From the Department of Ocular Oncology and Vitreoretina, Sankara Nethralaya, Chennai, India.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Vikas Khetan, DNB, Department of Ocular Oncology and Vitreoretina, Sankara Nethralaya, 18 College Road, Chennai 600006, India. E-mail: email@example.com
Diffuse infiltrating retinoblastoma is a rare but well-known form of retinoblastoma. This form of retinoblastoma has been shown to have variable amount of retinal involvement ranging from near-complete tumor involvement of the retina causing diffuse, mild thickening of the retina in the absence of a discrete tumor mass1,2 to small foci of retinal involvement in the periphery.3 It tends to present unilaterally and in relatively older children, usually at approximately 6 to 8 years of age,2 although the first report by Schofield had an age range of 1 to 9 years.1 Anterior segment involvement is common in this form, confusing the clinical picture with that of uveitis. We report a case that presented as unresolving uveitis and no conspicuous retinal focus.
A 3-year-old girl was being treated for unresolving anterior uveitis with secondary glaucoma for the past 4 months and was referred to us for further treatment. At presentation, the child was receiving prednisolone 1% eye drops 6 times a day, homatropine eye drops twice a day, and timolol maleate 0.5% + brimondine acetate 0.2% eye drops twice a day.
On examination, vision in both eyes was central, steady, and maintained. The child was not cooperative for detailed visual acuity assessment. Anterior segment examination of the right eye was unremarkable; the left eye showed mild conjunctival congestion, clear cornea, and mid dilated pupil that sluggishly reacted to light. The anterior chamber of the left eye showed white, fluffy exudates (Fig. 1). The lens was clear. Indirect ophthalmoscopic examination of both eyes revealed no abnormalities up to the equator. Blood investigations, complete blood count, and erythrocyte sedimentation rate were within normal limits.
Figure 1. Exudates in the Anterior Chamber.
To decide on the etiology of the uveitis, the child was subjected to examination under anesthesia. Intraocular pressure with applanation tonometer was 14 and 31 mm Hg in the right and left eyes, respectively. Fundus examination of the right eye was normal, whereas that of the left eye showed healthy optic disc and attached normal retina. Ciliary processes were studded with tumor seeds for 360° (Fig. 2). Ultrasound biomicroscopy was suggestive of tumor seeds over the ciliary body all around, more inferiorly.
Figure 2. Fundus Showing Ciliary Body/pars Plana Studded with Tumor Seeds.
To arrive at a definitive diagnosis, anterior chamber tap was done with tuberculin syringe and 30-gauge needle with long intracorneal track to prevent metastasis associated with needle biopsy in case of retinoblastoma. Cytological analysis of the aspirate revealed numerous basophilic cohesive cells with hyperchromatic nuclei and scanty cytoplasm and surrounded by necrotic cells, which was highly suggestive of retinoblastoma (Fig. 3).
Figure 3. Cytological Analysis of Aspirate Revealed Numerous Basophilic Cohesive Cells with Hyperchromatic Nuclei and Scanty Cytoplasm and Surrounded by Necrotic Cells, Which Was Highly Suggestive of Retinoblastoma (hematoxylin–Eosin; Original Magnification ×20).
Ultrasonography and magnetic resonance imaging findings were normal. Diagnosis of retinoblastoma was made and the parents were counseled about the course and prognosis of disease and need for enucleation. Enucleation with ball implant was done 6 weeks later.
Gross pathology of the enucleated globe showed fluffy whitish material in the anterior chamber over the ciliary body, lens zonules, and anterior vitreous (Fig. 4). Histopathology showed basophilic tumor cells on the iris surface and the entire ciliary body region (Fig. 5). The choroid and sclera were normal. The surgical end of the optic nerve was free of tumor cells. Serial sections of lateral calotte and pupil optic nerve section block were performed to determine the origin of the tumor, but did not reveal any retinal tumor focus.
Figure 4. Gross Pathology of the Enucleated Globe Showed Fluffy Whitish Material in the Anterior Chamber over the Ciliary Body, Lens Zonules, and Anterior Vitreous.
Figure 5. Histopathology Showed Basophilic Tumor Cells on the Iris Surface and Entire Ciliary Body Region (hematoxylin–Eosin; Original Magnification ×20).
Because the child did not have histopathologic high-risk features, such as optic nerve or choroidal invasion, she was not treated with systemic chemotherapy. The patient was thoroughly evaluated by a pediatric oncologist and had no other tumor involvement. Family members were evaluated and were normal.
In this patient, cytological analysis of aqueous humor revealed malignant cells suggestive of retinoblastoma. Uveitic entities were initially thought to be relevant as differential diagnoses, but all of the systemic investigations turned out to be negative. Medulloepithelioma is likely in this age group; however, absence of any tumor mass and clear lens ruled it out.
Grossniklaus et al.4 were the first to use the term diffuse anterior retinoblastoma in 1998 to describe this highly unusual pattern of tumor growth. The average age at presentation is 6 years and almost all cases are sporadic and have unilateral involvement.2 Ultrasonography is not particularly helpful and fails to reveal calcification as in typical retinoblastoma. Diffuse retinoblastoma has slow progression and shows poor response to conservative therapy. It is almost always accompanied by primary tumor focus in retina. Cases with absence of conspicuous retinal mass and presence of vitreous or anterior chamber seeding mimicking an inflammatory process results in a clinical dilemma. Cases have been reported that predominantly involved the structures of the anterior segment and only microscopic foci of retinal involvement.3 All of these cases with microscopic tumor foci in the retina were seen in children 6 years or older who were being treated for uveitis before being diagnosed as having retinoblastoma.
Longmuir et al. recently reported a similar case of an 8.5-year-old boy with features of anterior uveitis.5 They treated the patient with steroids with minimal response to therapy. The patient was subjected to fine needle aspiration biopsy, which revealed cells with features suggestive of retinoblastoma. Our case was similar to the one described by Longmuir et al. where retinal focus of the tumor could not be found, although there is a possibility of missing the retinal focus owing to its small size or the focus might have involuted before presentation.
Although diffuse infiltrating retinoblastoma is more common in children older than 6 years of age, our case shows that it can also be seen in younger children. A high index of suspicion is needed in pediatric cases presenting as unresolving uveitis.
- Schofield PB. Diffuse infiltrating retinoblastoma. Br J Ophthalmol. 1960;44:35–41. doi:10.1136/bjo.44.1.35 [CrossRef]
- Bhatnagar R, Vine AK. Diffuse infiltrating retinoblastoma. Ophthalmology. 1991;98:1657–1661.
- Garner A, Kanski JJ, Kinnear F. Retinoblastoma: report of a case with minimal retinal involvement but massive anterior segment spread. Br J Ophthalmol. 1987;71:858–863. doi:10.1136/bjo.71.11.858 [CrossRef]
- Grossniklaus HE, Dhaliwal RS, Martin DF. Diffuse anterior retinoblastoma. Retina. 1998;18:238–241. doi:10.1097/00006982-199805000-00005 [CrossRef]
- Longmuir SQ, Syed NA, Boldt HC. Diffuse anterior retinoblastoma without retinal involvement. Ophthalmology. 2010:117;2034–2038. doi:10.1016/j.ophtha.2010.02.010 [CrossRef]