A one-year-old girl with leukokoria of the right eye

A 1-year-old girl was found to have leukokoria (white reflex on ophthalmoscopic examination) of the right eye upon routine examination by her pediatrician. The patient was also noted to have subtle strabismus. Further tests revealed an elevated intraocular pressure and complete right eye blindness. Ultrasonography revealed a lesion with foci of calcification filling more than three-quarters of the vitreous volume. Head MRI revealed no other lesions. Due to the large size of the tumor, eye-sparing therapy was not an option in this case. The eye was exenterated and sent for pathologic evaluation. The following is a photomicrograph of tumor:

This is a case of retinoblastoma, the most common primary intraocular malignancy of childhood.

Retinoblastoma is a primitive neuroectodermal tumor characterized by malignant cells (retinoblasts) that arise within the immature retina. The neoplastic cells are characterized by a high nuclear:cytoplasmic ratio. Mitotic figures are easily identified. Necrosis and calcification are typical, particularly in larger tumors. In some cases, Flexner-Wintersteiner rosettes, circular arrangements of cells surrounding a true lumen, are present (see photograph). Homer Wright rosettes (which should probably be called “pseudo-rosettes” in that they lack a true lumen) are also frequently present. In occasional cases, rosetting photoreceptor-type retinoblasts, known as fleurettes, may also be observed (not seen in this case). When extensive, choroidal involvement is a negative prognostic sign. Optic nerve extension is another feature that must be noted by the pathologist, as this too confers a worse prognosis.

The retinoblastoma gene is a tumor suppressor gene on chromosome 13. About 60% of retinoblastoma occurrences are secondary to somatic, nonhereditary mutations. Such mutations typically result in unilateral tumors. The remainder of cases are in patients with germline mutations, usually of new onset (i.e., with a negative family history). Retinoblastoma can extend into the central nervous system via either direct invasion of the optic nerve or seeding through the cerebrospinal fluid. Systemic hematogenous metastasis is also possible. If left untreated, most patients die of intracranial extension and disseminated disease within about three years. However, the prognosis is good if treatment is promptly initiated. Eye-sparing treatment with such modalities as laser thermotherapy, cryotherapy, radioactive plaques, external beam radiotherapy, and chemotherapy are often successful in eradicating the tumor. If the tumor is large, however, enucleation is required.

References:

1. Young JL, Smith MA, Roffers SD, Liff JM, Bunin JR. Retinoblastoma. In: Ries LA, ed. Cancer incidence and survival among children and adolescents: United States SEER program 1975-1995. Bethesda, Md.: National Cancer Institute, 1999.

2. Augsburger J, Bornfeld N, Giblin ME. In: Yanoff M and Duker JS, eds. Ophthalmology, 2^nd ed. Chapter 146: Retinoblastoma: CV Mosby. 2003;1043-1051.

3. Melamud A, Palekar R, Singh A. Retinoblastoma. American Family Physician 73:6. March 15, 2006.