Cancers of the eye and related structure are rare but can be uniformly fatal if left untreated. Since these tumors appear on the face and affect visual functions early on, they can be detected and diagnosed early. However, lack of awareness about the early signs and symptoms often makes these potentially curable tumors present at an advanced stage, making vision, eye, and sometimes life salvage difficult. Comprehensive ophthalmologists are often the first and sometimes the only point of contact for these patients. Hence, awareness about the early warning signs of common eye cancers can facilitate prompt diagnosis and referral, affecting the prognosis Figure 1. The aim of this perspective is to simplify the recognition of the common eye cancers, clarify triggers for referral, and provide guidance on patient counseling.Figure 1: Typical and atypical presentation of common ocular tumors. (a) Typical presentation of eyelid sebaceous gland carcinoma (SGC) as a nodulo-ulcerative eyelid mass. Atypical presentation of SGC as recurrent chalazion (b), unilateral diffuse blepharoconjunctivitis (c), and placoid palpebral conjunctival thickening (d). (e) Typical presentation of ocular surface squamous neoplasia (OSSN) as a keratinized limbal nodule with feeder vessels. Atypical presentation of OSSN as corneal scar with fimbriated edges (f), peripheral ulcerative keratitis with limbal thickening (g), and perforated corneal ulcer with keratinized thickening superior limbus (h). (i) Leukocoria or white reflex is the typical presentation of retinoblastoma. Atypical presentation of retinoblastoma as hypopyon in a white eye (j), spontaneous phthisis bulbi following tumor necrosis (k), and orbital cellulitis (l)TOP FOUR EYE CANCERS ONE MUST KNOW Sebaceous gland carcinoma It is the great masquerader, often mimicking chronic meibomitis, blepharitis, or blepharoconjunctivitis.1 Red flags for diagnosis Chronic unilateral blepharoconjunctivitis/meibomitis, not responding to conventional treatment, especially in an elderly patient. Recurrent chalazion at the same site, especially with localized loss of eyelashes and diffuse eyelid thickening. Yellowish eyelid nodule or thickening with loss of eyelashes and lid margin thickening. Management pearls for eyelid malignancies Confirm diagnosis based on clinical findings and histopathology. Conjunctival map biopsy in cases with diffuse conjunctival inflammation in suspected sebaceous gland carcinoma (SGC). Rule out local and systemic spread – Do metastatic workup, orbital imaging if extension beyond the conjunctival fornix, and positron emission tomography–computed tomography to rule out systemic involvement. Localized eyelid disease – Complete excision with margin clearance, preferably intraoperative frozen section margin clearance, followed by eyelid reconstruction. Diffuse conjunctival involvement in SGC – Surgical excision and ocular surface reconstruction and topical chemotherapy for the involvement of <50% ocular surface. Extensive ocular surface involvement might necessitate exenteration. Local spread to orbit and surrounding structures – Consider neoadjuvant chemotherapy followed by exenteration/exenteration. Postoperative external beam radiotherapy to the orbit for residual disease. Newer treatment modalities for selected patients include Hedgehog signal pathway inhibitor (vismodegib) for basal cell carcinoma and immunotherapy with epidermal growth factor receptor inhibitor cetuximab for eyelid squamous cell carcinoma. Ocular surface squamous neoplasia It is the most common malignant conjunctival tumor. It can mimic infective and inflammatory ocular surface diseases, including peripheral ulcerative keratitis, corneal degeneration, keratitis, infective scleritis, and limbal stem cell deficiency.2–6 Red flags for suspecting ocular surface squamous neoplasia Acquired, progressive limbal nodule Papillary or gelatinous surface with keratin Fimbriated edges of a corneal epithelial lesion Presence of intrinsic or feeder vessels. Pearls for management Topical chemotherapy or immunotherapy is suitable only for cases without deeper invasion, which can be assessed by anterior segment optical coherence tomography or ultrasound biomicroscopy or clinical mobility of the lesion over episcleral tissues. Invasive lesion – Surgical excision with clear margin. Extensive lesion with sclera or corneal invasion – Selected cases can be managed with plaque brachytherapy. Intraocular or orbital invasion – Needs extended enucleation or exenteration. Retinoblastoma It is the most common intraocular malignant tumor in children. It is also the pediatric cancer with the highest survival if detected on time. Advanced disease with local or systemic metastasis has high mortality. Early diagnosis can salvage life, eye, and vision. General ophthalmologists are often the first point of contact in children with suspected retinoblastoma.7,8 Red flag signs: When to suspected retinoblastoma White pupillary reflex in a child is retinoblastoma unless proven otherwise. Acquired squint in a child – Do dilated fundus evaluation to rule out retinoblastoma. Unexplained phthisis bulbi in a child – Ultrasound B scan must rule out a spontaneously regressed retinoblastoma. Orbital cellulitis with history of white reflex in child – Likely necrotic retinoblastoma. Hypopyon, especially unilateral with white eye in a child – Mimic uveitis, do a B-scan to rule out retinoblastoma. Management pearls Examination under anesthesia mandatory for children suspected with retinoblastoma to confirm diagnosis and for disease staging. Enucleation should not be done without appropriate imaging and disease staging. Management should be done by a multidisciplinary team with experience in treating retinoblastoma. Uveal melanoma It is the most common intraocular malignant tumor in adults. Smaller tumors, especially not involving the posterior pole, can be asymptomatic till late stage. Diagnosis is clinical and based on a detailed and dilated fundus evaluation. Red flags for diagnosis Melanoma can be brown in color or amelanotic. Any acquired brown pigmented choroidal mass in an adult – Need to rule out melanoma. Need to differentiate from a nevus or another benign choroidal lesion like hemangioma. Remembering the red flag signs such as the presence of orange pigment, subretinal fluid around the lesion, thickness more than 2 mm, and documented growth will help in early diagnosis. Eye salvage is possible with plaque brachytherapy or proton beam radiotherapy if diagnosed at an early stage. RED FLAGS NOT TO BE MISSED: WHEN TO SUSPECT EYE CANCER Pediatric red flags Leukocoria. Strabismus with reduced vision. Unexplained phthisis bulbi or orbital cellulitis. Hypopyon with a white eye. Adult red flags Any recurrent eyelid lesion or chalazion, especially in the elderly. Any conjunctival lesion with surface keratin. Pigmented intraocular lesions with symptoms. WHEN TO REFER AND WHEN NOT TO TREAT A comprehensive ophthalmologist plays an important role in the diagnosis and management of ocular malignancies. The diagnosis and management of ocular tumors have important ethical and medical considerations and hence should be managed by a multidisciplinary trained team. The first intervention is often the most important oncological decision. Referral should be considered when in doubt, and a malignancy cannot be ruled out conclusively. Consider immediate referral if Ocular malignancy suspected – Based on the red flag signs. Recurrent or aggressive eyelid lesions. Pediatric intraocular tumors – Retinoblastoma. Avoid Repeated incisions of a recurrent chalazion or eyelid nodule in an elderly. Conservative management of persistent unilateral blepharoconjunctivitis or meibomitis in an elderly. Incomplete excision of a suspected eyelid tumor without margin control. Any intraocular surgery or observation in a child with a history of leukocoria. Empirical treatment of any limbal or conjunctival nodule with the presence of keratin with topical antibiotics or steroids. Empirical steroid use in undiagnosed lesions. WHERE TO REFER: THINGS TO CONSIDER WHEN REFERRING A PATIENT WITH SUSPECTED OCULAR MALIGNANCY Appropriate and timely referral plays an extremely important role in determining the prognosis in patients with ocular cancers. Consider appropriate counseling of the patient and family to alleviate fear associated with cancer diagnosis and ensure compliance with timely treatment. When in doubt, definitive statements about diagnosis should be avoided, and need for further evaluation and investigations should be emphasized. Consider referral to a tertiary care setup having: Dedicated ocular oncology unit. Multidisciplinary ocular oncology team. Access to imaging, pathology, oncology, radiotherapy, genetics, interventional radiology, etc. Facility for visual or prosthetic rehabilitation available post treatment completion. The referring ophthalmologist also plays an important role in long-term post-treatment follow-up of patients, working alongside the oncology team to monitor for recurrence and treatment-related complications. CONCLUSION Most eye cancers are initially seen by general ophthalmologists – Awareness about red flag signs should aid early diagnosis. Early suspicion saves vision and life. Do not biopsy or excise unless trained and equipped. Timely referral to appropriate centers is essential. Compassionate counseling matters as much as diagnosis. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.ABOUT THE AUTHORDr. Sima Das is the Director of Oculoplasty and Ocular Oncology Services and Director of the Medical Education Department at Dr. Shroff’s Charity Eye Hospital, New Delhi. The integrated and dedicated ocular oncology unit established by the author is one of its kind in North India, catering to patients with eye cancers from across the country and from all socioeconomic backgrounds, providing state-of-the-art diagnostic and treatment facilities at an affordable cost. The author also mentors a dedicated Ocular Oncology long-term fellowship training program and has trained more than 40 fellows from across the country and around the globe.
Sima Das (Thu,) studied this question.