Retinoblastoma

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  • Retinoblastoma
    • It is the most common intraocular tumour of childhood (MCQ)
    • usually seen between 1 and 2 years of age.
    • There is no sex predisposition.
    • In 25-30 percent cases, there is bilateral involvement,
    • Genetics and heredity
      • Retinoblastoma (RB) gene
        • identified as 14 band on the long-arm of chromosome 13 (13q 14) (MCQ)
        • is a ‘cancer suppressor’ or ‘antioncogenic’ gene.
        • Deletion or inactivation of this protective gene by two mutations (Knudson’s two hit hypothesis) results in occurrence of retinoblastoma. (MCQ)
      • Retinoblastoma may arise as hereditary and non- herditary forms.
      • Hereditary or familial cases.
        • first hit (mutation)
          • occurs in one of the parental germ cells before fertilization.
          • This means mutation will occur in all somatic cells (predisposing to develop even non- ocular tumour).
        • Second hit (mutation)
        • occurs late in postzygote phase
        • affects the second allele, resulting in development of retinoblastoma.
        • Some facts about hereditary retinoblastoma are:
          • Accounts for 40% of all cases.
          • All bilateral cases and about 15% of the unilateral cases are hereditary.
          • Most hereditary cases are multifocal.
          • Some hereditary cases have trilateral retinoblastoma
          • have associated pinealoblastoma (MCQ)
          • Inheritance is autosomal dominant and the risk of transmitting the gene mutation is 50%.
          • Because of high peneterance 40% of offspring of a surviver of heraditary retinoblastoma will develop the tumour.
          • There are 40% chances of developing tumour in a sibling of a child with bilateral retinoblastoma (with unaffected parents).
      • Non-hereditary or sporadic cases.
        • both hits (mutations) occur in the embryo
        • after fertilization and in the same retinal cell.
        • Some facts about non-hereditary (somatic) retinoblastoma are:
        • Accounts for 60% of all cases.
        • All non-hereditary cases are unilateral and unifocal
        • accounts for 85% of the all unilateral cases of retinoblastoma.
        • Patient is not predisposed to get second non-ocular cancer.
        • Tumour is not transmissible.
    • Pathology
      • It arises as malignant proliferation of the immature retinal neural cells called, retinoblasts, which have lost both antioncogenic genes.
      • Growth chiefly consists of small round cells with large nuclei, resembling the cells of the nuclear layer of retina.
      • Microscopic features of a well differentiated tumour include
        • Flexner-Wintersteiner rosettes, (highly specific of retinoblastoma)
        • Homer-Wright rosettes
        • pseudorosettes and fleurettes formation
        • presence of areas of necrosis and calcification
    • Clinical picture
      • Quiescent stage.
        • It lasts for about 6 months to one year.
        • Leukocoria or yellowish-white pupillary reflex
          • also called as amaurotic cat’s eye appearance
          • commonest feature noticed in this stage
        • Squint – usually convergen
        • Nystagmus  is  noticed in bilateral cases.
        • Defective vision.
          • when the tumour arises late (3-5 years of age), the child may complain of defective vision.
        • Ophthalmoscopic features of tumour
        • Endophytic retinoblastoma
          • In the presence of calcification, it gives the typical ‘cottage cheese’ appearance.
        • Exophytic retinoblastoma
          • On fundus examination it gives appearance of exudative retinal detachment
      • Glaucomatous stage.
      • Stage of extraocular extension.
      • Stage of distant metastasis
        • Lymphatic spread first occurs in the preauricular and neighbouring lymph nodes.
        • Direct extension by continuity to the optic nerve and brain is common.
    • Differential diagnosis of leukocoria. (MCQ)
      • congenital cataract
      • inflammatory deposits in vitreous following a plastic cyclitis or choroiditis
      • coloboma of the choroid
      • retrolental fibroplasia (retinopathy of prematurity)
      • persistent hyperplastic primary vitreous
      • toxocara endophthalmitis
      • exudative retinopathy of Coats.
    • Diagnosis
      • Plain X-rays of orbit may show calcification
      • Lactic dehydrogenase (LDH) level is raised in aqueous humour.
    • Treatment
      • Tumour destructive therapy
        • Indication
          • When tumour is diagnosed at an early stage
          • when tumour is involving less than half of retina
          • optic nerve is not involved (usually in the second eye of bilateral cases)
        • sequential aggressive local therapy (SALT)
          • Chemoreduction followed by local therapy
            • (Cryotherapy, thermochemotherapy or brachy- therapy)
            • recommended for large tumours (>12 mm in diameter)
          • Radiotherapy (external beam radiotherapy i.e., EBRT or brachytherapy) combined with chemotherapy
            • recommended for medium size tumour <12 mm in diameter and <8mm in thickness).
          • Cryotherapy
            • indicated for a small tumour (<4.5 mm indiameter and <2.5 mm in thickness) located anterior to equator.
          • Laser photocoagulation
            • used for a small tumour located posterior to equator <3 mm from fovea.
          • Thermotherapy with diode laser
            • used for a small tumour located posterior to equator away from macula.
      • Enucleation
        • is the treatment of choice when:
          • Tumour involves more than half of the retina.
          • Optic nerve is involved.
          • Glaucoma is present and anterior chamber is involved.
        • The eyeball should be enucleated along with maximum length of the optic nerve taking special care not to perforate the eyeball.
        • If optic nerve shows invasion, postoperative treatment should include:
          • Radiotherapy (5000 rads) should be applied to the orbital apex.
          • Chemotherapy, consisting of vincristine, carboplatin, and etoposide which may be combined with cyclosporin should be supplemented.
      • Palliative therapy is given in following cases where prognosis for life is dismal in spite of aggressive treatment:
        • Retinoblastoma with orbital extension,
        • Retinoblastoma with intracranial extension
        • Retinoblastoma with distant metastasis.
      • Palliative therapy should include combination of :
        • Chemotherapy
        • Surgical debulking of the orbit or orbital exentration
          • now not preferred by many surgeons.
        • External beam radiotherapy (EBRT)
      • Prognosis
        • Rarely spontaneous regressionwith resultant cure and shrinkage of the eyeball may occur due to necrosis followed by calcification; suggesting role of some immunological phenomenon.
        • Poor prognostic factors are:
          • Optic nerve involvement
          • undifferentiated tumour cells
          • massive choroidal invasion.

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