Abstract
Clinical diagnosis is always challenging in cases with atypical presentation. Herein, we present two cases which masqueraded as ocular infection/inflammation on presentation, were clinically suspicious for retinoblastoma, and histopathology revealed the diagnosis of retinal dysplasia. Case 1 had left corneal perforation with anterior chamber exudates on presentation. On ultrasound B-scan, ill-defined mass was noted, raising a suspicion of malignancy. MRI showed dilated ventricles with midline shift. Vitreous cytology was inconclusive. Enucleation was performed as malignancy could not be ruled out. Histopathology revealed detached retina with dysplastic rosettes in addition to inflammation and multinucleate giant cell reaction. Case 2 presented with right eye anterior chamber pseudohypopyon. Fundus examination revealed diffuse vitreous haze and a suspicious mass in the retinal periphery raising suspicion for retinoblastoma. Histopathology revealed the diagnosis of retinal dysplasia.
Keywords: paediatric oncology, retina
Background
Retinal dysplasia is an uncommon and non-progressive disorder which presents as part of chromosomal abnormalities like trisomy 13 and 18, x-linked disorder like Norrie’s disease or systemic disorders like Walker-Warburg syndrome.1 Retinal dysplasia occurs due to abnormal differentiation of the retinal cells owing to secondary cause rather than primary cause.1 Coincidental retinal dysplasia in patients presenting with pseudohypopyon is rare. We present two cases of retinal dysplasia which presented with pseudohypopyon secondary to underlying infection/inflammation.
Case presentation
Case 1: A 2-month-old male child presented with chief complaints of watering and white reflex in the left eye (OS) for 1 month as noticed by the mother. There was no significant history of prenatal or perinatal infections, trauma during birth or in the neonatal period. Family history was unremarkable. Systemic examination revealed no obvious abnormality. The referral diagnosis was retinoblastoma. On examination under anaesthesia, OS revealed diffuse conjunctival congestion with corneal perforation and fluffy white deposits admixed with blood in the anterior chamber (AC, figure 1), on the surface of the lens and on the corneal surface in the area of corneal perforation. The lens was cataractous with no view of fundus details.
Figure 1.
Clinical presentation, gross examination and histopathological examination of case 1. (A) Case 1 with diffuse conjunctival congestion, corneal perforation with organised exudate and fluffy exudates admixed with blood in the anterior chamber, (B) B-scan ultrasonography revealed an intraocular mass, (C) MRI of the orbit and brain revealed small left globe with a relatively well-defined intraocular lesion hypointense on T2 within an area of possible haemorrhage and (D) massive hydrocephalus of the frontal and occipital horns of the right lateral ventricle with a midline shift. (E) Photomicrograph of gross specimen showing retrolental detached retina with haemorrhagic exudates in the vitreous (F) cataractous lens with posterior capsular dehiscence (H&E; x100 magnification), (G) photomicrograph showing large, multilayered dysplastic rosettes with lumen lined by external limiting membrane (H&E; x100 magnification). (H) Rosettes stained positive for synaptophysin (x100 magnification), (I) neuron-specific enolase (x100 magnification) and (J) Ki67 (x100 magnification).
Case 2: A 7-year-old boy presented to the emergency clinic for diminution of vision in the right eye (OD) following trauma with stick 2 days ago while playing. His best-corrected visual acuity was 20/200 in OD and 20/20 in OS. OD anterior segment showed the presence of clear cornea with 4+ cells in the AC along with the presence of pseudohypopyon of 2 mm and a clear lens. OD fundus evaluation revealed a hazy media with 3+ vitritis and normal appearing optic disc with first and second order of vessels. Peripheral fundus evaluation showed the presence of mound-like elevation at ora serrata nasally (figure 2).
Figure 2.
Clinical presentation, gross examination and histopathological examination of case 2. (A) Right eye slit lamp photograph with quiet conjunctiva, clear cornea and presence of hypopyon. (B) Right eye B-scan showing low echo spikes membranous opacities. (C) Right eye UBM showing thickened ciliary body. (D) RetCam image of the right eye showing hazy media normal appearing optic disc and first-order vessels. (E) RetCam image of the right eye showing the presence of hypopigmented mound-like elevation near ora serrata. (F) Gross specimen of an enucleated eyeball showing hazy vitreous with whitish mass lesion near ciliary body. (G) Photomicrograph shows image from ciliary body area showing focal retinal dysplasia and chronic inflammatory infiltrates.
Investigations
Case 1: Corneal scrapings sent for microbiological cultures did not show growth of any organism and on histopathology, scrapping showed acute inflammatory cell infiltrate. Ocular ultrasonography revealed diffuse echoes in retrolental region and an ill-defined intraocular lesion with moderate echoes. MRI orbit revealed massive hydrocephalus of the frontal and occipital horns of the right lateral ventricle with a midline shift. Ocular features included a small left globe, with a relatively well-defined intraocular lesion which was isointense on T1 and hypointense on T2.
Case 2: Ultrasound B-scan showed low echo spikes membranous opacities in the vitreous cavity and ultrasound biomicroscopy (UBM) showed the presence of thickened ciliary body. Uveitic profile was within normal limits and no mass lesions or calcification were identified on CT of the orbit.
Differential diagnosis
A diagnosis of endogenous endophthalmitis was considered in case 1. A differential diagnosis of retinoblastoma was also considered.
In case 2, a diagnosis of retinoblastoma versus panuveitis was considered.
Treatment
In view of hydrocephalus and midline shift in case 1, ventriculoperitoneal shunt was placed prior to ocular intervention. OS enucleation and implant was performed 2 months after shunt surgery, when the globe had become phthisical.
Case 2 underwent OD enucleation and implant since retinoblastoma could not be ruled out.
Outcome and follow-up
After enucleation, both specimens were assessed on histopathology.
Case 1: On gross examination, cornea showed a healed perforation with clear AC. There was yellowish-white mass in the retrolental space to which the detached retina was attached. Vitreous cavity was filled with haemorrhagic exudates. Microscopic examination revealed scarred cornea with clear AC. Lens showed cataractous changes in the form of pyramidal projection of anterior capsule and posterior capsular dehiscence with collection of foamy macrophages. Fibrous tract with central artery indicating persistent fetal vasculature was seen to which detached and folded retina was seen attached. Numerous single or multilayered dysplastic rosettes having disorganised retinal layers with central lumen lined by external limiting membrane were seen. Retinal cells within rosettes showed intense expression of synaptophysin, neuron-specific enolase and low Ki67 index. Vitreous cavity was filled with haemorrhage admixed with chronic inflammatory cells, multinucleate giant cells and haemosiderin laden macrophages.
Case 2: Gross examination revealed thickened ora serrata nasally. Histopathological examination revealed presence of multiple retinal folds with occasional dysplastic rosette formation near the nasal ciliary body. These rosettes were lined by external limiting membrane with disorganised retinal cells surrounding it. Fibrous metaplasia of retina was also noted.
Discussion
Most common causes of leucocoria in a child include congenital cataract, Coats’ retinopathy, persistent fetal vasculature, endophthalmitis and retinoblastoma.2 3 Hypopyon/pseudohypopyon in the paediatric age group can occur either due to an infection or inflammation or masquerades.4 But in the clinical setting of hypopyon in a white eye, it should be considered as pseudohypopyon and it is an absolute must to rule out the masquerades before planning any diagnostic intraocular procedure.
In case 1, intraocular mass on imaging probably lead to a referral diagnosis of retinoblastoma. However, corneal perforation, AC exudates and an intraocular mass lead to our clinical suspicion of endogenous endophthalmitis with subretinal abscess. Sometimes, retinoblastoma and endophthalmitis can simulate each other resulting in a diagnostic dilemma.5
The intense inflammation with evidence of AC exudation on clinical examination and chronic inflammatory cells, multinucleate giant cells and haemosiderin-laden macrophages in the posterior chamber on histopathology can be attributed to lens-induced granulomatous reaction secondary to traction by the persistent fetal vasculature in case 1. These intense inflammatory responses mimicked endogenous endophthalmitis. Pseudohypopyon in case 1 could be related to corneal perforation or lens-induced granulomatous inflammation.
Retinal dysplasia occurs due to the disruption of architectural polarity of retinal layers leading to folds and rosettes, which are characteristically large and unilayered to multilayered with layers, directed inside out with central luminal lining of external limiting membrane containing Muller glia which are absent in rosettes of retinoblastoma.5 6 Exact pathogenesis of retinal dysplasia is unknown and many theories have been proposed. Retinal dysplasia could be secondary to an unknown stimulus including persistence of fetal vasculature, secondary to detachment from the underlying retinal pigment epithelium, secondary to congenital absence of retinal pigment epithelium and rarely an in situ dysplastic process with no evidence of detachment from underlying retinal pigment epithelium.6–8 In case 1, we hypothesise that the retinal dysplasia is related to the stimulus by persistent fetal vasculature.
Retinal dysplasia can have syndromic associations. Hydrocephalus, agyria and retinal dysplasia along with muscular dystrophy constitute Walker-Walburg syndrome, which has autosomal recessive inheritance and has poor prognosis.9 In case 1, the child had hydrocephalus and retinal dysplasia with no evidence of agyria or any other systemic association. However, genetic testing was not performed in our case.
In case 2, the patient presented with hypopyon in a white eye associated with a history of trauma and when signs of ocular trauma or inflammation could not be ruled out, we considered the differential diagnosis of anterior retinoblastoma which classically presents with pseudohypopyon where neoplastic cells get aggregated in AC and angles. The presence of pseudohypopyon in case 2 could be related to history of trauma, with traumatic uveitis manifesting as pseudohypopyon and vitreous haze, and retinal dysplasia could have been a coincidental finding. Histopathologically, rosettes are seen in both retina dysplasia and retinoblastoma.10 But the presence of positive staining of rosettes for photoreceptor protein rod opsin and cellular retinaldehyde-binding protein rules out retinoblastoma.11
Diagnostic precision is needed while reporting challenging cases as the above two cases, as the treatment course is completely different for an infectious aetiology and a malignancy. Presence of pseudohypopyon with a suspicious intraocular mass has mislead the approach in our cases. AC aspiration and cytological examination of the pseudohypopyon could have aided to rule out retinoblastoma, thus avoiding enucleation as the primary treatment in both cases. Two pathologies can coexist and retinal dysplasia could only be a coincidental finding as in both our cases.
Learning points.
Pseudohypopyon and leucocoria with intraocular mass is not always indicative of retinoblastoma and rule out all differential diagnoses.
Retinal dysplasia may sometimes be a coincidental finding in cases presenting with pseudohypopyon.
Histopathology is always a gold standard for a definitive diagnosis.
Cytological examination of pseudohypopyon can help to differentiate retinoblastoma from underlying ocular inflammation.
Acknowledgments
The authors acknowledge Dr Dilip K Mishra for providing the pathological support.
Footnotes
Contributors: SJ made the first draft and also contributed in histopathological diagnosis. APate helped in first draft and also in critical revision of the final draft. APath and SK were involved in patient care and critical revision of the manuscript.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Parental/guardian consent obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
- 1.Fulton AB, Craft JL, Howard RO, et al. Human retinal dysplasia. Am J Ophthalmol 1978;85:690–8. 10.1016/S0002-9394(14)77107-7 [DOI] [PubMed] [Google Scholar]
- 2.Shields CL, Schoenberg E, Kocher K, et al. Lesions simulating retinoblastoma (pseudoretinoblastoma) in 604 cases: results based on age at presentation. Ophthalmology 2013;120:311–6. 10.1016/j.ophtha.2012.07.067 [DOI] [PubMed] [Google Scholar]
- 3.Balmer A, Munier F. Differential diagnosis of leukocoria and strabismus, first presenting signs of retinoblastoma. Clin Ophthalmol 2007;1:431–9. [PMC free article] [PubMed] [Google Scholar]
- 4.Ramsay A, Lightman S. Hypopyon uveitis. Surv Ophthalmol 2001;46:1–18. 10.1016/S0039-6257(01)00231-4 [DOI] [PubMed] [Google Scholar]
- 5.Shields JA, Shields CL, Eagle RC, et al. Endogenous endophthalmitis simulating retinoblastoma. The 1993 David and Mary Seslen Endowment lecture. Retina 1995;15:213–9. [PubMed] [Google Scholar]
- 6.Godel V, Nemet P, Lazar M. Retinal dysplasia. Doc Ophthalmol 1981;51:277–88. 10.1007/BF00143890 [DOI] [PubMed] [Google Scholar]
- 7.Chan A, Lakshminrusimha S, Heffner R, et al. Histogenesis of retinal dysplasia in trisomy 13. Diagn Pathol 2007;2:48 10.1186/1746-1596-2-48 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Silverstein AM, Osburn BI, Prendergast RA. The pathogenesis of retinal dysplasia. Am J Ophthalmol 1971;72:13–21. 10.1016/0002-9394(71)91586-8 [DOI] [PubMed] [Google Scholar]
- 9.Gerding H, Gullotta F, Kuchelmeister K, et al. Ocular findings in Walker-Warburg syndrome. Child's Nerv Syst 1993;9:418–20. 10.1007/BF00306196 [DOI] [PubMed] [Google Scholar]
- 10.Agarwal N, Gupta P, Agarwal A, et al. Retinal dysplasia: a mimic of malignant ocular pathology. J Clin Diagn Res 2011;5:367–8. [Google Scholar]
- 11.Prasanna M, Kwatra K, Calton N, et al. Retinal dysplasia mimicking retinoblastoma. Indian J Pathol Microbiol 2013;56:64–5. 10.4103/0377-4929.116156 [DOI] [PubMed] [Google Scholar]