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Retinoblastoma is the most common intra-ocular malignancy in children worldwide. Current treatment modalities include focal therapy such as laser or cryotherapy, intravenous chemotherapy, intra-arterial chemotherapy and surgical enucleation. According to the current retinoblastoma staging systems, there are a few common features indicating advanced disease stage, which can subsequently predict the prognosis and the necessity of surgical enucleation and adjuvant chemotherapy. This review uses annotated magnetic resonance (MR) images to illustrate these features, which include (1) retinal detachment, (2) vitreous and subretinal seeding, (3) choroidal invasion, (4) anterior segment invasion and increase in intra-ocular pressure, (5) iris neovascularization, (6) vitreous haemorrhage, (7) aseptic orbital cellulitis with lens dislocation, (8) post-laminar optic nerve invasion and (9) distant and systemic metastasis. Prompt identification of these features is important for paediatric radiologists to guide the clinical team for appropriate management.
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Introduction
Retinoblastoma is the most common intra-ocular malignancy in children worldwide, with an estimated incidence of 1 per 18,000–30,000 live births [1]. It is diagnosed by the age of 3 years in 80% of the patients and by the age of 5 years in 95% of patients [2]. Current treatment modalities include focal therapy such as laser or cryotherapy, intravenous chemotherapy, intra-arterial chemotherapy and surgical enucleation [3]. According to the current retinoblastoma staging systems including the American Joint Committee on Cancer (AJCC) Clinical Staging 8 th edition and the International Classification for Intraocular Retinoblastoma (ICRB), there are a few common features indicating advanced disease, which can predict the success rate of surgical enucleation and disease prognosis. Therefore, prompt identification of these features and accurate staging are important for oncologists, ophthalmologists and interventional radiologists to formulate the treatment plan and guide disease prognostication for parental counselling. This pictorial review aims to highlight salient MR imaging features which indicate advanced disease in patients with retinoblastoma and highlight their implications in treatment.
Retinoblastoma staging and its implication on management
According to the current retinoblastoma staging systems, including the AJCC Clinical Staging 8 th edition and the ICRB, features indicating advanced disease include retinal detachment, vitreous and subretinal seeding, choroidal invasion, anterior segment invasion and increase in intra-ocular pressure, iris neovascularization, vitreous haemorrhage, aseptic orbital cellulitis, lens dislocation and post-laminar optic nerve invasion [4, 5].
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Contemporary treatment modalities for retinoblastoma include focal therapy such as laser or cryotherapy, intravenous chemotherapy, intra-arterial chemotherapy and surgical enucleation. However, focal therapy is proven to be effective only in early stages, in particular ICRB group A and B diseases [3]. Surgical enucleation and systemic chemotherapy (neoadjuvant or adjuvant) are recommended for advanced disease to improve overall survival and reduce recurrence (Table 1) [3]. However, surgical enucleation results in permanent loss of vision in one eye and can negatively impact the patient’s quality of life. Therefore, accurate staging, in particular prompt recognition of imaging features indicative of advanced disease, is essential to avoid overtreatment or undesirable delay of life-saving surgery and adjuvant therapy.
Table 1
The American Joint Committee on Cancer Clinical Staging 8th edition and the International Classification for Intraocular Retinoblastoma with the corresponding recommended treatment options
American Joint Committee on Cancer Clinical staging 8th edition, 2017 [4]
International Classification for Intraocular Retinoblastoma group (Shields, 2006) [5]
Recommended treatment
cT1 Intra-retinal tumour(s) with subretinal fluid ≤ 5 mm from base of any tumour
cT1a Tumours ≤ 3 mm and further than 1.5 mm from disc and fovea
A, > 3 mm to fovea or B, 1.5 to 3 mm
For ICRB group A or B:
• Laser coagulation
• Thermotherapy
• Cryotherapy
• Brachytherapy
cT1b Tumours > 3 mm or closer than 1.5 mm from disc or fovea
B, ≤ 3 mm or C, 3 to 5 mm
cT2 Intraocular tumour(s) with retinal detachment, vitreous seeding, or subretinal seeding
cT2a Subretinal fluid > 5 mm from the base of any tumour
C, or E, tumour > 50% of eye volume
For ICRB group C:
• Systemic chemotherapy
• Intra-arterial chemotherapy
• Intra-vitreal chemotherapy
cT2b Vitreous seeding and/or subretinal seeding
C, ≤ 3 mm or D, > 3 mm or E, tumour > 50% of eye volume
cT3 Advanced intraocular tumour(s)
cT3a Phthisis or pre-phthisis bulbi
E
For ICRB group D or E:
• Systemic chemotherapy
• Intra-arterial chemotherapy
• Intra-vitreal chemotherapy
• Surgical enucleation
• Adjuvant systemic chemotherapy in selected high-risk cases
cT3b Tumour invasion of choroid, pars plana, ciliary body, lens, zonules, iris, or anterior chamber
E
cT3c Raised intraocular pressure with neovascularization and/or buphthalmos
E
cT3 d Hyphaema and/or massive vitreous haemorrhage
E
cT3e Aseptic orbital cellulitis
E
cT4 Extraocular tumour(s) involving orbit, including optic nerve
cT4a Radiologic evidence of retrobulbar optic nerve involvement or thickening of optic nerve or involvement of orbital tissues
cT4b Extraocular tumour clinically evident with proptosis and/or an orbital mass
Magnetic resonance imaging for retinoblastoma staging
MR is an important imaging modality in the assessment of status of retinoblastoma, and obtaining high-quality MR images is essential in accurate disease staging. The guideline from the European Retinoblastoma Imaging Collaboration (ERIC) outlines the minimum standard for MR imaging in retinoblastoma to ensure adequate sensitivity to delineate features necessary for addressing the clinical questions [6]. In our institution, we use a 3-T MRI MAGNETOM Vida scanner (Siemens Healthineers, Erlangen, Germany) to image patients with retinoblastoma. A summary of our institutional protocol (Table 2) is attached as reference.
Table 2
Institutional magnetic resonance imaging protocol for brain and orbital imaging in patients with suspected retinoblastoma
Sequence
Plane
Fat saturation
Section thickness
Repetition time (ms)
Time to echo (ms)
Matrix
Pixel size (mm)
Main use
Orbit
3-D T2 weighted
Axial
No
0.3 mm
1400
156
512 × 512
0.3 × 0.3
For evaluation of vitreous, subretinal seeding and anterior segment invasion
T2 weighted
Oblique sagittal
Yes
2 mm
3,000
75
608 × 608
0.2 × 0.2
For evaluation of vitreous, subretinal seeding and anterior segment invasion
T1 weighted
Axial
Yes
2 mm
539
11
608 × 608
0.2 × 0.2
For evaluation of vitreous haemorrhage and retinal detachment
T1 weighted
Oblique sagittal
No
2 mm
600
7.3
544 × 544
0.3 × 0.3
For evaluation of vitreous haemorrhage and retinal detachment
3-D contrast-enhanced T1 weighted
Sagittal
Yes
0.3 mm
550
14
385 × 385
0.3 × 0.3
For evaluation of choroidal invasion, iris neovascularization, aseptic cellulitis and post-laminar optic nerve invasion
Contrast-enhanced T1 weighted
Oblique sagittal
Yes
2 mm
558
7.3
544 × 544
0.3 × 0.3
For evaluation of choroidal invasion, iris neovascularization, aseptic cellulitis and post-laminar optic nerve invasion
Brain
T2 weighted
Sagittal (pineal)
No
2 mm
3,000
86
384 × 384
0.2 × 0.2
For identification of any synchronous suprasellar and pineal tumour
Diffusion-weighted imaging
Axial
NA
5 mm
3,000
65.2
400 × 400
0.5 × 0.5
For better tumour characterization
3-D fluid attenuated inversion recovery
Sagittal
Yes
0.3 mm
5,000
311
320 × 320
0.3 × 0.3
For screening of any intracranial abnormality
Susceptibility-weighted imaging
Axial
NA
2 mm
30
20
288 × 252
0.7 × 0.7
For better assessment of any intralesional calcifications
D dimensional, NA not applicable
Case selection
MR brain and orbits performed at a territory-wide paediatric ocular tumour referral centre, from 2019 to 2024, were reviewed retrospectively. MR studies of patients with newly diagnosed retinoblastoma were analysed by two paediatric radiologists, who has 13-year and 5-year experience respectively. Salient imaging features indicating advanced disease were selected for this pictorial review.
Retinal detachment
Retinal detachment is a common finding in patients with retinoblastoma. It corresponds to stage cT2 in AJCC staging [4] and group D tumour in ICRB grouping [5]. Up to 80% of retinal detachments resolve after chemotherapy, and the 5-year survival rate of these patients can be up to 96–98% [7]. On MR images, retinal detachment is characterized by T2-weighted hypointense line which is limited anteriorly by the ora serrata, and converges posteriorly on the optic disc (Fig. 1).
Fig. 1
Retinal detachment caused by left eye retinoblastoma in a 23-month-old boy with bilateral retinoblastomas. Axial unenhanced T1-weighted magnetic resonance image shows a hypointense retinoblastoma in the left eye, with adjacent V-shaped hyperintense subretinal tissue converging to the optic disc (arrows), which is characteristic of retinal detachment
Vitreous and subretinal seeding is a common finding in retinoblastoma. It corresponds to group C-D tumour in ICRB grouping [5]. On MR images, the seedings are seen as small foci of T2 hypointense signal, which are of similar signal intensity as the primary tumour, in a background of T2 hyperintense vitreous or along the retina (Fig. 2). It is important to note that the gold standard of detection of seeding is fundus photography [8]. Due to the small size of vitreous or subretinal seed, MR cannot reliably exclude its absence.
Fig. 2
Subretinal seeding in the right globe of a 2-month-old girl with bilateral retinoblastomas. Axial T2-weighted (a) and axial contrast-enhanced T1-weighted (b) magnetic resonance images show a T2 hypointense focus (arrow in a) with contrast enhancement (curved arrow in b) on the nasal aspect of the right retina, indicative of subretinal seeding
The choroid is a highly vascularized layer of tissue situated underneath the retina and supports the metabolism of photoreceptors [9]. Choroidal invasion corresponds to stage cT3b in AJCC staging and predisposes the patient to distant metastasis [4]. Traditionally, enucleation of the globe is recommended for retinoblastoma patient with choroidal invasion. Recently, increasing number of case reports demonstrated the utility of systemic and intra-arterial chemotherapy in controlling such pattern of tumour growth and thereby improving the rate of globe salvage [10]. Massive choroidal invasion (MCI), which is defined as more than 3 mm at its largest diameter on histopathological assessment of the post-enucleated globe, indicates high-risk disease and is associated with increase in all-cause mortality. The detection of MCI warrants the use of adjuvant chemotherapy to reduce the risk of metastasis.
On MR images, the choroid is a thin avidly enhancing layer located just deep to the non-enhancing sclera. Therefore, any interruption of the normal smooth linear enhancement along of the choroid is indicative of choroidal invasion (Fig. 3).
Fig. 3
Choroidal invasion by left eye retinoblastoma in a 40-day-old girl. Axial contrast-enhanced T1-weighted magnetic resonance image shows a focal defect in enhancement at the posterior aspect (arrow) of the choroid layer of the left globe. Of note, there was also aseptic cellulitis involving the left orbit, which is another imaging feature indicative of high-grade retinoblastoma
Anterior segment invasion and increase in intra-ocular pressure
The anterior segment refers to the anterior one-third of the globe, and its involvement by retinoblastoma is a high-risk feature for distant metastasis. Anterior segment invasion corresponds to stage cT3c in AJCC staging [4] and group E in ICRB grouping [5]. Tumour invasion of the anterior segment can cause volume reduction of the anterior chamber. Together with the associated inflammatory changes secondary to anterior chamber involvement, the intra-ocular pressure can be elevated simultaneously [11].
On MR imaging, anterior segment invasion is shown by loss of normal plane between the tumour and the anterior chamber structure, in particular the lens and the ciliary body. Increase in intra-ocular pressure must be suspected when there is increase in size of the globe or reduction in depth of the anterior chamber (Fig. 4).
Fig. 4
Anterior chamber invasion by retinoblastoma of the right eye in a 19-month-old boy. Axial T2-weighted magnetic resonance image shows a large tumour at the posterior aspect of the right globe which was inseparable from the ciliary body and lens of the right eye (arrow). The anterior chamber depth of the right eye is reduced, raising suspicion of elevated intra-ocular pressure
Neovascularization of the iris is another high-risk feature of retinoblastoma. It corresponds to stage cT3c [4] in AJCC staging and group E in ICRB grouping [5]. It is hypothesized that the iridal vascularity increases due to the reduction of the orbital glymphatic drainage secondary to the mass effect of retinoblastoma, resulting in the release of a myriad of vascular endothelial growth factors. The permeable new vessels along the iris promote contrast leakage and manifest as anterior chamber enhancement on MR imaging [12] (Fig. 5).
Fig. 5
Iris neovascularization associated with left eye retinoblastoma in a 13-month-old boy. Axial contrast-enhanced T1-weighted magnetic resonance images demonstrate increase in enhancement of the left eye anterior chamber when comparing with that in the normal right eye (arrows)
Vitreous haemorrhage is a high-risk feature of retinoblastoma for distant metastasis. It corresponds to stage cT3 d [4] in AJCC staging and group E in ICRB grouping [5]. On MR images, it is evidenced by diffuse T1 hyperintense signal, which does not show signal drop in fat saturated sequence, and T2 hypointense signal in the vitreous humor [2] (Fig. 6).
Fig. 6
Vitreous haemorrhage associated with left eye retinoblastoma in a 13-month-old-boy. Axial unenhanced T1-weighted magnetic resonance image shows diffuse increase in T1-weighted hyperintense signal in the vitreous humor (curved arrow), particularly at its dependent region (arrow)
Retinoblastoma can promote inflammatory changes in the globe leading to aseptic orbital cellulitis [13]. This is a high-risk imaging feature, corresponding to stage cT3e in AJCC staging [4] and group E in ICRB grouping [5]. On MR imaging, aseptic orbital cellulitis is characterized by periocular T2-weighted hyperintense signal with contrast enhancement (Fig. 7). Often, lens subluxation is seen at the same time secondary to ciliary body necrosis (Fig. 8).
Fig. 7
Aseptic orbital cellulitis associated with left eye retinoblastoma in a 13-month-old-boy. Oblique sagittal contrast-enhanced T1-weighted magnetic resonance image shows an increase in enhancement of the periorbital soft tissue (arrow), with extension posterior to the orbital septum
Lens dislocation due to aseptic orbital cellulitis in the same 13-month-old boy with left eye retinoblastoma. Axial T2-weighted magnetic resonance image shows posterior subluxation of the lens (arrows) adjacent to the T2-weighted hypointense tumour
Optic nerve invasion is frequently seen in patients with retinoblastoma, and the involvement of the segment of optic nerve posterior to lamina cribrosa is a high-risk feature associated with increased risk of orbital recurrence after enucleation and a high mortality rate, up to 89% [14]. It corresponds to stage cT4a in AJCC staging [4]. Its presence is a contraindication to intra-arterial chemotherapy [15], and the involved segment of optic nerve should be resected together with the enucleated globe to achieve disease-free margin [16].
The caliber of the involved optic nerve can be normal on MR imaging. The radiologist should carefully search for any abnormal enhancement or signal in the post-laminar segment as evidence of optic nerve involvement (Fig. 9).
Fig. 9
Post-laminar optic nerve invaded by right eye retinoblastoma in a 14-month-old-boy. Oblique sagittal contrast-enhanced T1-weighted (a) and axial T2-weighted (b) magnetic resonance images show subtle fan-shaped enhancement (arrow in a) and T2 hyperintense signal (curved arrow in b) along the post-laminar segment of right optic nerve
Systemic metastases can occur in patients with retinoblastoma, commonly involving the lungs, liver and bone (Fig. 10). Patients with post-laminar optic nerve invasion or choroidal invasion contain higher risk for systemic metastases [2]. Whole-body imaging, including MR, bone scintigraphy or positron emission tomography/computed tomography (PET/CT), may be useful for detection of metastatic lesions in patients with such suspicion. MR imaging is particularly helpful for delineation of the locoregional extent of the metastatic lesion if local treatment is contemplated.
Fig. 10
Images of the right knee in a 10-year-old boy, who had surgical enucleation performed for bilateral retinoblastoma when he was 2 years old, and found retinoblastoma metastasis involving the right proximal tibia. a Anteroposterior radiograph shows an ill-defined sclerotic lesion at the medial metaphyseal region of the proximal right tibia (arrow). b Coronal T2-weighted magnetic resonance image shows an aggressive lesion at the metaphyseal region of proximal tibia with epiphyseal extension and cortical destruction (arrow). Image-guided biopsy was subsequently performed and confirmed retinoblastoma metastasis
According to the current staging systems, advanced retinoblastomas require surgical enucleation and systemic chemotherapy. With careful acquisition and analysis of MR images, paediatric radiologists play a crucial role in identification of MR features indicative of high-risk disease and provide important information to the clinical team to optimize patient management.
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We the authors declare that Ethics Committee approval has been obtained.
Conflicts of interest
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Fabian ID, Sagoo MS (2018) Understanding retinoblastoma: epidemiology and genetics. Community Eye Health 31:7PubMedCentral
2.
Rauschecker AM, Patel CV, Yeom KW et al (2012) High-resolution MR imaging of the orbit in patients with retinoblastoma. Radiographics 32:1307–1326CrossRef
3.
Ancona-Lezama D, Dalvin LA, Shields CL (2020) Modern treatment of retinoblastoma: a 2020 review. Indian J Ophthalmol 68:2356–2365CrossRefPubMedCentral
4.
(2018) TNM8: the updated TNM classification for retinoblastoma. Community Eye Health 31:34
5.
Fabian ID, Reddy A, Sagoo MS (2018) Classification and staging of retinoblastoma. Community Eye Health 31:11–13PubMedCentral
6.
de Graaf P, Göricke S, Rodjan F et al (2012) European Retinoblastoma Imaging Collaboration (ERIC). Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol 42:2–14. https://doi.org/10.1007/s00247-011-2201-5
7.
Tomar AS, Finger PT, Gallie B et al (2022) Metastatic death based on presenting features and treatment for advanced intraocular retinoblastoma: a multicenter registry-based study. Ophthalmology 129:933–945
8.
Khurana A, Eisenhut CA, Wan W et al (2013) Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the staging of retinoblastoma. Eur Radiol 23:1271–1280CrossRef
9.
de Graaf P, Barkhof F, Moll AC et al (2005) Retinoblastoma: MR imaging parameters in detection of tumor extent. Radiology 235:197–207CrossRef
10.
Schaiquevich P, Francis JH, Cancela MB et al (2022) Treatment of retinoblastoma: what is the latest and what is the future. Front Oncol 12:822330CrossRefPubMedCentral
11.
de Leon JM, Walton DS, Latina MA, Mercado GV (2005) Glaucoma in retinoblastoma. Semin Ophthalmol 20:217–222CrossRef
12.
Deike-Hofmann K, von Lampe P, Eerikaeinen M et al (2022) Anterior chamber enhancement predicts optic nerve infiltration in retinoblastoma. Eur Radiol 32:7354–7364CrossRefPubMedCentral
13.
Mehta A, Singh M, Banerjee N et al (2021) Aseptic orbital cellulitis: a master masquerade of intraocular malignancy. Eur J Ophthalmol 31:NP1-NP4
14.
Berry JL, Zolfaghari E, Chen A et al (2017) Optic nerve obscuration in retinoblastoma: a risk factor for optic nerve invasion? Ocul Oncol Pathol 3:283–291CrossRefPubMedCentral
15.
Manjandavida FP, Stathopoulos C, Zhang J et al (2019) Intra-arterial chemotherapy in retinoblastoma - a paradigm change. Indian J Ophthalmol 67:740–754. Erratum. In: Indian J Ophthalmol 67:1385
16.
Cho SJ, Kim JH, Baik SH et al (2021) Diagnostic performance of MRI of post-laminar optic nerve invasion detection in retinoblastoma: a systematic review and meta-analysis. Neuroradiology 63:499–509CrossRef
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