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Retinoblastoma

Retinoblastomas

Retinoblastoma is a hereditary or sporadic malignant tumor of the retina that occurs predominantly in children under 5 years of age. It is the most common intraocular tumor of childhood. The most common signs and symptoms are leukokoria and strabismus and sometimes, red eye, glaucoma and orbital cellulitis.


Presentation

The following signs and symptoms present in patients with retinoblastoma:

  • Eye redness or injection: This is due to the irritation of the sclera when the tumor encroaches from within the vitreous humor to affect the outer eye.
  • Eye swelling: The eye orbit may enlarge or swell due to an enlarging tumorous growth. The eyes lymphatic and venous drainage may be blocked by tumor seeding in exophytic cancer growth in the retina.
  • Eyes gazing at the wrong direction: Tumor seeding of the ciliary nerves may affect the orbital musculature causing strabismus in some cases.
  • Leukocoria: White opacities reflected on the pupils during pupillary reflex testing. This reflects the white opacity formed during retinal encroachment of the retinoblastoma.
Subcutaneous Mass
  • Five patients presented with solitary and one with multiple subcutaneous masses measuring 5 to 9cm (median, 7.5cm). Affected sites were upper arm (3), shoulder (2), neck (1), trunk (1) and chest wall (1).[ncbi.nlm.nih.gov]
Strabismus
  • The most common signs and symptoms are leukokoria and strabismus and sometimes, red eye, glaucoma and orbital cellulitis.[symptoma.com]
  • The most common presentation is leukocoria, followed by strabismus. Heritable retinoblastoma accounts for 45% of all cases, with 80% being bilateral. Treatment and prognosis of retinoblastoma is dictated by the disease stage at initial presentation.[ncbi.nlm.nih.gov]
  • J Pediatr Ophthalmol Strabismus. 2005 Jul-Aug. 42(4):228-32. [Medline]. Khan AO, Al-Mesfer S. Lack of efficacy of dilated screening for retinoblastoma. J Pediatr Ophthalmol Strabismus. 2005 Jul-Aug. 42(4):205-10; quiz 233-4. [Medline].[emedicine.com]
Eye Pain
  • Five months postoperatively, she presented with sudden eye pain, lid swelling and proptosis. The ancillary workups were consistent with panophthalmitis and was treated as such.[ncbi.nlm.nih.gov]
  • Other symptoms can include: Crossed eyes Double vision Eyes that do not align Eye pain and redness Poor vision Differing iris colors in each eye If the cancer has spread, bone pain and other symptoms may occur.[nlm.nih.gov]
  • Other possible signs and symptoms Less common signs and symptoms of retinoblastoma include: Vision problems Eye pain Redness of the white part of the eye Bleeding in the front part of the eye Bulging of the eye A pupil that doesn’t get smaller when exposed[cancer.org]
  • “Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction; persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye.”[ibtimes.com]
  • There might be eye pain. The pupil is constantly dilated. The eye(s) might be red. Cleveland Clinic News & More Cleveland Clinic News & More[my.clevelandclinic.org]
Retinal Lesion
  • We report the case of a 23-month-old girl with bilateral retinoblastoma that demonstrated absence of retinal lesions in one eye but had an isolated white tumor in the posterior chamber.[ncbi.nlm.nih.gov]
  • Retinomas are non-progressive retinal lesions which may be benign precursors to Rb. Rarely, they remain benign and do not progress.[patient.info]
  • Toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment. 4.[en.wikipedia.org]
Visual Impairment
  • In order to learn how your child uses any remaining vision, your child’s teacher of students with visual impairments should perform a functional vision assessment .[afb.org]
  • They include parents of visually impaired children, visually impaired children themselves, Community Paediatricians, Ophthalmologists, Educationalists and Psychologists.[ssc.education.ed.ac.uk]
  • Symptoms Leukocoria, visual impairment, blindness, and enlargement of the eye orbit occur. Diagnosis Retinoblastoma is diagnosed by direct ophthalmologic eye examination and confirmed through biopsy or imaging modalities.[symptoma.com]
  • In developed countries, 97% of those who live have moderate-to-severe visual impairment, or lose one or both eyes. Extraocular retinoblastoma is very rare in developed countries (reported incidence is approximately 2-5%).[patient.info]
Rubeosis Iridis
  • Eyes with elevated intraocular pressure, rubeosis iridis, tumor in the anterior chamber, buphthalmus and evidence for optic nerve involvement need to be enucleated.[atlasgeneticsoncology.org]
  • Enucleation Enucleation has become less common with earlier diagnosis and better alternative therapies, but remains the treatment of choice for advanced cases (massive involvement of the retina/vitreous, rubeosis iridis, secondary glaucoma) with no visual[nature.com]
Neglect
  • To inform about a case of neglected retinoblastoma that was left untreated for more than 3 years by parents.[ncbi.nlm.nih.gov]

Workup

The following tests are done to confirm and assess the extent of spread of the cancer in retinoblastoma among patients:

  • Eye examination: Screening tests for retinoblastoma.
  • Head and eye echoencephalogram: May demonstrate masses between the eyes and the skull .
  • CT scan and High resolution MRI of the head: This will detect the actual size and location of the tumor as well as its metastatic locations [6].
  • Bone marrow biopsy: This will elucidate metastasis to the hematopoietic tissues of the bone.
  • Cerebrospinal fluid cytology: For aggressive and metastatic tumors.

Treatment

The treatment option available for retinoblastoma varies on the size, location and spread of the tumor. The following common treatment modalities are available for the treatment of primary and metastatic forms of Retinoblastoma:

  • Laser and Cryotherapy are ideal for small non-aggressive tumors that are detected early.
  • Radiation therapy is implored for small and large local tumors of the eye and retina.
  • Chemotherapy is used for cases with extraocular metastasis using carboplatin, vincristine and etoposide [7]. The preferred routes for chemotherapy includes intravenous route, intra-arterial, intravitreal, and periocular routes to effectively reach the carcinoma [8].
  • Surgical enucleating is the last recourse for refractory cases or may be the first recourse if tumor spread is to be avoided.
  • Combination therapy is the use of chemotherapy (vincristine, etoposide and carboplatin) followed by cryotherapy, photocoagulation, and plaque treatment with (I 125) which has been arbitrarily used for advanced cases of retinoblastoma to improve vision and to do away from the unnecessary enucleating of the eye [9].

Prognosis

Intraocular retinoblastoma which is treated early may garner a 90% survival rating. However, extraocular metastasis in retinoblastoma carries a poorer prognosis.

Patients with the inherited gene mutation have a higher likelihood to develop a second cancer in the affected eye and the irradiated region. Within a 30 year period from diagnosis, second cancers may develop in up to 70% of patients who survive. The more common second cancer observed are malignant melanoma and sarcomas.

Complications

The following clinical conditions may complicate from the primary retinoblastoma and from its post-radiation condition:

  •  Blindness: A dysfunctional orbit may be enucleated.
  •  Optic nerve neuroma
  •  Metastasis to the brain, lungs and bones
  •  Sarcoma 
  •  Malignant melanoma 
  • Unilateral retinoblastoma may complicate and affect the other eye [5]

Etiology

Retinoblastoma evolves from a gene mutation that triggers an uncontrolled cell division in the retina attributing for its carcinogenesis.

A modifier gene called MDM2 has been discovered to increase the catabolism of p53 and pRB in the chromosome 13 band [2]. In half of retinoblastoma cases, patients may have family members with the gene mutation that presents with this type of eye cancer. Parents with retinoblastoma mutation gene increase the risk of their siblings to develop the cancer many folds over.

Epidemiology

Retinoblastoma has an incidence rating of 0.5 to 1 case per 30,000 live births representing 3% of all cancers in childhood. It is commonly diagnosed among children from the age of 1 to 2 years old.

The worldwide occurrence scores at 11 cases per million children population occurring before the age of 5 years old representing 90% of all cases of retinoblastoma. In the United States, an estimated 250 to 500 new cases of retinoblastoma is diagnosed per year. Survival rating ranges from 86-92% but may subsequently drop with age. There is no predilection to either sex.

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of retinoblastoma revolves around its origin as a multi-potential precursor cell that may develop to either the inner or the outer endothelium of the retina. Theories postulates that the carcinogenesis in retinoblastoma arises from the photoreceptor cell layer of the retina [3]. In retinoblastoma, gene mutations are identified in the locus of the long arm of chromosome 13 band 13q14.

Leading theories points to either endophytic spread of tumorous growth where it invades towards the vitreous humor by seeding, or by exophytic spread involving the backside of the retina spreading through the vessels and ciliary nerves. A diffuse infiltrating spread within the retina may rarely occur where only an infiltrating whitish discoloration is observed instead of an infiltrating mass.

As of 2007, studies conducted in St. Jude’s Research Hospital, Minnesota revealed that the progenitors of the retinoblastoma tumor may arise from matured horizontal interneuron cells explaining the rare pathology that may still express during adulthood [4].

Prevention

The origin of retinoblastoma is still unclear and being currently researched; thus, actual prevention by modifiable factors in lifestyle isn’t possible yet. However, the genetic correlations found in retinoblastoma enables one to do genetic screening very early.

Massive drives of genetic screening may be performed amongst children to screen early detection of retinoblastoma and prevent the formation of the second cancer [10]. Families with high risk of gene mutation may have their children’s eyes checked very early to spot the retinoblastoma at an early stage to afford excellent cure rate and save the normal vision of the affected eye.

Summary

Retinoblastoma is a common carcinoma of the eye that originates from the immature retina lining. Retinoblastoma usually affects young children but may rarely occur in adults. It may arise singly from one eye but it can simultaneously affect both concurrently.

Patients usually present with strabismus, inflammatory pain, impaired vision and leukocoria (white reflex in the pupils). Its occurrence is generally rare but it is known as the most common eye carcinoma. Retinoblastoma may spread to contiguous structures like the optic nerve and the brain, and may later metastasize to distant parts of the body [1].

Patient Information

Definition

Retinoblastoma is the most common eye cancer in childhood. It evolves from the immature linings of the retina and may spread to contiguous structures or metastasize to distant body organs.

Cause

Retinoblastoma is a gene mutation in chromosome 13 that causes uncontrolled cell division in the retina.

Symptoms

Leukocoria, visual impairment, blindness, and enlargement of the eye orbit occur.

Diagnosis

Retinoblastoma is diagnosed by direct ophthalmologic eye examination and confirmed through biopsy or imaging modalities.

Treatment and follow up

Small and early neoplasms may be treated with laser or cryosurgery. Extensive ones are subjected to a combination of chemotherapy and radiation therapy. Surgical enucleating of the eye orbit may be done when everything else fail. Patients should lookout for signs of metastasis after the treatments and report them immediately to their family eye doctor.

References

Article

  1. Wardrop J. Observations on the fungus haematodes. Edinburgh: Constable; 1809.
  2. Castera L, Sabbagh A, Dehainault C, et al. MDM2 as a modifier gene in retinoblastoma. J Natl Cancer Inst. Dec 1 2010; 102(23):1805-8. 
  3. Tso MO, Zimmerman LE, Fine BS. The nature of retinoblastoma, I: photoreceptor differentiation: a clinical and histopathological study. Am J Ophthalmol. 1970; 69:339-49.
  4. Science Daily. St. Jude Children's Research Hospital (2007, October 21). Specific Cell That Causes Eye Cancer Identified, Disproving Long-held Theory. sciencedaily.com. 
  5. Viehmann A, Biewald E, Lohmann DR, Temming P. Sporadic unilateral retinoblastoma or first sign of bilateral disease? Br J Ophthalmol. 2013; 97(4):475-80 
  6. Rauschecker AM, Patel CV, Yeom KW, Eisenhut CA, Gawande RS et al. High-resolution MR imaging of the orbit in patients with retinoblastoma. Radiographics; 2012 Sep-Oct;32(5):1307-26
  7. Kingston JE, Hungerford JL, Madreperla SA, et al. Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol. Nov 1996; 114(11):1339-43.
  8. Fulco EM, Arias JD, Alarcon C, Pellegrini M, Rishi P, Kaliki S, Bianciotto CG, Shields JA. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye (Lond). 2013; 27(2):253-64 
  9. Shields CL, Shields JA, Needle M, et al. Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology. Dec 1997; 104(12):2101-11.
  10. Temming P, Lohmann D, Bornfeld N, Sauerwein W, Goericke SL, Eggert A. Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming for safe tumor control and vision preservation. Klin Padiatr. 2012; 224(6):339-47 (ISSN: 1439-3824)

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Last updated: 2019-07-11 22:02