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 Table of Contents  
Year : 2015  |  Volume : 10  |  Issue : 3  |  Page : 316-319

Lesions simulating retinoblastoma at a tertiary care center

Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission21-Mar-2014
Date of Acceptance16-Mar-2015
Date of Web Publication26-Nov-2015

Correspondence Address:
Fariba Ghassemi
Eye Research Center, Farabi Eye Hospital, Qazvin Square, Tehran 13366
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2008-322X.170351

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Purpose: To determine the types and frequency of ocular conditions simulating retinoblastoma (pseudo-retinoblastoma) at Farabi Eye Hospital, Tehran, Iran. Methods: We reviewed data of patients who were referred with a diagnosis of retinoblastoma to Farabi Eye Hospital oncology clinic, from January 2009 to July 2013. Examination under general anesthesia was performed for all patients. Other investigations, such as ultrasonography, were performed as required. Results: Of a total of 331 patients (aged 1-60 months), 138 (42%) were found to be suffering from a benign disorder. Among these pseudo-retinoblastoma cases, Coats' disease was the most prevalent codition (n = 36, 26%); persistent hyperplastic primary vitreous (PHPV) and familial exudative vitreo-retinopathy (FEVR) were the next two common pseudo-retinoblastoma cases in our series. Conclusion: The rate of misdiagnosis upon referral to our center was close to 40%. The most common pseudo-retinoblastomas entities include Coats' disease, PHPV and FEVR. An accurate diagnosis is essential for management of pseudo-retinoblastoma cases.

Keywords: Coats' Disease; Pseudo-retinoblastoma; Retinoblastoma

How to cite this article:
Ghassemi F, Bazvand F, Makateb A. Lesions simulating retinoblastoma at a tertiary care center. J Ophthalmic Vis Res 2015;10:316-9

How to cite this URL:
Ghassemi F, Bazvand F, Makateb A. Lesions simulating retinoblastoma at a tertiary care center. J Ophthalmic Vis Res [serial online] 2015 [cited 2020 Sep 24];10:316-9. Available from: http://www.jovr.org/text.asp?2015/10/3/316/170351

  Introduction Top

Lesions with clinical similarities to retinoblastoma are known as pseudo-retinoblastoma. Differentiation of pseudo-retinoblastoma lesions is essential for proper management and to avoid unnecessary chemotherapy or enucleation. The two conditions commonly confused with retinoblastoma are Coats' disease and PFV.[1] In 1965, the first report of lesions that simulated retinoblastoma was published by Howard and Ellsworth.[2] They noted that 265 (53%), out of 500 children referred for suspected retinoblastoma had pseudo-retinoblastoma. The conditions included persistent hyperplastic primary vitreous (PHPV, or more recently known as persistent fetal vasculature [PFV]), retrolental fibroplasia or retinopathy of prematurity (ROP) and posterior cataracts, which together accounted for 46% of pseudo-retinoblastoma cases. Later, many case series of pseudo-retinoblastoma were reported.[3],[4],[5],[6],[7] In the reported series, different abnormalities simulating retinoblastoma were presented from different centres.[8],[9]

Herein, we report the rate and types of lesions simulating retinoblastoma at Farabi Eye Hospital as a referral center, during 5 years period.

  Methods Top

This study includes all patients who were referred specifically for suspicion of retinoblastoma to the ocular oncology clinic at Farabi Hospital, Tehran University of Medical Sciences, between January 2009 and July 2013. Institutional review board approval was obtained. Patients data were reviewed for age, gender, and signs and symptoms at presentation. A complete ocular examination was done under general anesthesia for each patient. A diagnosis was established, based on clinical findings and the results of diagnostic test results. Statistical analysis was performed using SPSS statistical software (Version 19, SPSS, Chicago, IL, USA). The data were reported in mean values ± standard deviation (SD).

  Results Top

A total of 331 patients (395 eyes) with mean age of 17.92 ± 15.16 (range, 1-60) months including 90 male patients (65%) were referred to our center during the specified time. The rate of pseudo-retinoblastoma diagnosis was 41.6% (138 cases). The right eye was involved in 50 cases (36.2%) and the left one was affected in 45 cases (32.6%). Both eyes were involved in 43 cases (31.2%). The common presentations were strabismus (n = 55, 39.9%) and leukocoria (n = 54, 39.1%), while microphthalmia (n = 8, 5.8%), nystagmus (n = 4, 2.9%), red eye (n = 3, 2.2%) and decreased vision (n = 2, 1.4%) were other presentations among our patients. The pseudo-retinoblastoma diagnoses are listed in [Table 1].
Table 1. The differential diagnosis of pseudo-retinoblastoma

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A total of 22 entities simulating retinoblastoma (pseudo-retinoblastoma) were encountered, the three most common of which included Coats' disease (n = 36; 26.1%), PHPV (n = 31; 22.5%), and familial exudative vitreoretinopathy (FEVR) (n = 14; 10.1%).

Bilateral cases of pseudoretinoblastoma included PHPV (14 subjects), spontaneously regressed ROP (9 cases), FEVR (7 subjects), coloboma (4 cases), astrocytoma (3 subjects), non-attached retina (2 cases), TORCH (toxoplasma, rubella, cytomegalovirus and herpes simplex virus infection) syndrome (2 subjects), Coats' disease (1 patient), and organized vitreous hemorrhage (1 patient).

  Discussion Top

The current series represents an extremely heterogeneous constellation of pseudo-retinoblastoma cases including 3 major conditions, namely Coats' disease, PHPV and FEVR, accounting for the majority (58.7%) of cases, along 19 other entities comprising the other 41.3% of cases.

The management of retinoblastoma has evlolved to globe-saving methods, leading to decreased enucleation rates in misdiagnosed cases of pseudo-retinoblastoma from 4% in 1960, to <1% in 2000.[10] Retinoblastoma may be detected by indirect ophthalmoscopy, as a yellow-white retinal tumor with a a dilated retinal artery and vein often with surrounding subretinal fluid, subretinal seeds and vitreous seeds.[11]

Other pediatric fundus abnormalities can mimic retinoblastoma, leading to difficulty in differentiation.[6],[10],[11] A precise ocular examination by an ocular oncologist is the best way to differentiate retinoblastoma from pseudo-retinoblastoma, due to distinguishing clinical features.[11],[12] However, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) may be helpful in diagnosis.[1],[13]

The rate of misdiagnoses varies from 5 to 50% and is influenced by several factors, including patient age, academic center versus non-academic center and laterality (6% in bilateral versus 12% in unilateral cases).[1],[2],[6],[14],[15] In the current series the rate of misdiagnosis was 42%.

The report by Howard and Ellsworth back in 1965 showed that the leading simulators of retinoblastoma cases, included PFV (19%), ROP (14%), posterior cataracts (14%), choroidal coloboma (12%), uveitis (10%), toxocara granuloma (7%), congenital retinal fold (5%) and Coats' disease (4%).[2] In 1991, Shields et al reported a slightly different spectrum that included PFV (28%), Coats' disease (16%), toxocariasis (16%), ROP (5%), combined hamartoma of the retina and RPE (4%), coloboma (4%), vitreous hemorrhage (4%), astrocytic hamartoma (3%) and FEVR (2%).[3] Maki et al found that 42 of 111 patients (38%) referred for retinoblastoma evaluation from 2004 to 2008 were pseudo-retinoblastoma cases.[16] PFV (31%) and Coats' Disease (29%) were the most common simulating lesions.

In the recent report by Shields et al from a larger series of 604 cases of pseudo-retinoblastoma, Coats' disease (40%), PFV (26%) and vitreous hemorrhage (5%) were the most common entities while ROP (1%) and cataract (1%) have become much less frequent.[1] Shields et al divided the patients into three age groups and the most frequent misdiagnoses belonged to PFV in patients ≤ one year old and Coats' disease in children older than 1 year.[1] Recent improvements in the clinical diagnosis and screening programs for ROP patients has changed the spectrum of pseudo-retinoblastomas.

Histopathologically, different etiologies have been reported.[3], 4, [17],[18],[19] In 1962, Kogan and Boniuk studied 257 enucleated eyes for suspected retinoblastoma and found pseudo-retinoblastoma in 24% of cases.[17] In 1969, Howard reported that the rate of mistaken diagnosis was 6% if the condition was bilateral, and 12% if it was unilateral.[4] In 1977, Robertson and Campbell evaluated 49 eyes enucleated for retinoblastoma at the Mayo Clinic from 1954 through 1974 and discovered 8 pseudo-retinoblastomas cases (16%).[5] Similarly, Margo and Zimmerman found that 15 of 56 (27%) eyes removed for retinoblastoma and submitted to the Armed Force Institute of Pathology between 1974 and 1980 were pseudo-retinoblastomas, most often Coats' disease and retinal detachment.[19] In the study by Balmer et al, Coats' disease was the most common misdiagnosis.[20] In another report, various congenital malformations and ocular inflammations were found as the most prevalent misdiagnosis causes.[21]

In an earlier study from our center, endophthalmitis was the most common diagnosis in pseudo-retinoblastoma.[7] The rate of pseudo-retinoblastoma in some consequent reports from a single center showed decreased rates of misdiagnoses.[1],[3] A reduction in erroneous enucleation for presumed malignancies, over the previous five decades, has been reported by Huang.[6]

Leukocoria was the most clinical presentation in pseudo-retinoblastoma among our cases. The clinical presentation in our series is in accordance with other studies reporting different signs and symptoms such as, leukocoria, strabismus, red eye, phthisis bulbi, hyphema, proptosis, pseudohypopyon, decreased vision and photophobia.[1],[15],[18]

In summary, ocular oncology centers continue to experience inaccuracy in referral diagnoses. A careful evaluation and accurate diagnosis is essential for proper management of pseudo-retinoblastoma cases and avoiding undue diagnostic or therapeutic procedures.

Financial Support and Sponsorship


Conflicts of Interest

There are no conflicts of interest.

  References Top

Shields CL, Schoenberg E, Kocher K, Shukla SY, Kaliki S, Shields JA. Lesions simulating retinoblastoma (pseudoretinoblastoma) in 604 cases: results based on age at presentation. Ophthalmology 2013;120:311-316.  Back to cited text no. 1
Howard GM, Ellsworth RM. Differential diagnosis of retinoblastoma. A statistical survey of 500 children. I. Relative frequency of the lesions which simulate retinoblastoma. Am J Ophthalmol 1965;60:610-618.  Back to cited text no. 2
Shields JA, Parsons HM, Shields CL, Shah P. Lesions simulating retinoblastoma. J Pediatr Ophthalmol Strabismus 1991;28:338-340.  Back to cited text no. 3
Howard GM. Erroneous clinical diagnoses of retinoblastoma and uveal melanoma. Trans Am Acad Ophthalmol Otolaryngol 1969;73:199-203.  Back to cited text no. 4
Robertson DM, Campbell RJ. Analysis of misdiagnosed retinoblastoma in a series of 726 enucleated eyes. Mod Probl Ophthalmol 1977;18:156-159.  Back to cited text no. 5
Huang S, Rutar T, Bloomer M, Crawford JB. Analysis of clinical misdiagnoses in children treated with enucleation. Arch Ophthalmol 2010;128:1009-1013.  Back to cited text no. 6
Asadi Amoli F, Piri N, Shams H. Etiologies of pseudoretinoblastomas in histopathologic speciemens of enucleated or exenterated eyes with clinical diagnosis of retinoblastoma. Acta Med Iran 2005;43:105-109.  Back to cited text no. 7
François J. Differential diagnosis of leukokoria in children. Ann Ophthalmol 1978;10:1375-1378, 1381-1382.  Back to cited text no. 8
Chuah CT, Lim MC, Seah LL, Ling Y, Chee SP. Pseudoretinoblastoma in enucleated eyes of Asian patients. Singapore Med J 2006;47:617-620.  Back to cited text no. 9
Shields CL, Kaliki S, Rojanaporn D, Al-Dahmash S, Bianciotto CG, Shields JA. Intravenous and intra-arterial chemotherapy for retinoblastoma: what have we learned? Curr Opin Ophthalmol 2012;23:202-209.  Back to cited text no. 10
Shields JA, Shields CL. Intraocular Tumors: An Atlas and Textbook. 2nd ed., Vol. 2. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 293-318.  Back to cited text no. 11
Bianciotto C, Shields CL. Clinical features. In: Ramasubramanian A, Shields CL, editors. Retinoblastoma. New Delhi, India: Jaypee Brothers Medical Publishers; 2012. p. 37-45.  Back to cited text no. 12
Potter PD, Shields CL, Shields JA, Flanders AE. The role of magnetic resonance imaging in children with intraocular tumors and simulating lesions. Ophthalmology 1996;103:1774-1783.  Back to cited text no. 13
McLean IW. Retinoblastomas, retinocytomas and pseudoretinolastomas. In: Spencer WH, Front RL, Gren WR, editors. Opthalmology: An Atlas and Textbook. 4th ed. Philadelphia: WB Saunders; 1996. p. 1332-1380.  Back to cited text no. 14
American Academy of Ophthalmology. Basic and Clinical Science Course: Ocular Pathology and Intraocular Tumors. San Francisco: The Fundation of American Academy of Ophthalmology; 2002-2003. p. 253-263.  Back to cited text no. 15
Maki JL, Marr BP, Abramson DH. Diagnosis of retinoblastoma: How good are referring physicians? Ophthalmic Genet 2009;30:199-205.  Back to cited text no. 16
Shields JA, Shields CL, Parsons HM. Differential diagnosis of retinoblastoma. Retina 1991;11:232-243.  Back to cited text no. 17
Kogan L, Boniuk M. Causes for enucleation in childhood with special reference to pseudogliomas and unsuspected retinoblastoma. Int Ophthalmol Clin 1962;2:507-524.   Back to cited text no. 18
Margo CE, Zimmerman LE. Retinoblastoma: The accuracy of clinical diagnosis in children treated by enucleation. J Pediatr Ophthalmol Strabismus 1983;20:227-229.  Back to cited text no. 19
Balmer A, Gailloud C, Uffer S, Munier F, Pescia G. Retinoblastoma and pseudoretinoblastoma: Diagnostic study. Klin Monbl Augenheilkd 1988;192:589-592.  Back to cited text no. 20
Hamburg A. Pseudoretinoblastoma. Differential diagnosis of 1 retinoblastoma. Klin Monbl Augenheilkd 1990;197:362-8.  Back to cited text no. 21


  [Table 1]

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