Neoplastic Disorders of the Conjunctiva

Vanee Virasch, M.D. Department of Ophthalmology November 2006

Tumors of Epithelial Origin

Epithelial inclusion cyst Benign epithelial tumors
Conjunctival papilloma Pseudoepitheliomatous hyperplasia

Preinvasive epithelial tumors

Conjunctival intraepithelial neoplasia

Malignant epithelial tumors

Squamous cell carcinoma Mucoepidermoid carcinoma Spindle cell carcinoma and Basal cell carcinoma

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

Epithelial Inclusion Cyst

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

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

Conjunctival Intraepithelial Neoplasia (CIN)

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 result lt of f acanthosis th i and dd dysplasia l i Leukoplakic hyperkeratosis, parakeratosis, and dyskeratosis

Mild inflammation and abnormal vascularization Classification: Mild, Moderate, Severe (Carcinoma in situ) Slow growing tumors Potential to spread to other ocular surfaces

Conjunctival Intraepithelial Neoplasia (CIN)

Management
Excisional biopsy with adjunctive cryotherapy
Recurrence rates at 10 y years
Negative surgical margins ~ 33% Positive surgical margins ~ 50%

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

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

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

Squamous Cell Carcinoma

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

Glandular Tumors
Oncocytoma Dacryoadenoma Sebaceous adenocarcinoma

Basal Cell Carcinoma

Rare to arise from conjunctiva

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

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

1% of all lid tumors 5% of lid malignancies Elderly individuals g p pts on radiation tx Younger Masquerade as chalazia or chronic unilateral blepharoconjunctivitis Pathogenesis
Most arise from meibomian gland Some arise from glands of Zeis, sebaceous glands of the caruncle, or pilosebaceous glands of lids and brows

Sebaceous Cell Adenocarcinoma

Clinical findings
Tend to involve lid margin More common on upper lid (greater # of Meibomian glands) May y see inflammation Can be multicentric Painless, slow-growing, firm, nonmobile, yellowish nodule Chronic papillary conjunctivitis
Intraepithelial pagetoid spread into the conjunctiva with inflammmation

Enlarged preauricular lymph node may indicate metastasis

Sebaceous Cell Carcinoma

Sebaceous Adenocarcinoma
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%

Tumors of Neuroectodermal Origin

Benign pigmented lesions
Congenital epithelial melanosis (freckle or ephelis) Benign acquired melanosis Ocular melanocytosis Nevus

Pigmented Lesions
Pigment spot of the sclera
Collection of melanocytes associated with an intrascleral nerve loop or perforating anterior ciliary vessel

Preinvasive pigmented lesions

Primary acquired melanosis

Melanosis
Excessive pigmentation without an elevated mass

Malignant pigmented lesions

Melanoma

Neurogenic and smooth muscle tumors

Neurofibromas, schwannomas, neuromas Neurilemoma Leiomyosarcoma

Epinephrine Silver Mascara

Congenital Epithelial Melanosis

Freckle or ephelis Flat, brown patch Usually bulbar conjunctiva near limbus More common in darkly pigmented individuals Present at an early age

Benign Acquired Melanosis

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
Congenital melanosis of the episclera
Occurs in ~ 1 in every 2500 individuals More common in blacks, Hispanics, Asians

Ocular Melanocytosis
Clinical findings
Patches of nonmobile slate gray pigmentation May have diffuse nevus of the uvea
Increased pigmentation of iris and choroid

Focal proliferation of subepithelial melanocytes (blue nevus)

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

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
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

Nevi

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

Primary Acquired Melanosis

Management
Excisional biopsy All palpebral pigmented lesions should be excised Lesions that show atypia
Adjunctive cryotherapy Mitomycin-C

Malignant transformation nodularity, enlargement or increased vascularity

Check regional lymph nodes

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 LNs 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

Other neuroectodermal tumors

Multiple endocrine neoplasia (MEN)
Subconjunctival peripheral nerve sheath tumors
Neurofibromas, shwannomas, neuromas

Vascular and Mesenchymal Tumors

Benign tumors
Hemangiomas Inflammatory vascular tumors
Pyogenic granulomas, juvenile xanthogranuloma, fibrous histiocytoma, nodular fasciitis

Neurilemoma
Very rare conj tumor originating form Schwann cell of a peripheral nerve sheath

Leiomyosarcoma
Very rare limbal lesion with potential for orbital invasion

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

Pyogenic Granuloma
Common reactive hemangioma Misnamed not suppurative, no giant cells May occur
Over chalazion Minor trauma Post op granulation tissue

Ataxia-telangectasia
Epibulbar telangectasis, cerebellar abnormalities, immune disorders

Rapidly growing red, pedunculated, smooth lesion Bleeds easily and stains with fluorescein dye

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 of f 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

Lymphatic and Lymphocytic Tumors

Lympohangiectasia Lymphangioma Lymphoid hyperplasia Lymphoma

Lymphangiectasia
Appears as irregularly dilated lymphatic channels in bulbar conjunctiva May y be developmental p anomaly y Can follow trauma or inflammation Anomalous communication with venule can lead to spontaneous filling of lymphatic vessels with blood

Lymphangioma
Proliferations of lymphatic channel elements Usually present at birth and enlarge slowly Patch of vesicles with edema Intralesional hemorrhage chocolate cyst

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

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Lymphoma
Neoplastic lymphoid lesion of conjunctiva Pathogenesis
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
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

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
Usually curative for lesions confined to conj

Metastatic Tumors
Breast Lung Kidney Cutaneous melanoma

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

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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 of f first fi t b branchial hi l arch h Epibulbar dermoid Coloboma of upper lid Preauricular skin tags Aural fistulae Vertebral anomalies

Epibulbar Dermoid Tumor

Management
No malignant potential Lesion often extends deep into underlying tissues El t d portion Elevated ti may b be excised i d Relaxing incision or other corrective measure may be considered Lamellar keratoplasty for cosmetic appearance Amblyopia treatment

Dermolipoma
Pale yellow dermoid containing adipose tissue Distinguish from herniation of orbital fat Occurs superotemporally and may extend posteriorly May be associated with
Goldenhar syndrome Linear nevus sebaceous syndrome

Ectopic Lacrimal Gland

Lacrimal gland tissue occurring outside of the lacrimal fossa Round, Round pink, pink vascularized mass at the limbus

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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?

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