Number Of Histologic Features Research Articles

A Plaque Instability Index Calculated by Histological Marker Analysis of the Endarterectomy Carotid Artery

(1) Background: Atherosclerosis is a pandemic condition that causes the development of ischemic syndromes including myocardial infarctions and many strokes, in addition to disabling peripheral artery disease. Progression of atheroma plaques has been associated with an increased risk of mortality. It is a challenge to determine in advance if atherosclerotic plaque will become unstable by calculating an index of instability. We proposed a score of ten parameters for the assessment of high-risk plaques, by quantification of 10 risk factors for acute cardiovascular events, most of them representing histological variables. (2) Methods: Carotid endarterectomy samples were collected from 10 highly symptomatic patients who matched for gender, age, risk factors, and plaque morphology. Samples were stained with hematoxylin-eosin, elastic van Gieson, Perls, and Mallory. Immunohistochemistry was performed using specific antibodies, such as CD31 for endothelial cells, CD68 for macrophages, and CD3 for T cells. (3) Results: For each plaque, the presence and/or number of histological features (fibrous cap thickness, lipid core size, plaque and cap infiltration with macrophages and lymphocytes, neovessels, intraplaque hemorrhage, parietal thrombi, and calcium deposits) were recorded on a simple semi-quantitative one- or two-grade scale. The study identified four stable plaques (SPs), two vulnerable plaques (VPs), and four unstable plaques (USPs). We found significantly more macrophages and neovessels in unstable plaques compared with stable plaques. The score for unstable plaques was higher than that for VP. (4) Conclusions: The study showed that symptomatic carotid disease is associated with an increased index score. The proposed algorithm for carotid plaque assessment may be useful for an imaging application.

Histological Features of Carotid Plaque in Patients With Ocular Ischemia Versus Cerebral Events

Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology. In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323). Compared with plaques from patients with ocular events only, those from patients with cerebral events had significantly more large lipid core (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.05-1.82; P=0.02), inflammation (OR, 1.32; 95% CI, 1.02-1.72; P=0.04) and overall plaque instability (OR, 1.37; 95% CI, 1.05-1.80; P=0.02), and less fibrous content (OR, 0.71; 95% CI, 0.54-0.92; P=0.01), and calcification (OR, 0.70; 95% CI, 0.54-0.91; P=0.008). The overall number of histological features known to be associated with vulnerable plaque was greater in patients with cerebral events than in those with ocular events (P=0.002). Carotid plaques from patients undergoing endarterectomy for previous ocular ischemic events have fewer vulnerable plaque features than those from patients with recent cerebral ischemic events, possibly explaining some of the differences in risk of stroke between these groups.

Abstract P4-12-03: Towards a risk prediction model for breast cancer that utilizes breast tissue risk features

Abstract Background: Optimal early detection and prevention strategies for breast cancer are predicated on our ability to accurately identify women at increased risk for disease. Current breast cancer risk prediction models rely on clinical and epidemiologic features. As demonstrated with other cancers, such as those of the cervix and colon, cancer risk assessment is enhanced when the tissue at risk is examined for evidence of premalignant abnormalities. Here, we present a multivariate model for individualized breast cancer risk prediction that incorporates tissue features identified from biopsies from women with benign breast disease (BBD). Methods: We used our cohort of more than 9000 women diagnosed with BBD at the Mayo Clinic from 1967–1991, and identified a nested case:control series of 377 women who developed cancer (cases) matched with 734 women who did not (controls). We identified a set of variables that either alone or in two-way interactions contributed to a multivariable risk prediction model. We combined this relative risk model with the baseline incidence of breast cancer and the baseline hazard of death from our full BBD cohort to develop a risk prediction tool that computes absolute risk estimates for breast cancer. We calculated 5-year risk predictions for these cases and controls using our model and using the Gail model and compared c-statistics from these risk predictions. We validated our model using an independent set of 378 breast cancer cases and 728 matched controls drawn from our BBD cohort. Results: Cases and controls in the model development data set differed significantly on a number of features when examined individually. Those included in a multivariable relative risk model for breast cancer among women with BBD are shown below. After including interactions between lobular involution, and histologic impression, with age at first live birth/number of children, and degree of involution with sclerosing adenosis, we devised a model that predicts the absolute risk of breast cancer. Predicted five-year risks in the model development series, we observed a c-statistic of 0.66, higher than the c-statistic of 0.61 for the Gail model. With risk prediction estimates from our validation series of cases and matched controls, the c-statistic of our model decreased to 0.59 and the c-statistic for the Gail model was 0.55. Conclusion: We have identified an initial risk prediction model for breast cancer in women with BBD. The identified model includes basic demographic information as well as a number of histologic features of the tissue samples. Its initial performance is promising, providing improved discrimination over the Gail model in our replication data set. Further work is needed to identify features which might provide additional predictive information for breast cancer risk. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-03.

Functional circuitry of a unique cerebellar specialization: the valvula cerebelli of a mormyrid fish

The valvula cerebelli of the mormyrid electric fish is a useful site for the study of cerebellar function. The valvula forms a part of the electrosensory-electromotor system of this fish, a system that offers many possibilities for the study of sensory-motor integration. The valvula also has a number of histological features not present in mammals which facilitate investigation of cerebellar circuitry and its plasticity. This initial study characterizes the basic physiology and pharmacology of cells in the valvula using an in vitro slice preparation. Intrinsic properties and synaptic responses of Purkinje cells and other cell types were examined. We found that Purkinje cells fire a small narrow Na + spike and a large broad Ca 2+ spike, generated in the axon initial segment and dendritic-soma region, respectively. Purkinje cells respond to parallel fiber inputs with graded excitatory postsynaptic potentials (EPSPs) and to climbing fiber inputs with all-or-none EPSPs. Efferent cells, Golgi cells, and deep stellate cells all fire a single type of large narrow spike and respond only to parallel fiber inputs. Both parallel fiber and climbing fiber responses in Purkinje cells appear to be entirely mediated by AMPA-type glutamate receptors, whereas parallel fiber responses in efferent cells and stellate cells include AMPA and NMDA components. In addition, a strong synaptic inhibition was uncovered in both Purkinje cells and efferent cells in response to the focal stimulation of parallel fibers. Dual cell recordings indicate that deep stellate cells contribute at least partially to this inhibition. We conclude that despite its unique histology, the local functional circuitry of the mormyrid valvula cerebelli is largely similar to that of the mammalian cerebellum. Thus, what is learned concerning the functioning of the mormyrid valvula cerebelli may be expected to be informative about cerebellar function in general.

Sertoliform Endometrioid Carcinoma of the Ovary: A Potential Diagnostic Pitfall

Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinically, SEC affects an older population (60-70 years), while patients with SLT have an average age of 25 years and may exhibit endocrine manifestations. A number of histologic features can be used to distinguish the 2 entities, the most important ones being (1) the presence of areas with the usual pattern of endometrioid carcinoma, and (2) the presence of mucin at the apical borders of the tumor cells. Cytokeratin stains positively, while inhibin and calretinin stain negatively in SEC; the converse is true for SLTs. Based on the clinicopathologic behavior of this entity, SEC should be considered a well-differentiated carcinoma with relatively good prognosis if limited to the ovary.

Sertoliform endometrioid carcinoma of the ovary: a potential diagnostic pitfall.

Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinically, SEC affects an older population (60-70 years), while patients with SLT have an average age of 25 years and may exhibit endocrine manifestations. A number of histologic features can be used to distinguish the 2 entities, the most important ones being (1) the presence of areas with the usual pattern of endometrioid carcinoma, and (2) the presence of mucin at the apical borders of the tumor cells. Cytokeratin stains positively, while inhibin and calretinin stain negatively in SEC; the converse is true for SLTs. Based on the clinicopathologic behavior of this entity, SEC should be considered a well-differentiated carcinoma with relatively good prognosis if limited to the ovary.

Treatment of primary focal segmental glomerulosclerosis

Urinalysis had 4 protein with 5 red blood cells/high-power field along with granular and waxy casts. A 24-hour urine collection contained 8.2 g of protein, and the creatinine clearance was 42 mL/min. The sedimentation rate was 64 mm/h; rheumatoid factor and ANA were normal; C3, 135 mg/dL; C4, 41 mg/dL; and both urine and serum immunoelectrophoresis were negative for paraproteins. A rapid plasma reagin test (RPR) was nonreactive. Hepatitis B surface antigen was negative as was an ELISA evaluation for HIV antibody. A chest radiograph demonstrated her heart to be normal in size, and her lungs were clear, but bilateral pleural effusions were noted. An ultrasound of the kidneys demonstrated them to be normal in size and echogenicity. The renal arteries and veins were patent. A sodiumand water-restricted diet was prescribed, and the patient was treated with furosemide with good response. She underwent a percutaneous renal biopsy 3 weeks after presenCASE PRESENTATION tation. At the time of the biopsy, her blood urea nitrogen was A 53-year-old African American woman who had previously 29 mg/dL; serum creatinine, 3.2 mg/dL; serum albumin, 1.1 been in excellent health presented 11 years ago with increasing g/dL; and cholesterol, 784 mg/dL. weight, leg edema, and facial swelling that had developed over The renal biopsy revealed 17 glomeruli by light microscopy; one month. She had no history of sickle cell disease, recurrent one was hyalinized. The remaining glomeruli manifested mildly urinary tract infections or pyelonephritis, vesicoureteral reflux, increased mesangial matrix and cellularity. The glomerular basediabetes mellitus, hypertension, renal or systemic diseases, or ment membranes were thin and delicate, and the capillary loops morbid obesity. There was no family history of hypertension were patent. One glomerulus had a segmental scar with hyalinoor renal disease. She had not been taking any prescribed medisis, and a second glomerulus had a segmental scar with a small cations nor had she been using nonsteroidal anti-inflammaadhesion to Bowman’s capsule. Acute tubular necrosis and intertory agents. stitial edema were evident but no significant tubulointerstitial Physical examination revealed: blood pressure, 120/84 mm Hg; atrophy or fibrosis was seen. Immunofluorescence examination no skin rashes; lungs were clear; cardiac examination was norof the tissue was negative. Electron microscopy disclosed difmal; no hepatosplenomegaly; and no significant lymphadenopfuse foot process fusion with villous transformation; no elecathy. Her joints were unremarkable but she had 3 pre-tibial tron-dense deposits were seen in the mesangium or along the edema bilaterally. Laboratory evaluation demonstrated a blood capillary wall. urea nitrogen of 32 mg/dL; serum creatinine, 1.8 mg/dL; albuThe patient was given oral prednisone, 60 mg/day; 2 weeks min, 1.6 g/dL; and cholesterol, 612 mg/dL. Hemoglobin was 14.6 later her serum creatinine had fallen to 0.9 mg/dL but the proteing/dL with a normal white blood cell count and platelet count. uria had risen to 12.4 g/day. However, after 2 months of highdose steroid therapy, the proteinuria had decreased to 0.1 g/day, the serum albumin level was 3.8 g/dL, and the cholesterol level Portions of this article are republished with permission from Korbet was down to 326 mg/dL; she was edema free. A steroid taper SM: Primary focal segmental glomerulosclerosis, in Therapy in Nephrolwas completed over an additional 2 months. One week after ogy and Hypertension: A Companion to Brenner and Rector’s The Kidney (2nd ed), edited by Brady RJ, Wilcox CS, Philadelphia, W.B. Saunders discontinuing steroids she had a relapse of the nephrotic syn(in press). drome (13.6 g/day) but again responded to a second course of high-dose prednisone with a complete remission. She remained The Nephrology Forum is funded in part by grants from Amgen, in a complete remission for 4 months after the discontinuation Incorporated; Merck & Co., Incorporated; Dialysis Clinic, Incorpoof steroids and then relapsed a second time (proteinuria of 13 rated; and Bristol-Myers Squibb Company. g/day). She was treated with prednisone and oral cyclophospha

Ependymomas in children: histologic and DNA-flow cytometric study.

Ependymoma, a common neoplasm in the central nervous system of children, expresses great variability of morphological appearances. Correlation with clinical behavior has been controversial in previous studies. In order to explore the potential value of DNA-flow cytometric analysis in predicting the clinical course of ependymomas in children, we studied 22 patients with this tumor, selected from two large pediatric institutions. In addition, a number of histologic features were reviewed, such as necrosis, mitoses, endothelial proliferation, cellularity, and pleomorphism. DNA analyses of paraffin-embedded tissue from these tumors showed 9 of 17 (53%) with DNA indexes less than 1.16 and 8 of 17 (47%) with DNA indexes above 1.16. Ten of 17 (59%) patients died, 2 (12%) were lost for follow-up, and 5 (29%) are alive. No statistical correlation was found between DNA index, outcome, and histology. In spite of the small sample size, our findings appear to support the general impression that ependymomas are morphologically highly variable tumors of potential aggressiveness without valuable prognostic histologic markers.

Histological-venographic correlates in portal hypertension.

Magnification hepatic wedge venography and manometry were evaluated in 40 patients with portal hypertension and in 6 normal individuals. Venography (alone or in combination with manometry) generally facilitated prediction of histology in cirrhosis, hepato-venular occlusive disease, periportal fibrosis, congenital hepatic fibrosis, and portal vein obstruction. The magnification wedge venograms demonstrated a number of histological features of cirrhosis that have not previously been described in vivo, including porto-hepatic vein shunts, micro- and macronodular regeneration, and obstructive changes which were more severe in hepatic than in portal veins.

Additional Histological Findings in the Chicken Reproductive Tract

DURING the course of a study of the reproductive tracts of laying pullets affected with Newcastle disease, a number of histologic features, which had not previously been recorded or had been given only passing notice were encountered in healthy pullets being used as controls. These are thought deserving of record and are therefore reported here.The histologic development of the ovum of the chicken (Gallus domesticus) has been studied by several workers (His, 1868; D’Hollander, 1904; Sonnenbrodt, 1908; Riddle, 1916; Romanoff, 1931; and Warren and Conrad, 1939). Bartelmez (1912) and Bissonnette and Zujko (1936) made histological studies of the follicular changes that occurred in the pigeon and starling, respectively, prior to sexual maturity. Romanoff (1943), confirming their findings, stated that the histological development of the ova of nidicolous birds like the pigeon (Bartelmez, 1912) or the starling (Bissonnette and Zujko, 1936) was not the same as that of nudifugous birds …