Histopathological pattern of Orbito-Ocular Lesions, a retrospective hospital-based study spanning 15 years

Background Many previous studies on orbito-ocular lesions are skewed in favour of the neoplastic lesions in general and the malignant lesions in particular. This, therefore, creates a vacuum on the spectrum of these lesions, thus may result in problematic diagnostic bias by the ophthalmologist and pathologist. Objective To give the spectrum and relative frequencies of orbito-ocular biopsies and by extension orbito-ocular lesions/diseases at the University of Benin Teaching Hospital (UBTH). Materials and Methods A retrospective descriptive study of all cases of orbito-ocular biopsies with histopathologic diagnosis. Results There were 236 orbito-ocular biopsies. The male to female ratio was slightly in favour of the females. Orbito-ocular biopsies had a wide age range that spanned from the 1st to 10th decade, mean age in the 3rd decade (20–29years) and a peak age in the 1st decade (0–9 years). The neoplastic lesions were the prevalent indication for orbito-ocular biopsies (63.72%) while the conjunctiva (58.10%) was the most common site for orbito-ocular biopsies. Conclusion This study noted a wide array of orbito-ocular lesions for which biopsies were done for histopathological diagnosis. This we hope will in no small measure increase the diagnostic precision of the ophthalmologist and the pathologists in our own environment.


Introduction
The orbit is that part of the skull that is formed by 7 bones. 1 These bones form the orbital cavities that house the eyeballs and its adnexal structures. 1 These structures are home to diseases that vary from the non-neoplastic lesions (degenerative, inflammatory, infective, traumatic) to the neoplastic lesion (benign, premalignant and malignant). 2 These diseases are a significant cause of morbidity and mortality, 3,4 however studies on lesions of the eye and its adnexal are mostly on neoplastic lesions, although limited histopathologic studies which include the complete spectrum of ophthalmic biopsies have been carried out. 3,[5][6][7][8][9][10] The rarity at which orbito-ocular lesions occur complicates the recognition of their fine and sometimes subtle presentations. 10,11 This can pose a huge diagnostic dilemma to the ophthalmologist and pathologist, more so that clinical signs and symptoms of ocular malignancies had been reported to mimic more commonly occurring benign conditions. 10 To this end, we aim to determine the spectrum of histopathological diagnosis of orbito-ocular lesions at the University of Benin Teaching Hospital (UBTH).

Materials and Methods:
This study was a retrospective chart review of all orbito-ocular biopsies that were received in the Department of Anatomic Pathology, UBTH. The Department of Anatomic Pathology UBTH, Edo State, South-South, Nigeria was the location for this study. This hospital is a referral centre to all other secondary and primary health care facilities within Edo and Delta sub-region and from elsewhere especially its catchment area of Ondo, Kogi and Anambra states. 12 This study was carried out over a15 year period from from 1st of January 2005 to 31 st of December 2019. Data for this study were obtained from the surgical pathology registers, histology request cards, and duplicate copies of histopathology reports. Information obtained included age, gender, nature of specimen, site of lesion and histopathologic characteristics. The data obtained were analysed using the Statistical Package for Social Sciences, version 20 (SPSS 20, IBM Corp. Armonk, NY, United States of America). Qualitative (sex, site and histopathological diagnosis) and quantitative (age) data were analysed for discussion. For the former, the respective frequency of orbito-ocular lesions and their corresponding rates in percentages were analysed. For the latter, the age range, mean age, standard deviation, peak age were analysed for the respective orbito-ocular lesions Ethical approval was sought from the ethics and research committee of the University of Benin Teaching Hospital. It was granted with an assigned ethical approval number, ADM/E22/A/VOL.VII/14831124.

Results:
Two hundred thirty six (236) ophthalmic biopsies were received during the period under review. The age group and sex distribution of the ophthalmic biopsies is as shown in the Table 1. The ages of 27 of the cases were not documented and analyses pertaining to age were done on the documented ages of the remaining 209 cases. Their ages ranged from 6 months to 96 years with a mean age and standard deviation of 26.76 ± 23.74 years, and a median age of 26.00 years. Orbito-ocular biopsies peaked in the 1st decade and accounted for 64 cases (27.12%). This decade also accounted for the peak age in the males and females. A slight female predilection was observed in the study population with a male to female ratio of 1:1.01 with a corresponding percentage of 49.6% (117 male) to 50.4% (118 female). The sex was not specified in a case. The malignant orbital tumours (MOTs) were the most common orbito-ocular lesions as they accounted for 36.0 % of cases while the benign orbito-ocular tumours (BOTs) (26.7%), degenerative lesions (11.0%), and infective/inflammatory lesions (9.0%) were next in frequencies in decreasing order as shown in Tables, 2, 3 and 4. Other less common orbito-ocular lesions are as shown in Table 4.
There are 85 cases of MOTs with squamous cell carcinoma (figure 1) and retinoblastoma (figure 2) accounting for 45.9% (39/85 cases) and 44.7% (38/85 cases) respectively. Other less common MOTs including but not limited to adenoid cystic carcinoma (figure 3) are as shown in Table  2. The peak age of MOTs was in the 3rd decade (20-29 years age group).    Squamous cell papilloma (figure 4) was the most common cause of BOTs seen in this study. It accounted for 31.8% (21/66cases) of cases of benign orbito-ocular tumours. This was followed in decreasing order of frequency by pyogenic granuloma (21%) and lipoma (12.1%) as shown in table 3. Other less common causes of primary benign orbito-ocular tumours are as shown in Table 3. Degenerative orbital lesion was secondary to pterygium (figure 5) in 100% of cases (26/26) as shown in Table 4. The 5 th to 7 th decade accounted for most (11/24) cases of this lesion.    Chronic panophthalmitis was the most common infective and inflammatory orbito-ocular lesion observed in this study. It accounted for 52.3% (11/21) of cases in this category while hyperplastic inflammatory polyp (1/21) was the least cause of infective and inflammatory orbito-ocular lesions observed in this study. Other causes of infective and inflammatory orbito-ocular lesions are shown in table 4. See photomicrograph of conjunctivitis in figure  6.
Ophthalmic cysts and premalignant lesions accounted for 8% and 5.9% of all orbito-ocular lesions in this study.
Other less common orbito-ocular lesions are as shown in table 4. The conjunctiva (58.1%) and the lacrimal gland (0.40%) are the most and least common sites for orbito-ocular biopsies as shown in Table 5. The site distribution of orbito-ocular biopsies are as shown Table 5.

Discussion
Orbito-ocular diseases are an important cause of morbidity-mortality and constitute a major health challenge in sub-Saharan Africa. 3,4,13 Pathological lesions that ranges from the non-neoplastic (trauma, degenerative, inflammatory and infective) to the neoplastic lesions can affect any of the different constituents of the orbito-ocular system. 2,14 Variations in the pattern of orbito-ocular diseases are noted especially with regard to age, sex, site and possible aetiological factors. 4 The University of Benin Teaching Hospital is a referral centre to all other secondary and primary health care facilities within Edo and Delta sub-region and also areas within its catchment area, hence the data generated from ocular and orbital specimens received in the Department of Anatomic Pathology may be regarded as representative indicator of the patterns in the distribution of ocular and orbital lesions in this part of the country.
Orbito-ocular lesions peaked in the 1st decade (0-9 years) in this study. This is consistent with the findings of previous studies in central India by Gupta 13,17,18 This is consistent with the findings of this study that noted a preponderance of orbito-ocular lesions in individuals less than 20 years of age. The mean age for those with orbito-ocular lesions in this study was in the 3rd decade. This is a decade less than what previous studies done in Nigeria had reported. 4,19,20 Again, this disparity may be related to samples size which is between 66 to 148 and this is less than the sample size in the present series. We also observed that orbito-ocular lesions have a wide age range spanning infancy (6 months) through old age ( 10,25 Common amongst these findings, including that of this study is that retinoblastoma is the most common malignant childhood tumour. 10,20,22,23,25 The benign ophthalmic neoplastic lesions were the second most common (26.7%) indication for ophthalmic biopsies in this study. This is consistent with the reports of Charles et al (Benin City) and Ackuaku-Dogbe (Korle-Bu, Ghana) who noted that 27.9 to 29.5% of ophthalmic biopsies were benign ophthalmic neoplastic lesions thus making it the second most common indication for ophthalmic biopsies in these series. 20,24 Unlike this study, higher frequencies (percentages) of benign ophthalmic neoplastic lesions ranging from 54.4% to 70% have been reported in Nepal and India thus making it the most common indication of ophthalmic lesions in these series. 15,16,21 This study showed that squamous cell papilloma (33.3%) was the most frequent benign ophthalmic lesion, followed by pyogenic granuloma and lipoma. Umar et al, Charles et al and Onwubuya et al had reported previously from their respective studies that squamous cell papilloma (13.6% to 32.58%) was the most common benign neoplastic lesion. 4,20,25 Gupta et al reported that vascular (angiomatous) tumours were the most common (44.7%) benign neoplastic lesion, unlike this study that noted that vascular tumours (pyogenic granuloma) occurred at a lesser percentage (23.8%). 10 Gupta et al and Charles et al reported that the benign tumour of adipocytes (lipoma) accounted for 2.6% representing the least common tumour and 12.9% representing the second most common tumour respectively of benign ophthalmic neoplastic lesions. 10,20 The percentage (12.7%) of lipoma in this study is comparatively similar to that of Charles et al from the same environment, however unlike Charles et al observation, it was the third most common lesion in this study. 20 We observed that degenerative ophthalmic lesion was the third most common (11%) indication for ophthalmic biopsies. Ackuaku (Korle-Bu, Ghana), Gupta 4,10,20,24 Pterygium accounted for all the cases of degenerative lesion in the report of Charles et al and cases were seen in the young and middle ages.20 This is similar to the findings of this study. A high lifetime exposure to UV (ultraviolet) rays had been shown to be strongly associated with the development of pterygium. 26,27 In the same vain, genetic alterations of proto-oncogenes such as K-RAS (Kirsten-Ras), alterations in the expression of tumour suppressor genes (p53 or p63), elaboration of several cytokines (including growth factors and growth factor receptors) by UV radiation mediated expression and a high prevalence of human papilloma viruses (HPVs) in pterygium tissue samples have been found in association with the development of this lesion. 27 To this end, pterygium may actually represent a proliferative lesion rather than a degenerative lesion. 27 The infective and inflammatory ophthalmic lesion was the 4th most common (9%) indication for ophthalmic biopsies. Its value falls within the range of inflammatory ophthalmic lesion (6.06 to 24.8%) with respect to the indication for ophthalmic biopsies as reported from previous studies. 4,10,20,21 Chronic panophthalmitis was the most common infective and inflammatory lesion observed in this study. This is contrary to the findings of Charles et al who reported that inflammatory lesions of the conjunctiva was the most prevalent cause of inflammatory ophthalmic lesion. 20 However in this study it was among the least indications of inflammatory ophthalmic biopsies. Chalazion accounted for 1.27% of ophthalmic biopsies in this study. This is comparatively similar to the findings of Bastola et al who reported that this lesion accounted for 1% of ophthalmic biopsies. 15 Ophthalmic cyst was the 5th most common indication for ophthalmic biopsies accounting for 8.01% of cases. Ophthalmic cyst accounting for a higher percentage (11.89 to 20%) of ophthalmic biopsies had been reported in Nepal and India. 10,15 Epidermal inclusion cyst (94.7%) was the most prevalent cyst in this study while the lacrimal gland cyst was less common (5.3%) in comparison to the former. Contrary to these findings, Bastola et al reported that dermoid cyst was the most prevalent cystic lesion accounting for 60% of cases in their study.15 This was followed by epidermal inclusion cyst (40%). 15 Ophthalmic premalignant lesion was the 6th most common (5.91%) indication for ophthalmic biopsies in this study. This falls within the percentage range (3.8-19.6%) of ophthalmic premalignant lesion as observed in previous studies. 4,20 The conjunctiva was the most common (58.1%) site of ophthalmic biopsies in this study. This is comparatively similar to the findings of previous studies in this environment. 13,20 It is however contrary to the findings of Anunobi et al and Bastola et al who reported that the conjunctiva was the second most common site for ophthalmic biopsies. 15,17 They reported that conjunctiva biopsies accounted for 20.1 -22.0% of ophthalmic biopsies. 15,17 In this study, intraocular (eyeball) biopsies were the second most common site (25.8%) of ophthalmic biopsies. This is comparatively similar to the findings of previous works in this environment. 13,20 This finding is in contrast to a previous report from Lagos by Anunobi et al who reported that the eyeball was the most common site for ophthalmic biopsies. 17 The eye lid was the third most common site (11.9%) of ophthalmic biopsies in this study. This finding is consistent with that of Aligbe et al and Charles et al from the same environment. 13,20 Contrary to the finding of this study, previous studies from Nepal and India have reported that the eyelid was the most common site of ophthalmic biopsies accounting for 33.6-57.0% of ophthalmic biopsies. 10,15 The surge in cystic eyelid lesion (dermoid cyst and epidermal inclusion cyst) and Rhinosporidiosis for the Nepal and India studies respectively accounted for this site (eyelid) being the most common site in these studies. 10,15 The eyeball, the conjunctiva and the eye lid constitute the vast majority of ophthalmic biopsies. This is consistent with the findings of previous researches. 10,13,15,17,20 There is paucity of published histopathological data on the widespread variation of ophthalmic biopsies and by extension ophthalmic lesions in Nigeria. This has greatly reduced the extent to which the observations of this study in comparison to others would have adequately helped to draw a conclusion on ophthalmic biopsies in Nigeria. This is a limitation of this study.

Conclusion
There exists a wide array of orbito-ocular lesions for which ophthalmic biopsies were performed for histopathologic diagnosis. This research gave the spectrum and relative frequencies of ophthalmic biopsies and by extension ophthalmic lesions/diseases in Edo State and its environs. This would increase the awareness of ophthalmologist and pathologists to the existing spectrum of orbito-ocular lesions in this region and at the same time improve their diagnostic judgement on these lesions.