HISTOPATHOLOGICAL PROFILE OF ORBITO-OCULAR LESIONS AT TERTIARY HOSPITAL IN NORTHERN MALAWI

Orbito-ocular lesions are common cause of morbidity and mortality in our population yet, there is paucity of data on their pattern which is crucial for developing an effective strategy for prevention, timely detection and management. This study sought to describe the burden and histopathological pattern of orbito-ocular lesions at Mzuzu Central Hospital (MCH) over a period of five years (July 2013 to June 2018). A retrospective review of the clinicopathological profile of orbito-ocular lesions diagnosed at MCH was done. Demographic, clinical and histopathological data was obtained from original histology reports. Data analysis was conducted using Stata, version 13.0 (Stata Corp. LP, College Station, TX, United States of America). Descriptive analyses were performed to summarize patients’ sociodemographic and clinical characteristics, and histopathological analysis results. and (214) malignant lesions. Therefore, there is need for appropriate strategies to improve preventive, diagnostic and management capacity for orbito-ocular lesions at MCH.


Background
Globally, it is estimated that at least 2.2 billion people have a vision impairment or blindness, of whom at least 1 billion have a vision impairment that could have been prevented or is yet to be addressed [1]. Visual impairment has an important economic cost implication and is associated with diminished quality of life.
Orbito-ocular tumours cause significant morbidity and mortality in our population with varying incidence, site distribution and pathological profiles globally and regionally. In a retrospective study involving 115 cases conducted in Nepal demonstrated that tumours were predominantly malignant [58.25%, (n= 67)] with bimodal distribution first, peak age less than 5 years and second peak 40 to 50 years and basal cell carcinoma was the most common histological findings [2]. This is in contrast to several studies conducted in West Africa and Taiwan where squamous cell carcinoma and melanoma respectively were the commonest malignant tumours in adults [3,4,5]. Most of the common benign tumours reported in many studies are conjunctival papilloma, dermoid cysts, nevus, cystic lesions, hemangiomas [2,5]. Studies have reported variation in common sites for orbito-ocular tumour however conjunctiva and eyelids are among the commonest sites [2,6].
Histopathology remains a gold standard for diagnosing orbito-ocular lesions. In addition, histology reveals whether the lesion is malignant or not. Patients with orbito-ocular lesions are usually referred from secondary level of care to tertiary facilities for diagnosis and management. However, in Malawi, like in many low-income countries, histopathological services are limited contributing to delay in making definitive diagnosis and initiation of treatment. As such histopathological pattern of orbito-ocular lesions may help to guide in developing effective preventive, diagnostic and management strategy.
However, in Malawi particularly in northern region, there is paucity of data on orbito-ocular lesions which can best describe our situation and guide in developing effective preventive, diagnostic and management strategy. Therefore, this study was instituted in order to describe the burden and histopathological pattern of orbito-ocular lesions in at Mzuzu Central Hospital (MCH) which is the northern region referral hospital over a period of five years (July 2013 to June 2018).

Aim, Design, setting and population
This study sought to describe the burden and histopathological pattern of orbito-ocular lesions at Mzuzu Central Hospital (MCH) over a period of five years (July 2013 to June 2018).
This was a record based retrospective cross-sectional study conducted at Mzuzu Central Hospital (MCH). MCH is the only tertiary facility located in northern part of Malawi, catering for a population of about 2,289,780 million people [7]. We carried out a retrospective review of 214 histopathological results of orbito-ocular specimens from July 2013 to June 2018. Relevant information such as sex, age, race, clinical and histological diagnosis were extracted from original biopsy reports. All patients' records with missing demographic, clinical and histopathological data and those with inconclusive results were excluded for further analysis.

Specimen Collection and processing
Tissue specimens were collected and preserved in 10% buffered formalin solution and then transported to Kamuzu Central Hospital/ University of North Carolina (KCH/UNC) pathology laboratory in Lilongwe. The KCH/UNC laboratory adheres to international quality assurance standards. Figure 1 below is a flow diagram showing the process involved in the processing and examination of specimens to make histopathological diagnosis.
Specimen is cut into 3-5mm slices put in the cassette and the lid is covered.
Cassette is placed in a container of an automatic tissue processor. There are 12 containers each containing different reagents. The tissue moves from one to the other through all twelve. This process takes 24hours.
The tissue is embedded using Leica Histocore Arcadia H-Heated Paraffin embedding station.
A manual rotary microtome is used to cut the tissue into 3-5µm thin slices A floatation bath and a slide warmer are then used to fix the tissue slice onto the microscope slide. The tissue slices are stained with haematoxylin and eosin then mounted on a microscope ready for examination by pathologist.
Immunohistochemical or special stains requested depending on primary differential diagnoses

RESULTS
In this study, a total of 214 orbito-ocular lesions cumulated over a period of five years (June 2013 to July 2018) were analysed. There were 60.3 % (129) females while 39.7% (85) were males with overall mean age of 34.81± 15.9 years while age range was 4 months to 91 years.

DISCUSSION
We carried out a study to describe the histological profile of orbito-ocular lesions at a tertiary hospital in Northern Malawi. The lesions were common in women (60.3%) than in men (39.7%). This is in contrast to other studies which reported predominance of orbitoocular lesions in men which was attributed to easy access to services by men who are economically empowered than women [4,5,8]. Gender roles and access to resources determine the ability to access health care, as it is the case in our set up, women have less power to make decisions about using the resources and seek approval from their husbands before seeking health care [9]. Surprisingly, there were less men in our study. This might be attributed to free services at the point of care in our set up therefore, economic empowerment might not be a barrier to women seeking health care. It has also been reported that in Malawi, women are more likely to visit a health facility than men and this has been attributed to cultural practices that emphasise macho characteristics in men [10].
In this study, the majority (65.0 %) of specimens analysed were conjunctival biopsies. This is consistent with findings from other studies which reported up to 45.3% [4] and 45.7% [11] of orbito-ocular specimens were from conjunctiva. This suggests that orbito-ocular tumours affect the conjunctiva more than any other orbito-ocular site. Squamous cell carcinoma was the most common orbito-ocular lesion, representing 31.8% of histological findings. This result is similar to what has been reported by other studies in Nigeria [4,6,8], implying that malignant lesions are the most common cause of orbito-ocular lesions. Therefore, for prompt diagnosis and management, clinicians must always suspect cancer as being one of the likely causes of orbito-ocular lesions in patients presenting to the facility with such lesions. Degenerative diseases such as pterygium, pinguecula and non-specific solar keratosis were the second most common diagnoses of all orbito-ocular diseases and the commonest non-malignant disease. Pterygium was identified as the most common degenerative lesion contributing 51.6% (28/54). This is consistent with other studies where up to 26.9% of all cases of orbito-ocular lesions have been reported [4,12,13]. It is disheartening to note that although degenerative conditions can be prevented by simply preventing direct exposure to ultraviolet light from the sun, they still constitute a substantial burden of eye conditions managed in our facilities.
Pyogenic and inflammatory lesions also contributed substantially (8.41%) to the burden of orbito-ocular tumour in the study population, though not as much as what has been reported elsewhere -19.2% [11] and 25% [12]. This variation may be due to the fact that at time spent in direct sunlight. Men spend more time outdoors, as such they are more exposed to harmful effects of ultraviolet radiation [16]. Therefore, people should be advised to wear sun protectors such as ultraviolet protected sunglasses or sun protection hats when outdoors in strong sunlight.
We observed two peaks in age distribution of malignant tumour, one in the first decade of life and the other in third and fourth decade of life. This observation has been reported in other studies where there was bimodal distribution of malignant tumours -first decade and firth decade [2,17]. We therefore encourage clinicians that all children less than 10 years of age and adults aged 31 -50 years of age presenting with orbito-ocular lesions should have biopsy taken for histopathological examination so as to make a prompt diagnosis and initiate timely management since the risk of cancer is high in this age groups. reported that rising incidence of orbito-ocular tumours especially conjunctival squamous cell carcinoma has been attributed to high rate of HIV infection [18,19]. It therefore becomes imperative that patients presenting with orbito-ocular lesions should be screened for HIV as part of routine care for proper management and timely initiation of Anti-Retroviral Therapy (ART). On the other hand, controlling HIV would reduce the incidence of orbito-ocular cancers.
We found that the most common malignancy seen in orbito-ocular specimens was squamous cell carcinoma (82.1%) followed by retinoblastoma (8.3%). The higher proportion of squamous cell carcinoma in our study group may also be attributed to high number of conjunctival biopsies compared with other sites. However, data of cancer registry among Chinese, the common malignancies were retinoblastoma (35.3%), melanoma (17.9%) and lymphoma (13.8%) [3]. These differences may be due to environmental factors, ethnicity and age. Our study population were predominantly black (malignant melanoma is prevalent in whites than blacks or those with light coloured eyes) and retinoblastoma is predominantly found in children [4,20] and our study population was older, mean age 34.8 ± 15.9 years.
We observed that the most common malignancy in children was retinoblastoma, this is in keeping with other studies which have demonstrated that worldwide retinoblastoma is the most common primary intraocular tumour in children [4,20]. Clinicians should therefore have high suspicion of retinoblastoma in children presentencing with intraocular lesions.
Although our study didn't find any adult case of retinoblastoma, cases of adult onset retinoblastoma have been reported elsewhere [11,21]. Therefore, clinicians must still be suspicious of retinoblastoma if an adult patient presents with a white mass lesion of unknown aetiology.
Lymphomas were uncommon in our study which is in keeping with other studies where lymphomas including Burkitt's lymphoma were uncommon contributing about 8.1% (3/37) of orbital and eye lid tumours [4]. Ocular melanoma is the second most common type of melanoma after cutaneous [22]. However, uveal Malignant melanomas were rare in our study, this confirms findings of previous studies that malignant melanoma is rare in Africans as compared to Caucasians [4,22,23,24]. Our study population was predominantly black therefore the rarity of malignant melanoma. Our findings demonstrated that all two cases of Kaposi sarcoma had HIV. Kaposi sarcoma is a common malignant lesion in patients with advanced HIV disease, although it was rare in similar studies [4,24]. Prompt initiation of ART is of paramount importance in preventing advanced HIV disease and management of Kaposi's sarcoma. Basal cell carcinoma was rare ocular malignancy in our population which is not in keeping with findings reported in other studies that it accounts for 30.6% of all malignant lesions [2].

Conclusion
Cancer constituted a substantial proportion of orbito-ocular lesions in our study population with squamous cell carcinoma being the most common malignancy in adults and retinoblastoma in children. Degenerative disease contributed a high proportion of nonmalignant lesions. It is therefore envisaged that these findings of this study will help to inform policy makers and other stakeholders to formulate appropriate intervention strategies for prevention, early detection and management of orbito-ocular lesions which may contribute to reduction in morbidity and mortality.

Ethical approval
Ethical approval to conduct the study was sought from National Health Sciences Research Committee (NHSRC) approval number 19/05/2316 and clearance was also obtained from Mzuzu Central Hospital authorities. All particulars that would link the information obtained to the identity of the patient such as name and surname were deliberately not captured to ensure privacy and confidentiality.

Availability of Data and Materials
All data related to this study can be accessed at Mzuzu Central Hospital upon consent from authorities.

Conflict of interest
Authors declare no conflict of interest

Author's contribution
All the authors contributed adequately towards study conception, study design, data collection and analysis and manuscript preparation. Their carrier background played important roles. All authors read and approved the manuscript.