Retinoblastoma Classification

The Reese-Ellsworth classification system for intraocular tumors is the traditional method for stratifying the intraocular extent of retinoblastoma. The system takes into account the number, size, and location of tumors and the presence or absence of vitreous seeding. Tumors are categorized from very favorable (group I) to very unfavorable (group V) by probability of eye preservation when treated with external beam radiotherapy (EBRT) alone. However, the Reese-Ellsworth classification does not stage extraocular disease, nor does it provide prognostic information about patient survival or vision. Moreover, in recent decades, EBRT has been supplanted by primary systemic and/or intra-arterial chemotherapy for treatment of retinoblastoma.

In 2005, the first international classification system for intraocular retinoblastoma was introduced: the International Intraocular Retinoblastoma Classification (IIRC). The IIRC is now the most commonly used system worldwide. In this system, tumors are grouped in terms of size, proximity to critical anatomical structures, presence of subretinal fluid, and extent of vitreous and subretinal seeding. Eyes are assigned a letter from A to E, indicating those most to least salvageable with chemotherapy. Eyes with anterior chamber involvement, neovascular glaucoma, vitreous hemorrhage, or necrosis are classified as group E and are generally considered unsalvageable (Table 19-3).

The goal of the IIRC was to predict ocular salvage with systemic chemotherapy combined with local therapy and to provide a uniform classification scheme to be applied broadly across centers. Unfortunately, small inconsistencies in published grouping systems have undermined this. For instance, the classification system for Children’s Oncology Group (COG) clinical trials includes a small deviation from the IIRC system in the allowed size of the fluid cuff for staging of group B eyes. The International Classification of Retinoblastoma (ICRB) described in 2006 differs from the IIRC in that tumor filling greater than 50% of the globe is a criterion for group E disease. Thus, some eyes classified as group D in the IIRC would be staged as group E in the ICRB scheme. This resulted in confusion in outcomes reporting, particularly in eyes with advanced disease.

The eighth edition of the American Joint Committee on Cancer TNM (tumor, node, metastasis) staging system was published in 2017 and introduced a comprehensive reclassification of intraocular disease in retinoblastoma. This clinical classification is based on a retrospective multicenter study of 1728 eyes diagnosed between 2001 and 2011, which addressed the proportion of eyes salvaged without EBRT. Notably, the system introduced a new specification, “H,” indicating “hereditary trait” (see sidebar on p. 360). The classification schemes are summarized and compared in Table 19-3.

• Mallipatna A, Gallie BL, Chévez-Barrios P, Lumbroso-Le Rouic L, Chantada GL, Doz F. Retinoblastoma. In: Amin MB, Edge SB, Greene FL, eds. AJCC Cancer StagingManual. 8th ed. Springer; 2017:819–831.

• Murphree AL. Intraocular retinoblastoma: the case for a new group classification. OphthalmolClin North Am. 2005;18(1):41–53.

• Reese AB. Tumors of the Eye. 3rd ed. Harper & Row; 1976.

• Shields CL, Shields JA. Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol. 2006;17(3):228–234.

Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.