The incidence of cancer in children and adolescents is
comparatively low [1,2], and the most common malignancies in
children include leukemia, lymphoma, and central nervous system
tumors [3].
Retinoblastoma has been reported in a population-based registry
study to be the fourth most common cancer in children aged 0 to
14 years, constituting 6% cases, but it was rare in older
children and adolescents (<1%) [3]. There is no big data
analysis focusing on ocular tumors in children and adolescents.
In this study, we describe the profile of benign and malignant
ocular tumors in Indian children and adolescents.
METHODS
This was a
retrospective hospital-based study of children diagnosed with
eye tumors presenting between November, 2015 and October, 2018
to four referral centers spread across four states in India. For
this study, a patient was considered as a child when the age was
21 years or lower [4]. They were further classified as neonate
(birth to 27 days), infant (28 days to 12 months), toddler (1 to
2 years), childhood (3 to 11 years), and adolescence (12 to 21
years) [4]. Consent for electronic data privacy was obtained
from the patient (if age at presentation was >18 years) or
parents/guardians (if age of the patient was
£18 years) at the time of registration. No identifiable
information of the patient was used for analytical purposes.
Each patient underwent a comprehensive ophthalmic examination,
and data were entered into a browser-based in-house developed
electronic medical records system (eyeSmart EMR). The study was
approved by the Institutional Ethics Committee of the institute.
The data of all children diagnosed
with eye tumors during the study period was retrieved from the
EMR database. The patients with a confirmed clinical and/or
histopathological diagnosis were included in this study. All
patients who underwent surgical intervention had a confirmed
histopathological diagnosis. Those with uncertain diagnosis or
inadequate data were excluded. The data on patient demographics,
ocular diagnosis, tumor status, and anatomical category were
used for analysis.
Statistical
analyses:
Descriptive
statistics was used to elucidata demographic and diagnostic data
using Microsoft Excel 2013 (Microsoft Corporation, Redmond,
USA).
RESULTS
Of the 728,077 new patients presenting to the four centers of
the network during the period under study, 118,648 (16%)
patients were at or below the age of 21 years. Of these, 3506
(2.9%) were diagnosed with eye tumors. Of these, 595 patients
who did not have a confirmed diagnosis of eye tumor were
excluded from the study, and 2,911 (2.4%) patients (51% males)
with a definitive diagnosis of benign or malignant tumor, either
by clinical examination or confirmed by histopathology were
included in the study.
The median age (range) at diagnosis was 7 years (2 days to 21
years). The age-wise distribution of patients with eye tumors
included neonates (n=18, 0.6%), infants (n=242,
8.3%), toddlers (n=511, 17.5%), childhood (n=1259,
43.2%), and adolescents (n=655, 22.5%).
Majority of patients (24%) were in the age group of 6 to 11
years.
There were 3,003 tumors (69% benign) in 2,911 patients, which
were segregated into nine anatomical categories. The most common
anatomical part involved was the conjunctiva with 949 (31.6%)
cases and the least was lacrimal sac with 1 case (Table
I).
Table I Anatomical Distribution of Ocular and Peribocular Tumors and Tumor Status According to Age Group
| Feature | Benign | Malignant | All cases |
| (n=2058) | (n=945) | (N=3003) |
| Tumor location | | | |
| Conjunctiva | 907 (96) | 42 (4) | 949 (32) |
| Retina | 68 (7) | 842 (93) | 911 (30) |
| Orbit | 483 (90) | 54 (10) | 536 (18) |
| Eyelid | 469 (99) | 5 (1) | 474 (16) |
| Choroid | 51 (98) | 1 (2) | 52 (2) |
| Iris | 49 (98) | 1 (2) | 50 (2) |
| Caruncle | 23 (100) | 0 | 23 (<0.8) |
| Ciliary body | 7 (100) | 0 | 7 (<0.2) |
| Lacrimal sac | 1 (100) | 0 | 1 (<0.2) |
| Age category | | | |
| Neonate | 15 (0.7) | 5 (0.4) | 20 (0.7 ) |
| Infant | 160 (8) | 94 (9.9) | 254 (8) |
| Toddler | 218 (11) | 308 ( ) | 526 (18) |
| Childhood | 835 (41) | 442 ( ) | 542 (43) |
| Adolescence | 830 (40) | 96 ( ) | 926 (30) |
| All values in n (%). |
The three most common tumors included retinoblastoma (835, 28%),
conjunctival nevus (445, 15%), and orbital dermoid cyst (206,
7%). Amongst the benign tumors, the three most common were
conjunctival nevus (445, 22%), orbital dermoid cyst (206, 10%),
and periocular infantile capillary hemangioma (181, 9%). Amongst
the malignant tumors, the three most common were retinoblastoma
(835, 88%), Xeroderma pigmentosa-related ocular surface squamous
neoplasia (OSSN) (38, 4%), and rhabdomyosarcoma (17, 2%). The
most common tumor in the eyelid was infantile capillary
hemangioma (n=181, 6%); in caruncle inclusion cyst (n=9,
<1%); in conjunctiva, conjunctival nevus (n=445, 15%); in
iris trauma-related iris stromal cyst (n=15, <1%); in
ciliary body,
medulloepithelioma (n=5, <1%), in retina,
retinoblastoma (n=835, 28%); in choroid, toxocara
granuloma (n=15, <1%), in orbit, dermoid cyst (n=206,
7%); and in lacrimal sac, granuloma (n=1, <1%).
The most common tumor in younger children (0-2 years, 800
tumors) and older
children (3 to 11 years, 1277 tumors) was retinoblastoma (50%
and 31%, respectively), In adolescents (12-21 years, 926
tumors), conjunctival nevus (194, 21%) was the most common.
Distribution according to the age is presented in Table
II.
Table II Ocular and Periocular Tumor Distribution According to Age in Indian Children and Adolescents
| Age group | Commonest tumor (n=3003) | No. (%) | Commonest benign tumor (n=2058) | No. (%) | Commonest malignant tumor (n=945) | No. (%) |
| Neonate | Retinoblastoma | 4 (20) | Dermolipoma | 2 (12) | Retinoblastoma | 4 (80) |
| Infant | Retinoblastoma | 95 (37) | Infantile capillary hemangioma | 94 (59) | Retinoblastoma | 95 (99) |
| Toddler | Retinoblastoma | 302 (57) | Infantile capillary hemangioma | 48 (22) | Retinoblastoma | 302 (98) |
| Childhood | Retinoblastoma | 394 (31) | Conjunctival nevus | 240 (29) | Retinoblastoma | 394 (89) |
| Adolescence | Conjunctival nevus | 194 (21) | Conjunctival nevus | 194 (24) | Retinoblastoma | 39 (40) |
Histopathological confirmation of diagnosis was available in 792
(26%) tumors, while the remaining 2211 (74%) tumors were
diagnosed clinically. Accurate clinico-pathological correlation
was noted in 747 (94%) tumors, while discordance between
clinical and histopathological diagnosis was noted in 45 (6%)
tumors. Of the cases with a discordant clinical and
histopathological diagnosis, three tumors had a clinical
diagnosis of benign tumor, while histopathology revealed a
malignant tumor; 9 (1.1%) tumors had a clinical diagnosis of
malignant tumor, while histopathology revealed a benign tumor;
and 26 (3.3%) tumors had a different diagnosis in the same
category of benign tumors; and 7 (0.9%) tumors had a different
diagnosis in the same category of malignant tumors.
DISCUSSION
Both benign and
malignant ocular tumors can occur during childhood and
adolescence [5-11]. We found conjunctival nevus to be most
common benign tumor in children and retinoblastoma as the most
common malignant tumor. Retinoblastoma was also the most common
tumor in children encountered in this
referral-based hospital setting.
The limitations of our study include
the retrospective nature of the study and possible referral bias
since it is a hospital-based study. However, the strength of the
study includes larger number of patients and accurate diagnosis
by a trained ocular/ophthalmic oncologist, resulting in a good
clinico-pathological correlation in 94% tumors, whenever
histopathological diagnosis was available.
Reddy, et al. [5] reviewed 75
ocular tumors in children aged 3 months to 12 years and found
52% to be benign; retinoblastoma (44%) was the most common
tumor, constituting 92% of all malignant ocular tumors in
children. In their study, non-specific conjunctival granuloma
was the most common benign tumor constituting 33% of all benign
tumors in children [5].
In a review of 806 children with
conjunctival tumors, 97% were benign and 3% were malignant with
the most common benign conjunctival tumor being nevus (61%)
[12]. Conjunctiva was the most common tissue involved by a tumor
in our study also, with nevus being the most common. OSSN was
the second most common malignant tumor in our patients.
All children and adolescents with OSSN had associated
xeroderma pigmentosum. It is well established that patients with
xeroderma pigmentosum develop ocular and periocular tumors at
younger age compared to the general population [13].
In conclusion, benign tumors are more common in children and
adolescents except in cases with retinal tissue involvement.
Eventhough benign tumors may not be life-threatening, immediate
intervention is warranted in cases which are vision-threatening.
Pediatricians, who are the first point of contact in most of
these cases, play an important role in diagnosis of pediatric
ocular tumors and appropriate referral.
Acknowledgement:
Mr Ranganath Vadapalli and Mr. Mohammad Pasha.
Contributors:
SK: contributed with the conceptualization, planning, data
validation, and first draft of the manuscript; AVD: contributed
with data acquisition, data validation, and review of
manuscript.
Funding:
None; Competing interest: None stated.
| What This Study Adds? |
• Retinoblastoma was the most
common ocular tumor encountered in a referral-based
ocular oncology set-up.
• The most common tumor
in each age group differs, with retinoblastoma being
common in children and conjunctival nevus in
adolescents.
|
REFERENCES
1. White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley
SJ. Age and cancer risk: a potentially modifiable relationship.
Am J Prev Med. 2014;46:S7-15.
2. Bleyer A. Young
adult oncology: The patients and their survival challenges. CA
Cancer J Clin. 2007;57:242-55.
3. Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya
A, Bray F, et al; IICC-3 contributors. International
incidence of childhood cancer, 2001-10:
A population-based registry study. Lancet Oncol.
2017;18:719-31.
4. Williams K, Thomson D, Seto I, Contopoulos-loannidis DG,
Ioannidis JP, Curtis S, et al. StaR Child Health Group.
Standard 6: age groups for pediatric trials. Pediatrics.
2012;129:S153-60.
5. Reddy SC, Sarma CS, Rao VV, Banerjea S. Ocular tumours in
children - A study of 75 cases. Indian J Ophthalmol.
1983;31:421-3.
6. Shields JA,
Shields CL. Ocular tumors of childhood. Pediatr Clin North Am.
1993;40:805-26.
7. Shields JA,
Shields CL. Pediatric ocular and periocular tumors. Pediatr Ann.
2001;30:491-501.
8. Castillo BV Jr,
Kaufman L. Pediatric tumors of the eye and orbit. Pediatr Clin
North Am. 2003;50:149-72.
9. Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd
NW 3rd. Presenting signs of retinoblastoma. J Pediatr.
1998;132:505-8.
10. Kaliki S, Patel A, Iram S, Ramappa G, Mohamed A, Palkonda
VAR. Retinoblastoma in India: Clinical presentation and outcome
in 1,457 patients (2,074 eyes). Retina. 2019;39:379-91.
11. Shields CL, Shields JA, Shah P. Retinoblastoma in older
children. Ophthalmology. 1991;98:395-9.
12. Shields CL, Sioufi K, Alset AE, Boal NS, Casey MG, Knapp AN,
et al. Clinical features differentiating benign from
malignant conjunctival tumors in children. JAMA Ophthalmol.
2017;135:215-24.
13. Kaliki S, Jajapuram SD, Maniar A, Mishra DK. Ocular and
periocular tumors in xeroderma pigmentosum: A study of 120 Asian
Indian patients. Am J Ophthalmol. 2019;198: 146-53.
