What is the most likely diagnosis and appropriate work‑up and management for an eye tumour in an infant?

Eye Tumour in Baby: Diagnosis and Management

Retinoblastoma is the most likely diagnosis for an eye tumour in an infant and requires immediate ophthalmologic referral—this is an emergency that must be assumed until proven otherwise. 1

Most Likely Diagnosis

Retinoblastoma is the most common intraocular malignancy of infancy and childhood, occurring in 1/15,000-20,000 live births. 2, 3 The two most frequent presenting signs are:

• Leukocoria (white pupillary reflex) - the most common presentation 2, 3
• Strabismus - the second most common presentation 2
• Other signs may include iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulitis, or exophthalmia 2

The presence of calcifications within well-demarcated retinal lesions in a child with leukocoria is pathognomonic for retinoblastoma. 1

Key Clinical Patterns

• Unilateral disease (60-70% of cases): Median age at diagnosis is 2 years; most are non-hereditary 2, 3
• Bilateral disease (30-40% of cases): Median age at diagnosis is 1 year; all bilateral cases are hereditary 2, 3
• All bilateral and multifocal unilateral forms are hereditary 2

Immediate Work-Up Algorithm

Step 1: Emergency Ophthalmologic Referral

Never delay ophthalmologic referral while attempting outpatient workup—leukocoria in a child is an ophthalmologic emergency. 1 Diagnosis is made by fundoscopy performed by a specialist. 2

Step 2: Imaging for Staging

MRI of the head and orbits with and without IV contrast is the most useful imaging modality for staging retinoblastoma. 4 This must be performed because:

• MRI demonstrates retrolaminar optic nerve infiltration, critical for determining tumor extension beyond the eye 4
• MRI shows choroid-scleral infiltrations and orbital invasion, which upstages disease and changes management from eye-preserving to aggressive treatment 4
• MRI detects concurrent intracranial tumors (trilateral retinoblastoma in hereditary cases), which dramatically alters prognosis 4
• MRI evaluates possible intracranial spread, essential for complete staging 4

CT with IV contrast may be helpful for detecting calcifications, which are characteristic of retinoblastoma and aid in differential diagnosis. 4, 1 However, CT provides less detailed soft tissue information than MRI. 4

Step 3: Genetic Testing

All at-risk infants should have ophthalmologic exam promptly after birth (within 24 hours if possible) to maximize visual sparing with early detection. 5

Germline genetic testing for RB1 pathogenic variants should be performed using blood, buccal, or saliva samples. 5 Key considerations:

• Individuals with bilateral disease should be offered surveillance for hereditary retinoblastoma regardless of germline testing results, as bilateral disease represents hereditary retinoblastoma 5
• Testing should assess for mosaicism, seen in 3-5% of patients with hereditary retinoblastoma 5
• Approximately 1.4% of unilateral sporadic retinoblastoma without RB1 mutations are initiated by MYCN oncogene amplification—these are more aggressive and occur at younger ages 5

Management Strategy

For Unilateral Disease

Enucleation is still often necessary in unilateral disease, with adjuvant treatment decisions based on histological risk factors. 2

For Bilateral Disease

Conservative treatment for at least one eye is possible in most bilateral cases. 2 This includes:

• Laser therapy alone or combined with chemotherapy 2
• Cryotherapy 2
• Brachytherapy 2
• Intraarterial or intravenous chemotherapy with focal consolidation therapies (transpupillary thermotherapy, cryotherapy, laser photocoagulation) is now standard multimodality care 3
• Intravitreal and intracameral chemotherapy for controlling intraocular seeds 3

External beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. 2

Critical Pitfalls to Avoid

Do Not Delay Referral

The most dangerous error is delaying specialist evaluation while pursuing imaging or other workup. Retinoblastoma must be assumed until proven otherwise in any child presenting with leukocoria. 1

Differential Diagnosis Considerations

Other causes of leukocoria that must be excluded include:

• Persistent hyperplastic primary vitreous (PHPV) - absence of calcification on CT differentiates this from retinoblastoma 1
• Coats disease - absence of calcification differentiates this from retinoblastoma 1
• Retinopathy of prematurity 1
• Congenital cataract 1
• Larval granulomatosis 1

Hereditary Implications

Hereditary retinoblastoma constitutes a cancer predisposition syndrome: patients with constitutional RB1 mutations have >90% risk of developing retinoblastoma and increased risk of other cancers throughout life. 2 More than half of children with germinal mutations will develop second tumors by the fourth decade of life, making vigilant lifelong follow-up mandatory. 6

Genetic counseling and screening of at-risk family members must be incorporated as essential parts of management. 3

Prognosis

Vital prognosis related to retinoblastoma alone is now excellent in patients with unilateral or bilateral forms. 2 Early detection and treatment by a multidisciplinary specialty team maximizes the chance for survival and ocular/vision salvage while minimizing treatment-related toxicity. 7

However, advanced extraocular or metastatic tumors still have a poor prognosis. 3