BackgroundPrimary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor.Case presentationWe describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neodjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis.ConclusionThe breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.
We previously showed increased expression of the ELR+, CXC chemokines in the lung after left pulmonary artery obstruction. These chemokines have been shown in other systems to bind their G protein-coupled receptor, CXCR(2), and promote systemic endothelial cell proliferation, migration, and capillary tube formation. In the present study, we blocked CXCR(2) in vivo using a neutralizing antibody and also studied mice that were homozygous null for CXCR(2). To estimate the extent of neovascularization in this model, we measured systemic blood flow to the left lung 14 days after left pulmonary artery ligation (LPAL). We found blood flow significantly reduced (67% decrease) with neutralizing antibody treatment compared with controls. However, blood flow was not altered in the CXCR(2)-deficient mice compared with wild-type controls after LPAL. To test for ligand availability, we measured macrophage inflammatory protein (MIP)-2 in lung homogenates after LPAL, because this is the predominant CXC chemokine previously shown to be increased after LPAL (22). MIP-2 protein was two- to fourfold higher in the left lung relative to the right lung in all treatment groups 4 h after LPAL and this increase did not differ among groups. We speculate that the CXCR(2)-deficient mice have compensatory mechanisms that mitigate their lack of gene expression and conclude that CXCR(2) contributes to chemokine-induced systemic angiogenesis after pulmonary artery obstruction.
A role for inflammation in modulating the extent of angiogenesis has been shown for a number of organs. The present study was undertaken to evaluate the importance of leukocyte subpopulations for systemic angiogenesis of the lung after left pulmonary artery ligation (LPAL) in a mouse model of chronic pulmonary thromboembolism. Since we (24) previously showed that depletion of neutrophils did not alter the angiogenic outcome, we focused on the effects of dexamethasone pretreatment (general anti-inflammatory) and gadolinium chloride treatment (macrophage inactivator) and studied Rag-1(-/-) mice (T/B lymphocyte deficient). We measured inflammatory cells in bronchoalveolar lavage fluid and lung homogenate macrophage inflammatory protein-2 (MIP-2) and IL-6 protein levels within 24 h after LPAL and systemic blood flow to the lung 14 days after LPAL with labeled microspheres as a measure of angiogenesis. Blood flow to the left lung was significantly reduced after dexamethasone treatment compared with untreated control LPAL mice (66% decrease; P < 0.05) and significantly increased in T/B lymphocyte-deficient mice (88% increase; P < 0.05). Adoptive transfer of splenocytes (T/B lymphocytes) significantly reversed the degree of angiogenesis observed in the Rag-1(-/-) mice back to the level of control LPAL. Average number of lavaged macrophages for each group significantly correlated with average blood flow in the study groups (r(2) = 0.9181; P = 0.01 different from 0). Despite differences in angiogenesis, left lung homogenate MIP-2 and IL-6 did not differ among study groups. We conclude that inflammatory cells modulate the degree of angiogenesis in this lung model where lymphocytes appear to limit the degree of neovascularization, whereas monocytes/macrophages likely promote angiogenesis.
. Inhibition of CXCR 2 attenuates bronchial angiogenesis in the ischemic rat lung. J Appl Physiol 104: 1470-1475, 2008. First published March 6, 2008 doi:10.1152/japplphysiol.00974.2007.-Under conditions of chronic pulmonary ischemia, the bronchial circulation undergoes massive proliferation. However, little is known regarding the mechanisms that promote neovascularization. An expanding body of literature implicates the glutamic acid-leucine-arginine (ELRϩ) CXC chemokines and their G protein-coupled receptor, CXCR 2, as key proangiogenic components in the lung. We used a rat model of chronic pulmonary ischemia induced by left pulmonary artery ligation (LPAL) to study bronchial angiogenesis. Using a methacrylate mixture, we cast the systemic vasculature of the rat lung at weekly intervals after LPAL. Twenty-one days after LPAL, numerous large, tortuous bronchial arteries were observed surrounding the left main bronchus that penetrated the left lung parenchyma. In stark contrast, the right lung was essentially devoid of vessels. We quantified bronchial neovascularization using 15-m radiolabeled microspheres to measure systemic blood flow to the left lung (n ϭ 12 rats). Results showed that by 21 days after LPAL, bronchial blood flow to the ischemic left lung had increased Ͼ10-fold compared with controls 2 days after LPAL (P Ͻ 0.01). Focusing on the predominant rat CXC chemokine that signals through CXCR 2, we measured increased levels of cytokine-induced neutrophil chemoattractant-3 protein expression in left lung homogenates early (4 and 24 h; n ϭ 10 rats) after LPAL relative to paired right lung controls (P Ͻ 0.01). Treatment with a neutralizing antibody to CXCR 2 resulted in a significant decrease in neovascularization 21 days after LPAL (n ϭ 9 rats; P Ͻ 0.01). Our results confirm the time course of bronchial angiogenesis in the rat and suggest the importance of CXC chemokines in promoting systemic neovascularization in the lung. bronchial artery; cytokine-induced neutrophil chemoattractant-3; microspheres THE BRONCHIAL CIRCULATION is the systemic vascular supply to the lung and provides nutrient blood flow to conducting airways down to the level of the terminal bronchioles as well as nerves, lymph nodes, visceral pleura, and walls of large pulmonary vessels. It normally provides less than 1% of cardiac output to the lung but has been shown to increase to as much as 30% of the original pulmonary blood flow after chronic unilateral pulmonary artery obstruction (13). This pathological feature of bronchial angiogenesis occurs during conditions of chronic inflammation such as cystic fibrosis (4), asthma (12), pulmonary fibrosis (27), lung cancer (16), and chronic thromboembolic disease (18). In animal models, pulmonary ischemia resulting from chronic pulmonary artery obstruction has been shown to cause proliferation of the systemic circulation to the lung in sheep (5), pigs (8), dogs (13), rats (28), and mice (14). However, little is known regarding the mechanisms that promote growth of bronchial arteries in chroni...
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