What are the recommended diagnostic tests for retinoblastoma?

Diagnostic Testing for Retinoblastoma

The diagnosis of retinoblastoma is primarily clinical through fundoscopic examination and ocular ultrasound performed by an ophthalmologist, but MRI of the head and orbits with and without IV contrast is the most useful imaging modality for staging and evaluating extent of disease. 1, 2

Initial Clinical Evaluation

• Fundoscopic examination is the primary diagnostic tool and establishes the diagnosis in most cases 1, 3
• Ocular ultrasound complements fundoscopy and may be sufficient for diagnosis without requiring additional imaging initially 1, 3
• The most common presenting symptoms are leukocoria (white pupillary reflex) and strabismus, which should prompt immediate ophthalmologic referral 4, 3
• Absence of red reflex on Brückner testing is a critical warning sign requiring urgent evaluation 3

Imaging Studies

MRI (First-Line for Staging)

MRI of the head and orbits with and without IV contrast is the gold standard imaging modality for evaluating retinoblastoma once the diagnosis is suspected 1, 2

MRI provides critical staging information:

• Demonstrates retrolaminar optic nerve infiltration, which determines whether tumor has extended beyond the eye 1, 2
• Shows choroid-scleral infiltrations and orbital invasion, which upstages disease and changes management from eye-preserving to aggressive treatment 1, 2
• Detects concurrent intracranial tumors in the sellar or pineal region (trilateral retinoblastoma in hereditary cases) 1, 2
• Evaluates intracranial spread of tumor, essential for complete staging 1, 2
• Postcontrast enhancement patterns differentiate retinoblastoma from benign mimics like Coats disease, persistent hyperplastic primary vitreous (PHPV), or retinopathy of prematurity 1, 2

When malignant intraocular mass is suspected, MRI of the head should always be performed in association with MRI of the orbits to ensure complete staging evaluation 1, 2

CT Scanning (Adjunctive Role)

• CT with IV contrast is helpful for detecting calcifications, which are characteristic of retinoblastoma and aid in differential diagnosis 1, 2, 3
• CT can evaluate extension along optic nerves and intracranially, but provides less detailed soft tissue information than MRI 1, 2
• Absence of calcification on CT helps differentiate PHPV and Coats disease from retinoblastoma 1, 3

Pathologic Evaluation (Post-Enucleation)

When enucleation is performed, the following pathologic features must be documented 1:

• Growth pattern: diffuse, unifocal, or multifocal 1, 5
• Bilaterality and trilaterality (bilateral with pineal gland involvement) 1, 5
• Differentiation features: presence of Flexner-Wintersteiner rosettes, Homer Wright rosettes, and fleurettes 1, 5
• Optic nerve invasion by layer: prelaminar, laminar, retrolaminar, or to optic nerve resection margin 1
• Extraocular extension 1
• Choroidal invasion, considered by some as a significant risk factor for metastasis 1

Genetic Testing

• Genetic testing for RB1 germline mutations should be performed in all cases, as approximately 40% of retinoblastomas are hereditary 6, 7
• All bilateral tumors are hereditary and require genetic counseling regardless of germline testing results 5, 7
• Bilateral disease presents earlier (18-24 months) compared to unilateral cases (36 months) 5, 6
• Carriers of constitutional RB1 mutations have >90% risk of developing retinoblastoma and increased risk of secondary cancers 4, 7

Critical Pitfalls to Avoid

• Never delay ophthalmologic referral while attempting outpatient workup—leukocoria in an infant is an ophthalmologic emergency 3
• Avoid corticosteroid treatment before ophthalmologic examination, as this may worsen infectious conditions or mask accurate diagnosis 3
• Do not rely on CT alone for staging, as MRI provides superior soft tissue detail for assessing optic nerve and intracranial involvement 1, 2
• Do not use CTA or MRA for initial evaluation—there is no relevant literature supporting their use in suspected retinoblastoma 1

Surveillance for Hereditary Cases

• Intensive ocular screening is recommended for patients with germline RB1 mutations to detect new retinoblastomas 7
• Neuroimaging surveillance for pineoblastoma should be performed in hereditary cases 7
• Long-term follow-up is essential due to 20% risk of second primary cancers, particularly in those who received radiotherapy 1, 4, 7