Ocular Surface Squamous Neoplasia (OSSN): A Retrospective Study

OSSN is an encompassing term for pre-cancerous and cancerous epithelial lesions of the conjunctiva and cornea. It includes the spectrum of Dysplasia, Carcinoma in-situ (CIS) and Invasive SCC [1–3].

CIS accounts for 39% of all premalignant and malignant lesions of the conjunctiva and incidence of invasive SCC varies from 0.02 to 3.5 per 1,00,000 population [4]. About 75% occur in men, 75% are diagnosed in older patients, 75% occur at the limbus [5,6].

OSSN is mostly unilateral and is seen in middle age and older patients. Rarely, it is bilateral in immunocompromised patients. Factors associated with the development of OSSN are exposure to sunlight, HPV type 16 infections and HIV infection [2,5]. A systemic association of the development of OSSN is Xeroderma Pigmentosum. Other factors associated are old age, heavy cigarette smoking, male sex and people of light complexion.

There are no consistent clinical criteria for distinguishing CIS from invasive SCC. The presence of feeder vessels, intrinsic vascularity and a nodular lesion raise suspicion of invasive SCC. OSSN usually presents either as a fleshy, gelatinous, elevated lesion or as a sessile, papillomatous lesion mostly in the interpalpebral region. Most often vision is not affected unless the lesion is encroaching onto the pupillary area. OSSN patients usually present with a swelling, redness and irritation and one can see large, dilated vessels (feeder vessels) surrounding the lesion [1,2,5,7,8].

Advanced cases can infiltrate the cornea and sclera [9] and rarely the tumour may extend into the orbit causing proptosis.

Complete surgical excision with 4mm margin clearance without touching the tumour called the ‘NO TOUCH TECHNIQUE’ is the treatment of choice [1,10,11]. A double freeze-thaw cycle of Cryotherapy is applied to the edges of the bulbar conjunctiva and if sclera involvement is suspected, cryo is applied to the bare sclera as well [8].

Reported recurrence rate of OSSN is 15-52%. Lee and Herst reported a 17% recurrence after excision of conjunctival dysplasia, 40% after excision of CIS and 30% for SCC of conjunctiva [2]. The recurrence rate can be limited to less than 5% with the above technique. OSSN has a good prognosis. With the modern techniques the recurrence rate is about 5% and regional metastasis of 2% [1,5,12,13].

A retrospective cross-section study was conducted on patients presenting to the out-patient department of Oculoplastics and Orbital diseases in Sarojini Devi eye hospital, Hyderabad over a period of 3 years from February 2012 to January 2015.

Materials and Methods

We analysed 113 subjects who were suspected clinically to have OSSN and included them in the study. A detailed history including demographic data of Age, Sex, Occupation, HIV status of all the patients was obtained. Clinical features regarding the type of lesion, location, involvement of cornea were evaluated. Routine investigations like Hb%, CT, BT and HIV test were done after obtaining informed consent of the subjects. After subjecting the lesion for impression cytology, the lesion was excised with a 4mm margin clearance. Cryotherapy was applied to the bare sclera using double freeze-thaw technique. The excised specimen was sent for histopathology examination.

We have excluded 20 cases from further analysis in whom histopathology had revealed a normal epithelium. The rest 113 histopathologically proven cases of OSSN were analysed further.

Statistical Analysis

All the data entered into an Excel sheet were analysed and the data tabulated under various clinicopathological headings. A Chi-square test was used for statistical analysis and a p-value of less than 0.05 was considered significant.

Results

The age range of the patients in this study is 18 to 78 years. In our study, 65.48% of those affected were males. Mean age was 45.20 years [Table/Fig-1]. There was no statistical significance of susceptibility to OSSN in people less than 40 years of age. (p-value=0.3042) [Table/Fig-2]. In our study 23% of the patients were positive for HIV and 77% tested negative [Table/Fig-3]. Of those who tested positive 5 out of 26 (19.23%) were found to have HIV after they presented with OSSN. Mean age among HIV positive individuals was 34 years. Statistical analysis showed a significant association between a young patient with OSSN and HIV status (p-value=0.00005133) [Table/Fig-2]. This necessitates testing for the presence of HIV in any young patient presenting with OSSN [Table/Fig-4].

[Table/Fig-1]:

Age distribution of patients

AGE RANGE of patients in this study= 18–78 Years

Mean age = 45.20 Years

[Table/Fig-2]:

Statistical data showing significance of association of age with other clinicopathological findings

PARAMETER	<40 YEARS AGE	>40 YEARS AGE	p-value
Gender
MALE	34	40	0.30426
FEMALE	14	25
Pathology
NON INVASIVE (mild, moderate, severe dysplasia and CIS)	36	37	0.14288
INVASIVE	14	26
HIV status
HIV POSITIVE	20	6	0.00005133
HIV NEGATIVE	28	59
	HIV POSITIVE	HIV NEGATIVE	p-value
Pathology
NON INVASIVE (mild, moderate, severe dysplasia and CIS)	8	65	0.00003932
INVASIVE	18	22

[Table/Fig-3]:

Association of HIV

[Table/Fig-4]:

OSSN in hiv positive patient

The most common clinical variety noted was the Nodular type in 56.63% followed by Leukoplakic in 26.54% [Table/Fig-5]. In our study, 57 patients had nasal lesions accounting for 50.44% and 56 patients had temporal lesions accounting for 49.56% [Table/Fig-6&7].

[Table/Fig-5]:

Distribution of clinical types

[Table/Fig-6]:

Location of lesion

[Table/Fig-7]:

OSSN on nasal side

In our study, Histopathological examination showed SCC in 40 patients (35.39%), Carcinoma in-situ in 30 (26.5%) and Mild to severe dysplasia in 43(38.05%) [Table/Fig-8].

[Table/Fig-8]:

Distribution of histopathological grades

In those with SCC, well-differentiated SCC is accounting for 57.5% of cases and poorly differentiated for 10% of cases of SCC [Table/Fig-9,10 and 11].

[Table/Fig-9]:

Distribution of various grades of SCC

[Table/Fig-10]:

Carcinoma in-situ (CIS)

[Table/Fig-11]:

Well differentiated SCC

Discussion

The age range of the patients in this study is 18 to 78 years and the mean age was 45.20 years. Mean age among HIV positive individuals was 34 years which necessitates testing for the presence of HIV in any young patient presenting with OSSN. Statistical analysis showed a significant association between a young patient with OSSN and HIV status (p-value=0.00005133) [Table/Fig-2].

In our study, 65.48% of those affected were Males. This observation is also mentioned in other studies where males outnumbered females. Male gender may be a risk factor for higher preponderance as they are more commonly employed in professions involving outdoor work thereby leading to increased exposure to UV-B rays which is a known risk factor for development of OSSN. In a similar study done by Rohit Bang et al.,, the nodular variant was reported to be as high as 48% [14]. In this study 50.44% of the lesions are on the nasal side. According to a study done at Bascom Palmer Eye Institute 54% presented with nasal lesions [15].

In our study, 23% of the patients were positive for HIV and 77% tested negative. Mean age among HIV positive individuals was 34 years. Statistical analysis showed a significant association between a young patient with OSSN and HIV status (p-value=0.00005133) [Table/Fig-2]. Out of 26 HIV positive cases 78.26% had SCC thereby indicating that HIV patients have a more aggressive form of OSSN Compared to HIV negative patients [16,17] which is shown by a significant statistical analysis with a p-value of 0.000039322 [Table/Fig-2]. In a study done by Tanuja G et al., the mean age in HIV positive OSSN patients was 36 years and 29% of the patients with OSSN were HIV positive and OSSN was the only detectable manifestation of Underlying HIV infection [18].

In another study conducted in Malawi by Spitzer MS et al., which looked at the prevalence of HIV in patients with OSSN and found invasive disease In HIV positive cases [19].

All the patients were subjected for surgical excision of the lesion with a 4mm margin clearance and the specimen sent for histopathological examination which is the gold standard for the diagnosis of OSSN. Those having SCC and CIS were kept on 0.04% topical Mitomucin-C (MMC) for 4 times a day (qid), 4 days in a week for 4 cycles.

Conclusion

Increased incidence of OSSN was observed in males and people with outdoor occupations. Nodular type of lesion is the commonest variety. HIV positive individuals have an increased incidence of OSSN with invasive characteristics.

Hence, ophthalmologists need to be aware of this association and a thorough workup is warranted for all patients presenting with OSSN, especially in the younger age group.

Our study also suggests that OSSN may be the first manifestation of underlying HIV infection.

[1]. Shields CL, Shields JA, Tumours of the conjunctiva and cornea Surv Ophthalmol 2004 49:3-24.  [Google Scholar]

[2]. Lee GA, Hirst LW, Ocular surface squamous neoplasia Surv Ophthalmol 1995 39:429-50.  [Google Scholar]

[3]. Pe’er J, Ocular surface squamous neoplasia Ophthalmol Clin North Am 2005 18:1-13.:vii  [Google Scholar]

[4]. Lee GA, Hirst LW, Retrospective study of OSSN Aust NZJ Ophthalmol 1997 25:269  [Google Scholar]

[5]. Shields JA, Shields CL, Eyelid, Conjunctival and Orbital Tumours. An Atlas and Textbook 2008 2nd edPhiladelphia, PALippincott Williams and Wilkins:250-445.  [Google Scholar]

[6]. Shields CL, Demirci H, Karatza E, Shields JA, Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumours Ophthalmology 2004 111:1747-54.  [Google Scholar]

[7]. Farah S, Baum TD, Conton MR, Tumours of cornea and conjunctiva. In: Albert DM, Jakobiec FA, editors Principles and Practice of Ophthalmology 2000 2nd edPhiladelphiaWB Saunders:1002-19.  [Google Scholar]

[8]. Honavar SG, Manjandavida FP, Tumours of the ocular surface: A review Indian J Ophthalmol 2015 63:187-203.  [Google Scholar]

[9]. Nicholson DH, Herschler J, Intraocular extension of squamous cell carcinoma of the conjunctiva Arch Ophthalmol 1977 95:843-46.  [Google Scholar]

[10]. Mauriello JA, Napolitano J, McLean I, Actinic keratosis and dysplasia of the conjunctiva: A clinicopathological study of 45 cases Can J Ophthalmol 1995 30:312-16.  [Google Scholar]

[11]. Shields JA, Shields CL, De Potter P, Surgical management of conjunctival tumours. The 1994 Lynn B. McMahan Lecture Arch Ophthalmol 1997 115:808-15.  [Google Scholar]

[12]. Cervantes G, Rodríguez AA, Leal AG, Squamous cell carcinoma of the conjunctiva: Clinicopathological features in 287 cases Can J Ophthalmol 2002 37:14-19.  [Google Scholar]

[13]. Shields CL, Fasiuddin AF, Mashayekhi A, Shields JA, Conjunctival nevi: Clinical features and natural course in 410 consecutive patients Arch Ophthalmol 2004 122:167-75.  [Google Scholar]

[14]. Bang R, Jadhav M, Verma S, 70th AIOC proceedings, Cochin 2012   [Google Scholar]

[15]. Kao AA, Galor A, Karp CL, Clinicopathological correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute 2001 to 2010 Ophthalmology 2012 119(9):1773-76.  [Google Scholar]

[16]. Mittal R, Rath S, Vemuganti GK, Ocular surface squamous neoplasia- Review of etiopathogenesis and an update on clinic-pathological diagnosis Saudi J Ophthalmol 2013 27(3):177-86.  [Google Scholar]

[17]. Kabra RC, Khaitan IA, Comparative analysis of clinical factors associated with ocular surface squamous neoplasia in HIV infected and Non HIV patients J Clin Diadn Res 2015 9(5):NC01-3.  [Google Scholar]

[18]. Thanuja Babu S, Mala B, Guruprasad BS, Durgappa R, Nagaraju GG R, 69th AIOC proceedings, Ahmedabad 2011   [Google Scholar]

[19]. Spitzer MS, Batumba NH, Chirambo T, Ocular surface squamous neoplasia as the first apparent manifestation of HIV infection in Malawi Clin Experiment Ophthalmol 2008 36:422-25.  [Google Scholar]