title: Histopathologic grading of anaplasia in retinoblastoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Retrospective clinicopathologic study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia.
authors.forename: Pia R
authors.initials: PR
authors.lastname: Mendoza
authors.affiliation: Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Specht
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia.
authors.forename: G Baker
authors.initials: GB
authors.lastname: Hubbard
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Wells
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lynn
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Informatics, Emory University, Atlanta, Georgia.
authors.forename: Jun
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia. Electronic address: ophtheg@emory.edu.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
mesh_terms: D000708:Anaplasia / Q000145:classification; D002648:Child; D002675:Child, Preschool; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D019572:Retinal Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D012175:Retinoblastoma / Q000145:classification / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D015996:Survival Rate