From the Department of Pathology, NRS Medical College and Hospital, Kolkata, India.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Saumitra Biswas, MD (Pathology), A.E. 219, Bidhannagar, Kolkata-7000064, India. E-mail: firstname.lastname@example.org
Retinal dysplasia is a rare cause of childhood leukocoria.1 It is often difficult to differentiate this lesion from malignant intraocular lesions on a clinical and radiological basis alone. The disease results from aberrant differentiation of the retina and is characterized histologically by tubular and rosette-like configurations.2 The lesion is unilateral in normal individuals and bilateral in congenital disorders.3 Histopathologic examination of the enucleated eye is required to establish the diagnosis. We present one such rare case of unilateral retinal dysplasia. A literature search revealed no similar documented case from the eastern region of India.
A 9-month-old boy was admitted at NRS Medical College and Hospital, Kolkata, India, with a history of smaller left eye, white opacity for the past 2 months, and watering of the same eye for the past few days. On clinical examination, vision was found to be absent in the left eye and white pupillary reflex was noted. The right eye showed normal vision and no other abnormality was noted.
Computed tomography (Fig. 1) showed a protruding left eyeball. A hyperdense area with fluid level was noted in the posterior part of the posterior segment. The rest of the posterior segment also showed increased density (heterogeneous soft tissue).
Figure 1. Computed Tomography Scan Illustrating Protrusion of the Left Eyeball. Posterior Segment Showing Increased Density with a Fluid Level in the Posterior Part.
The patient’s parents had normal vision. They did not have a consanguineous marriage. His 3-year-old brother was apparently healthy with normal vision in both eyes. His mother had an uneventful antenatal period and normal vaginal delivery at full term. The newborn cried immediately after birth and had no history of oxygen therapy.
On the basis of clinical and computed tomography reports, the case was diagnosed as retinoblastoma. The eye was enucleated and sent for histopathological examination.
Grossly, an eyeball measuring 1.5 × 1.5 cm with a stump of optic nerve measuring 0.5 cm was received. The cut surface showed a 0.2 × 0.5 cm whitish area in the posterior chamber behind the vitreous. Hematoxylin–eosin stained sections showed a series of straight branching tubes and rosette-like structures composed of abortive elements of the retina. No tumor mass was found. Retinal detachment was present. The sclera, cornea, and uvea were normal (Figs. 2 and 3). The optic nerve was histologically unremarkable. The histopathological diagnosis was retinal dysplasia.
Figure 2. Histologic Section of the Enucelated Eye Showing Proliferation of the Retina on the Left and Normal Sclera on the Right (Hematoxylin–Eosin, Original Magnification ×50).
Figure 3. Formation of Straight Branching Tubes and Rosette-Like Structure in the Abnormally Proliferated Retina (Hematoxylin–Eosin, Original Magnification ×400).
A postoperative follow-up examination of the patient after 1 year detected normal fundus in the right eye (Fig. 4). Bilateral fundus examination of his sibling did not reveal any abnormality (Fig. 5).
Figure 4. Photograph Showing the Normal Fundus of the Patient’s Right Eye.
Figure 5. Both Eyes of the Patient’s Sibling are Normal on Fundus Photograph.
Unilateral retinal dysplasia occurs in normal individuals as an isolated disorder and the cause is obscure.3 The disease is bilateral in congenital disorders such as Norrie disease, trisomy 13, and Walker–Warburg syndrome and is associated with systemic and central nervous system abnormalities.1 It can rarely be transmitted as an X-linked recessive disorder.4
Retinal dysplasia is believed to be the result of disturbed differentiation of neural ectoderm.3 It results in abnormal retinal proliferation leading to formation of heaped up areas of non-specific rosette formation by immature cells with or without gliosis.3 It appears to be a non-specific response to separation of the retina from its underlying pigment epithelium at a critical stage of differentiation.4
Clinically, retinal dysplasia presents with a whitish reflex behind the pupil resulting from simple to massive infolding of the retina, central stalks with retinal tissue extending from the optic disc to the back of the lens, and complete retinal detachment leading to highly disorganized micropthalmic eyes.1 It may be unilateral or bilateral. Intrauterine trauma, viral infection, and environmental factors are implicated in some cases.4 In the current case, no history of infection or other factors was available.
The lesion is unrelated to prematurity.3 Hunter et al.5 described a series of 16 cases where the pregnancies were normal with full-term delivery as in our case.
Histologically, retinal dysplasia is characterized by a series of straight branching tubes composed of abortive elements of rod and cone layers. The photoreceptor cell layer forms rosette-like structures that are two to three cell layers thick with a central lumen. No anaplasia is seen in the rosettes. It also shows reduction or complete absence of ganglion cells, their nerve fibers, and retinal blood vessels leading to congenital retinal detachment. Our case presented with identical features.
Differential diagnosis of leukocoria (a whitish reflex behind the pupil) includes retinoblastoma, persistent hyperplastic primary vitreous, and medulloepithelioma. The cause of leukocoria can usually be determined by opthalmoscopy, ultrasonography, or both. Magnetic resonance imaging occasionally helps in diagnosis.1 Histopathology helps to characterize and differentiate between intraocular pathologies, as in our case. Computed tomography delineates the size and shape of the eyeball and demonstrates any focal mass lesion or hemorrhage if present.
Retinoblastoma is a malignant tumor composed of small round cells with hyperchromatic nuclei and scanty cytoplasm. The tumor cells form rosettes where clusters of cuboidal or short columnar cells are arranged around a central lumen. No such histologic features were noted in the excised eyeball. Persistent hyperplastic primary vitreous is a unilateral congenital anomaly often associated with cataract, where there is persistence and hyperplasia of the fibrovascular tunic of the lens. Histologically, there is a dense fibrovascular retrolental mass and the elongated ciliary processes are enmeshed in this tissue. The retina may appear normal or show evidence of retinal dysplasia. Remnants of the hyaloid artery system are usually present. Medulloepithelioma is a rare tumor that resembles the embryonal retina. It usually arises from the ciliary epithelium or rarely from the optic nerve or retina. In contrast, retinal dysplasia is a congenital anomaly that does not show any mass lesion such as retinoblastoma or medulloepithelioma on imaging. The rosettes of retinal dysplasia are unlike Flexner–Wintersteiner rosettes.
Retinal dysplasia is often associated with some degree of persistent hyperplastic primary vitreous. A study by Lahav et al.6 showed that three of four patients with retinal dysplasia had coexisting persistent hyperplastic primary vitreous. Parsons et al.7 postulated that contraction of retrolental fibrovascular tissue leads to retinal detachment in Norrie disease.
Retinal dysplasia is a rare congenital anomaly of the retina that clinically mimics retinoblastoma. Enucleation of the affected eye is the only treatment. Retinoblastoma is a malignant neoplasm, whereas retinal dysplasia is a non-neoplastic condition. Recognition of such lesions requires histopathological study of the excised specimen and is essential to rule out a neoplastic process.
- de Graaf P, van der Valk P, Moll AC, Imhof SM, Schouten-van Meeteren AY, Castelijns JA. Retinal dysplasia mimicking intraocular tumor: MR imaging findings with histopathologic correlation. Am J Neuroradiol. 2007;28:1731–1733. doi:10.3174/ajnr.A0635 [CrossRef]
- Lawrence MMG. The eye. In: Gilbert-Barness E, ed. Potter’s Pathology of the Fetus, Infant and Child, 2nd ed. Philadelphia: Elsevier; 2007:2129–2180.
- Wilkinson A, Mahore S, Joshi A. Unilateral retinal dysplasia: a case report. Indian J Pathol Microbiol. 2006;49:426–428.
- Lloyd IC, Colley A, Tullo AB, Bonshek R. Dominantly inherited unilateral retinal dysplasia. Br J Ophthalmol. 1993;77:378–380. doi:10.1136/bjo.77.6.378 [CrossRef]
- Hunter WS, Zimmerman LE. Unilateral retinal dysplasia. Arch Ophthalmol. 1965;74:23–30.
- Lahav M, Albert DM, Wyand S. Clinical and histopathological classification of retinal dysplasia. Am J Ophthalmol. 1973;75:648–667.
- Parsons MA, Curtis D, Blank CE, Hughes HN, McCartnev ACE. The ocular pathology of Norrie disease in a fetus of 11 weeks’ gestational age. Graefes Arch Clin Exp Ophthalmol. 1992;230:248–251. doi:10.1007/BF00176299 [CrossRef]