Clinical History:

A 2-year-old child has decreasing vision in the left eye. Pain and tenderness are noted as well. An MRI scan reveals a 2.5 cm mass involving the left posterior orbital region. The left eye is enucleated.

Gross and Microscopic Pathology:

The gross appearance of the eye reveals leukocoria (white pupil) resulting from an intraocular mass lesion that partially fills the globe, as seen in the gross specimen. The microscopic features of the lesion at low power include small blue cells forming Flexner-Wintersteiner rosettes and microcalcifications. Necrosis and dystrophic calcification are commonly seen within this tumor. This neoplasm arises from a cell of neuroepithelial orgin in the posterior retina.

Questions:

1. What is the diagnosis?

This is a retinoblastoma, the most common intraocular tumor in children.

2. Explain the molecular biology of this lesion.

There is either inheritance of a mutated Rb tumor suppressor gene, or a sporadic mutation, followed by loss of the remaining normal Rb gene. This is the classic "two hit" etiology for a neoplastic disease arising from loss of tumor suppressor genes.

3. What is the significance of a family history of this condition?

About 60 to 70 % of retinoblastomas are familial. In familial cases, bilateral retinoblastomas are more likely, and affected persons are at risk for osteosarcoma or other soft tissue neoplasms, due to the loss of tumor suppression.

4. What is the prognosis?

Enuclection of the affected eye, followed by chemotherapy and radiotherapy, results in a good prognosis in most cases.