Retinoblastoma differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Simrat Sarai, M.D. [3]

Overview

Retinoblastoma must be differentiated from other diseases that cause leukocoria. leukocoria may occur in several ocular conditions including tumors, vascular disease, inflammatory disorders, and also due to trauma.

Differentiating Retinoblastoma from Other Diseases

Retinoblastoma must be differentiated from other diseases that cause leukocoria. Differential diagnosis of leukocoria in children include:

Leukocoria

Tumors

Congenital malformations

Vascular diseases

Inflammatory diseases

Trauma

Retinoblastoma Medulloepithelioma Leukemia Combined retinal hamartoma Astrocytic hamartoma (Bourneville’s tuberous sclerosis)

Persistent fetal vasculature (PFV) Posterior coloboma Retinal fold Myelinated nerve fibers Morning glory syndrome Retinal dysplasia Norrie’s disease Incontinentia pigmenti Cataract

Retinopathy of prematurity (ROP) Coats’ disease Familial exudative vitreoretinopathy (FEVR)

Ocular toxocariasis Congenital toxoplasmosis Congenital cytomegalovirus retinitis Herpes simplex retinitis Other types of fetal iridochoroiditis Endophthalmitis

Intraocular foreign body Vitreous hemorrhage Retinal detachment

The above algorithm is adopted from Clinical Ophthalmic Oncology book

Retinoblastoma should be differentiated from the following conditions that cause leukocoria:

Disease/Condition	Clinical presentation	Demographics/History	Diagnosis	Other notes
Retinoblastoma	Retinal mass Gross examination reveals a whitish tumor with prominent vascularity Vitreous seeding in endophytic tumors exudative retinal detachment in exophytic tumor	Sporadic in 90% of the cases The median age of diagnosis is 18 months Bilateral in 70% of the cases	P/E: leukocoria Ultrasound imaging: A dome or placoid-shaped intraocular mass +/- intralesional calcification CT imaging: Presence of calcification within the tumor	Associated with 13q deletion syndrome
Coats'disease	Yellowish appearance of leukocoria P/E: Exudative retinal detachment with vascular tortuosity and telangiectasia +/- neurovascular glaucoma Absence of calcification	Sporadic in 100% of the cases Almost always unilateral More common among boys The median age of diagnosis 5 to 9 years	P/E is diagnostic in most of the cases Ultrasound imaging: Complete retinal detachment Absence of calcification Exudative, mobile lipid material under retina	Fluorescein angiography reveals characteristic telangiectasias of small to medium-sized retinal vessels
Persistent fetal vasculature (formerly known as persistent hyperplastic primary vitreous)	Presence of leukocoria in infancy which is commonly accompanied by microphthalmia Presence of retrolental fibrovascular tissue +/- secondary cataract	Sporadic in the majority of cases Always congenital (present at birth) Rarely bilateral	P/E: microphthalmia and increasedintraocular pressure Presence of elongated ciliary processes contracting into the retrolental mass Ultrasound imaging: Vitreous band from lens to optic nerve Short axial length of eyes	Bilateral cases has been accompanied byprotein C deficiency
Astrocytic hamartoma	Presence of gray-yellow or translucent tumors involving the posterior pole near optic nerve	Presents at any age Some has been associated with neurofibromatosis type 1/tuberous sclerosis	P/E: A sessile shape tumor arising from the inner aspect of the sensory retina Presence of small areas of calcification/complete calcification in older patients	Reticular pattern of fine blood vessels on fluorescein angiography
Retinopathy of prematurity (ROP)	Absence of calcification Presence of retinal contraction in one or both eyes	History of: Prematurity (< 32 weeks gestation) Low birth weight (< 1.5 kg/3.3 lbs) Oxygen supplementation Leukocoria is a late presentation of the disease Always bilateral	P/E: Bilateral retinal avascularity and non-perfusion in temporal peripheral retina with fibrovascular proliferation in advanced cases Ultrasound imaging: Retinal detachment with retinal bands	Short axial length of eyes
Ocular toxocariasis	Presence of retinal and/or vitreous traction in approximately all of the cases	Presents at any age Mostly unilateral Ingestion of larvae leads to the infection	P/E: Presence of granuloma and retinal traction Ultrasound imaging: Peripheral mass Vitreoretinal band Traction retinal detachment Presence of eosinophils in the anterior chamber tap	Classified into three sub-types: Macular granuloma Peripheral granuloma Endophthalmitis
Familial Exudative Vitreoretinopathy (FEVR)	Presents at birth The majority are asymptomatic May present with leukocoria, strabismus, and vision loss	Autosomal dominant pattern of inheritance May occur sporadically Findings include asymmetry of both eyes	P/E: Avascularity of the temporal retina with peripheral fibrovascular proliferation Fluorescein angiography: Peripheral non-perfusion of the fundus	Fundus findings are similar to retinopathy of prematurity except for the history of prematurity
Norrie’s Disease	Presents with microcephaly, congenital blindness, deafness, and progressive neuropsychiatric illness	X-linked disorder More common in males	P/E: bilateral retinal dysplasia, sometimes with anterior segment abnormalities and microphthalmia	-
Coloboma	Presents at birth Failure of the embryonic fissure to close completely results in an absence of normal retina and choroid	The majority are sporadic Congenital disorder that affects male and female equally May be unilateral or bilateral	P/E: Whitish depressed lesion of retina which is typically inferonasal and its margins may encompass the macula or optic nerve	It may be accompanied by CHARGE syndrome

MRI of the orbit showing Coats disease - Case courtesy of Dr Michael Sargent, https://radiopaedia.org/. From the case https://radiopaedia.org/cases/6089	MRI of the orbit showing retinal detachment - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/. From the case https://radiopaedia.org/cases/3134	MRI of the orbit showing retinoblastoma - Case courtesy of https://radiopaedia.org/. From the case https://radiopaedia.org/cases/11877	CT head showing hyperthyroid-induced orbitopathy - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/. From the case https://radiopaedia.org/cases/4854

References

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