Retinoblastoma overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]
|
Retinoblastoma Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Retinoblastoma overview On the Web |
|
American Roentgen Ray Society Images of Retinoblastoma overview |
|
Risk calculators and risk factors for Retinoblastoma overview |
Overview
Retinoblastoma is the most common malignant intraocular tumor in children.[1] Retinoblastoma exists in sporadic and germline forms.[2][3][4] Retinoblastoma may be classified into several subgroups based on the International Retinoblastoma Staging System (IRSS).[5][6][7] On gross pathology, viable tumor cells near blood vessels and zones of necrosis in avascular areas are characteristic findings of retinoblastoma. On microscopic histopathological analysis, small round-cell tumor of neuroepithelial origin, Flexner-Wintersteiner rosettes, and Homer-Wright rosettes are characteristic findings of retinoblastoma. Retinoblastoma can be bilateral or unilateral, spontaneous or familial. In 30% to 40% of cases, retinoblastoma is accompanied by a germinal mutation in the RB1 gene.[8][9] The incidence of retinoblastoma in United States is approximately .43 cases per 100,000 children under 15 years of age.[10] The median age at diagnosis of retinoblastoma is 18 months. An average age at diagnosis of retinoblastoma for children with bilateral and unilateral disease is 12 months and 24 months respectively.[11] Retinoblastoma affects males and females equally.[4] There is no racial predilection to the development of retinoblastoma.[4] Common risk factors in the development of retinoblastoma are advanced paternal age, positive family history, and viral exposure.[12][13][14] The hallmark of retinoblastoma is leukocoria which is an abnormal appearance of the retina as viewed through the pupil, also known as amaurotic cat's eye reflex.[15][16] A positive family history of retinoblastoma may be present. Less common symptoms of retinoblastoma include deterioration of vision, a red and irritated eye, eye pain, squint, proptosis, and fever.[9] Common physical examination findings of retinoblastoma include leukocoria, strabismus, proptosis, anisocoria, orbital cellulitis, hyphema, heterochromia iridis, poor vision, unilateral mydriasis, rubeosis iridis, vitreous hemorrhage, and fundocopic examination with findings of chalky white-gray retinal mass. The optimal therapy for retinoblastoma depends on several factors such as tumor size, tumor location, presence or absence of vitreous or subretinal seeds, and patient age. The various treatment modalities for retinoblastoma include, enucleation, external beam radiation therapy, radioactive plaques (I-125 brachytherapy), cryotherapy, laser photocoagulation, thermotherapy, and chemotherapy (which includes systemic, intra-arterial, and intravitreal).[9] When the retinoblastoma is too large to be treated by other treatment modalities, surgery may be used. In these situations, enucleation may help to prevent metastasis.
Historic Perspective
Retinoblastoma was first described in 1809 by James Wardrop.[17]
Classification
Retinoblastoma may be classified into several subgroups based on the International Retinoblastoma Staging System (IRSS).[5][6][7]
Pathophysiology
On gross pathology, viable tumor cells near blood vessels and zones of necrosis in avascular areas are characteristic findings of retinoblastoma. On microscopic histopathological analysis, small round-cell tumor of neuroepithelial origin, Flexner-Wintersteiner rosettes and Homer-Wright rosettes are characteristic findings of retinoblastoma. Retinoblastoma can be bilateral or unilateral, spontaneous or familial. In 30% to 40% of cases retinoblastoma is accompanied by a germinal mutation in the RB1 gene.[8]
Causes
Retinoblastoma is caused by a mutation in the RB1 gene.[9]
Differential Diagnosis
Retinoblastoma must be differentiated from other diseases that cause leukocoria, such as congenital cataract, persistent fetal vasculature, Coats disease, cloboma of choroid or optic disc, toxocariasis, astrocytic hamartoma, retinopathy of prematurity, vitreous hemorrhage, uveitis, retinal dysplasia, and medulloepithelioma.[9]
Epidemiology and Demographics
The incidence of retinoblastoma in United States is approximately .43 cases per 1000,000 children under 15 years of age.[10] The median age at diagnosis of retinoblastoma is 18 months. An average age at diagnosis of retinoblastoma for children with unilateral disease and bilateral disease is 24 months and 12 months respectively.[11] Retinoblastoma affects males and females equally.[4] There is no racial predilection to the development of retinoblastoma.[4]
Risk factors
Common risk factors in the development of retinoblastoma are advanced paternal age, positive family history, and viral exposure.[12][13][14]
Screening
According to the United States Preventive Services Task Force, screening for retinoblastoma is not recommended in the general population. However, children with an increased risk of retinoblastoma such as those with a known 13q deletion or family history should be evaluated by an ophthalmologist shortly after birth. Dilated fundus examinations are recommended in siblings and siblings of patients with retinoblastoma.[18]
Natural history,Complications and Prognosis
If left untreated, retinoblastoma may progress to develop seeding in the eye, leading to retinal detachment, necrosis and invasion of the orbit, optic nerve invasion, and central nervous system invasion. The majority of untreated patients die of intracranial extension and disseminated disease within one year. Spontaneous regression of the tumor is a rare occurrence but may occur in a small number of cases.[19][20][21] Common complications of retinoblastoma include metastasis, tumor recurrence, trilateral retinoblastoma, and subsequent neoplasms. Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95%, in the United States.[22]
History and Symptoms
The hallmark of retinoblastoma is leukocoria which is an abnormal appearance of the retina as viewed through the pupil, also known as amaurotic cat's eye reflex.[15][16] A positive family history of retinoblastoma may be present. Less common symptoms of retinoblastoma include deterioration of vision, a red and irritated eye, eye pain, squint, proptosis, and fever.[9]
Physical Examination
Common physical examination findings of retinoblastoma include leukocoria, strabismus, proptosis, anisocoria, orbital cellulitis, hyphema, heterochromia iridis, poor vision, unilateral mydriasis, rubeosis iridis, vitreous hemorrhage, and fundoscopic examination with findings of chalky white-gray retinal mass.
Laboratory Tests
There are no diagnostic lab findings associated with retinoblastoma.
Chest X Ray
There are no chest x ray findings associated with retinoblastoma.
CT scan
Head and neck CT scan may be diagnostic of retinoblastoma. Findings on CT scan suggestive of retinoblastoma include retrolental mass that is usually calcified and a dense vitreous due to haemorrhage.[23]
MRI scan
On head and neck MRI, retinoblastoma is characterized by isointense to hypointense mass on T1-weighted MRI and hyperintense mass on T2-weighted MRI.[23]
Ultrasound
On ultrasound, retinoblastoma is characterized by echogenic soft-tissue masses with variable shadowing due to calcifications and heterogeneity due to necrosis and/or hemorrhage.[23]
Other Imaging Studies
Other imaging studies for retinoblastoma include wide-field fundus photography and spectral domain optical coherence tomography.
Other Diagnostic Studies
Other diagnostic studies for retinoblastoma include fluorescein angiography, bone marrow aspiration, lumbar puncture, bone scan and genetic testing.
Medical therapy
The optimal therapy for retinoblastoma depends on several factors such as tumor size, tumor location, presence or absence of vitreous or subretinal seeds, and patient age. The various treatment modalities for retinoblastoma include, enucleation, external beam radiation therapy, radioactive plaques (I-125 brachytherapy), cryotherapy, laser photocoagulation, thermotherapy, and chemotherapy (which includes systemic, intra-arterial, and intravitreal).[9]
Surgical therapy
The feasibility of surgery depends on the tumor size, tumor location, and presence or absence of vitreous or subretinal seeds at diagnosis. When the retinoblastoma is too large to be treated by other treatment modalities, surgery may be used. In these situations, enucleation may help to prevent metastasis.
Primary Prevention
There are no primary preventive measures available for retinoblastoma.
Secondary Prevention
Secondary prevention strategies following retinoblastoma include cessation of smoking, reduction in sun exposure, and reduction in exposure to ionizing radiation.
References
- ↑ Villegas VM, Hess DJ, Wildner A, Gold AS, Murray TG (2013). "Retinoblastoma". Curr Opin Ophthalmol. 24 (6): 581–8. doi:10.1097/ICU.0000000000000002. PMID 24100372.
- ↑ Dryja TP, Morrow JF, Rapaport JM (1997). "Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene". Hum Genet. 100 (3–4): 446–9. PMID 9272170.
- ↑ Dryja TP, Mukai S, Petersen R, Rapaport JM, Walton D, Yandell DW (1989). "Parental origin of mutations of the retinoblastoma gene". Nature. 339 (6225): 556–8. doi:10.1038/339556a0. PMID 2733786.
- ↑ 4.0 4.1 4.2 4.3 4.4 Broaddus E, Topham A, Singh AD (2009). "Incidence of retinoblastoma in the USA: 1975-2004". Br J Ophthalmol. 93 (1): 21–3. doi:10.1136/bjo.2008.138750. PMID 18621794.
- ↑ 5.0 5.1 Pratt CB, Fontanesi J, Lu X, Parham DM, Elfervig J, Meyer D (1997). "Proposal for a New Staging Scheme for Intraocular and Extraocular Retinoblastoma Based on an Analysis of 103 Globes". Oncologist. 2 (1): 1–5. PMID 10388023.
- ↑ 6.0 6.1 Shields CL, Mashayekhi A, Demirci H, Meadows AT, Shields JA (2004). "Practical approach to management of retinoblastoma". Arch Ophthalmol. 122 (5): 729–35. doi:10.1001/archopht.122.5.729. PMID 15136321.
- ↑ 7.0 7.1 Linn Murphree A (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.
- ↑ 8.0 8.1 Schefler AC, Abramson DH (2008). "Retinoblastoma: what is new in 2007-2008". Curr Opin Ophthalmol. 19 (6): 526–34. doi:10.1097/ICU.0b013e328312975b. PMID 18854698.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Retinoblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Retinoblastoma Accessed on October 10 2015
- ↑ 10.0 10.1 Retinoblastoma. SEER(2015) http://seer.cancer.gov/csr/1975_2012/results_merged/sect_29_childhood_cancer_iccc.pdf#search=retinoblastoma Accessed on October 2, 2015
- ↑ 11.0 11.1 Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW (1998). "Presenting signs of retinoblastoma". J Pediatr. 132 (3 Pt 1): 505–8. PMID 9544909.
- ↑ 12.0 12.1 Richter, Suzanne; Vandezande, Kirk; Chen, Ning; Zhang, Katherine; Sutherland, Joanne; Anderson, Julie; Han, Liping; Panton, Rachel; Branco, Patricia; Gallie, Brenda (2003). "Sensitive and Efficient Detection of RB1 Gene Mutations Enhances Care for Families with Retinoblastoma". The American Journal of Human Genetics. 72 (2): 253–269. doi:10.1086/345651. ISSN 0002-9297.
- ↑ 13.0 13.1 Orjuela M, Castaneda VP, Ridaura C, Lecona E, Leal C, Abramson DH; et al. (2000). "Presence of human papilloma virus in tumor tissue from children with retinoblastoma: an alternative mechanism for tumor development". Clin Cancer Res. 6 (10): 4010–6. PMID 11051250.
- ↑ 14.0 14.1 Dryja, Thaddeus P.; Mukai, Shizuo; Petersen, Robert; Rapaport, Joyce M.; Walton, David; Yandell, David W. (1989). "Parental origin of mutations of the retinoblastoma gene". Nature. 339 (6225): 556–558. doi:10.1038/339556a0. ISSN 0028-0836.
- ↑ 15.0 15.1 Abramson DH, Beaverson K, Sangani P, Vora RA, Lee TC, Hochberg HM; et al. (2003). "Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular survival". Pediatrics. 112 (6 Pt 1): 1248–55. PMID 14654593.
- ↑ 16.0 16.1 Abramson DH, Ellsworth RM, Grumbach N, Sturgis-Buckhout L, Haik BG (1986). "Retinoblastoma: correlation between age at diagnosis and survival". J Pediatr Ophthalmol Strabismus. 23 (4): 174–7. PMID 3746592.
- ↑ Albert DM (1987). "Historic review of retinoblastoma". Ophthalmology. 94 (6): 654–62. PMID 3306547.
- ↑ Rothschild, P-R; Lévy, D; Savignoni, A; Lumbroso-Le Rouic, L; Aerts, I; Gauthier-Villars, M; Esteve, M; Bours, D; Desjardins, L; Doz, F; Lévy-Gabriel, C (2011). "Familial retinoblastoma: fundus screening schedule impact and guideline proposal. A retrospective study". Eye. 25 (12): 1555–1561. doi:10.1038/eye.2011.198. ISSN 0950-222X.
- ↑ Sanborn GE, Augsburger JJ, Shields JA (1982). "Spontaneous regression of bilateral retinoblastoma". Br J Ophthalmol. 66 (11): 685–90. PMC 1039901. PMID 7126513.
- ↑ Kao LY, Yang ML (2005). "Spontaneous regression of retinoblastoma in a Taiwan series". J Pediatr Ophthalmol Strabismus. 42 (4): 228–32. PMID 16121553.
- ↑ Khodadoust AA, Roozitalab HM, Smith RE, Green WR (1977). "Spontaneous regression of retinoblastoma". Surv Ophthalmol. 21 (6): 467–78. PMID 898013.
- ↑ Lin P, O'Brien JM (2009). "Frontiers in the management of retinoblastoma". Am J Ophthalmol. 148 (2): 192–8. doi:10.1016/j.ajo.2009.04.004. PMID 19477707.
- ↑ 23.0 23.1 23.2 Retinoblastoma. Radiopedia(2015) http://radiopaedia.org/articles/retinoblastoma Accessed on October 10, 2015