Plaque rupture is more frequent in symptomatic than asymptomatic patients and in symptomatic patients in which the fibrous cap is thinner with greater inflammatory infiltrate. The aim of this study was to evaluate the role of major cardiovascular risk factors and histomorphological characteristics, in particular of macrophages and mast cells and of microvascular density, in atherosclerotic plaques collected from 33 consecutive symptomatic and asymptomatic patients undergoing carotid endoarterectomy for carotid disease. Patients were divided in two groups: symptomatic patients [defined according to the North American Symptomatic Carotid Endoarterectomy Trial Classification presenting with cerebrovascular TIAs or stroke within the last three months, and asymptomatic patients, exhibiting progressive ipsilateral internal carotid artery stenosis. Morphological analysis revealed an higher neovascularization in plaques from symptomatic patients, as compared to asymptomatic patients. New-formed blood vessels were located in the intima, interfacing the necrotic core, and at the shoulder area. In parallel, we found a significant increased number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Morphological evidence concerning microvascular density, CD68-positive macrophages and tryptase-postive mast cells have been confirmed by morphometric analysis. Increased plaque vascularity may contribute to lesion progression; being a source of nutrient, inflammatory cell recruitment, and intraplaque hemorrhage, which tends to weaken the plaque and predispose to plaque rupture with ensuing clinical sequelae, such as stroke.

Si riporta il caso di una donna di anni 46 ricoverata in ambiente internistico per lieve dispnea da sforzo e mialgie diffuse per cui viene fatta diagnosi di scompenso cardiaco in paziente con ipertensione polmonare severa. Durante il ricovero non emergono elementi significativi cardiologici in grado di giustificare l’ipertensione polmonare né altra patologia concomitante. La paziente viene pertanto dimessa in apparenti buoni condizioni ma, nel giro di pochi giorni la dispnea diventa ingravescente e viene accompagnata in PS dove è deceduta. Al tavolo autoptico viene rilevata una stasi epato-splenica e una congestione pluriviscerale. Il cuore, del peso di g 390 presenta una dilatazione delle sezioni destre cardiache e una lieve ipertrofia ventricolare sinistra. Al taglio, la parete ventricolare sinistra mostra una estesa cavitazione della metà interna del miocardio e all’istologia presentava recessi intramurali di tipo sinusoidale associati a focale fibrosi interstiziale e subendocardica. Sulla base dei dati morfologici e della esclusione di altre patologie cardiache concomitanti viene posta la diagnosi di cardiomiopatia da mancata compattazione miocardica (IVCN). Si tratta di una rara cardiomiopatia, di verosimile natura genetica, inserita dal WHO nel gruppo delle “non classificate”, dovuta ad un arresto intrauterino dello sviluppo cardiaco. La sua frequenza è riportata del 9.2% fra le cardiomiopatie di interesse pediatrico, mentre solo dello 0.014% fra le forme dell’adulto. E’ una patologia emergente spesso misconosciuta, la cui diagnosi può essere sospettata in vivo con l’ecocardiografia, ma che può risultare difficile anche al tavolo autoptico, se non ci si pensa.

OBJECTIVES: Primary tumors of the inferior vena cava are rare, with leiomyosarcoma representing the vast majority. METHOD: A 60-year-old man was admitted in emergency for fainting and mild anemia. A whole-body computed tomography revealed a retroperitoneal mass of approximately 8 cm in diameter, invading the lumen of the inferior vena cava, extending to the renal vein confluence. An en bloc resection of the solid mass was performed. Macroscopically the tumor did not seem to insist on the resection margin. RESULTS: Histopathological examination confirmed the diagnosis of leiomyosarcoma of the inferior vena cava. Postoperative recovery was uneventful and the patient was discharged after eight days, starting adjuvant chemotherapy. During the follow-up, the patient did not show other fainting episode, and at 24 months he is disease free. Conclusions: Unusually, fainting could even be the isolated sign of a large leiomyosarcoma of the inferior vena cava, also when it affects its middle portion.

Myocarditis is an inflammatory disease of myocardium, associated with nonischemic necrosis and degeneration of myocytes. Although the clinical course is rapid, myocarditis can lead to dilated cardiomyopathy with chambers dilatation and ventricular dysfunction. The pathophysiology of myocarditis in humans is not completely understood. There are several etiological agents implicated, mainly viral agents. The clinical presentation is extremely various, with nonspecific systemic symptoms until sudden death. The great variability of symptoms makes the diagnosis, therefore, extremely difficult. We report the case of a 40-year-old woman who developed, after childbirth, hyperthermia associated with neck and left arm pain; initially treated with acetaminophen, without any benefit, the young woman, after few days, died suddenly. The autopsy documented the presence of edematous lungs and enlarged and congested liver. The microbiological tests performed 4 days after death were negative. The heart was normal in shape and volume; a section of the left ventricle wall showed subendocardial discromic areas histologically characterized by multifocal perivascular and interstitial inflammatory infiltrates. These infiltrates consisted mainly of neutrophils with eosinophil component associated with myocyte necrosis and hemorrhagic interstitial infiltration.

Aims: To evaluate the use of the Wilms’ tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). Methods and results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. Highgrade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (£25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05–3.71] versus 31.5 months (95% CI: 20.4–42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

The aim of this study was to evaluate the role of macrophages and mast cells and of microvascular density in atherosclerotic plaques collected from 63 consecutive symptomatic and asymptomatic patients undergoing carotid endarterectomy for carotid disease. Results have shown no statistically significant differences between the two groups as concerns: (i) the degree of stenosis; (ii) the extention of the lipidic core; (iii) the thickness of the fibrous cup; (iv) the inflammatory infiltrate; (v) the degree of calcification; (vi) the intraplaque hemorrhage. Otherwise, statistically significant difference was found in microvascular density, in the number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Overall, this study indicate that although advanced symptomatic and asymptomatic carotid plaques present similar histomorphological characteristics, the degree of macrophage and mast cell infiltration and differences in microvascular density could help to discriminate between symptomatic and asymptomatic patients.

Vasculitides are characterized by inflammation and necrosis of blood vessels leading to vessel occlusion and ischemic damages of tissues. Among the inflammatory cells involved in vasculitides, neutrophils, T cells, and macrophages have been identified as the predominant cell type. This review article is focused on the role of mast cells in these chronic inflammatory processes. Mast cells are characterized by their complex plasticity. Increasing evidences document that mast cells exert both pro- and anti-inflammatory functions depending on the cell types and the microenvironment they reside in. In this context, mast cell mediators able to modulate progression of vasculitides at different levels and the anatomic localization of mast cells in different vasculitides will be described. Finally, therapeutic approach including inhibition of recruitment of mast cells to the inflammatory infiltrate and blockade of their proinflammatory effects and proangiogenic functions as potential new targets for the treatment of these diseases will be discussed.

Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of mast cells in gastric cancer angiogenesis has not been clarified completely. In this study, we correlated microvascular density and tryptase- and chymase-positive mast cells with histopathological type in gastric cancer. Specimens of primary gastric adenocarcinomas obtained from 30 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 antibody to stain endothelial cells and anti-tryptase and anti-chymase antibodies to stain mast cells. The results showed that stage IV gastric carcinoma has a higher degree of vascularization than other stages and that both tryptase- and chymase-positive mast cells increase in parallel with malignancy grade even if the density of chymase-positive mast cells was significantly lower than the density of tryptase-positive mast cells and is highly correlated with the extent of angiogenesis. This study has demonstrated that mast cell density correlates with angiogenesis and progression of patients with gastric carcinoma. Understanding the mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an antiangiogenic therapy in patients with this malignancy.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated. METHODS: We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan-Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS). RESULTS: DOG1 was expressed in 66 % of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis. CONCLUSIONS: These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification.

This study aims to evaluate the diagnostic accuracy of 16-row multidetector CT (MDCT) and vessel probe reconstructions in the T staging of gastric carcinoma. Fifty-three patients (39 men, 14 women, mean age 57.5) with an endoscopic diagnosis of gastric adenocarcinoma underwent CT examination. A hypotonic drug was administered, and the gastric walls were distended by the ingestion of 400–600 ml of water. A biphasic technique with 40-s and 70-s delay was used after endovenous contrast material injection. All patients underwent surgery, and preoperative and histological stagings were compared. The diagnostic accuracy of T staging was 68% for axial images and 94% for VP reconstructions. In the T1, T2, T3 and T4 parameter evaluation, diagnostic accuracy values were 87%, 73.5%, 81% and 96%, respectively, for axial images and 96%, 96%, 98% and 100%, respectively for VP reconstructions. MDCT is an accurate technique for the preoperative staging of gastric cancer. The VP reconstructions obtained by isotropic data can evaluate the T parameter with a higher accuracy.

Background: The aim of this study was to determine both prognostic clinical-morphological and predictive biomolecular factors affecting course of disease and survival in malignant pleural mesothelioma (MPM). Methods: We retrospectively analyzed (2004-2014) clinical and pathological data of 108 consecutive patients with diagnosis of MPM. Age, stage (WHO 2015), chemotherapy, histotype, nuclear atypia, mitotic count (1/mm2), Ki-67 percentage and 9p21 (p16/CDKN2A) deletion (43 cases) were analyzed and correlated to survival. Survival was evaluated with Kaplan-Meier method and statistical significance with Log-Rank test (SPSS software, 18.0). Results: There were 83 (76.9%) males, 25 (23.1%) females (ratio 3.3/1); median age at diagnosis was 68 (mean 67.2±9.8; range 42-90) years; 94 (87%) patients had asbestos exposure. Overall median survival was 13.3 (mean 19.15±22.4; range 1-136) months. Mean survival (months) was: 30.2±4.6 and 12.4±1.6 in age ≤ 65 and > 65 years (p=0.0001); 24±4.3 in stage I, 21.3±4.5 in II, 21.1±5.8 in III, 9.7±1.7 in IV (p=0.005); 25.9±2.8 and 5±1.3 in patients receiving complete (n=73) and palliative (n=35) chemotherapy (p=0.0001); 21.4±2.5, 11.6±2.7 and 8.5±2.3 in epithelioid, biphasic and sarcomatoid histotypes (p=0.0001); 26.3±3.3 and 12.4±2.5 in moderate and severe nuclear atypia (p=0.0001); 26±3.4 and 9.9±1,3 in low (≤ 5 mm2) and high (> 5 mm2) mitotic count (p=0.0001); 27.2±3.4 and 9.1±1.1 in low (≤ 25%) and high (> 25%) Ki-67 expression (p=0.0001); 35.8±7.7 in absence of p16/CDKN2A deletion, 17.4±3.4 in heterozygous and 8.9±1.9 in homozygous deletion (p=0.0001). Mean survival (months) in patients receiving complete chemotherapy compared to those receiving palliative one was: stage I 30.7±5.4 and 8.2±4.4 (p=0.0001), stage II 25.8±5.3 and 4.2±1.0 (p=0.0001), stage III 25.2±6.8 and 3.0±0.4 (p=0.0001), stage IV 17.7±2.5 and 3.8±0.7 (p=0.0001). Conclusion: Age, stage, chemotherapy, histotype, nuclear atypias, mitoses, proliferating index and loss of 9p21 gene are predictors of survival in MPM and strongly influence the therapeutic strategy. Chemotherapy significantly affects survival in different stages of MPM.

Background: The reports of ultrasound evaluation of lower limb veins are difficult to understand by general practitioners (GPs) and physicians who are not specialized. We developed software for a three-dimensional (3D) electronic report of venous hemodynamic mapping (MEVeC®) in order to represent lower limb venous vasculature in a 3D way. The aim of the study is to compare the novel 3D report with the standard report. Methods: Thirty subjects (medical students and GPs) evaluated a standard report and a novel 3D report of the lower limb veins of a prespecified patient. The cases were randomly and blindly taken from an archive of 100 cases. GPs and students answered a questionnaire made up of 13 questions that were structured in order to investigate the readability and comprehension of the two reports. A score ranging from 0 to 10 (0= not understandable; 10= full comprehension) was attributed to each report for each question according to the readability of the venous scheme proposed. Results: The scores from each question of the questionnaire were compared. The 3D report (MEVeC®) obtained higher scores than those from the evaluation of the standard report (P<0.0001). Each question revealed the superiority of the 3D report (MEVeC®) as compared with the standard report of the ultrasound evaluation of lower limbs. When dividing the scores according to percentiles, the 3D report (MEVeC®) still continued to show more readability than the standard report in a statistically significant way (P<0.0001). Conclusion: The new 3D report (MEVeC®) concerning ultrasound evaluation of lower limb veins is more reproducible than the standard report when evaluated by medical physicians not specialized in the evaluation of the vein tree of lower limbs.

Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide. Several studies on angiogenic blocking agents in gastric cancer revealing promising results by the use of monoclonal antibodies against VEGFA or its receptor VEGFR2 or against VEGFA activating pathway. The validation of biomarkers useful to better organize the clinical trials involving anti-angiogenic therapies is crucial. Molecular markers such as RNA are increasingly used for cancer diagnosis, prognosis, and therapy guidance as in the case of the targeted therapies concerning the inhibition of angiogenesis. The aim of this study is to set the conditions for evaluating the expression of VEGFA and VEGFR2 in gastric cancer specimens and in healthy gastric mucosa by the use of RNAscope, a novel RNA in situ hybridization (ISH) method that allows the visualization of a specific gene expression in individual cells. We found the increased expression of VEGFA in the tubular glands and VEGFR2 in the endothelium of gastric cancer samples mainly in the T2, T3 and T4 stages of tumor progression as compared to the healthy controls. These results obtained by the application of this highly sensitive method for oligonucleotide detection the role of angiogenesis in gastric cancer progression already highlighted by conventional immunohistochemical methods, and offer significant promise as a new platform for developing and implementing RNA-based molecular diagnostics also in the conditions in which immunohistochemistry is not applicable.