In the initial staging EUA, patients with retinoblastoma may receive fundus photography, fluorescein angiography (FA), handheld optical coherence tomography (OCT), and B-scan ultrasonography. Results of color fundus photography enable documentation of the appearance and location of retinal tumors and the sites of vitreous and subretinal seeding; serial images over time are helpful for determining treatment efficacy and disease recurrence. Common findings of retinoblastoma on FA include retinal vascular dilatation, capillary telangiectasia, intrinsic tumor vessel formation, and retinal venous leakage; subclinical iris neovascularization may also be seen.
Figure 19-6 Retinoblastoma. Large endophytic tumor with extensive vitreous seeding (arrows).
(Courtesy of Matthew W. Wilson, MD.)
Figure 19-7 Retinoblastoma, clinical photograph. Pseudohypopyon resulting from migration of tumor cells into the anterior chamber. Note the clumped appearance of the cells, which is somewhat different from the appearance of inflammatory cells in a true hypopyon. Also note the tumor nodule on the iris surface at the 10 o’clock position, which is atypical for an inflammatory hypopyon.
In eyes with small tumors or a visible macula, OCT with a handheld device can be helpful in assessing macular anatomy and in identifying and monitoring retinal tumors. Small retinoblastoma tumors are smooth, round, cream-colored, homogeneous, and isodense on OCT. Small tumors may involve the inner nuclear layer (INL) and the outer nuclear layer (ONL), whereas very small tumors have been described as limited to the ONL, with draping of the overlying inner retinal layers beginning with the outer plexiform layer (Fig 19-8). So-called invisible tumors that are very early may be detected on OCT before ophthalmoscopic visualization is possible. OCT also can be used to evaluate the extent and morphology of vitreous seeds (Fig 19-9). Ultrasonographic findings of a dome-shaped retinal lesion with scattered intratumoral calcifications are critical for diagnosing retinoblastoma, particularly when ophthalmoscopic visualization of the tumor is limited (Fig 19-10). Results of EUA are used to classify each eye, as discussed in the Retinoblastoma Classification section. The group classification is useful in determining therapeutic options, visual prognosis, and potential for ocular salvage.
Retinoblastoma may invade the optic nerve head and spread through the lamina cribrosa into the central nervous system (CNS). Rarely, in bilateral cases, retinoblastoma can be associated with a separate CNS tumor called a pinealoblastoma (a condition referred to as trilateral retinoblastoma; Fig 19-11). Hence, imaging studies of the optic nerve, orbits, and brain are essential for complete staging of a child with retinoblastoma. Magnetic resonance imaging (MRI) is the preferred diagnostic modality for this purpose. MRI enables better soft-tissue resolution than does computed tomography (CT) and does not expose the patient to potentially harmful radiation, which is especially important in children with a genetic cancer syndrome (see the Genetic Counseling section). Aside from MRI of the brain, systemic metastatic evaluation with bone marrow and lumbar puncture is not indicated in children without neurologic abnormalities or evidence of extraocular extension. If extension of the retinoblastoma into the retrobulbar optic nerve is suspected, lumbar puncture and bone marrow biopsy may be performed as part of the workup, but they should not delay definitive enucleation or neoadjuvant chemotherapy.
Figure 19-8 Optical coherence tomography (OCT) of retinoblastoma. A, Color fundus photograph of a left eye with 3 retinoblastoma tumors. B, Color fundus photograph of the same eye with the 3 retinoblastoma tumors labeled Rb1–3. The tumors are marked by lines through the body of the tumors correlating with the OCT slice. The smallest one, barely visible on ophthalmoscopy, lies just superior to the optic nerve. C, Spectral-domain OCT of the 3 tumors shows homogenous dome-shaped masses with overlying inner retinal draping. Tumor 3 is located in the outer retina involving the outer nuclear layer and possibly the outer plexiform layer. The inner nuclear layer and inner plexiform layer drape over the tumor. There is also an outer retinal abnormality in all tumors affecting the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). There is shadowing on OCT from the retinal vessels overlying the tumor, which are also seen clinically. RPE = retinal pigment epithelium.
(Reproduced with permission from Berry JL, Cobrinik DC, Kim JW. Detection and intraretinal localization of an ‘invisible’ retinoblastoma using optical coherence tomography. Ocul Oncol Pathol. 2016;2(3):149.)
A, Clinical photograph shows a large, spherical vitreous seed (arrow) in retinoblastoma.B, OCT findings in a child with advanced retinoblastoma demonstrated an intact fovea, a dusting of small hyperreflective seeds on the retinal surface, and a hollow reflective cystic structure floating above the retina consistent with a spherical vitreous seed (arrow).
(Reproduced from Berry JL, Anulao K, Kim JW. Optical coherence imaging of large spherical seed in retinoblastoma. Ophthalmology. 2017;124(8):1208.)
Figure 19-10 B-scan ultrasonographic findings demonstrate a dome-shaped retinal lesion with characteristic scattered calcifications within the tumor (arrows).
(Courtesy of Jesse L. Berry, MD, and Jonathan W. Kim, MD.)
Figure 19-11 Contrast-enhanced sagittal T1-weighted magnetic resonance image of the brain demonstrates a large midline cerebral lesion (asterisk) involving the pineal region in a child with bilateral retinoblastoma; this is consistent with a pinealoblastoma (primitive neuroectodermal tumor [PNET]). The presence of the bilateral retinoblastomas and the pineal tumor is referred to as trilateral retinoblastoma.
(Courtesy of Jonathan W. Kim, MD.)
Figure 19-12 Advanced extraocular extension of retinoblastoma. Severe proptosis caused by retinoblastoma with orbital invasion.
In the United States, patients rarely present with metastases or intracranial extension at the time of diagnosis; in contrast, advanced presentations are common in resource-limited countries. The most frequently identified sites of metastatic involvement in children with retinoblastoma are the orbit, brain, distal bones, lymph nodes, skull bones, spinal cord, and abdominal viscera. Retinoblastoma cells may escape the eye by invading the optic nerve and extending into the cerebrospinal fluid. In addition, tumor cells may massively invade the choroid before traversing emissary canals, thereby spreading hematogenously or eroding through the sclera to enter the orbit. Extraocular extension may result in proptosis as the tumor grows in the orbit (Fig 19-12). In the anterior chamber, tumor cells may invade the trabecular meshwork, gaining access to the conjunctival lymphatics. Subsequently, palpable preauricular and cervical lymph nodes may develop.
Kim JW, Ngai LK, Sadda S, Murakami Y, Lee DK, Murphree AL. Retcam fluorescein angiography findings in eyes with advanced retinoblastoma. Br J Ophthalmol. 2014;98(12):1666–1671.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.