Tumors of conjunctiva and
cornea
Dr. Aric Vaidya
Introduction
• Ocular surface composed of conjunctiva and
cornea
• Conjunctiva -mucous membrane which covers
globe and inner part of eyelids
• Nonkeratinized stratified epithelia
• Goblet cells - 10% of basal cells of conjunctival
epithelium
Introduction
• Cornea -transparent, avascular tissue
• Corneal epithelium -stratified squamous
epithelial cells
• Corneal epithelial stem cells give rise tosuperficial cells
• Regulation of cell growth and metabolism are
critical
Conjunctiva
Cornea
Introduction
• Primary tumors of conjunctiva and cornea
grouped into:
1. Congenital
2. Acquired
Classification
1)Tumors of epithelial origin
2)Glandular tumors of conjunctiva
3) Tumors of Neuroectodermal origin
4)Vascular and Mesenchymal tumors
5)Lymphatic and lymphocytic tumors
6)Metastatic tumors
Classification
1)Tumors of epithelial origin:
• Benign:
– Papilloma
– Inclusion cysts
– Pseudoepitheliomatous
hyperplasia
– Benign hereditary
intraepithelial dyskeratosis
• Preinvasive:
– Conjunctival and corneal
intraepithelial neoplasia
• Malignant:
– Squamous cell carcinoma
– Mucoepidermoid carcinoma
2)Glandular tumors of conjunctiva:
– Oncocytoma
– Sebaceous gland carcinoma
3) Tumors of Neuroectodermal origin:
• Benign pigmented lesions:
– Congenital epithelial melanosis
– Benign melanosis
– Ocular melanocytosis
– Nevus
• Preinvasive pigmented lesions:
– Primary acquired
melanosis(PAM)
• Malignant pigmented lesions:
– Melanoma
Classification
4)Vascular and
Mesenchymal tumors:
• Benign:
– Hemangioma
– Inflammatory vascular
tumors
• Malignant:
– Kaposi sarcoma
5)Lymphatic and
lymphocytic tumors:
– Lymphagiectasia and
lymphangioma
– Lymphoid hyperplasia
– Lymphoma
6)Metastatic tumors
Ocular Surface Squamous
Neoplasia(OSSN)
Classification of Ocular Surface Squamous Neoplasia(OSSN)
Benign
Preinvasive
Malignant
Papilloma
Conjunctival and corneal
intraepithelial neoplasia
grades I-III
Squamous cell carcinoma
Pseudoepitheliomatous
hyperplasia
Benign hereditary
intraepithelial dyskeratosis
Mucoepidermoid
carcinoma
Introduction
• Lee & Hirst, 1995 -term “Ocular surface
squamous neoplasia” (OSSN)
• Denote a spectrum of neoplasm originating
from squamous epithelium
• Relatively high recurrence after treatment and
may metastasize
• Considered as a low grade malignancy but
invasive lesion can spread to globe or orbit
Epidemiology
• Uncommon disease with geographic incidences vary from 0.2 to 3.5 per 100,000
• Greater frequency near the equator (Lee & Hirst
1995)
• Predominantly in elderly - third most common
oculo-orbital tumor
• Rare in the United States, with an incidence rate
of 0.03 per 100,000 persons
• Approximately 5-fold higher in males and
Caucasians (Sun et al. 1997)
Pathogenesis
• Specific etiologic factors yet to be known
• Main associated factors
– exposure to ultraviolet (UV) radiation
– human papilloma virus infection and
– human immunodeficiency virus (HIV)
seropositivity
– immunosuppression
Pathogenesis
• Ultraviolet (UV) B radiation:
– incidence rate -increased with proximity to
equator
– incidence of squamous cell carcinoma(SCC)
declined by 49% for each 10 degree increase in
latitude
– SCC decreased by 29% per unit reduction in UV
exposure. (Newton et al. 1996)
– Lesions - often found at corneal limbus in
interpalpebral area
Pathogenesis
• Ultraviolet (UV) B radiation:
– role of limbal stem cells in development of OSSNcontroversial
– mutations in the P53 tumor suppressor
gene (TP53 gene)
– Stimulates expression of some proteolytic
enzymes, such as MMPs and their tissue inhibitors
(TIMPs)
Pathogenesis
Human Papilloma Virus:
– role not clear
– low risk HPV type 6 and 11
• a/w conjunctival papilloma
– high risk HPV type 16 and 18
• commonly found in high grade dysplasia, or invasive
squamous cell carcinoma
– several studies have failed to demonstrate HPV in
malignant conjunctival epithelial tumors
Pathogenesis
Human Immunodeficiency virus:
– OSSN- now recognized as an AIDS-related cancer
– occurred earlier in HIV-infected individuals
– increased prevalence of HIV among patients with
CIN -younger than 50 years
– tissue analysis in HIV patients identified multiple
oncogenic viruses
Pathogenesis
• Immunosuppression :
– localized immune suppression of skin from sun damage
may lead to
• increased susceptibility to HPV infection
– immunosuppressed cancer patients and organ transplant
patients
– after corneal graft
• due to local immunosuppression, HPV, or possibly that neoplastic
cells in donor corneal epithelia
• Other factors:
– old age, male sex , and fair skin pigmentation
– heavy cigarette smoking, exposure to petroleum products
– genetic conditions like xeroderma pigmentosum
Clinical manifestations
• Conjunctival papilloma
• Conjunctival intraepithelial neoplasia (CIN)
• Squamous cell carcinoma
Conjunctival papilloma
• Pedunculated:
– HPV, type 6 or 11
– Fleshy, exophytic growth with
fibrovascular core
– Originates from a stalk with
multilobulated appearance
– 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
Conjunctival papilloma
• Signs of dysplasia:
– Keratinization
– Symblepharon formation
– Inflammation
– Invasion
Treatment
Pedunculated:
–
–
–
–
–
–
Most regress spontaneously
Observation
Cryotherapy alone
Excision with cryotherapy to base
Excision with adjunctive application of IFN-alpha 2b
Frequent recurrences
• Sessile:
– Observed closely or excised
– Excisional biopsy with adjunctive cryotherapy
Conjunctival intraepithelial
neoplasia(CIN)
3 clinical variants:
– Papilliform –sessile papilloma harboring dysplastic
cells
– Gelatinous –result of acanthosis and dysplasia
– Leukoplakic –hyperkeratosis, parakeratosis, and
dyskeratosis
CIN
CIN
• Mild inflammation and abnormal
vascularization
• Classification:
– Mild dysplasia or CIN 1
– Moderate dysplasia or CIN 2
– Severe dysplasia or CIN 3
– Carcinoma-in-situ
• Slow growing tumors
• Potential to spread to other ocular surfaces
Management
Management
Squamous cell carcinoma(SCC)
• Final stage of this tumour
• Dysplastic epithelium invade beyond
basement membrane
• Larger and more elevated than CIN
• Pathogenesis:
– Risk factors: UV radiation, viral, genetic
– More common and aggressive in:
• HIV
• Xeroderma pigmentosa
scc
Clinical features
• Broad based lesion at or near limbus in
interpalpebral fissure
• Grow outward with sharp borders
• Can be leukoplakic
• Usually remains superficial rarely penetrating
sclera or Bowman’s layer
Clinical features
•
•
•
•
Pigmentation in dark-skinned patients
Engorged conjunctival vessels feeding tumor
Locally invasive and can metastasize
Intraocular invasion a/w
– iritis, glaucoma, retinal detachment, or rupture of
the globe
• Regional lymph nodes
Investigations and diagnosis
• Clinical feature of lesion
• Assessment of extension of lesions :
– Intraocular invasion
– Orbital invasion- CT scan or MRI
– Regional lymph node spread
• Pathologic diagnosis:
– Gold standard for definite diagnosis -tissue histology
– Incisional or excisional biopsy
• Cytology
Histology
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
Nevus
•
•
•
•
•
Most common melanocytic conjunctival tumor
Malignant transformation - 1%
Presentaion- 1st to 2nd decades
Most common site- juxtalimbal area
Histology- similar to cutaneous nevi except no
dermis
• Types– Junctional
– Compound
– Subepithelial
Nevus
Nevus
• Flat near limbus, elevated
elsewhere
• Pigmentation variable
• Signs of malignancy
• Rapid enlargement at puberty
• Management :
– Excision of suspicious lesions
– Excise nevi on palpebral or
forniceal conjunctiva
Dermoid
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
Dermoid
• Clinical features:
– 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
Treatment
• No malignant potential
• Lesion often extends deep into underlying
tissues
• Elevated portion may be excised
• Relaxing incision
• For cosmetic appearance
• Amblyopia treatment
Lipodermoid:
• Found at limbus or outer canthus
• Appears as soft, yellowish white, movable
subconjunctival mass
• Consists of fatty tissue and surrounding
dermis-like connective tissue
• May be a/w accessory auricles and other
congenital defects (Goldenhar's syndrome)
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
Pyogenic granuloma
• Management:
– Topical steroids
– Resistant cases- surgical excision
Kaposi sarcoma
• Malignant neoplasm of vascular endothelium
• Involves skin, mucous membrane and internal
organs
• Pathogenesis:
– Infection with HHV-8
– Occurs in setting of AIDS
Kaposi sarcoma
• 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 - effective
Primary Acquired Melanosis(PAM)
• Preinvasive
intraepidermal lesion of
sun-exposed skin
• Flat, brown noncystic
lesions of conjunctival
epithelium
• PAM associated with
cellular atypia
– progress to melanoma in
~ 46%
Primary Acquired
Melanosis(PAM)
• Pathogenesis:
– Abnormal melanocytes proliferate in basal conjunctival
epithelium
– Malignant transformation
• nodularity, enlargement or increased vascularity
• Management :
– Excisional biopsy
– All palpebral pigmented lesions should be excised
– Lesions that show atypia
• Adjunctive cryotherapy
• Mitomycin-C
– Check regional lymph nodes
Melanoma
• 2% of all 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 -rare
– Intralymphatic spread increases risk of metastasis
– Underlying ciliary body melanoma can extend
through sclera
– Cutaneous melanoma -rarely metastasize to
conjunctiva
Melanoma
Clinical features:
• Most common on bulbar conjunctiva or at
limbus
• Variable pigmentation
• Highly vascularized –bleed easily
• Grow in nodular fashion
• Can invade globe or orbit
Melanoma
Melanoma
• Outcome:
– Bulbar melanomas -better prognosis than those
on palpebral conjunctiva, fornix, or caruncle
– Metastasis in ~ 26%
• Cytologic risk factors for metastasis:
– Large size, multicentricity,
– Epithelioid cell type, lymphatic invasion
• Can metastasize to regional lymph nodes,
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 conjunctival/amniotic membrane
graft
– Topical MMC –for residual disease
– Orbital exenteration–advanced disease or palliative Rx
Melanoma
• Prognosis :
– Overall mortality 12% at 5 years and 25% at 10 years
– Poor prognostic factors:
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Invasion into deeper tissues
Multifocal tumors
Extralimbal tumors
Thickness >1.8 mm
Involvement of eyelid margin
Recurrence
Lymphatic or orbital spread
Summary
• Ocular surface composed of conjunctiva and
cornea
• Various benign and malignant tumors involving
ocular surface
• OSSN denotes a spectrum of neoplasms
originating from squamous epithelium
• Nevus -most common melanocytic conjunctival
tumor
• Surgical excision along with various adjuvant
therapies are modalities of management
Bibliography
• American Academy of Ophthalmology, BCSC,
section 8, 2013-2014
• Albert Jakobiec’s Principles and Practice of
Ophthalmology Third edition. Part2: Volume
1, Section 6- cornea and conjunctiva
• Clinical Ophthalmology A Systematic Approach
Jack J Kanski ,7th edition
• Myron Yanoff & Jay Duker Ophthalmology,3rd
edition,2009.
Thank you