Knowledge of normal lung anatomy and function is important for the interpretation of lung biopsies and resections. An understanding of different cell structures and functions allows for a greater appreciation of disease states. In addition basic pulmonary embryology explains congenital pulmonary defects. At the other extreme of life, knowledge of how the lung ages is important, not only for consideration of other diseases, such as hiatus hernias with co-existent aspiration, but also because of the world's increasing elderly population.
Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms.Differential Diagnosis: Idiopathic Pulmonary Fibrosis. The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis.Differential Diagnosis: Respiratory Bronchiolitis.-Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis.Role of Asbestos Bodies.-Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5-mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests.Role of Fiber Analysis.-Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population. (Arch Pathol Lab Med. 2010; 134: 462-480)
Introduction Haemoptysis in pregnancy is frequently assumed to be caused by a pulmonary embolism. However, it can also be an indicator of serious pathology. Case presentation We report the case of a 27-year-old Caucasian woman who presented with haemoptysis in pregnancy that was discovered to be caused by a well-differentiated fetal adenocarcinoma of the lung. Conclusion This case demonstrates the importance of establishing an accurate diagnosis when a pregnant woman presents with haemoptysis and that more serious pathology should be considered if the clinical symptoms persist and/or the presumed diagnosis of pulmonary embolism is not confirmed.
Primary pulmonary osteosarcoma is very rare. Most cases are secondary deposits from primaries arising in the appendicular skeleton. Four cases of primary osteogenic sarcoma of the lung are described and the literature reviewed for previously reported cases. These pulmonary tumors occur in patients who are in their fourth to seventh decades, that is, an older age group than their primary bone equivalent. There is a slight male predominance. There appears to be a propensity for the left lung, especially the left upper lobe. The clinical presentation is similar to primary (epithelial) lung cancer. Differentiation from pleomorphic carcinomas and other sarcomas is discussed. We know of no predisposing factor(s) in our cases for the development of this tumor.
INTRODUCTION:Advances in the pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) have demonstrated important new prognostic features that have led to changes in classification and diagnostic criteria.METHODS:The literature and a set of cases were reviewed by a pathology/CT review panel of pathologists and radiologists who met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The group addressed the question of whether sufficient data exist to modify the 2004 World Health Organization (WHO) classification of adenocarcinoma and BAC to define a "minimally invasive" adenocarcinoma with BAC. The problems of diffuse and/or multicentric BAC and adenocarcinoma were evaluated.RESULTS:The clinical concept of BAC needs to be reevaluated with careful attention to the new 2004 WHO criteria because of the major clinical implications. Existing data indicate that patients with solitary, small, peripheral BAC have a 100% 5-year survival rate. The favorable prognostic impact of the restrictive criteria for BAC is already being detected in major epidemiologic data sets such as the Surveillance Epidemiology and End-Results registry. Most lung adenocarcinomas, including those with a BAC component, are invasive and consist of a mixture of histologic patterns. Therefore, they are best classified as adenocarcinoma, mixed subtype. This applies not only to adenocarcinomas with a solitary nodule presentation but also to tumors with a diffuse/multinodular pattern. The percentage of BAC versus invasive components in lung adenocarcinomas seems to be prognostically important. However, at the present time, a consensus definition of "minimally invasive" BAC with a favorable prognosis was not recommended by the panel, so the 1999/2004 WHO criteria for BAC remain unchanged. In small biopsy specimens or cytology specimens, recognition of a BAC component is possible. However, it is not possible to exclude an invasive component. The diagnosis of BAC requires thorough histologic sampling of the tumor.CONCLUSION:Advances in understanding of the pathology and CT features of BAC and adenocarcinoma have led to important changes in diagnostic criteria and classification of BAC and adenocarcinoma. These criteria need to be uniformly applied by pathologists, radiologists, clinicians, and researchers. The 2004 WHO classification of adenocarcinoma is readily applicable to research studies, but attention needs to be placed on the relative proportion of the adenocarcinoma subtypes. Other recently recognized prognostic features such as size of scar, size of invasive component, or pattern of invasion also seem to be important. More work is needed to determine the most important prognostic pathologic features in lung adenocarcinoma.
Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.
Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.
Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.
Acute cardiac allograft rejection is an immune-mediated response, hallmarked by cellular infiltration and myocyte damage in the transplanted heart. Cardiac biopsy sampling has been the 'gold' standard for routinely monitoring episodes of acute rejection. As cardiac biopsy is invasive, attention has focused on other non-invasive methods, such as serum analysis, for monitoring purposes. Tumour necrosis factor alpha (TNF-alpha) is a lymphocyte- and macrophage-derived cytokine that is pleiotropic in its actions. Its proinflammatory functions suggest that it may play an important role in initiating and orchestrating the rejection response. Studies demonstrating a correlation in the expression of TNF-alpha with the severity of the rejection episode have placed TNF-alpha as a prime candidate marker of rejection, and have prompted further study to elucidate these findings. This review discusses the limitations of the methodologies used to identify TNF-alpha, and how intragraft expression of TNF-alpha is not reflected in the serum. Furthermore, we describe how other stimuli besides the rejection response can affect TNF-alpha production, arguing against its use as a 'rejection-specific' marker. Nevertheless, genetic studies suggest that TNF-alpha may influence transplant outcome, and offer a new tool for studying the role of TNF-alpha in acute transplant rejection