High-Risk Features and Tumor Differentiation in Retinoblastoma: A Retrospective Histopathologic Study

Abstract

Abstract Context.—Certain histopathologic risk factors in enucleated eyes are important indicators for adjuvant chemotherapy in patients with retinoblastoma. Objectives.—To determine the frequency of histopathologic risk factors in a large series of retinoblastomas treated by enucleation on file in the pathology laboratory of a large American eye hospital, assess the relationship between tumor differentiation and age at enucleation, and investigate the frequency of photoreceptor differentiation and the role of retinoma/retinocytoma as retinoblastoma precursor. Design.—Retrospective histopathologic review of 387 eyes with retinoblastoma treated by enucleation including 297 with no prior treatment. Results.—Fifty-five of 297 untreated eyes (18.5%) had high-risk features. Retrolaminar optic nerve invasion was present in 31 (10.4%), and 24 (8.1%) had massive uveal invasion (defined as >3 mm in diameter). Of the high-risk eyes, 70.9% had iris neovascularization and 60% had neovascular glaucoma. There was a statistically significant inverse relationship between age at enucleation and the degree of tumor differentiation, evidenced by the presence of rosettes. Tumors in older children tended to be poorly differentiated, while rosettes were often numerous in the tumors of younger infants. In all, 20.4% of tumors contained foci of photoreceptor differentiation, which localized in the base of a predominantly endophytic tumor in about one-fourth. Lack of correlation between photoreceptor differentiation and age at enucleation is consistent with early or prenatal malignant transformation. Both preceding observations provide evidence for the hypothetical role of retinoma as a retinoblastoma precursor. Conclusions.—Slightly less than 1 in 5 infants with retinoblastoma treated by enucleation at a large American eye hospital would require adjuvant chemotherapy on the basis of existing high-risk histopathologic features. Retinoblastomas become progressively less differentiated with time and may be spawned by precursor retinomas.