1. SDL 22 Retinoblastoma

2. CT Retinoblastoma

3. Retinoblastoma Definition and Epidemiology  Def: malignant tumor of the immature retina.  Epidemiology  Two hit hypothesis (Rb1 gene) bt 3 months (fetal) and 4 years old  Cell origin probably from a cone or multipotent retinoblast.  Probably not gonna see this in pts over 15yo.  Third highest intraocular malignancy there is.  The highest is choroidal melanoma (55yo typically)

4. What Happened?  Inactivation, deletion, mutation of the tumor suppressor gene, Rb1  Locus 13q14  Two-hit hypothesis prediction from Knudson  Rb1 regulates cell cycle bt G1 and S phase

5. Hereditary (40%)  (auto dom w/ incomplete penetrance)  One allele is lost at Germline  Other allele is lost=immediate carcinogenesis  Watch out for osteosarcoma!  Pts can have ReBa (retinoblastoma) in the same or contralateral eye  If they survive ReBa, also at risk for many other malignancies (all kinds of osteosarcomas, pinealoblastoma, Hodgkin’s disease, lungs, breasts, brain tumors, cutaneous melanomas…I think you get the point)  Mutation during embryogenesis still leaves pt at risk, even if there is no family history of ReBa  Probably during spermatogenesis

6. Nonhereditary (60%)  Unilateral eye  The same developing retinal cell loses both alleles of Rb1 gene.  1/25,000 infants  Since somatic mutation, passing malignancy on is not an issue.  Secondary malignancy risk is NOT increased either Osteosarcoma Pinealoblastoma Hodgkin’s Cutaneous melanoma

7. Pathogenesis  Cell origin:  Probably from a multipotent retinoblast…inner OR outer retinal cell.  What do we look for?  Red reflex will present white (60%) Leukocoria  Pts will have strabismus (20%)-macular involvement  Other 20% is atypical; inflammation, pain, orbital cellulitis Leukocoria

8. Growth Pattern  Endophytic: within internal retina and towards vitreous  Exophytic: Retinal detachment!  Inner retinal layer to subretinal space  Diffuse infiltrating ReBa.  Very very rare…flag opaque, no obvious mass, progresses towards anterior retina.

9. Morphology  Macroscopically:  Soft, friable, creamy white mass, chalky-white calcifications.  Microscopically:  Immature retinoblasts=neuroblasts: small, round/polygonal, densely-packed cells. Hyperchromatic nuclei, scant cytoplasm  High mitosis, high necrosis pink necrosis  “islands of blue cells in a sea of pink necrosis”

10. Histology  “islands of blue cells in a sea of pink necrosis” Flex- Wintersteiner Pseudorosettes: Perivascular cuff cells.

11. Homer-Wright Rosette not specific to ReBa. Could be medulloblastoma or neuroblastoma also

12. Dissemination Pathways  Anteriorly: reaches the ciliary body and anterior chamber, creating a pseudohypopyon  Posteriorly: towards optic nerve and CSF and into cranium  Extraocular extension: sclera and choroid lets it get to orbit…then can go pretty much anywhere. Nonfunctional eye; Result of untreated ReBa.

13. Metastasis  Orbital invasion is biggest risk factor!  Into optic nerve: important, depends on stage of tumor though.  Insignificant:  Anterior to lamina cribosa  Choroidal invasion  Significant if it has reached surgical resection line  50%-85% = DEATH! Surgical resection line: really Bad. Orbit and optic nerve: huge risk factors.

14. Secondary tumahs  Rb1 mutation of all cells = predisposing them to secondary tumors  Most common cause of death in pts with ReBa.  Radiotherapy is a contributing factor too  Tumahs where?  Soft tissue in head (irradiated field)  Bone  Skin  Brain

15. Retinocytoma  Rare benign tumors, numerous fleurettes…show NO evidence of necrosis or mitotic activity.  Some pts with Rb1 germline mutations can get these.  Genetics:  Auto dom, just like ReBa.  Both alleles lost, just like ReBa.  Truly benign or regressed ReBa?  Need some other event to transform from retinocytoma to the malignant retinoblastoma.  Make sure pts follow up and are carefully monitored.