Retinoblastoma diagnostic study of choice

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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

Ultrasound imaging is the gold standard test for the diagnosis of retinoblastoma. MRI can also be helpful in the diagnosis making. A common method of retinoblastoma classification is critical to plan treatment, evaluate prognosis and compare outcomes. Available grouping systems include the International Intraocular Retinoblastoma Classification (IIRC), Intraocular Classification of Retinoblastoma (ICRB) and cTNMH systems diseases.

Diagnostic Study of Choice

Study of Choice

Ultrasound imaging is the gold standard test for the diagnosis of retinoblastoma.
Ultrasound biomicroscopy (UBM) has been observed to have 81% sensitivity and 100% specificity in the evaluation of the anterior extension of tumor and assessment of posterior chamber involvement.^[1]
MRI is recommended for the following goals:^[2]

- Confirmation of the diagnosis
- Evaluation of local tumor extent
- Assessment of associated developmental malformation of the brain
- Detection of trilateral retinoblastoma (pinealoblastoma)

Staging

Extraocular Disease

This category is sub-classified via International Retinoblastoma Staging System which is given below:^[3]

International Retinoblastoma Staging System

Stage	Description
Stage 0	Eye enucleated and no dissemination of the disease
Stage I	Eye enucleated, completely resected histologically
Stage II	Eye enucleated, microscopic residual tumor
Stage III	Regional extension	a. Overt orbital disease b. Preauricular or cervical lymph node extension
Stage IV	Metastatic disease	a. Hematogenous metastasis (without CNS involvement) Single lesion Multiple lesions b. CNS extension (with or without any other site of regional or metastatic disease) Prechiasmatic lesion CNS mass Leptomeningeal and CSF disease

Intraocular Disease

The intraocular disease can be sub-classified by International Intraocular Retinoblastoma Classification (IIRC).^[4]

IIRC grouping system sub-classifies the tumor based on the tumor characteristics, such as:
- Size
- Location
- Presence of retinoblastoma ‘seeds’ (small colonies of cancerous cells in the vitreous)
- Retinal detachment

In 2006, Intraocular Classification of Retinoblastoma (ICRB) was developed by Dr. Shields and colleagues.^[5]
IIRC and ICRB are now the most commonly used classification systems for retinoblastoma.^[6]





American Joint Committee on Cancer (AJCC) Staging System

The table below is adopted from Community Eye Health Journal ^[7]


Primary tumour (cT)*
Stage	Sub-stage	Finding
cTX		Unknown evidence of intraocular tumor
cT0		No evidence of intraocular tumor
cT1	a	Intraocular tumor(s) with sub-retinal fluid ≤ 5mm from the base of any tumor Tumors ≤ 3mm and further than 1.5 mm from the disc and fovea
cT1	b	Intraocular tumor(s) with sub-retinal fluid ≤ 5mm from the base of any tumor Tumors > 3 mm or closer than 1.5 mm to the disc and fovea
cT2	a	Intraocular tumor(s) with retinal detachment, vitreous seeding or sub-retinal seeding Sub-retinal fluid > 5 mm from the base of any tumor
cT2	b	Intraocular tumor(s) with retinal detachment, vitreous seeding or sub-retinal seeding Tumors with vitreous seeding and/or sub-retinal seeding
cT3	a	Advanced intraocular tumor(s) Phthisis or pre-phthisis bulbi
cT3	b	Advanced intraocular tumor(s) Tumor invasion of the pars plana, ciliary body, lens, zonules, iris or anterior chamber
cT3	c	Advanced intraocular tumor(s) Raised intraocular pressure with neovascularization and/or buphthalmos
cT3	d	Advanced intraocular tumor(s) Hyphema and/or massive vitreous hemorrhage
cT3	e	Advanced intraocular tumor(s) Aseptic orbital cellulitis
cT4	a	Extraocular tumor(s) involving the orbit, including the optic nerve Radiological evidence of retrobulbar optic nerve involvement or thickening of the optic nerve or involvement of the orbital tissues
cT4	b	Extraocular tumor(s) involving the orbit, including the optic nerve Extraocular tumor clinically evident with proptosis and orbital mass
Regional lymph nodes (cN)
Stage	Sub-stage	Finding
cNX		Regional lymph nodes cannot be assessed
cN0		No regional lymph node involvement
cN1		Evidence of preauricular, submandibular, and cervical lymph node involvement
Distant metastasis
Stage	Sub-stage	Finding
cM0		No signs or symptoms of intracranial or distant metastasis
cM1	a	Distant metastasis without microscopic confirmation Tumor(s) involving any distant site (e.g. bone marrow, liver) on clinical or radiological tests
cM1	b	Distant metastasis without microscopic confirmation Tumor involving the central nervous system on radiological imaging (not including trilateral retinoblastoma)
pM1	a	Distant metastasis with microscopic confirmation Histopathological confirmation of tumor at any distant site (e.g. bone marrow, liver, or other)
pM1	b	Distant metastasis with microscopic confirmation Histopathological confirmation of tumor in the cerebrospinal fluid or CNS parenchyma
Heritable trait (H)
Stage	Sub-stage	Finding
HX		Unknown or insufficient evidence of a constitutional RB1 gene mutation
H0		Normal RB1 alleles in blood tested with demonstrated high sensitivity assays
H1		Bilateral retinoblastoma, retinoblastoma with an intracranial CNS midline embryonic tumor (i.e. trilateral retinoblastoma), patient with a family history of retinoblastoma, or molecular definition of constitutional RB1 gene mutation

References

↑ Moulin, Alexandre P; Gaillard, Marie-Claire; Balmer, Aubin; Munier, Francis L (2012). "Ultrasound biomicroscopy evaluation of anterior extension in retinoblastoma: a clinicopathological study". British Journal of Ophthalmology. 96 (3): 337–340. doi:10.1136/bjophthalmol-2011-300051. ISSN 0007-1161.
↑ Syed, Reema; Ramasubramanian, Aparna (2017). "Advances in Management of Retinoblastoma". Advances in Ophthalmology and Optometry. 2 (1): 87–100. doi:10.1016/j.yaoo.2017.03.005. ISSN 2452-1760.
↑ Chantada G, Doz F, Antoneli CB, Grundy R, Clare Stannard FF, Dunkel IJ, Grabowski E, Leal-Leal C, Rodríguez-Galindo C, Schvartzman E, Popovic MB, Kremens B, Meadows AT, Zucker JM (November 2006). "A proposal for an international retinoblastoma staging system". Pediatr Blood Cancer. 47 (6): 801–5. doi:10.1002/pbc.20606. PMID 16358310.
↑ Linn Murphree A (March 2005). "Intraocular retinoblastoma: the case for a new group classification". Ophthalmol Clin North Am. 18 (1): 41–53, viii. doi:10.1016/j.ohc.2004.11.003. PMID 15763190.
↑ Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA (December 2006). "The International Classification of Retinoblastoma predicts chemoreduction success". Ophthalmology. 113 (12): 2276–80. doi:10.1016/j.ophtha.2006.06.018. PMID 16996605.
↑ Scelfo C, Francis JH, Khetan V, Jenkins T, Marr B, Abramson DH, Shields CL, Pe'er J, Munier F, Berry J, Harbour JW, Yarovoy A, Lucena E, Murray TG, Bhagia P, Paysse E, Tuncer S, Chantada GL, Moll AC, Ushakova T, Plager DA, Ziyovuddin I, Leal CA, Materin MA, Ji XD, Cursino JW, Polania R, Kiratli H, All-Ericsson C, Kebudi R, Honavar SG, Vishnevskia-Dai V, Epelman S, Daniels AB, Ling JD, Traore F, Ramirez-Ortiz MA (2017). "An international survey of classification and treatment choices for group D retinoblastoma". Int J Ophthalmol. 10 (6): 961–967. doi:10.18240/ijo.2017.06.20. PMC 5515152. PMID 28730089.
↑ "TNM8: The updated TNM classification for retinoblastoma". Community Eye Health. 31 (101): 34. 2018. PMC 5998398. PMID 29915471.

[MoulinGaillard2012-1] Moulin, Alexandre P; Gaillard, Marie-Claire; Balmer, Aubin; Munier, Francis L (2012). "Ultrasound biomicroscopy evaluation of anterior extension in retinoblastoma: a clinicopathological study". British Journal of Ophthalmology. 96 (3): 337–340. doi:10.1136/bjophthalmol-2011-300051. ISSN 0007-1161.

[SyedRamasubramanian2017-2] Syed, Reema; Ramasubramanian, Aparna (2017). "Advances in Management of Retinoblastoma". Advances in Ophthalmology and Optometry. 2 (1): 87–100. doi:10.1016/j.yaoo.2017.03.005. ISSN 2452-1760.

[pmid16358310-3] Chantada G, Doz F, Antoneli CB, Grundy R, Clare Stannard FF, Dunkel IJ, Grabowski E, Leal-Leal C, Rodríguez-Galindo C, Schvartzman E, Popovic MB, Kremens B, Meadows AT, Zucker JM (November 2006). "A proposal for an international retinoblastoma staging system". Pediatr Blood Cancer. 47 (6): 801–5. doi:10.1002/pbc.20606. PMID 16358310.

[pmid15763190-4] Linn Murphree A (March 2005). "Intraocular retinoblastoma: the case for a new group classification". Ophthalmol Clin North Am. 18 (1): 41–53, viii. doi:10.1016/j.ohc.2004.11.003. PMID 15763190.

[pmid16996605-5] Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA (December 2006). "The International Classification of Retinoblastoma predicts chemoreduction success". Ophthalmology. 113 (12): 2276–80. doi:10.1016/j.ophtha.2006.06.018. PMID 16996605.

[pmid28730089-6] Scelfo C, Francis JH, Khetan V, Jenkins T, Marr B, Abramson DH, Shields CL, Pe'er J, Munier F, Berry J, Harbour JW, Yarovoy A, Lucena E, Murray TG, Bhagia P, Paysse E, Tuncer S, Chantada GL, Moll AC, Ushakova T, Plager DA, Ziyovuddin I, Leal CA, Materin MA, Ji XD, Cursino JW, Polania R, Kiratli H, All-Ericsson C, Kebudi R, Honavar SG, Vishnevskia-Dai V, Epelman S, Daniels AB, Ling JD, Traore F, Ramirez-Ortiz MA (2017). "An international survey of classification and treatment choices for group D retinoblastoma". Int J Ophthalmol. 10 (6): 961–967. doi:10.18240/ijo.2017.06.20. PMC 5515152. PMID 28730089.

[pmid29915471-7] "TNM8: The updated TNM classification for retinoblastoma". Community Eye Health. 31 (101): 34. 2018. PMC 5998398. PMID 29915471.

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