Management of a conjunctival tumor is multifaceted, depending significantly on the differential diagnosis established and the lesion’s size and extent. The approach can range from careful observation to more interventional treatments like biopsies (incisional or excisional), cryotherapy, chemotherapy, radiotherapy, and in severe cases, modified enucleation or orbital exenteration. In cases requiring extensive conjunctival tissue removal, grafts such as mucous membrane from the opposite eye’s conjunctiva, buccal mucosa, or amniotic membrane might be necessary to aid in reconstruction.
Observation
For many benign and asymptomatic conjunctival tumors, observation is often the preferred initial strategy. Conditions like pingueculum, dermolipoma, and nevus are frequently managed through observation. Accurate documentation is crucial, thus external or slit-lamp photographs are recommended for all lesions, especially those raising suspicion. Regular follow-up examinations, typically every 6 to 12 months, are essential to monitor for any signs of growth, malignant transformation, or adverse effects on surrounding healthy tissues. This watchful waiting approach is integral in the differential diagnosis process, allowing for assessment of lesion behavior over time before more invasive interventions are considered.
Incisional biopsy
Incisional biopsy is indicated for extensive, symptomatic, or suspicious tumors where malignancy is a concern in the differential diagnosis. Examples include large squamous cell carcinomas, primary acquired melanosis, melanoma, and conjunctival invasion by sebaceous gland carcinoma. For bulbar conjunctival tumors spanning four clock hours or less, excisional biopsy is generally favored. However, for larger lesions, incisional wedge or punch biopsies are appropriate. The biopsy results guide subsequent definitive treatment strategies. Incisional biopsy is also suitable for conditions best treated with radiotherapy, chemotherapy, or topical medications, such as lymphoid tumors, metastatic tumors, extensive papillomatosis, and certain cases of squamous cell carcinoma and primary acquired melanosis. It’s generally advisable to avoid incisional biopsy for melanocytic tumors, particularly melanoma, as it might elevate the risk of tumor recurrence.
Excisional biopsy
Excisional biopsy is the primary approach for smaller tumors (≤4 clock hours limbal or ≤15 mm basal dimension) that are symptomatic or suspected to be malignant. In these scenarios, it is preferred over incisional biopsy to minimize the risk of tumor seeding. Both benign and malignant lesions that benefit from excisional biopsy include symptomatic limbal dermoids, epibulbar osseous choristomas, steroid-resistant pyogenic granulomas, squamous cell carcinomas, and melanomas. When located in the conjunctival fornix, these lesions can often be completely excised, and the conjunctival defect can be closed primarily using absorbable sutures, sometimes with fornix deepening sutures or a symblepharon ring to prevent adhesions. If primary closure is not feasible, a mucous membrane graft may be required.
Most primary malignant conjunctival tumors, such as squamous cell carcinoma and melanoma, typically arise in the interpalpebral area near the limbus. Surgical techniques for limbal tumors differ from those for forniceal tumors due to the potential for limbal neoplasms to invade through the corneal epithelium and sclera into the anterior chamber, and into the orbit via soft tissues. Consequently, removing a thin scleral lamella is often necessary to achieve tumor-free margins and reduce recurrence risk. A partial lamellar sclerokeratoconjunctivectomy with primary closure is frequently employed for these tumors (Fig. 1). Given the friable nature of these tumors and the risk of cell seeding, a gentle, “no-touch” surgical technique is recommended. Microscopic surgery and maintaining a dry operative field until tumor removal are advised to ensure cells adhere to the resected tissue. While various surgical excision techniques exist, the principles outlined above are widely supported in ocular oncology.
Figure 1.
Surgical excision of conjunctival malignancy using the “no touch” technique. (a) Absolute alcohol application for controlled corneal epitheliectomy. (b) Corneal epithelium scrolled off with a beaver blade. (c) Conjunctival incision outside tumor margin. (d) Conjunctival malignancy removal with tumor-free margins. (e) Cryotherapy application to resection site. (f) Conjunctival closure with absorbable sutures.
The surgical technique for resecting limbal tumors (Fig. 1) begins with retrobulbar anesthesia and an operating microscope. The corneal epithelial component is addressed first, followed by the conjunctival component, aiming for en bloc excision. Absolute alcohol on an applicator is gently applied to the corneal component to devitalize epithelial cells and facilitate tumor cell release from Bowman’s layer. A beaver blade microscopically outlines the malignancy within the corneal epithelium using a delicate epitheliorhexis technique, 2 mm outside the corneal component. The affected corneal epithelium is then gently swept towards the limbus, forming a scroll. Next, a pentagonal or circular conjunctival incision, 4–6 mm outside the tumor margin, is made at the limbus, extending through Tenon’s fascia to expose the sclera, ensuring full-thickness conjunctiva and Tenon’s fascia are included in the excisional biopsy. Cautery is used for hemostasis. A superficial scleral groove, approximately 0.2 mm deep and 2.0 mm outside the conjunctival mass base, is then outlined and extended to the limbus. Flat dissection removes the tissue within this groove, including a superficial scleral lamella, overlying Tenon’s fascia, conjunctiva with tumor, and the corneal epithelium scroll. This “no-touch” technique ensures en bloc removal with tumor-free margins. The specimen is placed flat on cardboard and fixed for histopathology to prevent folding and allow margin assessment. Instruments are replaced to prevent tumor cell contamination of healthy tissue.
Post-excision, cryotherapy is applied to the remaining bulbar conjunctival margins by freezing the tissue as it’s lifted from the sclera with a cryoprobe. Once the ice ball reaches 4–5 mm, it’s thawed, and the cycle is repeated. This process is repeated across all margins. Corneal margins do not require cryotherapy. The tumor bed is treated with absolute alcohol and bipolar cautery, avoiding direct cryotherapy to the sclera.
Using clean instruments, the conjunctiva is mobilized for defect closure by loosening the intermuscular septum with Steven’s scissors and creating transpositional conjunctival flaps. Closure is achieved with interrupted absorbable 6-0 or 7-0 sutures. While bare sclera near the limbus is an option, complete closure is preferred for better healing and facilitating potential future surgery for recurrence. Topical antibiotics and corticosteroids are prescribed for two weeks, followed by 3- to 6-month follow-up intervals.
Cryotherapy
Cryotherapy serves as a valuable adjunct to excisional biopsy in conjunctival tumor management. It effectively eliminates subclinical, microscopic tumor cells and reduces recurrence risk, particularly for malignant tumors like squamous cell carcinoma and melanoma. Cryotherapy can also be a primary treatment for primary acquired melanosis and pagetoid invasion of sebaceous gland carcinoma. By devitalizing malignant or potentially malignant cells, it can often defer or prevent radical surgeries like orbital exenteration. However, cryotherapy can cause conjunctival chemosis lasting over a week, and misuse, leading to globe freezing, may result in cataract, uveitis, scleral and corneal thinning, and phthisis bulbi.
Chemotherapy
Topical chemotherapy eyedrops containing mitomycin C, 5-fluorouracil, or interferon have demonstrated efficacy against epithelial malignancies such as squamous cell carcinoma, primary acquired melanosis, and pagetoid invasion of sebaceous gland carcinoma. Mitomycin C or 5-fluorouracil are particularly effective for squamous cell carcinoma, especially in cases of post-surgical recurrence. Typically, these medications are applied topically four times daily for one week, followed by a one-week hiatus for ocular surface recovery [Table 1]. This cycle is usually repeated for a total of two weeks of topical chemotherapy. While effective for squamous cell carcinoma, mitomycin C and 5-fluorouracil are less effective for primary acquired melanosis and pagetoid sebaceous gland carcinoma invasion and are most effective for intraepithelial disease, with limited efficacy for deeper invasion. Potential toxicities include dry eye, superficial punctate epitheliopathy, and punctal stenosis. Corneal or scleral melt and cataract are risks with open conjunctival wounds or excessive use. Topical interferon, though less toxic to the surface epithelium, can also treat squamous epithelial malignancies but may require prolonged use to achieve results.
Table 1.
Protocol for Mitomycin C Use in Conjunctival Squamous Cell Neoplasia and Primary Acquired Melanosis
| Time | Medication and Frequency |
|---|---|
| Week 1 | Slit-lamp biomicroscopy, punctal plugs placement, Cycle 1: mitomycin C 0.04% qid to affected eye |
| Week 2 | No medication |
| Week 3 | Cycle 2: mitomycin C 0.04% qid to affected eye |
| Week 4 | No medication, Slit-lamp biomicroscopy, Further cycles if tumor persists, punctal plugs removal after medication completion |
Radiotherapy
Radiotherapy for conjunctival tumors includes external beam radiotherapy and custom-designed plaque radiotherapy. External beam radiotherapy, delivering 3,000–4,000 cGy, treats conjunctival lymphoma and metastatic carcinoma when lesions are too large or diffuse for local excision. Anticipated side effects include dry eye, punctate epithelial abnormalities, and cataract.
Custom-designed plaque radiotherapy, also at doses of 3,000–4,000 cGy, can treat conjunctival lymphoma or metastasis. Higher doses (6,000–8,000 cGy) are used for radiation-resistant melanoma and squamous cell carcinoma. Plaque radiotherapy is generally reserved for diffuse, incompletely resected tumors or recurrent cases. Two techniques exist for conjunctival custom plaque radiotherapy: conformer plaque (fractionated outpatient sessions) and reverse plaque (inpatient with episcleral suturing). Low-dose plaque radiotherapy (2,000 cGy) is occasionally used for benign conditions like steroid-resistant pyogenic granuloma recurring post-resection. Experienced radiation and ocular oncologists should administer these treatments. Comparative data on radiotherapy techniques is limited in published reports.
Modified enucleation
Modified enucleation is considered for primary malignant conjunctival tumors invading through limbal tissues into the globe, causing secondary glaucoma. While rare, this can occur with squamous cell carcinoma and melanoma, particularly uncommon mucoepidermoid and spindle cell variants of conjunctival squamous cell carcinoma, which have a higher propensity for intraocular invasion. Enucleation requires intact removal of the involved conjunctiva with the globe to prevent tumor cell spread. The peritomy begins at the limbus, extending posteriorly to encircle tumor-affected tissue by at least 3–4 mm. Sutures may secure the tumor to the globe to prevent displacement during manipulation. Enucleation proceeds gently, removing the globe with the adherent tumor after optic nerve transection nasally. Cryotherapy with a double freeze-thaw cycle treats margins of the remaining conjunctiva. This technique may leave limited residual conjunctiva for closure, potentially necessitating mucous membrane or amniotic membrane grafts for adequate closure and fornix reconstruction for prosthesis fitting. In some cases, a horizontal inferior forniceal conjunctival incision with a conformer template may suffice for fornix regeneration.
Orbital exenteration
Orbital exenteration is typically the treatment of choice for primary malignant conjunctival tumors invading the orbit or exhibiting complete conjunctival involvement. Depending on eyelid involvement, either eyelid-removing or eyelid-sparing exenteration is performed. Eyelid-sparing techniques are favored for better cosmetic outcomes and faster healing (2–3 weeks), specifically when the anterior eyelid lamella is uninvolved. Radiotherapy, using external beam or brachytherapy, is an alternative to exenteration, but comparative scientific data is scarce.
Mucous membrane graft
Mucous membrane grafts are sometimes necessary to replace significant conjunctival tissue lost during extensive tumor resection. Ideal donor sites include the forniceal conjunctiva of either eye and buccal mucosa from the lower lip or mouth’s lateral aspect. Grafts are usually harvested freehand, shaped to fit the defect, and secured with absorbable 6-0 or 7-0 sutures. Amniotic membrane grafts are now frequently used to replace lost conjunctiva. Frozen tissue requires 20 minutes of thawing before careful peeling from its backing and suturing into place, basement membrane side up, with absorbable sutures. Topical antibiotics and steroid ointments are applied post-grafting.
Minimizing tumor manipulation during resection is crucial. Clean, sterile instruments are preferred for both donor and recipient sites during grafting to prevent tumor cell transfer and implantation into uninvolved areas.
