Retinoblastoma is the most common intraocular tumor of childhood (Donaldson et al., 1993). It is a malignant tumor that arises from the embryonic neural retina. This tumor is thought to be congenital, although it may not be recognized at birth. Although it usually presents during early childhood, there hasbeen at least one report of retinoblastoma diagnosed in utero (Maat-Kievit et al., 1993). Retinoblastoma occurs in both sporadic and inherited forms, with the hereditary type predisposing to other malignant tumors (Abramson et al., 1984; Murphree and Benedict, 1984; Roarty et al., 1988; Wilson et al., 1996). Retinoblastoma is usually characterized by rapid growth, enlarging over a period of only weeks to destroy increasing amounts of the retina. The tumor can fill the eye, either by direct enlargement or by growth of tumor seeds. Once the globe is filled by the tumor, orbital and intracranial extension may occur. Retinoblastoma has been said to have a spontaneous regression rate of 1%, but this figure is sometimes confused with two separate processes (Gallie and Phillips, 1982). In the first process there is true regression after an enlarged intraocular tumor becomes totally necrotic. The tumor subsequently atrophies, resulting in a small, disorganized blind eye. The second process occurs in a functional eye as a benign variant of retinoblastoma, which has been termed “retinocytoma” or “retinoma” (Gallie and Phillips, 1982; Marga et al., 1983; Zimmerman, 1985). These tumors are usually composed of viable, benign-appearing tumor cells with a high degree of photoreceptor differentiation. On ophthalmoscopic examination, retinomas have an appearance similar to retinoblastomas that have undergone regression following radiotherapy. Despite the presence of the retinoma, vision is usually normal, but the genetic implications are the same as for retinoblastoma.

The majority of cases of retinoblastoma are diagnosed while the tumor remains confined to the eye. In contrast, in prenatal diagnosis, because of the insensitivity of sonographic evaluation of the eye, to be detected there must be gross extension to the orbit (Maat-Kievit et al., 1993). The most common postnatal sign in retinoblastoma is leukokoria of one or both eyes, which has been termed the “cat’s-eye reflex” but which parents described as an unusual appearance of the eye (Donaldson et al., 1993). The next most common presenting sign is strabismus, which occurs when the tumor arises in the macula, causing loss of central vision and, therefore, loss of the fusional reflex so that the eye may drift, resulting in esotropia or exotropia. Other less common signs are orbital inflammation, hyphema, fixed pupil, and heterochromic irides. Vision loss is not a typical symptom at presentation because young children do not report unilaterally decreased vision. In addition, intraocular tumors are not painful unless secondary glaucoma or inflammation is present. Between 20% and 30% of cases are bilateral at the time of initial diagnosis. In these cases the disease is often multifocal, with several tumors in each eye. The presentation in utero is that of a sonographically detected ocular mass, which is irregular and echogenic, with extension beyond the orbit itself.

The incidence of retinoblastoma is estimated to be 1 in 15,000 to 1 in 34,000 livebirths (Devesa, 1975; Shields and Shields, 1990; Salim et al., 1998). The estimated frequency of bilateral cases of retinoblastoma in children is between 20% and 30% (Donaldson et al., 1993). There is no known racial or gender predisposition for this tumor. Retinoblastoma is a congenital tumor and is present at birth, although it is not often recognized at that time. Eighty percent of cases are diagnosed before the age of 3 to 4 years, with a mean time of presentation at 2 years of age. Bilateral retinoblastoma typically becomes clinically apparent earlier; the average age at diagnosis is 12 months (Shields and Shields, 1990). In rare cases, multiple congenital anomalies may be seen in association with retinoblastoma. However, these cases represent only 0.05% of cases of retinoblastoma reported in the United States (Jensen and Miller, 1971). The reported anomalies include congenital heart disease, cleft palate, Bloch–Sulzberger syndrome, infantile corital hyperasthosis, dentinogenesis imperfecta, incontinentia pigmenti, and familial congenital cataracts (Green, 1985).

Only a few cases of retinoblastoma have been antenatally diagnosed (Maat-Kievit et al., 1993; Salim et al., 1998; Kodzov et al., 2002; Lehman, 2003). In the case reported by Maat-Kievit et al. (1993), a fetus at 21 weeks of gestation had an oval-shaped mass protruding from the right side of the face (Figure 114-1). The tumor was an irregular echogenic mass measuring 8 x 6 x 3 cm. The tumor was covered by a thin membrane with an echolucent rim between the membrane and the tumor. The majority of the face was obscured by the tumor. The tumor deformed the normal anatomy of the facial bones, and the contralateral orbit could not be seen. The differential diagnosis of a facial tumor detected by prenatal ultrasound examination and the features that distinguish them are listed in Table 114-1. It should be noted that ultrasound examination is an extremely insensitive screening technique for heritable retinoblastoma in families at risk for recurrence. In these cases, percutaneous umbilical blood sampling, CVS, or amniocentesis to obtain fetal tissue is recommended, as DNA-based prenatal diagnosis is available.

The case of retinoblastoma diagnosed at 21 weeks of gestation was found to have a very large oval-shaped mass protruding from the right side of the fetal face (Maat-Kievit et al., 1993). Histologic studies confirmed the diagnosis of retinoblastoma with extension beyond the orbit with an 8 x 6 x 3-cm mass rounded by a transonic area covered by a thin membrane. Because of the location and the size ofthis tumor the differential diagnosis included most causes of facial tumors (see Table 114-1). Epignathus is a tumor that grows through the floor of the mouth, is usually quite irregular in shape, and is localized primarily in the nasopharyngeal area. Although it has a heterogeneous appearance, with sonolucent and highly echogenic areas, its location usually distinguishes it from retinoblastoma. Encephalocele (see Chapter 12) is usually associated with intracranial abnormalities, such as hydrocephalus and calvarial defects. It is usually smooth, contoured, round in shape, and localized to the skull. In contrast, hemangiomas are usually readily identified by color flow Doppler studies, which show significant blood flow within the tumor mass. Myoblastomas are ordinarily localized to the oral cavity and tend to be echogenic, with other sonolucent areas within it. Dacryocystocele may be more difficult to distinguish from retinoblastoma because of its proximity to the eye. It is usually localized in the inframedial aspect of the orbit. Retinoblastoma is an irregular echogenic mass that may be surrounded by the sonolucent area that arises specifically from the eye (see Figure 114-1).