Retinoblastoma

Basics & Genes - Eye Spy a Bad Gene

• Most common childhood intraocular malignancy.

  ⭐ Retinoblastoma is the most common intraocular malignancy in childhood, typically diagnosed before 5 years of age.

• Genetics: RB1 gene (Chr 13q14) mutation; tumor suppressor.
  • Knudson's "two-hit" hypothesis.
• Forms:
  • Hereditary (40%): Germline RB1 mutation. Often bilateral, multiple foci. ↑ risk of secondary cancers (osteosarcoma, pineoblastoma).
  • Sporadic (60%): Somatic RB1 mutations. Usually unilateral, unifocal.

Signs & Scans - The White Reflex

• Clinical Presentation:
  • Leukocoria (Cat's Eye Reflex): Most common sign. White pupil, often noted in photos.

    ⭐ Leukocoria (white pupillary reflex) is the most common presenting sign of retinoblastoma, followed by strabismus.

  • Strabismus: Second most common, due to vision loss.
  • Others: Proptosis, hyphema, red/painful eye, ↓vision.
• Imaging & Diagnosis:
  • Indirect Ophthalmoscopy: Reveals chalky-white retinal mass ± calcification.
  • USG B-scan (Eye): Detects mass & pathognomonic calcification; differentiates mimics.
  • MRI (Orbit & Brain): Assesses optic nerve/extraocular spread, pineal gland (trilateral RB). Avoid CT (radiation).

Staging & Outlook - Grading the Threat

• Intraocular Staging (Key):
  • IIRC (Groups A-E): Current standard, predicts salvage.
  • ICRB: Older classification.
• Extraocular/Metastatic:
  • AJCC TNM (8th ed.).
  • IRSS: For orbital/metastatic disease.
• High-Risk Factors (↑ recurrence/metastasis):
  • Optic nerve invasion (post-laminar critical).
  • Massive choroidal invasion (>3mm).
  • Anterior segment involvement.
  • Scleral/Orbital extension.

⭐ The International Intraocular Retinoblastoma Classification (IIRC) groups eyes from A (very low risk) to E (very high risk of treatment failure with conservative measures).

• Prognosis:
  • Intraocular disease: Excellent survival (>95%).
  • Metastatic disease: Poor.

Treatment Tactics - Saving Sight & Life

Treatment aims to save life and preserve vision, tailored to disease stage.

• Primary Goal: Globe salvage & vision preservation if possible; life-saving paramount.
• Chemoreduction (Systemic): VEC (Vincristine, Etoposide, Carboplatin) often initial for bulky intraocular tumors (Groups C, D, E).
• Focal Therapies (Consolidation/Primary for small tumors - Groups A, B):
  • Laser photocoagulation (Transpupillary Thermotherapy - TTT)
  • Cryotherapy
• Targeted Chemotherapy:
  • Intra-arterial Chemotherapy (IAC): e.g., Melphalan, for localized disease, reducing systemic toxicity.
  • Intravitreal Chemotherapy: For vitreous seeds.
• Enucleation: For advanced disease (e.g., Group E with no visual potential, neovascular glaucoma, optic nerve invasion).
• External Beam Radiotherapy (EBRT): Reserved for orbital extension or salvage; high risk of secondary malignancies.

⭐ Trilateral retinoblastoma refers to bilateral hereditary retinoblastoma associated with a pinealoblastoma or other primitive neuroectodermal tumor (PNET) in the suprasellar or parasellar region.

Aftermath & Alerts - Beyond the Eye

• Long-term Follow-up: Lifelong.
  • Ophthalmic exams: initially every 2-4 months, then spaced.
  • Brain/orbit MRI: every 6-12 months for 3-5 years (pineoblastoma surveillance).
• Secondary Malignancies (SMN):

  ⭐ Patients with germline RB1 mutations have a significantly increased lifetime risk of developing secondary malignancies, most commonly osteosarcomas, soft tissue sarcomas, and melanomas.

  • Annual whole-body MRI for hereditary cases.
• Treatment Complications:
  • Hearing loss (carboplatin).
  • Cosmetic: orbital implant/prosthesis post-enucleation.
  • Radiation effects: cataracts, retinopathy, orbital hypoplasia.
  • Chemotherapy: renal toxicity, growth impairment.

High‑Yield Points - ⚡ Biggest Takeaways

• Most common intraocular malignancy in childhood; from retinal neuroblasts.
• RB1 gene mutation (chromosome 13q14, tumor suppressor).
• Leukocoria ("cat's eye reflex") is most common sign; strabismus second.
• Flexner-Wintersteiner rosettes (pathognomonic); calcification on imaging.
• Hereditary form (40%): often bilateral, multifocal; risk of trilateral retinoblastoma.
• ↑ Risk of secondary cancers (e.g., osteosarcoma), especially post-radiotherapy.
• Treatment: Enucleation (large tumors); chemotherapy, focal therapies (smaller tumors).