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]

Differential diagnosis

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 adopted from Clinical Ophthalmic Oncology book

Differential diagnosis of leukocoria

Disease/Condition	Clinical presentation	Demographics/History	Diagnosis	Other notes
Retinoblastoma	Retinal mass Physical exam(P/E) 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 US 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 commonly accompanied with microphthalmia presence of retrolental fibrovascular +/- secondary cataract	Sporadic in the majority of cases Always congenital (present at birth) Rarely bilateral	P/E:microphthalmia and intraocular 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 with protein 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 and 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 in 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) Oxygen supplementation Leukocoria is the late presentation of the disease Always bilateral	P/E:Bilateral retinal avascularity and nonperfusion 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 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 subtypes: 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 May happen sporadicaaly Findings involve both eyes asymmetrically	P/E:avascularity of the temporal retina with peripheral fibrovascular proliferation Fluorescein angiography:the peripheral nonperfusion 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, resulting 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 with 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