OCULAR SURFACE

SQUAMOUS
NEOPLASIA(OSSN)
 INTRODUCTION

• The term Ocular Surface Squamous Neoplasia

[OSSN] presently refers to the entire spectrum
of dysplastic, pre-invasive and malignant
squamous lesions of the conjunctiva and
cornea
• We have suggested the use of the "umbrella“
term ocular surface epithelial dysplasia (OSED)
but now feel that ocular surface squamous
neoplasia (OSSN) is a better terminology.
• OCULAR SURFACE denotes involvement of the
conjunctiva or cornea;
• SQUAMOUS excludes other epithelial cells such
as basal cells and melanocytes
• and NEOPLASIA includes both dysplastic and
carcinomatous lesions.

Ocular Surface Squamous Neoplasia

Graham a. lee, MBBS, and Lawrence w. hirst, MD
Survey of ophthalmology volume 39, number 6. may-june
1995
The term Ocular Surface Squamous Neoplasia (OSSN) was
coined by Lee and Hirst which has three grades :-

I. BENIGN DYSPLASIA
• Papilloma
• Pseudoepitheliomatous hyperplasia
• Benign hereditary intraepithelial dyskeratosis

II. PREINVASIVE OSSN

• Conjunctival/corneal carcinoma in situ

III. INVASIVE OSSN

• Squamous carcinoma
• Mucoepidermoid carcinoma
 EPIDEMIOLOGY
• Third most common ocular tumour after
melanoma and lymphoma
• Common in Caucasians
• Common in older age group(6-7 decade)
Males are affected more commonly than females
• Earlier onset in areas in latitude 30 degree from
equator, declines considerably with increase in
latitude
• Pts with HIV and Xeroderma pigmentosum
present earlier
All young patients with OSSN should be screened
for HIV.
 ETIOLOGY
• LIMBAL TRANSITION ZONE/STEM CELL
THEORY
• Stem cells in the limbal epithelial crypts are
the likely originators of this disease, and may
take on cancer stem cell properties.
 Effects of solar ultraviolet radiation
• UVB radiation causes direct DNA damage by
crosslinking adjacent bases to form cyclobutane
pyrimidine dimers (CPDs) and 6-4
photoproducts (6-4 PPs)
• Specific CC/TT dimer transitions of the p53
tumour-suppressor gene have been observed in
OSSN lesions
• 29% increase in incidence of SCC per unit
increase in exposure to ambient solar ultraviolet
radiation
• Other eye diseases thought to be related to
UV-B exposure also have a high association
with OSSN.
• pterygium
• pingueculum
• climatic droplet keratopathy
• cataract
• corneal degeneration
 Reactivation of latent HPV infection.
• UV radiation also reactivates latent viruses
such as HPV 16
• HPV's E7 protein keeps infected cells in a
proliferative state
• while E6 inhibits cell cycle arrest of DNA-
damaged cells.
 Failure of DNA repair mechanisms

• An increased incidence of OSSN has been

reported in conditions like Xeroderma
Pigmentosa, where the DNA repair
mechanism is defective
 Immunosuppression
• UV radiation
• HIV and
• vitamin A deficiency weakens the tumour
surveillance system and allows DNA damaged
cells to proliferate into tumours.
• Vitamin A deficiency interferes with ocular
surface integrity creating micro-abrasions
through which HPV may invade the conjunctival
basement membrane and epithelial cells.
 Miscellaneous
• Chronic exposure keratopathy secondary to long
• standing facial nerve palsy may be associated
with OSSN
• exposure to petroleum products
• heavy cigarette smoking
• chemicals such as trifluridine and arsenicals
• ocular surface injury
• Chronic inflammatory conditions-pemphigoid,
atopic eczema, chronic blepharoconjunctivitis
 Clinical Features
• Patients with OSSN may be asymptomatic or
present with chronic redness and irritation of
the eye.
• Visual acuity is not affected unless there is
extensive corneal involvement
• OSSN may grow within weeks to years; in
most cases, the history is of several months
• The lesions are described as being slightly
elevated, variably shaped, relatively sharply
demarcated from the surrounding normal
tissues, accompanied by feeder blood vessels
and colored from pearly gray to reddish gray
depending on the vascularity of the tumor
• They most commonly straddle the nasal or
temporal limbus between the palpebral
fissures
• The following appearances may be seen.
• a Gelatinous mass with superficial vessels
b White leukoplakic plaque that covers the
lesion
c Papillomatous lesion with corkscrew-like
surface blood vessels
• In clinical practice, gelatinous type is the
commonest.
• The gelatinous lesion can again be
• circumscribed, which are most common
• nodular variety , which has a propensity for
rapid growth
• diffuse variety, the least common, which can
masquerade as chronic conjunctivitis
• The corneal side of the lesion may be seen as
an opalesence of the epithelium, slightly
raised in comparison to adjacent normal
epithelium the edges of which are usually
sharply defined.
• It is best appreciated by retroillumination.
• The lesion is usually nonpigmented though
pigmented OSSN may also occur.
• OSSN may sometimes mimic a pterygium or a
pinguecula. It has also been known to occur in
a pre-existing pinguecula or pterygium.
• It is nearly impossible to categorise OSSN as
benign or malignant based on clinical
appearance alone.
• Larger lesions that are fixated to the
underlying tissue are usually malignant.
• Staining with fluorescein sodium or Rose
Bengal helps in the diagnosis by showing up
the papillary or granular nature of the lesion
and by delineating its extent
• Anterior segment OCT may be done to find
out the extent of deep involvement as well as
intraocular and angle invasion
• Intraocular invasion is rare ,heralded by onset
of iritis, glaucoma, scleral thinning or retinal
detachment.
• Regional and systemic metastases are also
uncommon.
• Common sites of metastasis include
preauricular,submandibular and cervical
lymph nodes, parotid gland, lungs, and bone.
 DIFFERENTIAL DIAGNOSIS
• Pterygium
• papilloma
• pingueculum,
• nevus.
• Malignant melanoma
• pyogenic granuloma
• pseudo-epitheliomatous hyperplasia
• Corneal pannus from any cause
• Mooren's ulcer,
• fatty degeneration of the cornea and epithelial
dystrophy of the cornea
• Papilloma may occur anywhere on the
conjunctiva, may be sessile or pedunculated,
has a punctate vascular pattern, occurs in
younger patients,but ultimately may only be
difterentiated by histologic examination
• Malignant melanoma has a regular smooth
surface, lacks gelatinous or leukoplakic surface
disturbances and may become ulcerated
• Benign nevi tend to occur in the interpalpebral
zone, from the limbus to the caruncle, to
occur in younger patients, and to have
distinctive cysts on slit-lamp examination
 HISTOPATHOLOGY
• DYSPLASIA:
• Mild - less than a third thickness occupied by atypical
cells
• Moderate - three quarters thickness occupied by
atypical cells
• Severe -- nearly full thickness occupied by atypical cells
• CARCINOMA IN SITU: as above with loss of the normal
surface layer
• INVASIVE SQUAMOUS CELL CARCINOMA: as above
when the basement membrane of the basal epithelial
layer has been breached and invasion of the substantia
propria has occurred.
• Spindle cell, Mucoepidermoid and Adenoid-
Squamous are three aggressive variants
 TREATMENT
• SURGICAL EXCISION
• video
 TOPICAL CHEMOTHERAPY

• Topical chemotherapy may be used

preoperatively, intraoperatively or
postoperatively.
Its preoperative use is seen in cases with
extensive lesions where it helps to reduce the
tumor size and makes the tumor more amenable
to surgical excision.
Intraoperatively, chemotherapy may have a role
in place of adjuvant cryotherapy
postoperatively can be beneficial for managing
cases with residual disease or positive surgical
margins.
 MITOMYCIN C
• Mitomycin C is the most commonly used topical
chemotherapy agent
• It is a non cell cycle specific ALKYLATING AGENT
that acts by alkylating the cross-linked DNA and
inhibits DNA, RNA, and protein synthesis.
• MMC is used in concentrations of 0.04% qid, 4
days a week for 4 weeks.
• Overall, success rates ranging from 87 to 100%
have been reported.
 5-FU
• Is a pyrimidine analogue that acts by
integrating with the DNA during S phase. It
also interferes with RNA synthesis.
• It is used as 1% topical solution.
• Side effects are similar to MMC
 INTERFERONS
• Interferons are protein molecules that bind to cell
receptors and trigger synthesis of effector
proteins that can inhibit viruses, activate
immunocompetent cells, and regulate
oncogenes.
• Reports are emerging on the use of topical IFN-
2b for OSSN.
• It is more expensive than MMC and 5 FU,
requires prolonged treatment but has a better
safety profile
 RADIOTHERAPY
• Plaque brachytherapy using radiation sources
like Strontium 90 or Rhuthenium 106 is useful
as an adjuvant to support surgical excision.
Complications include conjunctival scarring,
symblepharon, dry eye, cataract, scleral and
corneal ulceration.
 SUMMARY
• [1] Suspected OSSN < 3 clock hours –Excision
biopsy + base/ edge cryotherapy +
alchoholepitheliectomy is done.
• [2] Suspected OSSN 3 – 6 clock hours – As
there is a risk of producing limbal stem cell
deficiency, excision biopsy + cryotherapy is
better avoided.
• A diagnostic biopsy is required
• In pre-invasive lesions topical chemotherapy
is likely to achieve tumour resolution.
• If invasive, surgery + cryotherapy is done after
chemoreduction with 4 to 6 cycles of topical
chemotherapy.
• [3] OSSN > 6 clock hours – A diagnostic biopsy is
required.
• In pre-invasive lesions topical chemotherapy is
quite likely to achieve tumour resolution.
• If invasive, surgery + cryotherapy is done after
chemoreduction with 4 to 6 cycles of topical
chemotherapy.
• If there is no response to chemotherapy palliative
radiotherapy or extensive surgery like
enucleation / exenteration may be required.