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Increasing Grade (increasing + grade)
Selected AbstractsHistopathologic grading of medulloblastomasCANCER, Issue 2 2002A Pediatric Oncology Group Study Abstract BACKGROUND Medulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results. METHODS Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan,Meier and log-rank analyses. RESULTS Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival. CONCLUSIONS Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility. Cancer 2002;94:552,60. © 2002 American Cancer Society. [source] Association of mast cells and liver allograft rejectionPEDIATRIC TRANSPLANTATION, Issue 3 2008Cigdem Arikan Abstract:, MCs are important effector cells in a broad range of immune responses. Their role in liver allograft rejection is not clear. Twenty-one liver transplant recipients (mean age ± s.d.; 10.2 ± 4.1 yr) who experienced a rejection episode are included in this study. Biopsy specimens from normal livers (allograft biopsy with normal histopathology n = 5 and naïve livers n = 6), transplanted livers with CR (n = 5), and transplanted livers with ACR (n = 26) were studied. The total number of PT in each biopsy specimen was documented, and the number of PT that contained MCs was expressed as a percentage of the total number of PT. MCs, percentage of PT containing MCs and the average number of MCs/PT was significantly higher in rejection specimens than in control biopsy samples. All parameters were significantly higher in CR group than AR groups. Increasing grades of rejection was also associated with progressively more MCs and MC/PT (r = 0.68 p = 0.000; r = 0.58 p = 0.002). Only serum bilirubin level was related to the MCs in AR group. Only MC/PT was detected as an independent predictor of graft survival (p = 0.011, RR 2.87 95% CI 1.3,6.5). Despite the fact that the role of MCs in liver allograft rejection is still unknown; they exist in inflammatory infiltrates during pediatric liver allograft rejection. MC-rich portal infiltrates may distinguish chronic liver rejection from other inflammatory states such as AR, hepatitis and biliary obstruction. [source] Risk factors of fibrosis in alcohol-induced liver diseaseHEPATOLOGY, Issue 3 2002Bruno Raynard In patients with nonalcoholic steatohepatitis (NASH), age, obesity, and diabetes mellitus are independent predictors of the degree of fibrosis. The relative risk for fibrosis adjusted for sex was also associated with increasing grade of Perls stain. The aim of this study was to determine whether the risk factors for fibrosis described in NASH are also risk factors in alcohol-induced liver disease. A total of 268 alcoholic patients with negative hepatitis B virus and hepatitis C virus serology underwent liver biopsy. Fibrosis was assessed semiquantitatively by a score fluctuating between 0 to 8. Liver iron overload was assessed by Perls staining and graded in 4 classes. We have used multivariate regression with partial correlation analysis to assess the variability of fibrosis score according to the value of 7 variables: sex, age, body mass index (BMI) in the past year before the hospitalization when the patient was asymptomatic, daily alcohol intake over the past 5 years, total duration of alcohol abuse, Perls grade, and blood glucose level. In the multivariate regression, fibrosis score was positively correlated with age (P = .001), BMI (P = .002), female sex (P < .05), Perls grade (P < .05), and blood glucose level (P < .05). Twenty percent of the variability of fibrosis score was explained by the 7 variables. In conclusion, after adjustment for daily alcohol intake and total duration of alcohol abuse, BMI, Perls grade, and blood glucose are also independent risk factors for fibrosis in alcohol-induced liver disease, raising therapeutic implications for the management of these patients. [source] Expression of tumour necrosis factor-related apoptosis-inducing ligand and caspase-3 in relation to grade of inflammation and stage of fibrosis in chronic hepatitis CHISTOPATHOLOGY, Issue 5 2007A Piekarska Aim:, To assess whether the distribution of the recently described proapoptotic ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and the apoptosis effector, caspase-3 alters with the degree of inflammation and fibrosis present in liver biopsy specimens from patients with chronic hepatitis C virus infection. Methods and results:, Expression of TRAIL and caspase-3 was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of TRAIL in hepatocytes correlated inversely with stage of fibrosis (P = 0.001), classified according to the Scheuer score; expression of caspase-3 in hepatocytes correlated with grade of inflammation (P = 0.012). Expression of TRAIL in hepatocytes was not correlated with grade of inflammation (P > 0.05); expression of caspase-3 was not correlated with stage of fibrosis (P > 0.05). Maximum expression of proapoptotic TRAIL protein was observed in cases with low grade inflammation (G0) and low stage fibrosis (S1). Maximum expression of caspase-3 in hepatocytes was observed in cases with high grade inflammation (G3,4) and high stage fibrosis (S3), but not with liver cirrhosis (S4). Conclusions:, There is a significant decrease in TRAIL expression with increasing grade of inflammation, whereas caspase-3 expression is significantly increased with advanced fibrosis, short of cirrhosis. [source] Fluid flow and Al transport during quartz-kyanite vein formation, Unst, Shetland Islands, ScotlandJOURNAL OF METAMORPHIC GEOLOGY, Issue 1 2010C. E. BUCHOLZ Abstract Quartz-kyanite veins, adjacent alteration selvages and surrounding ,precursor' wall rocks in the Dalradian Saxa Vord Pelite of Unst in the Shetland Islands (Scotland) were investigated to constrain the geochemical alteration and mobility of Al associated with channelized metamorphic fluid infiltration during the Caledonian Orogeny. Thirty-eight samples of veins, selvages and precursors were collected, examined using the petrographic microscope and electron microprobe, and geochemically analysed. With increasing grade, typical precursor mineral assemblages include, but are not limited to, chlorite+chloritoid, chlorite+chloritoid+kyanite, chlorite+chloritoid+staurolite and garnet+staurolite+kyanite+chloritoid. These assemblages coexist with quartz, white mica (muscovite, paragonite, margarite), and Fe-Ti oxides. The mineral assemblage of the selvages does not change noticeably with metamorphic grade, and consists of chloritoid, kyanite, chlorite, quartz, white mica and Fe-Ti oxides. Pseudosections for selvage and precursor bulk compositions indicate that the observed mineral assemblages were stable at regional metamorphic conditions of 550,600 °C and 0.8,1.1 GPa. A mass balance analysis was performed to assess the nature and magnitude of geochemical alteration that produced the selvages adjacent to the veins. On average, selvages lost about ,26% mass relative to precursors. Mass losses of Na, K, Ca, Rb, Sr, Cs, Ba and volatiles were ,30 to ,60% and resulted from the destruction of white mica. Si was depleted from most selvages and transported locally to adjacent veins; average selvage Si losses were about ,50%. Y and rare earth elements were added due to the growth of monazite in cracks cutting apatite. The mass balance analysis also suggests some addition of Ti occurred, consistent with the presence of rutile and hematite-ilmenite solid solutions in veins. No major losses of Al from selvages were observed, but Al was added in some cases. Consequently, the Al needed to precipitate vein kyanite was not derived locally from the selvages. Veins more than an order of magnitude thicker than those typically observed in the field would be necessary to accommodate the Na and K lost from the selvages during alteration. Therefore, regional transport of Na and K out of the local rock system is inferred. In addition, to account for the observed abundances of kyanite in the veins, large fluid-rock ratios (102,103 m3fluid m,3rock) and time-integrated fluid fluxes in excess of ,104 m3fluid m,2rock are required owing to the small concentrations of Al in aqueous fluids. It is concluded that the quartz-kyanite veins and their selvages were produced by regional-scale advective mass transfer by means of focused fluid flow along a thrust fault zone. The results of this study provide field evidence for considerable Al mass transport at greenschist to amphibolite facies metamorphic conditions, possibly as a result of elevated concentrations of Al in metamorphic fluids due to alkali-Al silicate complexing at high pressures. [source] The initiation and development of metamorphic foliation in the Otago Schist, Part 1: competitive oriented growth of white micaJOURNAL OF METAMORPHIC GEOLOGY, Issue 6 2005A. STALLARD Abstract The 3D shape, size and orientation data for white mica grains sampled along two transects of increasing metamorphic grade in the Otago Schist, New Zealand, reveal that metamorphic foliation, as defined by mica shape-preferred orientation (SPO), developed rapidly at sub-greenschist facies conditions early in the deformation history. The onset of penetrative strain metamorphism is marked by the rapid elimination of poorly oriented large clastic mica in favour of numerous new smaller grains of contrasting composition, higher aspect ratios and a strong preferred orientation. The metamorphic mica is blade shaped with long axes defining the linear aspect of the foliation and intermediate axes a partial girdle about the lineation. Once initiated, foliation progressively intensified by an increase in the aspect ratio, size and alignment of grains, although highest grade samples within the chlorite zone record a decrease in aspect ratio and reduction in SPO strength despite continued increase in grain size. These trends are interpreted in terms of progressive competitive anisotropic growth of blade-shaped grains so that the fastest growth directions and blade lengths tend to parallel the extension direction during deformation. The competitive nature of mica growth is indicated by the progressive increase in size and resultant decrease in number of metamorphic mica with increasing grade, from c. 1000 relatively small mica grains per square millimetre of thin section at lower grades, to c. 100 relatively large grains per square millimetre in higher grade samples. Reversal of SPO intensity and grain aspect ratio trends in higher grade samples may reflect a reduction in the strain rate or reduction in the deviatoric component of the stress field. [source] Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathologyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2005Ian S. Scott An immunohistochemical method for assessing cell cycle phase distribution in neurosurgical biopsies would enable such data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in glial neoplasms, without the requirement for flow cytometric analysis. Paraffin-embedded sections of intracerebral gliomas (n = 48), consisting of diffuse astrocytoma (n = 9), anaplastic astrocytoma (n = 8) and glioblastoma (n = 31), were analysed by immunohistochemistry using markers of cell cycle entry, Mcm-2 and Ki67, and putative markers of cell cycle phase, cyclins D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis). Double labelling confocal microscopy confirmed that the phase markers were infrequently coexpressed. Cell cycle estimations by immunohistochemistry were corroborated by flow cytometric analysis. There was a significant increase in Mcm-2 (P < 0.0001), Ki67 (P < 0.0001), cyclin A (P < 0.0001) and cyclin B1 (P = 0.002) expression with increasing grade from diffuse astrocytoma through anaplastic astrocytoma to glioblastoma, suggesting that any of these four markers has potential as a marker of tumour grade. In a subset of glioblastomas (n = 16) for which accurate clinical follow-up data were available, there was a suggestion that the cyclin A:Mcm-2 labelling fraction might predict a relatively favourable response to radical radiotherapy. These provisional findings, however, require confirmation by a larger study. We conclude that it is feasible to obtain detailed cell cycle data by immunohistochemical analysis of tissue biopsies. Such information may facilitate tumour grading and may enable information of prognostic value to be obtained in the routine diagnostic laboratory. [source] Follicular miniaturization in female pattern hair loss: clinicopathological correlationsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006A.G. Messenger Summary Background, The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles. Objectives, To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization. Methods, We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values. Results, There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm,2; grade 5, 243 cm,2) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm,2; grade 5, 96 cm,2). The absolute number of vellus follicles increased from 33 cm,2 (grade 1) to 71 cm,2 (grade 4), declining to 51 cm,2 at grade 5. The terminal/vellus ratio fell from 12·8 (grade 1) to 2·3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13·7% (grade 1) to 31·4% (grade 5). Conclusions, Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion. [source] | ||||||||||