Retinoblastoma

Dr Jeremy Jones et al.

Retinoblastomas are the most common intraocular neoplasm found in childhood, and with modern treatment modalities are, in most cases, curable.

On imaging, they are generally characterised by a heterogeneous retinal mass with calcifications, necrotic components, and increased vascularisation on Doppler ultrasound/enhancement on CT/MRI. 

Retinoblastomas may be sporadic or secondary to a germline mutation of the retinoblastoma protein tumour suppressor gene (RB), which is usually inherited. It may be unilateral or bilateral:

  • bilateral (30-40% of cases) essentially always have a germline mutation 5-6
  • unilateral tumours (60-70% of cases) are caused by a germline mutation in approximately 15% of cases, whereas 85% are sporadic 5-6

Thus, ~55% of cases are due to a germline mutation. This mutation is inherited in an autosomal dominant fashion with ~90% penetrance (i.e., the child of a retinoblastoma survivor who has a germline mutation has a 50% chance of inheriting a mutation, and if they do so a 90% chance of developing a retinoblastoma. They thus an overall probability of 45% of having a retinoblastoma (50% x 90%).

Most cases are diagnosed within the first four years of life, with a median age of diagnosis of 18-24 months 5-6.

Children with germline mutations are also at increased risk of developing trilateral retinoblastoma (bilateral retinoblastomas and pineoblastoma) and osteosarcoma 2-3 and usually present early (median age of diagnosis 12 months) 6.

Presentation is most frequently with leukocoria or loss of red-eye reflex. Overall approximately 30-40% are bilateral and often synchronous. The bilateral occurrence is even higher in inherited forms, and tend to occur at a younger age 5-6.

Three patterns of growth are recognised 4-5:

  1. endophytic
    • growth occurs inwards into the vitreous
    • cell clusters may detach ad float in the vitreous (vitreous seeding)
  2. exophytic
    • growth occurs outwards
    • associated with non-rhegmatogeneous retinal detachment
  3. combined endophytic and exophytic

Retinoblastoma may metastasise via direct spread into the orbit, along the optic nerve into the brain, or into the subarachnoid space resulting in leptomeningeal metastases. It can also haematogenously metastasise preferentially to the bone, bone marrow and liver. Rarely it will spread to regional lymph nodes 9.

Macroscopic appearance

Macroscopic and funduscopic examination reveals a white elevated mass with fine surface vessels 4.

Histology

Histology demonstrates a small round-cell tumour of neuroepithelial origin. Flexner-Wintersteiner rosettes (relatively specific for retinoblastoma), and Homer-Wright pseudorosettes (also found in other PNETs) may be seen on microscopy.

Ultrasound

Orbital sonography can be performed without sedation and can be repeated multiple times without exposing the child to ionising radiation. Retinoblastomas appear as echogenic soft-tissue masses with variable shadowing due to calcifications and heterogeneity due to necrosis and haemorrhage 5. At diagnosis, tumours are usually vascular on Doppler examination.

The vitreous may have multiple areas of 'floating' debris, which may represent vitreous seeding or, alternatively, necrotic debris, haemorrhage or increased globulin content 5.

CT

CT demonstrates a contrast-enhancing retrolental mass that is usually calcified. A dense vitreous due to haemorrhage is also common.

MRI

MRI is the modality of choice for pre-treatment staging on retinoblastoma (see retinoblastoma staging) 4.

  • T1: intermediate signal intensity, hyperintense c.f. vitreous 4-5
  • T2: hypointense c.f. vitreous
  • T1 C+ (Gd)
    • the mass usually enhances relatively homogeneously when small
    • larger tumours often have areas of necrosis, rendering it heterogeneous
    • linear enhancement of the choroid beyond the margins of the tumour should raise the possibility of choroidal involvement, although inflammation may lead to similar appearance 4
    • enhancement of the anterior chamber need not represent tumour involvement, with hyperaemia, uveitis and iris neovascularisation all leading to asymmetric enhancement 4
    • careful assessment of the optic disc and optic nerve should be carried out to assess for involvement
    • extra-ocular extension through the sclera will be visible as an interruption of the otherwise hypointense non-enhancing sclera by enhancing tumour
  • DWI
    • the tumour shows restricted diffusion on DWI at high b values. It exhibits low ADC values in contrast to the high intensity of the vitreous in the ADC maps
    • ADC map can be used to differentiate viable and necrotic tumour 7
    • DWI is valuable in evaluating the response to eye-preservation treatment 7

Treatment depends on tumour size and the stage of disease (see retinoblastoma staging) and involves one or more modalities:

  • conservative
    • external-beam radiation therapy
    • cryotherapy
    • laser photocoagulation
    • radioactive plaque therapy
    • thermochemotherapy
    • tumour reduction chemotherapy
  • surgical
    • enucleation
    • en bloc resection

Prognosis depends on the stage. Overall the cure rate has risen to over 90% in first world nations 4.

Patients with retinoblastoma rarely (<1%) go on to develop rhabdomyosarcoma, which itself perhaps arises due to chemotherapy, radiation therapy and/or an underlying genetic susceptibility 10.

For imaging differentials consider:

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Article Information

rID: 1976
Section: Pathology
Tags: orbit, eye
Synonyms or Alternate Spellings:
  • Retinoblastoma (RB)
  • RB
  • Retinoblastomas

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Cases and Figures

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    Retinoblastoma fu...
    Figure 1: fundoscopy
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    Bilateral retinob...
    Case 1
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    Retinoblastoma - ...
    Figure 2: clinical photograph : leukocoria
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    Case 2: bilateral
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    Retinoblastoma : T2
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