RETINOBLASTOMA

Retinoblastoma represents 3% of childhood cancers, being the most common intraocular malignancy of childhood.

Epidemiology: Over 95% cases of retinoblastoma occur lt;5 years of age and ~40% are hereditary, associated with abnormal retinoblastoma suppressor gene (RB1) on chromosome 13q14.

Two-hit model suggests involvement of two mutational events in oncogenesis of retinoblastoma - first one being inherited RB1 mutation from parents and second being the acquired mutation in somatic retinal cells. In sporadic retinoblastoma, both mutations occur in somatic cells. Risk of retinoblastoma in the offspring of a parent with RB gene mutation is as high as 97%.

Pathology: Nearly 25% tumors are bilateral. Retino­blastoma usually develops in the posterior portion of the retina, histologically consisting of small, round, blue malignant cells forming rosette. Tumor may spread locally with vitreous seeding or choroidal/optic nerve invasion, followed by distant metastasis.

Clinically, Retinoblastoma presents with leukocoria (cat-eye reflex) with/without diminished vision and strabismus. Advanced disease may present with pupillary irregularity, hyphema, orbital pain due to glaucoma and proptosis.

Diagnosis is confirmed on fundoscopic examination under anesthesia, showing chalky white-grey retinal mass with soft-friable consistency. Orbital CT/MRI is necessary to assess the extent of the tumor, e.g., optic nerve invasion and intracranial extension. Bone marrow aspirate, bone scan and CSF examination may be required in suspected cases to detect extraocular metastasis. Biopsy of the mass is not indicated.

Cases with suspected hereditary retinoblastoma should also be screened for RB1 mutations in peripheral blood or tissue samples.

Treatment aims to improve the survival as well as preserve the vision and depends on the size, location and extent of tumor, guided by an international classification.

While focal treatment is preferred for intraocular disease, those with large localized lesions may required enucleation. Extraocular extension or distant metastasis may need high-dose chemotherapy, external beam radiotherapy and sometimes, hematopoietic stem cell transplant. Intra-arterial or intra-vitreal chemotherapy has emerged as promising alternatives for refractory disease to preserve the vision.

Genetic counseling is required in all cases of here­ditary retinoblastoma. All first-degree relative of a case of hereditary retinoblastoma must be followed up till 7 years of age for development of tumor.

Prognosis in terms of survival is excellent (gt;90%), though vision may be lost in cases with—(a) large tumors or those located anterior to equator, (b) bilateral disease, and (c) massive orbital or optic nerve involvement. Secondary malignancies, e.g. osteogenic sarcoma, lung and breast cancers are common in hereditary disease.

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