Dataset Information

Histopathologic grading of anaplasia in retinoblastoma.

ABSTRACT: To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients.Retrospective clinicopathologic study.The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features.Increasing grade of anaplasia was associated with decreased overall survival (P = .003) and increased risk of metastasis (P = .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P < .0001), choroidal invasion (P < .0001), and anterior segment invasion (P = .04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P = .01 for metastasis, P = .03 for death) but anaplasia was not (P = .63 for metastasis, P = .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P = .0004) and death (P = .01).Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy.

SUBMITTER: Mendoza PR

PROVIDER: S-EPMC4361305 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Histopathologic grading of anaplasia in retinoblastoma.

Mendoza Pia R PR Specht Charles S CS Hubbard G Baker GB Wells Jill R JR Lynn Michael J MJ Zhang Qing Q Kong Jun J Grossniklaus Hans E HE

American journal of ophthalmology 20141219 4

<h4>Purpose</h4>To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients.<h4>Design</h4>Retrospective clinicopathologic study.<h4>Methods</h4>The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as ...[more]

PMID: 25528954

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Project description:We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas. The described cases (n = 9) all demonstrated a discrete spindle-cell (pseudosarcomatous) component with brisk mitotic activity (12-14 mitoses/10 HPF), elevated Ki-67 (mean 75.5 ± 25.0%, quantified), absence of PR, SSTR2A, or EMA expression, and potential SMA expression (50%). Despite these high-grade features, all nine patients remained free of progression or recurrence post resection (follow-up mean: 49.8 months). In contrast, among a comparison (control) cohort of consecutive WHO grade II and III meningiomas (n = 16), as expected, progression rate was high (68.8%, P = 0.002, Fisher's exact, average time to progression = 25 months, follow-up mean: 39.8 months). While necrosis was a frequent feature among atypical/anaplastic meningiomas (12/16, 75%), and elevated mitoses and proliferative index were present consistent with histologic grade, a well-defined zonal pattern with pseudosarcomatous component was not present among these tumors. DNA methylation-based analysis readily distinguished meningiomas by copy number profiles and DNA-based methylation meningioma random forest classification analysis (meningioma v2.4 classifier developed at University of Heidelberg); all pseudosarcomatous cases analyzed (4/9) matched with high level calibrated classifier score to "MC benign-1", with isolated loss of chromosome 22q identified as the sole copy number alteration. In contrast, multiple chromosomal losses were detected among the comparison cohort and classifier results demonstrated good concordance with histologic grade. Our findings suggest that pseudosarcomatous alterations represent reactive changes to central meningioma infarction, rather than focal anaplasia, and further support the use of DNA methylation-based analysis as a useful adjunct for predicting meningioma behavior. These indolent tumors should be distinguished from their atypical and anaplastic counterparts.

Project description:BackgroundClinical examination of trachoma is used to justify intervention in trachoma-endemic regions. Currently, field graders are certified by determining their concordance with experienced graders using the kappa statistic. Unfortunately, trachoma grading can be highly variable and there are cases where even expert graders disagree (borderline/marginal cases). Prior work has shown that inclusion of borderline cases tends to reduce apparent agreement, as measured by kappa. Here, we confirm those results and assess performance of trainees on these borderline cases by calculating their reliability error, a measure derived from the decomposition of the Brier score.Methods and findingsWe trained 18 field graders using 200 conjunctival photographs from a community-randomized trial in Niger and assessed inter-grader agreement using kappa as well as reliability error. Three experienced graders scored each case for the presence or absence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI). A consensus grade for each case was defined as the one given by a majority of experienced graders. We classified cases into a unanimous subset if all 3 experienced graders gave the same grade. For both TF and TI grades, the mean kappa for trainees was higher on the unanimous subset; inclusion of borderline cases reduced apparent agreement by 15.7% for TF and 12.4% for TI. When we assessed the breakdown of the reliability error, we found that our trainees tended to over-call TF grades and under-call TI grades, especially in borderline cases.ConclusionsThe kappa statistic is widely used for certifying trachoma field graders. Exclusion of borderline cases, which even experienced graders disagree on, increases apparent agreement with the kappa statistic. Graders may agree less when exposed to the full spectrum of disease. Reliability error allows for the assessment of these borderline cases and can be used to refine an individual trainee's grading.

Project description:BackgroundFaculty and students debate the fairness and accuracy of medical student clerkship grades. Group decision-making is a potential strategy to improve grading.ObjectiveTo explore how one school's grading committee members integrate assessment data to inform grade decisions and to identify the committees' benefits and challenges.DesignThis qualitative study used semi-structured interviews with grading committee chairs and members conducted between November 2017 and March 2018.ParticipantsParticipants included the eight core clerkship directors, who chaired their grading committees. We randomly selected other committee members to invite, for a maximum of three interviews per clerkship.ApproachInterviews were recorded, transcribed, and analyzed using inductive content analysis.Key resultsWe interviewed 17 committee members. Within and across specialties, committee members had distinct approaches to prioritizing and synthesizing assessment data. Participants expressed concerns about the quality of assessments, necessitating careful scrutiny of language, assessor identity, and other contextual factors. Committee members were concerned about how unconscious bias might impact assessors, but they felt minimally impacted at the committee level. When committee members knew students personally, they felt tension about how to use the information appropriately. Participants described high agreement within their committees; debate was more common when site directors reviewed students' files from other sites prior to meeting. Participants reported multiple committee benefits including faculty development and fulfillment, as well as improved grading consistency, fairness, and transparency. Groupthink and a passive approach to bias emerged as the two main threats to optimal group decision-making.ConclusionsGrading committee members view their practices as advantageous over individual grading, but they feel limited in their ability to address grading fairness and accuracy. Recommendations and support may help committees broaden their scope to address these aspirations.

Dataset Information

Histopathologic grading of anaplasia in retinoblastoma.

Publications

Histopathologic grading of anaplasia in retinoblastoma.

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