Retinoblastoma overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Jyostna Chouturi, M.B.B.S [2]
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Overview
Retinoblastoma is a cancer of the retina. Development of this tumor is initiated by mutations[1] that inactivate both copies of the RB1 gene, which codes for the retinoblastoma protein.[2]It is a primitive neuroepithelial neoplasm. Retinal photoreceptor cells are developed from immature neural epithelium from which retinoblastoma is thought to arise from.[3]It is also known as Retinal Neuroblastoma, Retinal Glioma and Retinal Glioblastoma.It occurs mostly in children younger than 5 years and accounts for about 3% of the cancers occurring in children younger than 15 years. Adult cases have also been clinically recorded.[4] The estimated annual incidence is approximately 4 per million children.[5]It begins with white blotches in one or both eyes (leukocoria) which can be seen in photographs (this is distinct from the red-eye effect which is normal); or when light reflects off the eye, as when watching television.The tumor may begin in one or both eyes. Retinoblastoma is usually confined to the eye but can spread to the brain via the optic nerve.As the retina is the light-sensitive part of the eye necessary for vision, loss of vision occurs.
Pathophysiology
Development of this tumor is initiated by mutations[6] that inactivate both copies of the RB1 gene, which codes for the retinoblastoma protein.[7]. The Retinoblastoma gene acts as a tumor suppressor gene. The RB1 gene is composed of 27 exons which encodes for a 110kd nuclear phosphoprotein.[8] The cDNA fragment detects atleast 70 kilobases(kb) in human chromosome band 13q14 of which a part of it or complete 70 kilobases in that band are frequently deleted in retinoblastomas and osteosarcomas.[9]
Causes
Retinoblastoma is caused by mutations[10] that inactivate both copies of the RB1 gene, which codes for the retinoblastoma protein.[11]
Differential diagnosis
Retinoblastoma must be differentiated from other diseases that cause leucokoria, strabismus, vision problems, and eye pain such as cataracts, retinopathy of prematurity etc.
Epidemiology and demographics
There is no predisposition for retinoblastoma by race or gender. Right and left eyes are affected equally. It is the most common intraocular tumor of the childhood. The incidence of retinoblastoma worldwide ranges from 1 in 14,000 live births to 1 in 34,000.[12] The mean age-adjusted incidence rate of retinoblastoma is 11.8 cases per million children aged 0-4 years in the USA and it is similar to rates reported from European countries and the age-adjusted incidence rate of retinoblastoma in the USA as well as bilateral cases (26.7%) versus unilateral cases (71.9%) remained stable from 1975-2004.[13] In a study which was done on 206 children with retinoblastoma, the mean age at diagnosis was 21.2 mo in the total study group and the mean age at diagnosis in the bilateral cases (14.6 months) was substantially less than in the unilateral ones (23.5 months) and the great majority of patients (approximately 75%) had advanced disease (group V in both Reese-Ellsworth and Essen prognosis classifications) in the affected eye (unilateral cases) or the more severely affected eye (bilateral cases).[14]
Risk factors
Development of this tumor is initiated by mutations[15] that inactivate both copies of the RB1 gene, which codes for the retinoblastoma protein.[16] While the genetics of retinoblastoma are well understood, there is much less known about the non-genetic factors in retinoblastoma.
Screening
According to American Academy of Pediatrics policy statement on Red Reflex Examinations in Neonates, Infants, and Children [17] for retinoblastoma recommends that all neonates, infants, and children should have an examination of the red reflex before discharge from the neonatal nursery and at all subsequent routine health supervision visits.
Natural history,complications and prognosis
Retinoblastoma is a rapidly growing tumor. If left untreated, the tumor fills the eye and completely destroys the globe in six months. Metastatic spread begins after six months and metastasized tumor is very rare at presentation. The tumor may spread through the subarachnoid space to the contralateral optic nerve or through the cerebrospinal fluid to the central nervous system or hematogenously to the lung, bone, or brain or by lymphatics if the tumor spreads anteriorly into the conjunctivae and eyelids, or extends into extraocular tissue. The most common routes of metastatic spread are direct infiltration via the optic nerve to the central nervous system, or spread via the choroid to the orbit. If untreated, death usually occurs in few years.
History and symptoms
Approximately 6% of the retinoblastoma is familial.[18] So family history should be inquired whenever there is suspicion of retinoblastoma.
Physical examination
Common physical examination findings of retinoblastoma include leukocoria, retinal detachment, vitreal opacification and hemorrhage, the diagnosis is difficult and challenging.
CT scan
CT scan may be helpful in the diagnosis of retinoblastoma.
MRI scan
High-resolution contrast enhanced MRI is the diagnostic technique of choice and the most sensitive technique for evaluating retinoblastoma.
Ultrasound
On ultrasound, retinoblastoma is characterized by an irregular mass, more echogenic than the vitreous body, with fine calcifications (highly reflective foci mostly with characteristic acoustic shadowing).The vitreous may have echogenic debris from hemorrhage, increased globulin content, or tumor seeding.
Other imaging studies
Bone scan may be helpful in the diagnosis of retinoblastoma metastasis to bones.
Other diagnostic finding
Bone marrow examination or lumbar puncture may also be performed in patients where there is concern regarding the extent of disease; particularly with extraocular extension to rule out cerebrospinal fluid (CSF) or bone marrow metastases.
Medical therapy
The priorities in the treatment of retinoblastoma are to preserve life, preserve globe and preserve vision, in that specific order. Minimizing side effects and complications of treatment are also of paramount importance in these very young patients.Treatment modalities that may be successful in globe salvage include systemic chemotherapy with focal consolidation, intra-arterial chemotherapy, and for small tumors, focally destructive therapy (cryopexy, laser photocoagulation, hyperthermia and plaque irradiation).[19]
Surgical therapy
Enucleation remains the definitive treatment of intraocular retinoblastoma, particularly in the majority of patients who present with unilateral disease.
References
- ↑ Knudson A (1971). "Mutation and cancer: statistical study of retinoblastoma". Proc Natl Acad Sci U S A. 68 (4): 820–3. PMID 5279gadgqetqer523 Check
|pmid=value (help). - ↑ Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D, Dryja T. "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–6. PMID 2877398.
- ↑ Smirniotopoulos JG, Bargallo N, Mafee MF (1994). "Differential diagnosis of leukokoria: radiologic-pathologic correlation". Radiographics : a Review Publication of the Radiological Society of North America, Inc. 14 (5): 1059–79, quiz 1081–2. PMID 7991814. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Takahashi T, Tamura S, Inoue M, Isayama Y, Sashikata T (1983). "Retinoblastoma in a 26-year-old adult". Ophthalmology. 90 (2): 179–83. PMID 6856254.
- ↑ CRI_2_4_1X_What_are_the_key_statistics_for_retinoblastoma_37.asp?sitearea= cancer.org
- ↑ Knudson A (1971). "Mutation and cancer: statistical study of retinoblastoma". Proc Natl Acad Sci U S A. 68 (4): 820–3. PMID 5279gadgqetqer523 Check
|pmid=value (help). - ↑ Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D, Dryja T. "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–6. PMID 2877398.
- ↑ Aerts I, Lumbroso-Le Rouic L, Gauthier-Villars M, Brisse H, Doz F, Desjardins L (2006). "Retinoblastoma". Orphanet Journal of Rare Diseases. 1: 31. doi:10.1186/1750-1172-1-31. PMC 1586012. PMID 16934146. Retrieved 2012-05-03.
- ↑ Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986). "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–6. doi:10.1038/323643a0. PMID 2877398. Retrieved 2012-05-03.
- ↑ Knudson A (1971). "Mutation and cancer: statistical study of retinoblastoma". Proc Natl Acad Sci U S A. 68 (4): 820–3. PMID 5279gadgqetqer523 Check
|pmid=value (help). - ↑ Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D, Dryja T. "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–6. PMID 2877398.
- ↑ Bishop JO, Madson EC (1975). "Retinoblastoma. Review of the current status". Survey of Ophthalmology. 19 (6): 342–66. PMID 1145423.
|access-date=requires|url=(help) - ↑ Broaddus E, Topham A, Singh AD (2009). "Incidence of retinoblastoma in the USA: 1975-2004". The British Journal of Ophthalmology. 93 (1): 21–3. doi:10.1136/bjo.2008.138750. PMID 18621794. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Augsburger JJ, Oehlschläger U, Manzitti JE (1995). "Multinational clinical and pathologic registry of retinoblastoma. Retinoblastoma International Collaborative Study report 2". Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie. 233 (8): 469–75. PMID 8537020. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Knudson A (1971). "Mutation and cancer: statistical study of retinoblastoma". Proc Natl Acad Sci U S A. 68 (4): 820–3. PMID 5279gadgqetqer523 Check
|pmid=value (help). - ↑ Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D, Dryja T. "A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma". Nature. 323 (6089): 643–6. PMID 2877398.
- ↑ http://eyewiki.org/Retinoblastoma#cite_ref-AAP_4-0
- ↑ Shields CL, Shields JA (2004). "Diagnosis and management of retinoblastoma" (PDF). Cancer Control : Journal of the Moffitt Cancer Center. 11 (5): 317–27. PMID 15377991. Retrieved 2012-05-29.
- ↑ http://eyewiki.org/Retinoblastoma#General_treatment