Retinoblastoma differential diagnosis

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

Overview

Retinoblastoma must be differentiated from other diseases that cause leukocoria such as congenital cataract, persistent fetal vasculature, Coats disease, coloboma of choroid or optic disc, toxocariasis, astrocytic hamartoma, retinopathy of prematurity, vitreous hemorrhage, uveitis, retinal dysplasia, and medulloepithelioma.

Differential diagnosis

Retinoblastoma must be differentiated from other diseases that cause leukocoria. The common causes of leukocoria in children include:

• Congenital cataract
• Persistent fetal vasculature
• Coats disease

Less common causes of leukocoria include:

• Coloboma of choroid or optic disc
• Toxocariasis
• Astrocytic hamartoma
• Retinopathy of prematurity (stage 4, 5)
• Vitreous hemorrhage
• Uveitis
• Retinal dysplasia
• Medulloepithelioma

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	Presence of 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 examination: Complete retinal detachment Absence of calcification Exudative, mobile lipid material under retina	Fluorescein angiographyr 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	Generally causes vitreoretinal traction and ocular inflammation not seen in retinoblastoma	Fundus examination reveals the characteristic signs
Hereditary retinal syndrome	Generally causes vitreoretinal traction and ocular inflammation not seen in retinoblastoma	Fundus examination reveals the characteristic signs

Differentiating features of some common and less common differential diagnosis are:

Disease/Condition	Age of presentation	Risk factors	Unilateral/bilateral	Differentiating Signs/Symptoms	Axial length	Imaging findings
Retinoblastoma	< 3 years of age in 90%	Family history	Unilateral/bilateral	Leukocoria	Normal	USG:Intraretinal/subretinal mass with calcification
Congenital Cataract	Presents at birth Lens opacification rare in retinoblastoma	Fundus examination reveals lens opacification Ultrasound shows increased echogenicity of lens
Coats disease (exudative retinitis or retinal telangiectasis)	Most cases are unilateral Mean age at presentation is 6 years More common in males	Fundus examination: lesion appears more yellow-colored (versus chalky white-gray in retinoblastoma); telangiectatic and aneurysmal retinal vessels are characteristic of Coats disease but uncommon in retinoblastoma Spectral domain optical coherence tomography may be helpful in distinguishing Coats disease from retinoblastoma Ophthalmic ultrasound: can be misleading because calcification can also be seen in Coats disease
Persistent fetal vasculature (formerly known as persistent hyperplastic primary vitreous)	Associated with a micro-ophthalmic eye (a small, malformed eye) Often associated with a cataract (rare in retinoblastoma) Congenital (retinoblastoma uncommonly presents at birth) Dragging of the ciliary processes on exam	Measurement of axial length using fundus examination and ultrasound shows short axial length in persistent fetal vasculature
Retinopathy of prematurity (ROP)	Generally occurs in premature children given high-dose oxygen Can result in total retinal detachment	Fundus examination: reveals gliotic-appearing retina, which is different from the retinal detachment associated with retinoblastoma
Ocular toxocariasis	Generally causes vitreoretinal traction and ocular inflammation not seen in retinoblastoma	Fundus examination reveals the characteristic signs

Differentiating ocular cysticercosis from other ocular lesions

Disease	Prominent clinical feature	Radiological findings
Ocular cysticercosis	Diagnosis made usually between 8-16 years (rarely in adulthood) Wide range of symptoms from being asymptomatic to decreased vision and strabismus. Decreased visual acuity at initial presentation has a poor prognosis.	Fundus examination reveals vascular lesions and exudates. Fluorescein angiography is the best method to visualize the lesions. CT and MRI are reserved for atypical cases.
Retinal detachment	Most common presenting symptoms are photophobia and floaters Visual field defects (described as curtain falling from periphery to the center)	Ophthalmoscope is not reliable in detecting retinal detachment as there might be associated hemorrhage Ultrasound can be used to identify and localize the detachment.
Hyperthyroid Ophthalmopathy	The hallmark is Eye protrusion, photophobia, lacrimation and later in the disease, diminished eye motility.	Ultrasonography: inflamed thickened extraocular muscles. CT: shows inflamed muscle and free tendon from inflammation MRI: shows periorbital fat expansion, increased water content of the muscles as a result of the inflammation.
Retinoblastoma	The most prominent sign is leukocoria, followed by strabismus The patient also may present with buphthalmos, corneal clouding and eye tearing.	Ultrasound: can detect the tumor as a result of the calcifications inside. MRI: assess sellar and parasellar regions .. it can also detect extraocular spread of the tumor.

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