Ocular surface squamous neoplasia - Review of etio-pathogenesis and an update on clinico-pathological diagnosis

Abstract

Ocular surface squamous neoplasia (OSSN) has a varied clinical presentation, the diagnosis of which rests on the histopathological examination of the excised lesion. The term OSSN includes mild dysplasia on one end of the spectrum and invasive squamous cell carcinoma on the other end. This lesion has a multi factorial aetiology with interplay of several factors like exposure to ultraviolet radiation, various chemical carcinogens and viral infections, however role of individual agents is not well understood. With the upsurge of infection with human immunodeficiency virus, a changing trend is seen in the clinical presentation and prognosis of patients of OSSN even in developed countries. Anterior segment optical coherence tomography (OCT) and confocal microscopy, hold promise in in-vivo differentiation of intraepithelial neoplasia from invasive squamous cell carcinoma. Variants of squamous cell carcinoma like Mucoepidermoid carcinoma, spindle cell carcinoma and OSSN associated with HIV infection should be suspected in a case of aggressive clinical presentation of OSSN or with massive and recurrent tumours. Surgery, chemotherapy and immunotherapy are the various treatment modalities which in combination show promising results in aggressive, recurrent and larger tumours.

Keywords: Clinical features; Conjunctival intra epithelial neoplasia; Histopathology; Management; Ocular surface squamous neoplasia; Variants.

Figure 1

Varied clinical presentation of OSSN (A). Slit lamp photograph under diffuse illumination shows papillary ocular surface tumour with prominent feeder (B). Figure shows a globular pink-coloured lesion arising with large feeder vessels. The lesion seems to be overlying a pterygium and was clinically mistaken to be a pyogenic granuloma (C). Figure shows a pigmented OSSN with feeder vessels (D). Slit lamp photograph under diffuse illumination showing large leukoplakic lesions with abnormal vessels.

Figure 2

(A) Slit lamp photograph of the left eye under diffuse illumination shows a large overhanging conjunctivo-corneal mass with surface keratin, large intrinsic and feeder vessels, involving more than half of the corneal surface with invasion into deeper stroma (B). Schematic diagram showing cross-sectional view of the left eye of the patient and large tumour with deep stromal invasion of the cornea. Surgical plane of dissection is shown as a dotted line (C). Scanner view of the main limbal mass shows an invasive tumour involving conjunctival lamina propria and corneal stroma. The tumour is composed of nests and cords of tumour cells that invaded the conjunctival lamina propria and corneal stroma (Haematoxylin-eosin, X 20) (D). Microphotograph shows the tumour cells with marked dysplasia and prominent mitotic figures (Haematoxylin-eosin, X400) (E). Microphotograph shows the tumour invading the deeper corneal stroma but not reaching up to the Descemet’s (Haematoxylin-eosin, X 100) (F). Slit lamp photograph of the left eye under diffuse illumination shows the scleral corneal graft twelve months after treatment. The corneal graft shows mild stromal haze.

Figure 3

(A) Slit lamp picture of the right eye under diffuse illumination shows scleral thinning and perforation from 7’0 clock to 11’0 clock on the temporal quadrant away from the limbus (B). Section of the eye after modified enucleation. Note the epibulbar nodular mass involving the peripheral cornea, limbus and sclera (C). Sections show squamous cell carcinoma with sheets of anaplastic tumour cells with focal keratinisation. (Haematoxylin-seosin X400) (D). Histopathology of the mass showing full thickness infiltration of sclera and involvement of choroidal tissue. There was focal retinal detachment and sub retinal exudates (Haematoxylin-eosin X100).

Figure 4

(A) Excised ocular surface squamous lesion placed on the filter paper. Exact laterality and position of the lesion can be made out with this pictorial documentation (B). Margins from the excised tissue are placed on separate filter papers and submitted in different cassettes.

Figure 5

The conjunctival epithelium is markedly thickened with an abrupt transition noted between the involved conjunctiva and the adjacent normal appearing conjunctival epithelium (arrow marked). Base of the excision biopsy is free of tumour involvement (Periodic Acid Schiff’s stain, X200).

Figure 6

(A) Moderate dysplasia-squamous intra epithelial lesion, abnormal transformation of epithelium involving more than 2/3rds of epithelial thickness, however the degree of cytological atypia is not sufficient to term this lesion as severe dysplasia (B). Severe dysplasia-there is almost full thickness replacement by abnormal epithelium, surface maturation is noted with keratinisation. Basement membrane is intact. (C). Carcinoma- in-situ- there is full thickness replacement by abnormal epithelium with marked nuclear pleomorphism. Basement membrane is intact, (arrow marked) (Haematoxylin-eosin, X 400) (D). Invasive Squamous cell carcinoma-invasion of stroma is seen as tumour nests and broad expansive tumour masses. Tumour is well differentiated with horn pearls and abundant keratinisation (Haematoxylin-eosin X 100).

Figure 7

(A) Corneal OSSN-slit lamp photograph under diffuse illumination shows minimally elevated lesion involving ¾ of the cornea-scleral limbus. The corneal surface is covered by a greyish membrane with abnormal vessels (B). Atypical epithelium of the cornea, infiltration of corneal stroma is limited by intact bowmans membrane (arrow marked). An inflamed fibrovascular membrane is seen above the corneal stroma (Haematoxylin-eosin X 400).

Figure 8

Pseudo epitheliomatous hyperplasia-section shows an abnormally thickened epithelium with surface keratinisation and stromal invasion as epithelial cords displaying irregular, jagged edges. There is minimal presence of nuclear hyperplasia, hyperchromasia with absence of nuclear pleomorphism (Haematoxylin-eosin X 200).

Figure 9

(A) Extended enucleation in a massive ocular surface tumour-extended enucleation specimen with a massive ocular surface tumour, enucleated eyeball is sectioned into one central and two peripheral calottes (B). Conjunctival margins are sent separately mounted on filter paper (C). Low magnification photomicrograph of the lesion altered scleral collagen, angle structures (arrow marked) and iris tissue. Densely cohesive spindle cell tumour is noted involving anterior one third of scleral fibres (Haematoxylin-eosin X100) (D). High magnification photomicrograph shows malignant spindle cells. Atypical mitotic figures are noted (arrow marked) (Haematoxylin-eosin, X 400).

Figure 10

(A) Papillary variant of squamous cell carcinoma. Slit lamp photograph under diffuse illumination shows a massive papillary variant of invasive squamous carcinoma invading into the orbit along the lateral rectus muscle (B). Scanner photomicrograph showing an exophytic squamous cell lesion with papillary pattern (Haematoxylin-eosin X 40) (C). Low magnification photomicrograph shows tumour cells with marked cytological atypia surrounding central fibrovascular core. (Haematoxylin-eosin X 100).