What are the classifications of retinoblastoma?

Classification of Retinoblastoma

Retinoblastoma is classified using two complementary systems: the International Classification of Retinoblastoma (ICRB) for intraocular disease based on tumor features and treatment prognosis, and the International Retinoblastoma Staging System (IRSS) for extraocular extension and metastatic disease. 1, 2, 3

International Classification of Retinoblastoma (ICRB)

The ICRB system categorizes intraocular tumors into five groups (A through E) based on tumor size, location, and presence of seeding, which directly predicts chemoreduction success rates: 1, 4

Group A: Small Tumors

• Retinoblastoma ≤3 mm in greatest dimension 1
• Tumor confined to retina without seeding 4
• Treatment success rate: 100% 1, 4

Group B: Larger or Macular Tumors

• Retinoblastoma >3 mm in size 1
• Macular location (regardless of size) 1
• Presence of minor subretinal fluid 1
• Treatment success rate: 91-93% 1, 4

Group C: Localized Seeding

• Retinoblastoma with focal/localized subretinal or vitreous seeds 1, 4
• Subcategories include focal subretinal seeds (3a) and focal vitreous seeds (3b) 4
• Treatment success rate: 59-90% 1, 4

Group D: Diffuse Seeding

• Retinoblastoma with diffuse subretinal or vitreous seeds 1, 4
• Subcategories include diffuse subretinal seeds (4a) and diffuse vitreous seeds (4b) 4
• Treatment success rate: 12-47% 1, 4

Group E: Advanced Intraocular Disease

• Massive retinoblastoma necessitating enucleation 1
• Presence of neovascular glaucoma or invasive retinoblastoma 4
• Typically managed with primary enucleation 1

International Retinoblastoma Staging System (IRSS)

The IRSS classifies disease based on extent of tumor spread beyond the eye: 2, 3

Stage 0: Conservative Management

• Patients treated conservatively without enucleation 3
• Subject to presurgical ophthalmologic classifications (ICRB groups) 3

Stage I: Complete Resection

• Eye enucleated with completely resected tumor histologically 3
• No microscopic residual disease 3

Stage II: Microscopic Residual Disease

• Eye enucleated with microscopic residual tumor 3

Stage III: Regional Extension

• Stage IIIa: Overt orbital disease 3
• Stage IIIb: Preauricular or cervical lymph node extension 3

Stage IV: Metastatic Disease

• Stage IVa: Hematogenous metastasis 3
  • IVa(1): Single lesion 3
  • IVa(2): Multiple lesions 3
• Stage IVb: CNS extension 3
  • IVb(1): Prechiasmatic lesion 3
  • IVb(2): CNS mass 3
  • IVb(3): Leptomeningeal disease 3

Pathologic Classification Features

Additional pathologic features documented for prognostic purposes include: 5, 6

Growth Pattern

• Diffuse, unifocal, or multifocal 5, 6
• Focal patterns generally have better prognosis 6

Bilaterality and Trilaterality

• Bilateral disease (30-40% of cases) indicates hereditary retinoblastoma 5, 7
• Trilateral retinoblastoma involves bilateral disease with pineal gland involvement 5

Differentiation Features

• Presence of Flexner-Wintersteiner rosettes 5, 6
• Homer Wright rosettes 5, 6
• Fleurettes 5, 6
• Better differentiation indicates improved prognosis 6

Invasion Patterns

• Optic nerve invasion by layer: prelaminar, laminar, retrolaminar, or to resection margin 5
• Choroidal invasion (controversial prognostic significance) 5
• Extraocular extension 5
• Presence or absence of vitreous seeding 5

Clinical Pitfalls

The older Reese-Ellsworth classification system showed erratic correlation with modern chemoreduction outcomes and has been largely replaced by the ICRB system. 1, 4 The ICRB provides smooth, predictable correlation with treatment success, making it superior for contemporary management planning. 4

Bilateral disease always represents hereditary retinoblastoma and requires genetic counseling regardless of germline testing results. 5 Approximately 40% of all retinoblastomas are hereditary, with bilateral tumors presenting earlier (18-24 months) compared to unilateral cases (36 months). 5, 7