Neoplastic Disorders of the Conjunctiva Tumors of Epithelial Origin • Epithelial inclusion cyst • Benign epithelial tumors – Conjunctival papilloma – Pseudoepitheliomatous hyperplasia • Preinvasive epithelial tumors Vanee Virasch, M.D. Department of Ophthalmology November 2006 – Conjunctival intraepithelial neoplasia • Malignant epithelial tumors – Squamous cell carcinoma – Mucoepidermoid carcinoma – Spindle cell carcinoma and Basal cell carcinoma Epithelial Inclusion Cyst Epithelial Inclusion Cyst • Pathogenesis – Congenital or acquired – Small cysts formed by apposition of conjunctival folds – Large, single cysts – epithelium implanted into the substantia propria by trauma, surgery, inflammation – Lined by normal conjunctival epithelium • Clinical findings – Appear clear • Management – Complete excision or marsupialization necessary to prevent recurrence – Simple incision will lead to recurrence d/t remaining inner epithelial cells Conjunctival Papilloma • Pedunculated – HPV, type 6 or 11 – Fleshy, exophytic growth with fibrovascular core – Emanates from a stalk with multilobulated appearance with smooth, clear epithelium and small corkscrew vessels – Inferior fornix, tarsal or bulbar conjunctiva – May be multiple – more in HIV pts Conjunctival Papilloma • Sessile – HPV, type 16 or 18 – More likely dysplastic or carcinomatous – Limbus – Flat base with glistening surface and numerous red dots – Signs of dysplasia • Keratinization (leukoplakia) • Inflammation • Invasion – Rare variant – Inverted papilloma 1 Conjunctival Intraepithelial Neoplasia (CIN) Conjunctival Intraepithelial Neoplasia (CIN) • Analogous to actinic keratosis of skin • Does not invade underlying basement membrane • Contributing factors: HPV, sunlight, host factors, petroleum t l products d t • Most common – Exposed areas of bulbar conjunctiva, at or near limbus – Light-complected, older male smokers • More rapid growth in AIDS pts • Potentiated by systemic immunosuppression Conjunctival Intraepithelial Neoplasia (CIN) Conjunctival Intraepithelial Neoplasia (CIN) • Clinical findings – 3 clinical variants: • Papilliform – sessile papilloma harboring dysplastic cells • Gelatinous G l ti – resultlt off acanthosis th i andd ddysplasia l i • Leukoplakic – hyperkeratosis, parakeratosis, and dyskeratosis – – – – Conjunctival Intraepithelial Neoplasia (CIN) • Management – Excisional biopsy with adjunctive cryotherapy • Recurrence rates at 10 yyears – Negative surgical margins ~ 33% – Positive surgical margins ~ 50% Mild inflammation and abnormal vascularization Classification: Mild, Moderate, Severe (Carcinoma in situ) Slow growing tumors Potential to spread to other ocular surfaces Squamous Cell Carcinoma • Pathogenesis – Risk factors: UV radiation, viral, genetic – More common and aggressive in: • HIV • Xeroderma pigmentosa – Topical chemotherapeutic agents • Interferon, MM-C, 5-FU • No long term recurrence studies 2 Squamous Cell Carcinoma • Clinical findings – Broad based lesion at or near limbus in interpalpebral fussure – Grow outward with sharp borders – Can C be leukoplakic – Usually remains superficial rarely penetrating sclera – Pigmentation in dark-skinned pts – Engorged conjunctival vessels feeding tumor – Inflammation – Locally invasive and can metastasize Squamous Cell Carcinoma Squamous Cell Carcinoma • Management – Complete local excision • 4 mm beyond clinically apparent margins • Thin lamellar scleral flap beneath tumor – – – – Absolute alcohol to remaining underlying sclera Adjunctive cryotherapy to margins Risk of recurrence related to surgical margins Extensive external spread • Orbital exenteration and possible radiation therapy Mucoepidermoid Carcinoma • Rare carcinoma of limbal conjunctiva, fornix, or caruncle • Clinically resembles aggressive variant of squamous cell carcinoma • Neoplastic epithelial cells + Malignant goblet cells – Demonstrated with mucin stains • More likely to invade globe or orbit • Treatment – Wide surgical excision – Adjuvant therapy: cryotherapy, radiation Other Carcinomas • Spindle Cell Carcinoma – Rare tumor of bulbar or limbal conjunctiva – Anaplastic cells appear spindle shaped • Basal Cell Carcinoma Glandular Tumors • Oncocytoma • Dacryoadenoma • Sebaceous adenocarcinoma – Rare to arise from conjunctiva 3 Oncocytoma • Slow-growing cystadenoma • Arises from ductal and acinar cells of main and accessory lacrimal glands • Reddish-brown nodule on surface of caruncle in elderly individuals Sebaceous Cell Adenocarcinoma • • • • • 1% of all lid tumors 5% of lid malignancies Elderly individuals g ppts on radiation tx Younger Masquerade as chalazia or chronic unilateral blepharoconjunctivitis • Pathogenesis Dacryoadenoma • Extremely rare • Children or young adults • Benign proliferation of accessory lacrimal gland cells • Round, pink elevation on palpebral or bulbar conjunctiva Sebaceous Cell Adenocarcinoma • Clinical findings – – – – – – Tend to involve lid margin More common on upper lid (greater # of Meibomian glands) Mayy see inflammation Can be multicentric Painless, slow-growing, firm, nonmobile, yellowish nodule Chronic papillary conjunctivitis – Most arise from meibomian gland – Some arise from glands of Zeis, sebaceous glands of the caruncle, or pilosebaceous glands of lids and brows – Enlarged preauricular lymph node may indicate metastasis Sebaceous Cell Carcinoma Sebaceous Adenocarcinoma • Intraepithelial pagetoid spread into the conjunctiva with inflammmation • Management – – – – – – – – Full-thickness biopsy Mapping biopsies may be needed because of skip lesions Wide excision with tumor-free tumor free margins necessary Exenteration – multifocial or spreading tumores Adjunctive radiotherapy Local recurrence ~ 10 – 20% Distant metastasis ~ 15 – 25% Tumor-related mortality ~ 10% 4 Tumors of Neuroectodermal Origin Pigmented Lesions • Benign pigmented lesions – – – – Congenital epithelial melanosis (freckle or ephelis) Benign acquired melanosis Ocular melanocytosis Nevus • Preinvasive pigmented lesions – Primary acquired melanosis • Malignant pigmented lesions – Melanoma • Neurogenic and smooth muscle tumors – Neurofibromas, schwannomas, neuromas – Neurilemoma – Leiomyosarcoma • • • • • • Pigment spot of the sclera – Collection of melanocytes associated with an intrascleral nerve loop or perforating anterior ciliary vessel • Melanosis – Excessive pigmentation without an elevated mass • Epinephrine • Silver • Mascara Congenital Epithelial Melanosis Benign Acquired Melanosis Freckle or ephelis Flat, brown patch Usually bulbar conjunctiva near limbus More common in darkly pigmented individuals Present at an early age • Increasing pigmentation of the conjunctiva of both eyes in middle aged individuals with dark skin • Light brown pigmentation of the perilimbal and interpalpebral bulbar conjunctiva • Striate melanokeratosis – streaks and whorls that extend into peripheral corneal epithelium • Stimulus to melanocytic hyperplasia may be related to sunlight exposure Ocular Melanocytosis Ocular Melanocytosis • Congenital melanosis of the episclera – Occurs in ~ 1 in every 2500 individuals – More common in blacks, Hispanics, Asians • Focal proliferation of subepithelial melanocytes (blue nevus) • Clinical findings – Patches of nonmobile slate gray pigmentation – May have diffuse nevus of the uvea • Increased pigmentation of iris and choroid – Oculodermal melanocytosis – in 50% of pts • Nevus of Ota – Ipsilateral dermal mealocytosis – proliferation of dermal melanocytes in periocular skin of CN V1 and V2 • 5% are bilateral 5 Ocular Melanocytosis Ocular Melanocytosis • Management – Secondary glaucoma occurs in affected eye in ~ 10% – Malignant transformation possible but rare • Occurs more often in fair-skinned pts • Lifetime risk ~ 1 in 400 • Can occur in skin, conjunctiva, uvea or orbit Nevus Nevi • Nevocellular nevi of conjunctiva – hamartia arising during childhood and adolescence • Junctional, Compound, Subepithelial • Flat near limbus, Elevated elsewhere • Pigmentation variable • Small S ll epithelial ith li l iinclusion l i cysts t ~ 50% • Secretion of mucin in inclusion cysts – enlargement • Rapid enlargement at puberty • High prevalence of junctional activity but rarely become malignant • Excision of suspicious lesions • Excise nevi on palpebral conjunctiva Primary Acquired Melanosis • Preinvasive intraepidermal lesion of sun-exposed skin • Flat, brown noncystic lesions of conjunctival epithelium • PAM associated with cellular atypia – progress to melanoma l iin ~ 46% • Pathogenesis – Abnormal melanocytes proliferate in basal conjunctival epithelium of middle-aged, light-skinned individuals • Malignant transformation – nodularity, enlargement or increased vascularity Primary Acquired Melanosis • Management – Excisional biopsy – All palpebral pigmented lesions should be excised – Lesions that show atypia • Adjunctive cryotherapy • Mitomycin-C – Check regional lymph nodes 6 Melanoma • Less than 1% of ocular malignancies • Prevalence: ~ 1 per 2 million in population of European ancestry – Rare in blacks and Asians • Better prognosis than cutaneous melanoma Melanoma • Pathogenesis – Arise from acquired nevi, PAM, or normal conjunctiva – Malignant transformation of congenital conjunctival nevus very rare – Intralymphatic spread increases risk of metastasis – Underlying ciliary body melanoma can extend through sclera – Cutaneous melanoma can rarely metastasize to conj Melanoma • Clinical findings – – – – – – Most common on bulbar conj or at limbus Variable pigmentation Highly vascularized – bleed easily Grow in nodular fashion Can invade globe or orbit Outcome • Bulbar melanomas have better prognosis than those on palpebral conj, fornix, or caruncle • Metastasis in ~ 26%, Mortality ~ 13% 10 yrs after surgical excision – Cytologic risk factors for metastasis: large size, multicentricity, epithelioid cell type, lymphatic invasion – Can metastasize to LN’s brain, and other sites Melanoma • Management – – – – – – – – Excisional biopsy Excision of conjunctiva 4mm beyond clinically apparent margins Excision of thin lamellar scleral flap beneath tumor Treat remaining sclera with absolute alcohol Cryotherapy to conjunctival margins Primary closure or conj/amniotic membrane graft Topical mitomycin-C – can be used for residual disease Orbital exenteration – advanced disease or palliative tx • Poor prognostic factors – Melanomas arising de novo – Tumors not involving limbus – Residual involvement at surgical margins 7 Other neuroectodermal tumors • Multiple endocrine neoplasia (MEN) – Subconjunctival peripheral nerve sheath tumors • Neurofibromas, shwannomas, neuromas • Neurilemoma – Very rare conj tumor originating form Schwann cell of a peripheral nerve sheath • Leiomyosarcoma – Very rare limbal lesion with potential for orbital invasion Vascular and Mesenchymal Tumors • Benign tumors – Hemangiomas – Inflammatory vascular tumors • Pyogenic granulomas, juvenile xanthogranuloma, fibrous histiocytoma, nodular fasciitis • Malignant tumors – Kaposi sarcoma – Other malignant tumors Hemangioma • Isolated capillary and cavernous hemangiomas of bulbar conjunctiva rare – likely extension from adjacent structures • Palpebral conjunctiva – Eyelid capillary h hemangioma i • Diffuse hemangiomatosis of palpebral or foniceal conjunctiva – Orbital capillary hemangioma • Cavernous hemangioma of orbit Hemangioma • Sturge-Weber syndrome – Nevus flammeus (port-wine stain), vascular hamartomas, secondary glaucoma, leptomeningeal angiomatosis i t i • Ataxia-telangectasia – Epibulbar telangectasis, cerebellar abnormalities, immune disorders Pyogenic Granuloma • Common reactive hemangioma • Misnamed – not suppurative, no giant cells • May occur – Over chalazion – Minor trauma – Post op granulation tissue • Rapidly growing red, pedunculated, smooth lesion • Bleeds easily and stains with fluorescein dye 8 Pyogenic Granuloma • Management – Topical or intralesional corticosteroids may be curative – Excision with cauterization to the base, primary closure and post-op steroids to minimize recurrence Other inflammatory vascular tumors • Juvenile xanthogranuloma – A histiocytic disorder that can present with conjunctival mass • Subconjunctival granulomas – around parasitic and mycotic infectious foci • Connective tissue diseases – RA nodules, sarcoid nodules (tan-yellow resemble follicles) • Fibrous histiocytoma – Fibroblasts and histiocytes with lipid vacuoles • Nodular fasciitis – Very rare benign tumor of fibrobascular tissue in lid or under conj – May originate at insertion of rectus muscle Kaposi Sarcoma • Malignant neoplasm of vascular endothelium involves skin, mucous membrans and internal organs • Pathogenesis – Infection with HHV-8 – Occurs O iin setting tti off AIDS • Clinical findings – Reddish, highly vascular subconjunctival lesion • Can be mistaken for subconjunctival hemorrhage – Orbital involvement – lid and conjunctival edema – Inferior fornix most common – Nodular or diffuse Kaposi Sarcoma • Management – – – – – – – Treatment may not be curative Nodular lesions less responsive to therapy Surgical debulking Cryotherapy Radiotherapy Local or systemic chemotherapy Intralesional interferon alpha-2a may be effective Other Malignant Tumors • • • • Malignant fibrous histiocytomas Liposarcomas Leiomyosarcomas Rhabdomyoisarcomas 9 Lymphatic and Lymphocytic Tumors • • • • Lympohangiectasia Lymphangioma Lymphoid hyperplasia Lymphoma Lymphangioma • Proliferations of lymphatic channel elements • Usually present at birth and enlarge slowly • Patch of vesicles with edema • Intralesional hemorrhage – “chocolate cyst” Lymphangiectasia • Appears as irregularly dilated lymphatic channels in bulbar conjunctiva • Mayy be developmental p anomalyy • Can follow trauma or inflammation • Anomalous communication with venule can lead to spontaneous filling of lymphatic vessels with blood Lymphoid Hyperplasia • Formerly called Reactive hyperplasia • Benign-appearing accumulation of lymphocytes and other leukocytes • May represent low-grade B-cell lymphoma • Pts > 40 y/o • Clinical findings – Minimally elevated salmon-colored subepithelial tumor with pebbly appearance – Often moderately to highly vascularized – Clinically indistinguishable from conj lymphoma – May appear similar to primary localized amyloidosis Lymphoid Hyperplasia • Management – – – – – May resolve spontaneously Local excision Topical corticosteroids Radiation Biopsy specimen may require special handling for special histo and immuno stains – General medical consultation 10 Lymphoma Lymphoma • Neoplastic lymphoid lesion of conjunctiva • Pathogenesis – – – – • Clinical findings – Salmon pink, mobile mass on conjunctiva – Diffuse lesion – masquerade as chronic conjunctivitis – Epibulbar mass – may be extension from uveal lymphoid neoplasia – Age > 50 yrs or immunosuppressed – AIDS increases risk Can arise from conj lymphoid follicles Some localized, localized some linked to systemic lymphoma Monoclonal B-cell lymphomas most common Less common • Conjunctival plasmacytoma • Hodgkin lymphoma • T-cell lymphomas Lymphoma • Management – Referral to oncologist for systemic evaluation – Excisional biopsy p y if small enough g – Incisional biopsy if too large – Local external beam radiation therapy Metastatic Tumors • • • • Breast Lung Kidney Cutaneous melanoma • Usually curative for lesions confined to conj – Systemic chemotherapy for systemic disease Epibulbar Choristomas • • • • • Epidermoid and dermoid cyst Epibulbar dermoid tumor Dermolipoma Ectopic lacrimal gland Other choristomas – – – – Complex choristoma Osseous choiristoma Neuroglial choristoma Phakomatous choristoma Epidermoid and Dermoid Cyst • Rare choristomatous anomaly • Epidermoid cyst – no accessory skin structures • Dermoid cyst – includes accessory skin structures • Most common at Frontozygomatic suture • Less common at Nasofrontal suture • Excision recommended when cyst threatens to cause amblyopia or cosmetic deformity 11 Epibulbar Dermoid Tumor • 1 in 10,000 individuals • Pathogenesis – Displaced embryonic skin tissue – Composed of fibrous tissue, hair with sebaceous glands – Covered by conjunctival epithelium • Clinical findings – Well-circumscribed, solid, smooth, porcelain white, round to oval elevated lesion embedded in superficial sclera or cornea – Most common in infertemporal limbus – Arcus-like deposit of lipid along anterior corneal border – Corneal astigmatism – anisometropic amblyopia Epibulbar Dermoid Tumor • Goldenhar syndrome – Oculoauriculovertebral dysplasia – Sporadic or AD syndrome off first fi t bbranchial hi l archh – Epibulbar dermoid – Coloboma of upper lid – Preauricular skin tags – Aural fistulae – Vertebral anomalies Dermolipoma • Pale yellow dermoid containing adipose tissue • Distinguish from herniation of orbital fat • Occurs superotemporally and may extend posteriorly • May be associated with Epibulbar Dermoid Tumor • Management – – – – No malignant potential Lesion often extends deep into underlying tissues El t d portion Elevated ti may bbe excised i d Relaxing incision or other corrective measure may be considered – Lamellar keratoplasty for cosmetic appearance – Amblyopia treatment Ectopic Lacrimal Gland • Lacrimal gland tissue occurring outside of the lacrimal fossa • Round, Round pink, pink vascularized mass at the limbus – Goldenhar syndrome – Linear nevus sebaceous syndrome 12 Other Choristomas • Complex choristoma – Superotemporal globe – Multiple tissues: cartilage, bone, lacrimal galnd lobules, hair follicles, hair, sebaceous glands, and adipose tissue • Osseous choristoma – Solitary nodule of bone surrounded by fibrous tissue – Superotemporal • Neuroglial choristoma – more diffuse • Phakomatous choristoma – Subcutaneous nodule in the inferomedial lid composed of disorganized lens cells Questions? 13