Leukocoria and retinoblastoma: SAQ

This child has the classic presentation of an intraocular retinoblastoma detected by the parent and confirmed by the red reflex test and the imaging, and the task is to outline the urgent referral pathway, the risk-adapted management and the genetic counselling, contrasting the heritable bilateral disease with the trilateral retinoblastoma and the global disparity in the survival. [1][2]

Question 1 (10 marks)

Outline the initial assessment and the urgent referral pathway for this fourteen-month-old boy with the leukocoria. [1]

A full-mark answer covers the red reflex test, the urgency of the referral, the examination under anaesthesia, the imaging and the genetic testing. [2]

The red reflex test and the urgency (2 marks). The leukocoria, the white pupillary reflex, is retinoblastoma until proven otherwise, and it demands a same-day referral to the ophthalmology service. The red reflex is performed in the dim room with the direct ophthalmoscope at thirty centimetres from the child, comparing the two eyes, and the cream-white reflex on the left is abnormal. The delay of the weeks can convert the curable intraocular tumour into the lethal extraocular disease, and the same-day referral is the non-negotiable step. [1][2]

The examination under anaesthesia (3 marks). The ophthalmology service performs the examination under anaesthesia with the indirect ophthalmoscopy, the fundus photography and the measurement of the tumour, and maps every tumour and assigns the International Intraocular Retinoblastoma Classification group. The ocular ultrasound confirms the intraocular mass with the calcification that is the hallmark of the retinoblastoma, and the contrast-enhanced magnetic resonance imaging of the orbits and the brain excludes the optic nerve invasion, the extraocular extension and the pineal mass of the trilateral retinoblastoma. The computed tomography is avoided because of the radiation and the second-malignancy risk in the heritable disease. [1][8]

The differential and the staging (3 marks). The retinoblastoma is distinguished from the congenital cataract by the retinal rather than the lens location of the opacity, from the Coats disease by the older age of the boy and the absence of the telangiectatic vessels, from the persistent fetal vasculature by the absence of the microphthalmia, and from the toxocariasis by the age and the serology. The intraocular calcification on the ultrasound confirms the retinoblastoma. The staging integrates the International Intraocular Retinoblastoma Classification group, the optic nerve and the choroidal invasion, and the absence of the metastatic disease. [1]

The genetic testing (2 marks). The RB1 gene is sequenced from the blood and, where possible, from the tumour tissue, and the identification of the germline mutation confirms the heritable form. The genetic testing is performed on every child with the retinoblastoma, including the unilateral disease, because roughly fifteen percent of the unilateral cases carry the germline mutation, and the identification changes the surveillance and the offspring counselling. [4][7]

Question 2 (10 marks)

Discuss the risk-adapted definitive management and the genetic counselling, contrasting the heritable bilateral disease with the trilateral retinoblastoma and the global disparity in the survival. [1]

A full-mark answer reproduces the risk-adapted treatment, the genetic counselling, the trilateral retinoblastoma and the global disparity. [2]

The risk-adapted treatment (4 marks). The goals are the cure of the life first, the salvage of the eye second and the preservation of the vision third. The focal therapy with the laser photocoagulation, the transpupillary thermotherapy and the cryotherapy treats the group A and the consolidation after the chemotherapy. The ophthalmic artery chemosurgery delivers the melphalan and the topotecan directly into the ophthalmic artery through the femoral catheter, at approximately three to five milligrams of melphalan per eye per session, repeated every three to four weeks for two to six cycles, and it salvages the group C and D eyes with the low systemic exposure. The systemic chemotherapy with the carboplatin, the etoposide and the vincristine treats the advanced intraocular, the extraocular and the high-risk histology. The enucleation removes the group E unsalvageable eye and allows the histology that guides the adjuvant chemotherapy. [1][10]

The genetic counselling of the heritable disease (3 marks). The child with the bilateral or the multifocal disease has the heritable germline RB1 mutation, passed with the near-complete penetrance and the fifty-percent offspring risk. The genetic counselling addresses the diagnosis, the offspring risk, the prenatal and the preimplantation testing, and the lifelong surveillance for the second malignancy, including the osteosarcoma, the soft-tissue sarcoma, the melanoma and the brain tumour. The surveillance includes the avoidance of the radiation, the sun protection and the prompt assessment of any new mass or bone pain. [4][7]

The trilateral retinoblastoma (1 mark). The bilateral heritable disease carries the risk of the trilateral retinoblastoma, the primitive neuroectodermal tumour of the pineal or the suprasellar region, presenting with the raised intracranial pressure and carrying the poor prognosis with the survival under twelve months. The routine brain magnetic resonance imaging at the diagnosis and through the surveillance is the standard for the heritable disease. [8][9]

The global disparity in the survival (2 marks). The survival of retinoblastoma is the most resource-dependent of any childhood cancer, and the Global Retinoblastoma Study showed that the national income is the single greatest determinant. The high-income setting presents with the leukocoria and the intraocular disease and carries the survival above ninety-five percent, while the low-income setting presents with the proptosis and the extraocular disease and carries the survival below forty percent, because the income determines the speed of the referral and the access to the specialist care. [2]