Conjunctival Squamous Cell Carcinoma: OSSN, HIV, Diagnosis and Management

Conjunctival squamous cell carcinoma (SCC) is the invasive end of ocular surface squamous neoplasia (OSSN), a spectrum that begins with epithelial dysplasia and can progress through carcinoma in situ to invasive cancer. In Uganda and other equatorial settings, a persistent unilateral red eye or fleshy, white, red or pigmented ocular-surface growth deserves careful assessment—especially when it is enlarging, recurrent, or present in a person with HIV or another immunosuppressive condition.

Learning objectives

• Define OSSN and distinguish epithelial dysplasia, carcinoma in situ and invasive conjunctival SCC by the basement-membrane boundary.
• Recognize common symptoms, appearance, location, risk factors and warning signs, including in people living with HIV.
• Perform and document a safe initial eye, eyelid, orbital and lymph-node assessment.
• Explain why histopathology is important and where slit-lamp photography, anterior-segment OCT, cytology and imaging fit.
• Describe specialist treatment options, recurrence monitoring and the limited role of enucleation or orbital exenteration.

Coverage of the supplied 43-slide presentation

The supplied SlideShare presentation contains 43 slides. The map below accounts for the full numbered sequence, including slides that are primarily clinical photographs or operative images. The deck begins with general and eyelid SCC, then concentrates on conjunctival/corneal OSSN, HIV, diagnostic work-up, treatment, recurrence, invasive disease and eye-removal procedures. Where older slides make simplified or outdated claims, the article preserves the teaching topic while giving current, specialist-led context.

1. Definitions: OSSN is a spectrum

Ocular surface squamous neoplasia describes abnormal squamous epithelial growth on the conjunctiva, cornea or both. It is an umbrella term used while the lesion is still being assessed; it does not mean that every lesion has become invasive cancer. Histology distinguishes stages along a continuum:

The visual appearance cannot reliably show where the basement membrane is. Dysplasia, CIS and invasive SCC can look alike at the slit lamp. Use “suspected OSSN” or “ocular-surface lesion suspicious for OSSN” until diagnostic tissue or a specialist’s assessment establishes the subtype. The term SCC should be reserved for histologically supported invasion when tissue is available.

Related sites are not interchangeable

The deck includes eyelid SCC as well as conjunctival SCC. They share the squamous histologic family but arise in different tissues, have different staging systems, patterns of spread and operative approaches. Eyelid SCC arises in eyelid skin or margin and can invade locally or spread through lymphatics; conjunctival SCC arises from surface epithelium and often begins near the limbus. Do not transfer eyelid metastatic percentages, biopsy techniques or staging directly to a conjunctival lesion.

2. Who is at risk?

OSSN develops from interacting environmental and host factors. High ultraviolet (UV) exposure is important, particularly in populations living near the equator. UV-related damage helps explain the common interpalpebral, limbal and bulbar location in the exposed “window” between the eyelids. Risk is higher with impaired immune surveillance, including HIV infection and other causes of immunosuppression. Associations have also been reported with human papillomavirus (HPV), especially high-risk types; the strength and causal role of HPV vary between populations and studies, so it is not a required explanation for an individual case.

• HIV: OSSN may present at a younger age, be larger or more locally advanced, and may be a clue to previously unrecognized HIV. It can occur in people already receiving antiretroviral therapy (ART) as well as in people not yet treated.
• UV exposure: long-term outdoor work and intense sunlight are relevant clinical history. UV exposure alone does not diagnose OSSN.
• Immune suppression: transplant medicines, chemotherapy, long-term immunosuppression and conditions such as xeroderma pigmentosum increase concern.
• Other reported factors: older age, male sex in some cohorts, chronic ocular surface irritation, smoking and HPV have been associated in some studies. Associations are not proof that any one exposure caused a given tumour.

In Uganda, never dismiss OSSN because the patient is young, female, has a dark complexion, or has no obvious sunlight history. Pigmented lesions occur in African populations, and OSSN may be amelanotic or pigmented. A persistent, growing lesion and its relationship to the limbus, cornea, sclera and orbit matter more than a single demographic feature.

3. Clinical presentation and lesion recognition

Symptoms

Symptoms are often gradual and non-specific: unilateral redness, irritation, foreign-body sensation, tearing, mild discomfort or a visible growth. Photophobia may occur. Early visual acuity is often preserved because the lesion is superficial and peripheral. Reduced vision can develop when the cornea, visual axis, globe or optic nerve becomes involved, or when there is coexisting ocular disease. Absence of pain does not rule out malignancy; severe pain may suggest inflammation, infection, advanced invasion or another diagnosis.

Appearance and location

Many lesions arise on bulbar conjunctiva in the interpalpebral area, often near the nasal or temporal limbus. The lesion may extend from conjunctiva onto corneal epithelium. Common descriptions include:

• Gelatinous or fleshy: a raised, pink or red mass with a broad base or lobulated surface.
• Leukoplakic: a white keratinized plaque or surface whitening.
• Papilliform: a frond-like or papillary surface.
• Opalescent or translucent: a grey-white superficial thickening.
• Nodular or thickened: a raised mass with prominent feeder vessels, inflammation or surface keratin.
• Pigmented: brown, grey or black colour can be present; pigmentation does not exclude OSSN and should also prompt consideration of melanocytic lesions.
• Diffuse and subtle: flat, poorly defined epithelial change may masquerade as chronic conjunctivitis, pterygium, scleritis or a recurrent surface lesion.

Feeder vessels, leukoplakia, a thickened irregular surface, recurrent growth after excision, rapid enlargement, corneal extension or a lesion fixed to deeper tissues raises suspicion. None of these signs is diagnostic alone. Benign lesions may look alarming, and OSSN may look modest early on.

Red flags for deeper invasion

• Restricted movement or fixation to sclera; deep ulceration, scleral thinning or a lesion extending into fornix or tarsal conjunctiva.
• Corneal or scleral invasion, intraocular inflammation or raised pressure not otherwise explained.
• Proptosis, diplopia, ophthalmoplegia, reduced vision, severe persistent pain, orbital fullness or cranial-nerve findings.
• Large neglected/recurrent tumour, eyelid distortion, non-healing ulceration or palpable regional nodes.

These signs need urgent specialist evaluation for globe, scleral, intraocular, orbital or metastatic disease. They do not justify an emergency-department biopsy or destructive procedure.

4. Focused history and examination for emergency clinicians

History

• When was the lesion first noticed? Has it changed in size, colour, shape or symptoms? Is there prior photography or a previous biopsy?
• Ask about redness, foreign-body sensation, tearing, pain, photophobia, vision change, diplopia, motility difficulty, bleeding, ulceration and recurrence after surgery.
• Ask about previous pterygium, papilloma, ocular tumour, trauma, radiotherapy or topical treatment. Identify prescribed and non-prescribed eye drops, especially steroids and cytotoxic preparations.
• Review HIV status sensitively and confidentially, ART use and engagement with care if known. Ask about other immune suppression, transplant, cancer treatment and relevant skin disease.
• Ask about lifetime sun exposure and occupational/outdoor exposures. Explain why this history is relevant without assigning blame.

Examination and documentation

1. Visual acuity: test and record each eye separately with usual correction and pinhole when appropriate. A measurable new reduction requires urgent ophthalmology assessment.
2. External inspection: look at eyelid skin and margins, lashes, puncta, lid position, conjunctival injection, chemosis, discharge, proptosis and facial asymmetry.
3. Map the lesion: state side, bulbar/palpebral/forniceal location, relation to the limbus, approximate dimensions, thickness, colour, vascularity, keratin, surface pattern and corneal extension. Record limbal clock hours if trained to do so.
4. Assess mobility and deeper structures: with appropriate equipment and expertise, the ophthalmologist evaluates whether the lesion is mobile over sclera, fixed, ulcerated or associated with anterior chamber or pressure findings. Do not force manipulation of a friable mass.
5. Check the whole ocular surface: slit-lamp review should include both eyes, cornea, fornices, palpebral conjunctiva after lid eversion when safe, limbus and anterior chamber. Record motility and pupil findings if invasion is possible.
6. Regional nodes: palpate preauricular, parotid, submandibular and cervical nodes when clinically appropriate. A normal examination does not exclude metastasis, and a palpable node has many non-malignant causes.
7. Image and refer: a clinical photograph with scale and appropriate consent can support comparison, triage and follow-up. Preserve privacy and follow local documentation policy.

Do not apply topical anaesthetic outside the examination, share eye-drop bottles, scrape off keratin or try to “see if it bleeds.” Avoid destructive treatment before ophthalmology review because it can obscure the lesion, compromise margins and remove tissue needed for diagnosis.

5. Differential diagnosis: what can mimic OSSN?

Uganda’s Ministry of Health clinical guidance specifically advises suspicion for conjunctival SCC in chronic conjunctivitis lasting more than three months and lists pterygium, solar keratosis and pinguecula among differentials. A suspicious lesion merits earlier referral; do not wait three months if it is enlarging, leukoplakic, recurrent, fixed or associated with visual/orbital red flags.

6. Diagnostic work-up and pathology

Histopathology is the diagnostic reference

Clinical examination can identify a suspicious OSSN lesion but cannot reliably separate dysplasia, CIS and invasive SCC. Histopathology evaluates epithelial atypia, maturation, basement-membrane invasion, stromal involvement, tumour grade and surgical margins. A planned excision biopsy is often appropriate for a small, localized lesion; a larger, diffuse, fixed or deeply invasive lesion may require carefully selected incisional biopsy, imaging and a multidisciplinary plan before definitive surgery. Ocular oncology decides the approach.

Where specialist access is limited, document the lesion, protect vision and expedite referral. If tissue sampling is performed by an eye surgeon, send the specimen with orientation/margin information according to local pathology capacity. Lack of immediate pathology access is not a reason for a non-specialist to destroy or repeatedly cauterize a lesion. Cytology or impression cytology can support evaluation in selected diffuse cases but does not replace histopathology for a suspected invasive tumour.

Useful tests selected by ophthalmology

• Slit-lamp photographs: baseline documentation of size, vascular pattern, surface and corneal extension.
• Anterior-segment optical coherence tomography (AS-OCT): can show a thickened, hyperreflective epithelium with an abrupt transition to normal epithelium and help map epithelial extent. It supports diagnosis and monitoring but does not prove or exclude invasion in every case.
• Impression cytology or vital staining: may assist when a lesion is diffuse or tissue diagnosis is difficult. Results depend on technique and should be interpreted with examination findings.
• Ultrasound biomicroscopy: may be used when the limbus, ciliary body or deeper structures need assessment.
• Orbital CT or MRI: indicated when orbital extension, globe invasion, bone involvement, deep mass or cranial-nerve/orbital-apex involvement is suspected. Imaging choice depends on the clinical question and local pathway.
• Systemic staging: not every localized OSSN needs whole-body imaging. If invasive disease, regional spread, symptoms or advanced extension is suspected, oncology/ophthalmology selects nodal or systemic investigations.

HIV and immune assessment

In a high-prevalence setting, offer confidential HIV testing according to national consent and testing guidance when status is unknown, particularly in younger patients or those with OSSN features. Do not make a diagnosis of HIV from an eye lesion, disclose status without consent, or delay tumour referral while awaiting HIV results. For known HIV, coordinate with the HIV team to review ART, adherence, viral suppression and CD4 testing as indicated in current HIV care. The old slide instruction to “check CD4 in every presumed OSSN” is too absolute: assessment should be individualized and follow current HIV protocols.

7. Management: specialist-led, stage-sensitive treatment

The aims are to eradicate the lesion, preserve the globe and ocular surface, obtain a tissue diagnosis, control risk at the margins, reduce recurrence and address the patient’s HIV/immune health. Treatment depends on lesion size, site, histology, invasion, recurrence, local expertise and availability of medicines or cryotherapy.

Small, localized lesions

Common specialist approaches include en-bloc excision using a no-touch technique with macroscopically clear margins, followed by cryotherapy to selected conjunctival/limbal edges. A commonly described surgical margin is approximately 3–4 mm, but it is not an emergency-department target or a universal instruction: ocular surgeons adapt the plan to anatomy and tumour extent. Corneal epithelial extension may be treated by ocular specialists using alcohol-assisted epitheliectomy; suspected scleral invasion may require lamellar sclerectomy or another tailored approach. Tissue is oriented and sent for histopathology.

The no-touch principle reduces manipulation and potential tumour-cell seeding. Operative details—speculum, peritomy, traction sutures, cryotherapy cycles, corneal alcohol exposure and grafting—belong to trained ophthalmic surgeons. They are included here as concepts for learners, not as a procedure recipe for emergency staff.

Topical medical therapy and adjuncts

Ophthalmologists may use topical interferon alfa-2b, 5-fluorouracil (5-FU) or mitomycin C for selected lesions. These drugs can be used as primary therapy in appropriately selected superficial lesions, for chemoreduction, or after surgery when pathology shows involved margins or when recurrence risk is high. Choice depends on lesion characteristics, ocular-surface health, access and monitoring. Deep stromal/scleral or orbital invasion is not safely treated with unsupervised topical drops alone.

• 5-FU: a randomized trial in Kenya found postoperative topical 5-FU reduced OSSN recurrence compared with placebo. It can cause surface irritation, pain, redness, photophobia, epithelial toxicity and lid inflammation; dosing cycles and rest periods are prescribed and monitored by the treating ophthalmologist.
• Mitomycin C: can control epithelial disease but is toxic to the ocular surface and may cause epithelial defects, punctal stenosis, inflammation and, rarely, limbal stem-cell damage. Requires specialist supervision and close follow-up.
• Interferon alfa-2b: may be better tolerated in some settings but availability and cost vary.
• Cryotherapy: is an adjunct to selected surgical margins; it is not a casual destructive treatment for an undiagnosed lesion.

Never share or self-start antimetabolite drops. Their concentration, formulation, schedule, handling and adverse-effect monitoring are specialist matters. Do not use topical steroid alone to make a suspicious mass look less red; it may mask an alternative diagnosis and delay the correct referral.

HIV care is part of tumour care

For a patient living with HIV, support ART initiation or re-engagement with the HIV clinic when clinically appropriate. ART improves overall immune health and may influence tumour behaviour, but it is not a substitute for eye-tumour diagnosis and treatment. Do not reassure a patient that ART alone will clear an invasive lesion. Communicate between ophthalmology, HIV services, pathology and oncology so that appointments, pathology review and ART follow-up are coordinated.

Advanced invasion and the eye-removal slides

Slides 33–40 show evisceration, enucleation and exenteration and include images of enucleation and orbital invasive SCC. These represent a narrow range of advanced situations, not the usual outcome for an early surface lesion:

• Evisceration removes intraocular contents but leaves the scleral shell and extraocular structures. It is generally inappropriate when an intraocular malignancy is suspected because tumour may remain; the specialist team chooses an oncologically safe operation.
• Enucleation removes the globe. It may be considered when tumour invades the eye, intraocular extension cannot be controlled, or the globe cannot be preserved safely.
• Orbital exenteration removes orbital contents and is reserved for extensive orbital invasion when required for disease control. It has major functional, cosmetic and psychosocial consequences and requires ocular-oncology, orbital, reconstructive and oncology planning.
• Radiotherapy or brachytherapy may be considered for selected residual or deep disease in specialist centres, depending on histology, extent and local expertise. These are not routine first steps for a limbal lesion.

The choice among globe-sparing excision, topical treatment, enucleation, exenteration or radiotherapy is individualized. “Wide excision, then amputation” is not a proper automatic sequence. Most patients with localized OSSN are considered for eye-sparing management.

8. Recurrence, invasion and prognosis

Earlier diagnosis generally allows less destructive treatment and better vision preservation. Recurrence can occur after surgery or medical therapy, especially if margins are involved, disease is diffuse, follow-up is missed or the tumour is biologically aggressive. A recent South African cohort used size-based treatment with histology, excision and cryotherapy for smaller lesions and 5-FU in selected larger or margin-positive disease; recurrence remained possible, and one patient developed intraocular extension. This reinforces why a reassuring appearance after treatment is not proof of cure.

Invasive conjunctival SCC can extend into cornea, sclera, globe and orbit. Regional-node or distant spread is uncommon compared with local invasion but is not zero; risks differ across case series and stage. Examine regional nodes when indicated and investigate symptoms or suspicious findings. For metastatic work-up, ophthalmology/oncology select tests rather than screening every small lesion with chest and bone imaging.

Follow-up intervals vary with pathology, treatment, margins and recurrence risk. Early review checks epithelial healing and treatment toxicity; longer surveillance detects late recurrence. Continue monitoring for years when the specialist recommends it, since recurrence may be delayed. Review both eyes and relevant regional nodes over time. A care plan needs a named service, a realistic appointment date and clear return instructions.

9. Referral and disposition for emergency medicine

Urgent same-day ophthalmology / ocular oncology discussion

• Reduced visual acuity, corneal/limbal extension threatening the visual axis, severe pain or inflammation, rapid growth, suspected scleral or intraocular invasion, high pressure or significant anterior-chamber signs.
• Proptosis, diplopia, restricted movement, fixed/deep mass, ulceration, orbital-apex findings, cranial neuropathy, palpable suspicious nodes or systemic red flags.
• Patient with HIV/immunosuppression and a large, recurrent or rapidly progressive lesion; inability to secure follow-up; or concern that definitive review will be delayed.

Prompt expedited referral

A stable, painless, peripheral lesion with preserved acuity still needs prompt ophthalmology assessment when OSSN is suspected. Give the patient a concrete appointment/referral pathway rather than a routine “see someone if it gets bigger.” If no ocular oncology service is nearby, refer to the nearest ophthalmologist with access to slit-lamp examination and pathology, who can coordinate tertiary review.

What the emergency team should do

1. Measure and document visual acuity in each eye.
2. Describe side, location, size, growth history and red flags; photograph only with consent and secure documentation.
3. Assess motility, pupils, proptosis, cornea and anterior chamber within training and available equipment; palpate relevant regional nodes.
4. Check medical stability, pain and known HIV/ART context; offer testing only through the local confidential consent pathway.
5. Contact ophthalmology, send an explicit referral with the concern “ocular-surface squamous neoplasia / possible conjunctival SCC,” and communicate any orbital or visual red flags.
6. Do not perform a non-specialist biopsy/excision, evisceration, steroid trial, cautery or chemotherapy-drop prescription.

10. Case-based discussion

Case 1: persistent red eye in a younger adult

A 34-year-old outdoor worker has had a painless red patch and foreign-body sensation in one eye for four months. A fleshy lesion at the temporal limbus is gradually enlarging, and a branching vessel reaches its base. Vision is 6/6 in both eyes. The patient does not know their HIV status.

Interpretation: OSSN is in the differential alongside pterygium, papilloma and other conjunctival lesions. Preserved acuity and absent pain do not exclude it. Age and unknown HIV status are not diagnostic.

Action: Document acuity and lesion appearance; arrange prompt ophthalmology review and histopathologic work-up as determined by the eye team. Offer confidential HIV testing under local guidance; do not delay ocular referral pending the test.

Case 2: pigmented lesion that resembles a benign spot

A 48-year-old patient has a slowly enlarging brown-pigmented conjunctival mass with leukoplakia and corneal extension. No nodes are palpable.

Interpretation: OSSN can be pigmented, but melanoma and other pigmented lesions also need consideration. A normal node exam does not rule out local invasion or malignancy.

Action: Ocular oncology assessment with slit-lamp mapping, imaging as indicated and biopsy/tissue diagnosis. Do not classify by colour alone or remove it in a non-specialist setting.

Case 3: orbital signs after years of neglected growth

A patient presents with a large ulcerated conjunctival tumour, proptosis, diplopia and restricted movement. Vision is reduced. A preauricular node is enlarged.

Interpretation: Advanced local invasion with possible regional disease must be excluded. Cellulitis and other orbital tumours remain in the differential.

Action: Urgent same-day ophthalmology/ocular oncology and hospital assessment; imaging and biopsy/staging are directed by the specialist team. Do not attempt debulking. Discuss the patient’s understanding, pain and support needs while coordinating cancer and HIV services if relevant.

Case 4: recurrent lesion after previous pterygium removal

A unilateral “pterygium” reappears after prior surgery. This time it is thicker, irregular and leukoplakic. The original tissue was not sent for histology.

Interpretation: Recurrent pterygium is possible, but recurrent OSSN can mimic it and may be missed without pathology.

Action: Refer for specialist examination, photography and planned tissue diagnosis. Do not repeat office excision or treat empirically before review.

11. Knowledge check

1. What tissue boundary distinguishes invasive SCC from dysplasia or carcinoma in situ?
2. Why is “OSSN” a useful working diagnosis before histopathology?
3. Which features make a persistent red eye or conjunctival growth more suspicious for OSSN?
4. Why should HIV testing be offered sensitively in an appropriate patient without delaying eye referral?
5. What can anterior-segment OCT add, and what can it not establish by itself?
6. Why are surgery margins and histopathology important?
7. When may topical 5-FU, mitomycin C or interferon be considered, and who should supervise it?
8. Why is evisceration generally unsuitable when intraocular malignancy is suspected?

Answers

1. Invasive SCC crosses the epithelial basement membrane into underlying stroma; dysplasia and CIS remain confined to the epithelium.
2. It names the pre-cancer/cancer spectrum without pretending that an unbiopsied lesion is already invasive SCC.
3. Progressive unilateral growth, gelatinous or papilliform surface, leukoplakia, feeder vessels, limbal location, corneal extension, recurrence, fixation or orbital signs.
4. HIV is associated with OSSN and disease may be a first clue to infection, but the lesion is not proof of HIV; testing requires confidentiality, consent and local guidance. Ocular assessment is time-sensitive and should proceed in parallel.
5. AS-OCT can help map epithelial thickening and an abrupt transition to normal epithelium. It cannot reliably replace histopathology for grading or confirming invasive disease in all cases.
6. They establish the diagnosis, grade, invasion and margin status; incomplete or involved margins can contribute to recurrence and further treatment decisions.
7. Selected lesions may be treated primarily or as an adjunct to excision, based on site, size, histology, ocular-surface health and access. An ophthalmologist prescribes and monitors for toxicity.
8. It leaves the scleral shell and can leave tumour behind or disseminate it; suspected intraocular malignancy requires an oncologically safe operation selected by specialists.

Key takeaways

• OSSN is a spectrum; only histology can reliably classify epithelial dysplasia, CIS and invasive conjunctival SCC.
• In equatorial Africa, consider OSSN in a persistent unilateral red eye or growing limbal mass, especially with HIV or immunosuppression.
• Record visual acuity, map and document the lesion, assess orbit and regional nodes, and arrange prompt ophthalmology review.
• Do not perform emergency-room excision, destructive treatment or empirical cytotoxic/steroid drops for an undiagnosed lesion.
• Specialist care may include no-touch excision, margin control, cryotherapy, topical medication or tailored treatment for deeper invasion.
• HIV/ART care, histopathology review and reliable long-term follow-up are part of the treatment plan.
• Enucleation and exenteration are reserved for selected extensive disease. They are not the routine course of OSSN.

References and further reading

1. Conjunctival Squamous Cell Carcinoma. Supplied 43-slide presentation on SlideShare.
2. Uganda Ministry of Health. Uganda Clinical Guidelines 2023, section 20.4.2: Squamous Cell Carcinoma of Conjunctiva.
3. American Academy of Ophthalmology EyeWiki. Ocular Surface Squamous Neoplasia.
4. American Academy of Ophthalmology EyeWiki. Conjunctival Epithelial Neoplasms.
5. Gichuhi S, Sagoo MS. Squamous cell carcinoma of the conjunctiva. Community Eye Health Journal. 2016;29(95):52–54.
6. Gichuhi S, et al. Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: randomized, double-blind, placebo-controlled trial. Lancet Global Health. 2016;4:e378–e385.
7. Höllhumer R, Williams S, Michelow P. Observational study of OSSN: risk factors, diagnosis, management and outcomes. PLOS ONE. 2020.
8. Höllhumer R, et al. Management and outcomes of ocular surface squamous neoplasia at a tertiary hospital, South Africa. Eye. 2025.

Educational material for emergency medicine students. It supports, but does not replace, local referral pathways, pathology review, ocular oncology or ophthalmology advice, HIV care and current national treatment protocols.