PA35.1 | Retinoblastoma & Neuro-Ophthalmic Morphology — Summary & Reflection

REFLECT

A 14-month-old boy is brought to your outpatient clinic. His father, now 32 years old, had his left eye removed for retinoblastoma at age 2. He received no genetic counselling at the time. Today, the father noticed that his son seems to have a white glow in the right eye in photographs taken over the past month.

Work through the following before reading further:
1. What is the most likely diagnosis and why does the father's history change your assessment?
2. What risk does this child carry for the left eye — is bilateral involvement certain?
3. What is the risk of second malignancies for this child over his lifetime?
4. What is your immediate management step?
5. If RB1 germline testing is negative in the child, does that rule out hereditary retinoblastoma?

Reflection anchor: The father's history of retinoblastoma means there is a 50% probability that he carries a germline RB1 mutation and passed it to this child. If the child has the germline mutation, his risk of developing retinoblastoma in either or both eyes is very high. The left eye must be examined under anaesthesia (EUA) to exclude early/subclinical disease — a normal-appearing left eye today does not mean the left eye is safe. All first-degree relatives of any retinoblastoma patient should be offered genetic counselling and testing.

KEY TAKEAWAYS

Retinoblastoma — Core Summary:

• Gene: RB1, chromosome 13q14; protein pRb is a G1/S brake via E2F sequestration
• Two-hit hypothesis (Knudson): both alleles must be inactivated; germline first hit → hereditary/bilateral; two somatic hits → sporadic/unilateral
• Hereditary: ~40%, bilateral/multifocal, earlier onset, second cancer risk (osteosarcoma), autosomal dominant transmission
• Sporadic: ~60%, unilateral, no elevated second cancer risk
• Presentation: leukocoria (white reflex, most common) → strabismus → advanced signs (proptosis, buphthalmos)
• Macro: white chalky mass, necrosis, calcification (pathognomonic on CT), endophytic or exophytic
• Micro: SRBC + Flexner-Wintersteiner rosettes (true lumen, PAS+) ± Homer-Wright rosettes ± fleurettes
• Spread: optic nerve → CNS (most dangerous), choroid → orbit, haematogenous → bone/liver
• Treatment: enucleation (advanced/unilateral) or globe-preserving chemoreduction + focal (early bilateral)

CNS/Eye Morphology Practical — Identification Keys:

• Bacterial meningitis: neutrophils in subarachnoid space
• TB meningitis: granulomas + caseation at base of brain (ZN+)
• Glioblastoma: pseudopalisading necrosis + glomeruloid vessels
• Oligodendroglioma: fried-egg cells + chicken-wire vessels
• Meningioma: whorls + psammoma bodies (dura-attached)
• Medulloblastoma: SRBC + Homer-Wright rosettes (posterior fossa, no true lumen)
• Schwannoma: Antoni A/B + Verocay bodies (nerve sheath, S100+)
• Retinoblastoma: SRBC + Flexner-Wintersteiner rosettes (true lumen, intraocular, calcification)

The one table to burn into memory: Flexner-Wintersteiner = true lumen = retinoblastoma. Homer-Wright = no lumen, fibrils = neuronal tumors. When in doubt, look for the lumen.