Eye
Retina
Retinoblastoma of retina

Author: Nat Pernick, M.D. (see Authors page)

Revised: 22 May 2018, last major update February 2014

Copyright: (c) 2004-2018, PathologyOutlines.com, Inc.

PubMed Search: Retinoblastoma [title] review[ptyp] pathology

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Cite this page: Pernick, N. Retina: retinoblastoma of retina. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/eyeretinaretinoblastoma.html. Accessed December 18th, 2018.
Definition / general
  • Most common intraocular tumor of children with incidence of 1 per 20,000 live births
  • May be congenital but not recognized until ages 6 months to 2 years
  • 60% sporadic, 40% familial (autosomal dominant)
  • Develops in 80 - 90% of those with mutant alleles in retinoblastoma (Rb) gene at 13q14
  • Need mutations in both alleles to inactivate Rb gene, a negative growth regulator
  • Patients with hereditary retinoblastoma have a germline mutation in one allele; develop tumors after somatic mutation in second allele ("second hit"); in sporadic cases, both alleles have somatic mutations
  • Bilateral in 30% of all cases, 90% of familial cases; some patients with bilateral tumors also have similar tumor of pineal gland, termed "trilateral" retinoblastoma, associated with poor prognosis
  • White reflex (leukokoria) present in affected eye; also retinal detachment
  • Tends to invade optic nerve (particularly large exophytic tumors with secondary glaucoma); can invade uveal tract
  • Distant metastases to cranial vault, skeletal system
  • Second primaries for familial tumors: 6 - 20% after 10 - 20 years, usually osteosarcoma (50% of tumors) and rhabdomyosarcoma, close to irradiated fields; also rhabdoid tumors
Whole mount images

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Small endophytic tumor

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Total retinal detachment and collapse of anterior
chamber due to partially necrotic tumor with viable
cells surrounding blood vessels in a sleeve pattern,
no involvement of choroid, sclera or optic nerve

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Large tumor fills globe with massive choroid and extraocular invasion

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Bilateral tumor (patient died of intracranial tumor):
left - multicentric tumor without optic nerve
invasion; right - regressed tumor after radiation
therapy without optic nerve invasion

Radiology images

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Ovoid retinal tumor

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Round retinal tumor with focal calcification

Prognostic factors
  • 5 year survival: 90% if unilateral, slightly less if bilateral
  • Poor prognostic factors: invasion of optic nerve (report as prelaminar or retrolaminar involvement, with or without resection line involvement), invasion of uveal tract or sclera, seeding of vitreous, involvement of anterior segment; extensive ocular tissue and tumor necrosis is associated with other factors (Arch Pathol Lab Med 2006;130:1669); differentiation does not appear to have prognostic value
Case reports
Treatment
  • Early: radiation therapy, cryopexy, xenon arc photocoagulation
  • Large tumors: enucleation
  • Involvement of optic nerve margin: radiation of orbit and systemic chemotherapy
  • Bilateral tumors: radiation therapy to less affected eye with possible chemotherapy or bilateral radiation
  • Recurrences: photocoagulation, cryotherapy or cobalt disks
Clinical images

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Leukocoria (white reflux) due to retinal tumor

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Strabismus without leukocoria (early clinical sign)

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Translucent intraretinal tumor
with focal opacified areas
representing calcification

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Fluffy retinal tumor has grown
into vitreous, retinal vessels
are obscured by tumor

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Retinal tumor invades
subretinal space - retinal
vessels pass over tumor

Gross description
  • Creamy white with chalky areas of calcification and yellow necrotic areas
  • May grow inward (endophytic) or outward toward choroid (exophytic)
  • Rarely are diffusely infiltrative; typically seeds intraocularly
Gross images

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Marked advanced tumor with
massive extraocular extension in
6 year old from 1917 (typical
of US cases at that time)

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Advanced tumor from African
patient with destruction of
anterior segment of eye
and extraocular extension

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Small retinal tumor with large white areas of necrosis

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Small retinal tumor with foci of calcification


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Three small retinal tumors

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Large area of choroidal
invasion next to partially
necrotic retinal tumor

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Large exophytic tumor with
focal calcification causes total
exudative retinal detachment

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Large exophytic tumor with
enlargement of optic nerve
due to invasion

Microscopic (histologic) description
  • Sheets, trabeculae and nests of small blue cells with scant cytoplasm, hyperchromatic nuclei and scanty stroma
  • Frequent necrosis of tumor cells away from vessels and calcification
  • Also Flexner-Wintersteiner rosettes (cells line up around empty lumen delineated by a distinct eosinophilic circle composed of terminal bars analogous to outer limiting membrane of normal retina)
  • Also Homer-Wright rosettes (nuclei are displaced away from lumen), fluerettes (tumor cells arranged side by side which show differentiation towards photoreceptors)
  • Frequent Azzopardi phenomena (basophilic deposits around blood vessels, also seen in small cell carcinoma); frequent mitotic figures; variable apoptotic cells
  • Differentiated retinoblastoma: bipolar-like cells are present
  • Undifferentiated retinoblastoma: large, anaplastic cells without rosette formation
  • Retinocytoma: marked photoreceptor differentiation; cells have abundant cytoplasm, less hyperchromatic nuclei; benign, with calcification but without necrosis or mitotic activity
Microscopic (histologic) images

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Nodules of tumor cells seed inner surface of retina

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Tumor cells involve anterior chamber, iris and angle structures

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Viable tumor cells
surround blood
vessels and
form sleeves

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Endophytic tumor
adjacent to optic
nerve head with
sleeve pattern

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Sleeve pattern and Flexner-Wintersteiner rosettes


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Flexner-Wintersteiner rosettes

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Homer-Wright rosettes

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Poorly differentiated tumor cells
with large hyperchromatic nuclei
and numerous mitotic figures

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DNA deposition (basophilic
staining) in blood vessel
walls (Azzopardi phenomenon)

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Spindle shaped glia


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Benign cytology - fleurettes consisting of small clusters of eosinophilic bulbous processes extending into lumen resembling photoreceptors

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Invasion of optic nerve head

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Invasion of optic nerve to level of lamina cribrosa

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Invasion of optic nerve
parenchyma posterior
to lamina cribrosa but
not involving the margin

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Invasion of full thickness of choroid



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Necrotic tumor


Cytology images

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Clumps and individual tumor cells

Positive stains
Negative stains
Electron microscopy description
  • Evidence of photodifferentiation
Electron microscopy images

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Bulbous process of
fleurette contains
numerous mitochondria