Lucia Anemona

Coronary calcification identifies the vulnerable patient rather than the vulnerable Plaque

OBJECTIVE Presence of coronary artery calcium (CAC) is associated with a high risk of adverse cardiovascular outcomes. Nevertheless, although CAC is a marker of atherosclerosis it is still uncertain whether CAC is a marker of plaque vulnerability. Therefore, the aim of this study was to verify if calcification identifies a vulnerable patient rather than the vulnerable plaque. METHODS A morphologic and morphometric study on 960 coronary segments (CS) of 2 groups of patients was performed: (i) 17 patients who died from AMI (510 CS); (ii) 15 age-matched control patients without cardiac history (CTRL, 450 CS). RESULTS Calcification was found in 47% CS of AMI and in 24.5% CS of CTRL. The area of calcification was significantly higher in AMI compared to CTRL (p = 0.001). An inverse correlation was found between the extension of calcification and cap inflammation (r(2) = 0.017; p = 0.003). Multivariate regression analysis demonstrated that the calcification was not correlated with the presence of unstable plaques (p = 0.65). Similarly, the distance of calcification from the lumen did not represent an instability factor (p = 0.68). CONCLUSION The present study suggests that CAC score evaluation represents a valid method to define the generic risk of acute coronary events in a population, but it is not useful to identify the vulnerable plaque that need to be treated in order to prevent an acute event.

Chromosomal Aberration of the 11q23 Locus in Acute Leukemia and Frequency of MLL Gene Translocation Results in 378 Adult Patients

Structural abnormality of the 11q23 band (11q23+) bearing the MLL gene translocation (MLL+) is a recurrent chromosome change observed in 3% to 7% of acute lymphoblastic leukemias and in 3% to 4% of acute myeloblastic leukemias. The resolution of conventional cytogenetics (CC) in detecting 11q23 rearrangement is limited when the translocative partner has a telomeric location; furthermore, CC can barely discriminate between true 11q23+/MLL+ and rearrangements clustering within the 11q22~25 region without MLL involvement (MLL–). We characterized a series of 378 consecutive patients with adult acute leukemia by using CC, fluorescence in situ hybridization (FISH), and multiplex karyotyping (MFISH) analysis. Our aim was to define the frequency of cryptic MLL+ cases and the frequency of MLL+ within 11q22~25+ cases. As expected, FISH was more sensitive than CC in detecting MLL+ cases, but rather unexpectedly, 9 (45%) of 20 patients with 11q22~25+ were MLL–. A better characterization of 11q22~25+/MLL– leukemias is relevant for the identification of new, recurrent translocations. Moreover, these cases should be readily distinguishable from 11q23+/MLL+ cases. We recommend that karyotypic analysis always be complemented by molecular or FISH methods to unravel MLL rearrangements.

Chromosomal Aberration of the 11q23 Locus in Acute Leukemia and Frequency of MLL Gene Translocation

Structural abnormality of the 11q23 band (11q23+) bearing the MLL gene translocation (MLL+) is a recurrent chromosome change observed in 3% to 7% of acute lymphoblastic leukemias and in 3% to 4% of acute myeloblastic leukemias. The resolution of conventional cytogenetics (CC) in detecting 11q23 rearrangement is limited when the translocative partner has a telomeric location; furthermore, CC can barely discriminate between true 11q23+/MLL+ and rearrangements clustering within the 11q22 to approximately 25 region without MLL involvement (MLL-). We characterized a series of 378 consecutive patients with adult acute leukemia by using CC, fluorescence in situ hybridization (FISH), and multiplex karyotyping (M-FISH) analysis. Our aim was to define the frequency of cryptic MLL+ cases and the frequency of MLL+ within 11q22 to approximately 25+ cases. As expected, FISH was more sensitive than CC in detecting MLL+ cases, but rather unexpectedly, 9 (45%) of 20 patients with 11q22 to approximately 25+ were MLL-. A better characterization of 11q22 to approximately 25+/MLL- leukemias is relevant for the identification of new, recurrent translocations. Moreover, these cases should be readily distinguishable from 11q23+/MLL+ cases. We recommend that karyotypic analysis always be complemented by molecular or FISH methods to unravel MLL rearrangements.

Carcinoma of the vulva with sarcomatoid features: a case report with immunohistochemical study.

A tumor of the vulva with sarcomatoid features was studied by immunocytochemistry to characterize the phenotype of the spindle-shaped and giant cells. Sarcomatoid-looking cells were positive for intermediate filament keratin polypeptides of stratified epithelium. These results favor histogenesis of the sarcomatoid-looking cells from a metaplastic alteration of the malignant squamous component.

Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

OBJECTIVE Several studies have demonstrated that carotid plaque rupture and thrombosis represent the most important factors correlated with the onset of acute cerebrovascular symptoms. Nevertheless, ruptured thrombotic plaques have been described also in asymptomatic patients. What still needs to be clarified is why a plaque rupture leads either to an acute ischemic syndrome or, in a minor group of patients, remains asymptomatic. The purpose of this study was to systematically compare the histologic features of thrombotic plaques both in asymptomatic and symptomatic patients in order to identify specific findings that could explain the peculiar clinical behavior that characterizes each of the clinical settings. METHODS A total of 157 thrombotic plaques from 60 asymptomatic patients and 97 with major stroke who consecutively underwent CEA were serially sectioned and studied by histology. RESULTS A minute cap disruption very frequently characterizes thrombotic plaques of asymptomatic patients and it was always smaller than large ulcers observed in thrombotic symptomatic plaques (651 ± 687μm vs. 4150 ± 3526, p=0.001). In asymptomatics this typical feature was associated with fewer inflammatory cells (20.1 ± 8.8 vs. 33.9 ± 26.1 cells × hpf, p=0.001), smaller lipidic-necrotic core (33.9%± 2.9% vs. 42.0% ± 2.4%; p=0.04) and larger calcification (16.2 ± 12.8% vs. 8.1 ± 12.2%, p=0.02). Symptomatic patients with thrombotic plaques showed higher incidence of metabolic syndrome (p=0.002) and moderate-high Framingham risk scores (p=0.001) comparing to asymptomatic individuals. CONCLUSION The transformation from a stable to a vulnerable plaque is a gradual process in the natural history of the disease and plaque rupture is an event not necessarily occurring at a late phase but also at earlier one. In this case, the rupture will be most likely smaller and clinically asymptomatic.

Flow cytometry analysis of atherosclerotic plaque cells from human carotids: a validation study

BACKGROUND Atherosclerotic plaques are heterogeneous vascular lesions. Changes in cell plaque composition are fundamental events inside the plaque microenvironment that are strictly related to the clinical outcome of these lesions (organ damage). The knowledge of these modifications may help to better understand the pathophysiological mechanisms of atherosclerosis. METHODS We report on a flow cytometry method to characterize and quantify the cell subpopulations in human atherosclerotic plaques. Cells were obtained from endarterectomy specimens after collagenase digestion. Both surface and intracytoplasmic antigens were labeled. RESULTS Our data demonstrated that the method we described allowed the characterization of cell populations that compose the atherosclerotic plaque, avoiding contamination by tunica media smooth muscle cells and the noise of cellular debris. Moreover this validation study showed that about 50% of cells in the atherosclerotic plaques are inflammatory mononuclear cells (T lymphocytes and monocytes/macrophages). CONCLUSIONS Reproducible quantitative methods for cell population characterization may increase the understanding of pathophysiological mechanisms responsible for plaque progression. The methodology herein described gave us the possibility of quickly calculating the relative amount of each cell population and studying both surface and intracellular markers to analyze the functional stage of the cells. The clinical correlation was not assessed in the present study, because we used a small patient group to validate the method, but should be the subject of further analyses in a larger patient population.

Elemental analysis of histological specimens: a method to unmask nano asbestos fibers

There is an increasing amount of evidence that nanoparticles may enhance toxicological potential in comparison to the same material in the bulk form. The aim of this study was to develop a new method to unmask asbestos nanofibers from Formalin-Fixed Paraffin-Embedded (FFPE) tissue. For the first time, in this study we applied Energy Dispersive X-ray (EDX) microanalysis through transmission electron microscopy to demonstrate the presence of asbestos nanofibers in histological specimens of patients with possible occupational exposure to asbestos. The diagnostic protocol was applied to 10 randomly selected lung cancer patients with no history of previous asbestos exposure. We detected asbestos nanofibers in close contact with lung cancer cells in two lung cancer patients with previous possible occupational exposure to asbestos. We were also able to identify the specific asbestos iso-type, which in one of the cases was the same rare variety used in the workplace of the affected patient. By contrast, asbestos nanofibers were not detected in lung cancer patients with no history of occupational asbestos exposure. The proposed technique can represent a potential useful tool for linking the disease to previous workplace exposure in uncertain cases. Furthermore, Formalin-Fixed Paraffin-Embedded (FFPE) tissues stored in the pathology departments might be re-evaluated for possible etiological attribution to asbestos in the case of plausible exposure. Since diseases acquired through occupational exposure to asbestos are generally covered by workers’ insurance in most countries, the application of the protocol used in this study may have also relevant social and economic implications.

Solitary metachronous gastric metastasis from pulmonary adenocarcinoma: Report of a case

INTRODUCTION Gastric metastases from lung adenocarcinoma are rare and usually associated with disseminated disease. The great majority is asymptomatic and in few cases discovered during autopsy studies. Reports of single metachronous metastases during the lifetime are anecdotal. We describe a case of solitary gastric metastasis 5 years after lung surgery. PRESENTATION OF CASE A 68-year-old male submitted in 2006 to right lobectomy for lung adenocarcinoma was referred at Emergency Room department in 01/2011 because of chronic epigastric pain. Radiologic and endoscopic evaluation showed a bulky lesion inside the stomach, originating from the muscular layer, suspected for GIST. He underwent a subtotal gastrectomy and the pathologic examination revealed an undifferentiated adenocarcinoma, positive for Thyroid Transcriptional Factor-1, Cytokeratin 7, AE 1/3 and CEA, confirming the pulmonary origin. DISCUSSION At the time of diagnosis about 50% of lung cancer are metastatic, with survival rates of 1% at 5-year. Gastric metastasis is very rare; autopsy studies report an incidence of 0.2-0.5%. They develop in the submucosa, usually without any symptom and the diagnosis is incidental during the staging of primary cancer or the follow-up. There are no guidelines about surgical treatment; however few cases of long-term survival following the operation were reported. Pathologic diagnosis is difficult, but the immunohistochemical staining helps to recognize the primary origin. CONCLUSION Solitary metachronous gastric metastasis from pulmonary adenocarcinoma is an exceptional event, but it could happen during the follow-up. It seems that a radical resection, in absence of systemic implants, might provide survival benefits in selected patients.

Densitometric and morphometric study of immunocytochemical estrogen receptors detection in breast carcinomas

Immunohistochemical quantitative evaluation of estrogen receptors (ER) detected in tissue sections from 30 breast tumors by monoclonal antibody was performed using a densitometric method. In particular, ER concentration was calculated by nuclear mean optical density (nMOD), while heterogeneity in ER content was calculated by the coefficient of variation (CV) of the nuclear optical density histogram. Tumors which showed more than 60% of positive cells had a mean value of ER-nMOD of 0.116 +/- 0.002 a.u. and of ER-CV of 33.74 +/- 0.68. Tumors which showed 30% to 60% of positive cells had a mean value of ER-nMOD of 0.082 +/- 0.006 a.u. (arbitrary units) and of ER-CV of 36.25 +/- 3.44. Tumors showing less than 30% of positive cells had ER-nMOD of 0.052 +/- 0.009 a.u. and ER-CV of 48.49 +/- 5.61. These results indicate that the greater the concentration the lower the ER heterogeneity within the tumor sample. No significant differences between ER-ICA results, nuclear size and form factors were found.

Increased Sympathetic Renal Innervation in Hemodialysis Patients Is the Anatomical Substrate of Sympathetic Hyperactivity in End‐Stage Renal Disease

Background Renal denervation represents an emerging treatment for resistant hypertension in patients with end‐stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach. Methods and Results The distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end‐stage renal disease on dialysis (DIAL group) and 16 age‐matched control nondialysis patients (CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri‐adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm2, P=0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm2, P=0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history. Conclusions The findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end‐stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients.