Current Eye Research, Early Online, 1–4, 2014 ! Informa Healthcare USA, Inc. ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2014.993086

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A 10-Year Survey: Prevalence of Ocular Surface Squamous Neoplasia in Clinically Benign Pterygium Specimens Fani Segev1,2, Michael Mimouni3, Gili Tessler2,4, Assaf Hilely2,4, Shay Ofir1,2, Deborah Kidron2,5, and Irit Bahar2,4 Curr Eye Res Downloaded from informahealthcare.com by Emory University on 08/07/15 For personal use only.

1

Department of Ophthalmology, Meir Medical Center, Kfar Sava, Israel, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel, 4Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel, and 5Department of Pathology, Meir Medical Center, Kfar Sava, Israel

ABSTRACT Purpose: It is essential to assess the yield of routine histopathological examination of pterygium specimens excised from clinically benign pterygium. The purpose of this study was to determine the rate of histopathologically identified ocular surface squamous neoplasia (OSSN) in clinically benign pterygium specimens. Materials and Methods: This retrospective consecutive study consisted of patients from the cornea services of the ophthalmology departments of Meir Medical Center, Kfar Sava, and Rabin Medical Center, Petah Tikva, Israel. Included patients were those with clinically benign pterygium who underwent pterygium excision between January 2002 and December 2011. The pterygium specimens were sent for histopathological examination and the pathology reports were reviewed for evidence of OSSN. Results: Overall, pathology reports of 682 eyes of 585 sequential patients were included in the study. There was a male predominance of cases (59%). Patients’ age ranged from 16 to 87 years with an average age of 56 years. Six hundred and forty-three cases were primary (94%) and 39 cases were recurrent (6%). Conclusions: Cases of clinically benign pterygium diagnosed and excised by an experienced corneal expert are less likely to harbor OSSN. The yield of routine histopathological examination of such specimens may be low. Keywords: Israel, ocular surface squamous neoplasia, prevalence, pterygium

INTRODUCTION

Ocular surface squamous neoplasia (OSSN) represents a spectrum of corneal or conjunctival epithelial neoplasias.6 Pterygium and OSSN share potential common risk factors such as exposure to UVB, chronic ocular surface irritation, or HPV infection.7–10 Pterygium and OSSN can coexist.11 In several studies, it has been suggested that pterygium is a stem cell disorder with premalignant features.12–15 Ocular surface squamous neoplasia may be the most common finding in ocular tumor surface biopsies (53%).16

Pterygium is a common ocular surface degenerative disorder. Its prevalence ranges from 0.3% to 12% depending on the geographic location.1 A ‘‘Pterygium belt’’ located between 37 degrees north and south of the equator has been described by Cameron ME.2 Countries with dry climates and exposure to ultraviolet B (UVB) light have higher rates.3,4 In Israel, the prevalence of pterygium has been reported to be approximately 2%.5

Received 16 May 2014; revised 25 October 2014; accepted 19 November 2014; published online 29 December 2014 Correspondence: Fani Segev MD, Department of Ophthalmology, Meir Medical Center, 59 Tchernichovsky St. Kfar Sava, 44410, Israel. Tel: +972 52 699 5044. Fax: +972 9 747 2427. E-mail: [email protected]

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F. Segev et al.

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The rate of OSSN in excised pterygia specimens has been studied in several different countries with a wide spectrum of results. An analysis of 612 eyes with conjunctival masses performed in Nigeria reported a rate of 0.5%.17 A retrospective study consisting of 26 squamous neoplasia specimens found that six were preoperatively diagnosed as pterygium.18 A recent observational case series of 498 clinically benign pterygia in Thailand reported an OSSN rate of 1.8%.19 The objective of this retrospective study was to measure the rate of histopathologically identified OSSN in pterygia specimens that appeared to be clinically benign. Identifying OSSN in clinically benign pterygium may justify routine histopathological examination of pterygium specimens, regardless of clinical appearance.

MATERIALS AND METHODS All data for the study were collected and analyzed in accordance with the policies and procedures of the Institutional Review Boards of Rabin Medical Center and Meir Medical Center and the tenets set forth in the declaration of Helsinki. Because of the retrospective nature of this study, the need for written informed consent was waived. Consecutive patients, diagnosed with pterygium requiring excision at the cornea services of the ophthalmology departments of Meir Medical Center, Kfar Sava, and Rabin Medical Center, Petah Tikva, Israel, from January 2002 through December 2011, were included. Ptergyium was defined as a wing-shaped fibrovascular conjunctival growth extending across the limbus onto the cornea.20,21 Only specimens from patients with clinically benign pterygium who had a pathology report were included in this study. Specimens belonging to patients in whom the pterygium was preoperatively clinically suspected for malignancy were excluded. The pathology reports were reviewed for evidence of OSSN, and the prevalence of OSSN was calculated.

than a third thickness), moderate (atypical cells occupying less than three quarters), and severe dysplasia (nearly full thickness occupied by atypical cells) or carcinoma in situ (full thickness occupied by atypical cells with loss of the normal surface layer).22,23 One hundred and thirty-five samples (20%) of the microscopic slides were reexamined by a third ocular pathologist who confirmed the diagnosis.

Data Collection Information recorded from the pathology reports included preoperative diagnosis, gender, age, ethnicity, involved eye, tumor grade, tumor location, and presence or absence at the surgical margins.

Statistical Analysis All statistical analyses were performed using the Statistical Package for the Social Sciences version 19.0 (SPSS Inc., Chicago, IL). Means and frequencies of demographic and clinical variables were calculated. Standard deviation (SD) was calculated.

RESULTS There were 682 sequential eyes with surgically excised pterygia specimens throughout the 10-year period that met the inclusion criteria. There was a male predominance of cases (59%). Patients’ age ranged from 16 to 87 years with an average age of 56 years. Ethnic distribution among our patients cohort was as followed: all patients were Caucasians while 78% of Jewish ethnic origin and 22% of the patients were of Arabic ethnic origin. Six hundred and forty-three cases were primary (94%) and 39 cases were recurrent (6%). The ratio of right to left eyes was 0.89:1.00. No cases of coexisting OSSN were detected in the included reports.

Surgical Technique DISCUSSION All lesions were removed by excising the lesion and using a conjunctival autograft or an amniotic membrane graft. Specimens were submitted for routine pathologic examination in formalin fixation. All specimens underwent paraffin embedding after which 4 mm sections were produced. Six sections at three different levels that underwent hematoxylin–eosin staining were mounted on slides and if determined necessary by the ocular pathologist a set of six sections were examined at six levels. In each of the centers, the pathologists who reviewed the specimens were trained ocular pathologists. The OSSN findings were classified as mild (atypical cells occupying less

In our study, the diagnosis of OSSN in clinically benign pterygia specimens occurred in 0% of the cases. This finding must be placed in the context of the potential catastrophic repercussions of undiagnosed OSSN.24–26 The rate of concomitant OSSN in pterygia specimens varies worldwide from 0% to 9.8% as summarized in Table 1. In a retrospective analysis of 2005 pterygia pathology records in Miami, FL, 1.7% were found to have OSSN of which 41% were clinically ‘‘suspected’’ preoperatively and 59% were unexpectedly found on histopathology.27 A retrospective Current Eye Research

Rate of OSSN in Clinically Benign Pterygium

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TABLE 1 Reported ocular surface squamous neoplasia (OSSN) rates in previous studies.

Population country Nigeria Canada Thailand Florida Florida Australia Australia

Study Akinsola et al.17 Yeung et al.29 Artornsombudh et al.19 Oellers et al.27 McClellan et al.11 Hirst et al.28 Chui et al.12

Only ‘‘unsuspected’’ pterygium No Yes Yes No No Nob Yes

Sample size

OSSN rate (%)

612 1227 498 2005 590a 533 100

0.5 0 1.8 1.7 1.4 9.8 5

Cornea service population Not Yes Not Not Not Not Not

specified specified specified specified specified specified

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Of 24,179 participants, 590 were preoperatively diagnosed with pterygium. Of 533 participants, three were preoperatively diagnosed with a clinically suspicious looking pterygium.

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analysis of 533 pterygia specimens conducted in Queensland, Australia, detected an OSSN rate of 9.8%.28 Only three of the specimens were suspicious for OSSN before surgery. A subsequent study in Australia found that 5% of 100 clinically benign pterygium cases had foci of OSSN on histopathological review.12 However, an 8-year survey of 1227 clinically benign pterygia specimens, collected from a cornea service in Canada, reported 0 cases of OSSN.29 Our study found a surprisingly low rate of OSSN (0%) when compared with other studies. Israel is a country with a high exposure of UVB and is located within the ‘‘pterygium belt’’ with a prevalence of pterygium being reported to be 2%.5 Therefore, it had been expected that the incidence of OSSN would be relatively high. A possible explanation for this difference is that three of the six studies listed in Table 1 did not exclude pterygia ‘‘suspicious’’ for OSSN. Another possible explanation is that the patients in this study were treated at the Cornea Services of two tertiary care facilities. Therefore, it may be that a cornea specialist is more experienced and has a higher index of suspicion when identifying a pterygia as being ‘‘suspicious’’ or ‘‘unsuspicious’’ for OSSN. A case report described by Hassani et al.30 suggested the use of in vivo confocal microscopy to diagnose invasive OSSN. Recently, the use of ultrahigh-resolution OCT for distinguishing OSSN and pterygium along with other ocular surface pathologies has been suggested.31,32 An alternative (1% toluidine blue eye drops) was suggested to be an efficient method for clinical diagnosis of OSSN and premalignant lesions.33 The above-mentioned studies are still small in terms of sample size and many more cases are needed to establish the sensitivity and the specificity of these modalities in a clinically benign pterygium, but they may further increase our ability to identify a ‘‘suspected’’ pterygium before surgery and thus reduce the rate of OSSN in clinically benign pterygium. A limitation of our study is that it was a retrospective one. However, it is the first study to !

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investigate the rate of OSSN in cases of clinically benign pterygia in Israel. An additional limitation of this study, potentially explaining the variation in reported OSSN rates in clinically benign pterygium, is that the thresholds for grading squamous dysplasia in conjunctival specimens may vary widely between pathologists and institutions. In summary, this study did not reveal coexistence of OSSN in surgically excised pterygia, thus the yield of routine histopathological examination of such specimens may be low. One must bear in mind that all the patients in this study were preoperatively examined by a cornea specialist and that a definitive diagnosis can only be made by histopathology. Thus, and with respect to previous studies published, our recommendation to the general ophthalmologist is still to perform histopathology studies for all pterygium specimens.

DECLARATION OF INTEREST All authors declare that they have no conflict of interest exists. All authors declare that no funding or financial support was received for this study.

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Current Eye Research

A 10-year survey: prevalence of ocular surface squamous neoplasia in clinically benign pterygium specimens.

It is essential to assess the yield of routine histopathological examination of pterygium specimens excised from clinically benign pterygium. The purp...
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