CASE SUMMARY:

A 3-year-old Honduran male presented to the emergency department with a 7 ¥ 10 ¥ 3 cm mass protruding from his right orbit. The mass, which had been enlarging for 1 year, was friable, with a wet, yellow, odoriferous exudate and occasional frank bleeding at the margins. Enucleation of the left eye for retinoblastoma had been performed on the patient at age 2, followed by chemotherapy.

DIAGNOSIS:

Invasive retinoblastoma with metastasis.

DISCUSSION:

Retinoblastoma is the most common intraocular malignancy affecting the pediatric population, with an incidence of 1 in 15,000 to 30,000 live births; approximately 200 new cases are reported in the United States each year. The diagnosis usually is made before 2 years of age, with 80% of cases diagnosed under 3 years of age.1,2,3 Both sexes are affected equally.4

Retinoblastoma is a primitive neuroendocrine tumor which originates in the nuclear layers of the retina and may push upon the retina, resulting in retinal detachment (endophytic type). It also may grow as a highly pedunculated mass on a short stalk, without retinal detachment (exophytic type).2 These tumors grow rapidly, and necrosis and calcification are common.3 Retinoblastomas are typically identified on computed tomography as intravitreous soft-tissue masses that enhance following the administration of intravenous contrast. Calcifications within an intravitreous soft-tissue mass are virtually pathognomonic of a retinoblastoma prior to age 3, and are seen in greater than 95% of cases.6 After age 3, calcifications are slightly less specific, as they may occasionally be seen in other entities simulating retinoblastoma such as retinal astrocytoma, toxocariasis, advanced Coats' disease with retinal necrosis and, rarely, advanced retinopathy of prematurity.1

Retinoblastoma is responsible for approximately 1% of all cancer deaths in children under 15 years of age.4 It is hereditary in 40% of cases, of which three-fourths arise as spontaneous mutations. When hereditary, retinoblastoma follows an autosomal dominant pattern, with 80% penetrance. The hereditary form occurs at an earlier age and is more likely to be bilateral.3 Bilateral disease occurs in 20 to 40% of all patients with retinoblastoma, and all patients with bilateral disease have the hereditary form regardless of family history.3 Associated pinealoma, or the so-called "trilateral retinoblastoma," occurs in 3% of those patients with bilateral ocular neoplasms.1,3 A deletion of the 13q14 segment in the long arm of chromosome 13 has been identified in some patients with retinoblastoma.5 Associated abnormalities include mental retardation, extra digits, imperforate anus, and failure to thrive.2

Initial detection is typically by ophthalmologic diagnosis of leukokoria (a white pupillary reflex), which is present in 60% of children with the disease. Strabismus is the second most common sign, followed by glaucoma, often with heterochromia (different colored irides).1,2,6 Less common features include a painful red eye, decreased vision, and orbital inflammation.1,3 In the developed world, an exophytic orbital mass is a rare presentation of retinoblastoma.

Metastatic disease appears, on average,12 months after initial diagnosis. Extracranial metastatic disease is rare in the United States.1,3 Intracranial metastatic lesions have been reported in virtually all patients dying of retinoblastoma and over 50% have distant organ metastasis.1,7 The tumor typically invades intracranially via the optic nerve into the subarachnoid space and central nervous system. It also can spread hematogeneously to distant sites following invasion of the optic vein. Prognosis is related to the stage of the orbital disease rather than the bilaterality.7 Mortality approaches 100% when there is extraocular extent of the tumor.2 Children who survive their retinoblastoma are at an increased risk for osteosarcoma and, less commonly, Ewing's sarcoma and peripheral neuroepithelioma. Secondary malignant neoplasms occur almost exclusively in patients with hereditary bilateral disease.5,8

Current options in the therapeutic armamentarium include enucleation, external beam radiation therapy, scleral plaque brachytherapy, cryotherapy, photocoagulation, and chemotherapy. Surgical enucleation remains the most commonly used treatment option.5 However, this is rarely performed for bilateral disease as it results in immediate blindness. Enucleation in a child under age 3 also results in a small disfigured orbit. Radiation therapy most often is used to treat the second eye in patients with bilateral disease.5 Chemotherapy generally is reserved for patients with extensive extraocular disease.3

References

1. Provenzale JM, Weber AL, Klintworth GK, McLendon RE: Radiologic-pathologic correlation: Bilateral retinoblastoma with coexistent pinealoblastoma. Am J Neuroradiol 16:157-165, 1995.

2. Abramson DH: Retinoblastoma: Diagnosis and Management. CA-A Cancer J Clin 32(3):130-140, 1982.

3. Cohen MD: Central nervous system tumors. In: Stamathis G (ed): Imaging of Children with Cancer, pp 305-307. St. Louis, Mosby Year Book, Inc., 1992.

4. Ralbert DM, Dryja TP: The eye. In: Contran RS, Kumar V, Robbins SL (eds): Robbin's Pathologic Basis of Disease, ed 4, pp 1462-1646. Philadelphia, WB Saunders 1989.

5. Shields JA, Shields CL: Current Management of Retinoblastoma. Mayo Clin Proc 69:50-56, 1994.

6. Lindahl S: Computed tomography of the retinoblastoma. Acta Radiologica Diagn 27:513-518, 1986.

7. MacKay CJ, Abramson DH, Ellsworth RM: Metastatic patterns of retinoblastoma. Arch Ophthalmol 102:391-396, 1984.

8. Helton KJ, Fletcher BD, Kun LE, et al: Bone tumors other than osteosarcoma after retinoblastoma. Cancer 71:2847-2853, 1993.

Prepared by James Ronald Hills, MD and Kathleen Dunne Eggli, MD, The

Pennsylvania State University College of Medicine, Milton S. Hershey Medical

Center, Hershey, PA.