Histopathologic Grading of Anaplasia in Retinoblastoma

Abstract

Purpose 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. Design 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's 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=0.003) and increased risk of metastasis (p=0.0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (p<0.0001), choroidal invasion (p=<0.0001), and anterior segment invasion (p=0.04). 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=0.01 for metastasis, p=0.03 for death) but anaplasia was not (p=0.63 for metastasis, p=0.30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (p=0.0004) and death (p=0.01). Conclusion 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.

A mouse model of MYCN-driven retinoblastoma reveals MYCN-independent tumor reemergence

“…In some animals, neuroblastic Homer Wright rosettes were present. In Rb/TET-MYCN mice, tumor cells were somewhat larger and more often elongated, angular, or molded together (Supplemental Figure 1B) anaplastic features that have been associated with MYCN amplification in human retinoblastoma and worse clinical outcomes (3,31). We found that anaplastic changes were even more prominent in Rb/p107/TET-MYCN tumors (Supplemental Figure 1C).…”

Retinoblastoma

“…84–86 Emerging evidence indicates that high grade anaplasia (loss of differentiated characteristics) may be a risk factor for metastasis and death. 87 High-risk features by the Murphree IIRC 78 were observed in 15–33% of Group D and 50–61% of Group E eyes, 85,88 , but by the Shields IIRC (which classifies less affected D eyes as E), only 24–39% 89 of Group E eyes showed high risk. Adjuvant systemic chemotherapy after high-risk features are observed in an enucleated eye may reduce risk of metastatic relapse.…”

The Biology of Retinoblastoma

“…The grading of cellular anaplasia and nuclear morphometry has recently been shown to have prognostic significance in the absence of high-risk histologic features. 32 The benign variant retinocytoma consists of well-differentiated cells often with associated calcifications. Retinocytoma cells have small, round, bland nuclei and abundant cytoplasm.…”