft recipients. This includes evaluation of allograft histology, or specimens from other native tissues, which nonetheless still have to be assessed in the setting of transplantation and immunosuppressive therapy. In this first review article we will provide an overview of the pathology of lung transplantation, and briefly describe heart and pancreatic transplants, as well as aspects of general surgical pathology and the role of the autopsy in these patients.

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.