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Ocular surface squamous neoplasia

Ocular surface squamous neoplasia (OSSN) typically arises adjacent to the limbus, over
a preexisting pinguecula, that is, over an area of solar elastosis, similar to actinic keratoses

of the skin. Ultraviolet light (UV) exposure, especially in individuals with light skin
pigmentation, is a known risk factor for OSSN, and the prevalence of OSSN is higher in
equatorial regions of the world. UV-associ ated mutations in tumor suppressor genes such
as p53 have been demonstrated in OSSN, and hereditary deficiency of DNA repair such
as in xeroderma pigmentosum increases the risk of OSSN formation. OSSN is also associated

with HPV infection, subtypes 16 and 18, as well as with human immunodeficiency
virus (HIV) infection. HIV-associated OSSN is especially common in sub-Saharan Africa,
and HIV should be suspected in any patient with OSSN youngerthan 50 years. Non-HIVrelated
immunosuppression is also a risk factor for OSSN. Other risk factors include older
age and smoking.
The clinical appearance of OSSN is characterized by epithelial thickening, and the
lesion may extend onto the peripheral cornea. There may be a prominent "corkscrew"
vascular pattern, or the surface may appear gelatinous or leukoplakic, indicative of surface

keratinization. Surface keratinization is not pathognomonic for OSSN and may


be seen over any elevated lesion not covered adequately by the tear film; however, it is very
commonly seen in OSSN and must therefore arouse suspicion. The adjacent conjunctiva

may appear injected, with prominent "feeder" vessels leading to the lesion.
Histologically, the epithelium exhibits hyperplasia, loss of goblet cells, loss of normal
cell polarity, nuclear hyperchromasia and pleomorphism, and mitotic figures. There is
often surface keratinization, correlating with the leukoplakia observed clinically. Dyskeratosis
(non-surface cells producing keratin) may also be seen. A chronic inflammatory
response is often present in the substantia propria.

The most important assessment to be made histologically in OSSN is whether


the neoplasia is contained by the basement membrane (ie, intraepithelial or in situ) or
whether neoplastic cells have traversed the epithelial basement membrane and invaded
the stroma. For lesions contained by the basement membrane, the term conjunctival intraepithelial
neoplasia (CIN) may be used. The neoplaSia may be graded as mild, moderate,

or severe, according to the degree of cellular atypia (although this grading does not
necessarily have clinical utility in terms of prognosis). In cases with the most severe atypia,
full -thickness involvement of the epithelium is seen, often with squamous eddies or keratin
whorls/pearls. For these more advanced lesions, the term squamous carcinoma in situ
may be used. If, however, the neoplastic cells have invaded the stroma, then the diagnosis
is invasive squamous cell carcinoma. Clinically, the term CIN has
fallen out of favor in preference to the more general term OSSN, because it is not possible
to determine on clinical examination whether stromal invasion has occurred. CIN should
be regarded as a histologic term, reserved for noninvasive lesions. Invasion through the
sclera or cornea and intraocular spread are uncommon complications of invasive squamous
carcinoma. When there is intraocular spread, it often occurs at the site of a previous
surgical procedure, such as cataract surgery. However, intraocular invasion may also
occur through previously nonviolated sclera, especially in immunosuppression -related
cases and cases occurring in ozone-depleted areas, as these cases tend to be more aggressive.

Although regional lymph node metastasis is not as common as it is with squamous


carcinomas of the skin or other sites, dissemination and death can occur.

Mucoepidermoid carcinoma and spindle cell carcinoma are rare variants of squamous
cell carcinoma. Both entities are more aggressive neoplasms with higher rates of recurrence
and intraocular spread.
Treatment options for suspected squamous neoplasms of the ocular surface include

excisional biopsy with 3-4 mm margins and cryotherapy to the edges of excision; or topical
chemotherapy with interferon (IFN) alfa -2b, 5-f1uorouracil (5 -FU), or mitomycin e
(MMC). For specimen submission, the lesion should be placed flat on filter paper and allowed
to dry for 30- 60 seconds (so that its flat orientation is retained on the paper and the
lesion is not folded over onto itself), and then the paper with specimen is gently placed in
a formalin jar. It is ideal for the surgeon to mark 2 adjacent margins with different-colored

sutures and to include a diagram depicting this orientation on the pathology requisition
form. The status of the lateral and deep margins is important for prognosis.