Epithelial tumors

Conjunctival intraepithelial neoplasia

Editor-in-Chief: Debra L. Zynger, M.D.
Pia Mendoza, M.D.

Topic Completed: 1 July 2018

Minor changes: 12 November 2021

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PubMed Search: Conjunctival intraepithelial neoplasia [title]

Pia Mendoza, M.D.
Page views in 2020: 9,049
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Cite this page: Mendoza P, Grossniklaus H. Conjunctival intraepithelial neoplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/eyecinconj.html. Accessed December 6th, 2021.
Definition / general
  • Spectrum of abnormal growth of atypical squamous epithelial cells of the conjunctiva graded based on thickness of epithelial involvement
  • Noninvasive; epithelial basement membrane remains intact
  • Precursor to invasive squamous cell carcinoma
Essential features
  • Dysplastic changes of conjunctiva
  • Precursor to squamous cell carcinoma (invasive)
  • Typical clinical presentation is lesion at the limbus within the interpalpebral fissure
  • Conjunctival intraepithelial neoplasia (1, 2 or 3)
  • Also called conjunctival dysplasia (mild, moderate or severe)
  • Falls within the broad spectrum of ocular surface squamous neoplasia (OSSN), which encompasses neoplastic squamous abnormalities of the conjunctival, limbal and corneal epithelium
Clinical features
  • Fleshy, gray or white conjunctival lesion, typically arising at the limbus (where stem cells reside) in the interpalpebral fissure (sun exposed area)
  • May be elevated or flat
  • May appear gelatinous, leukoplakic, papilliform or diffuse (Optometry 2011;82:15)
  • Lesions commonly with associated feeder vessels
  • Lesions may be pigmented and resemble melanoma due to intratumoral pigmented dendritic melanocytes (Ophthalmology 2008;115:1673)
  • Depends on depth of conjunctival epithelial involvement by dysplasia:
    • Conjunctival intraepithelial neoplasia 1 (mild dysplasia): involves lower 1/3 of epithelial thickness
    • Conjunctival intraepithelial neoplasia 2 (moderate dysplasia): involves lower 2/3
    • Conjunctival intraepithelial neoplasia 3 (severe dysplasia): involves > 2/3 of thickness
    • Carcinoma in situ: involves entire epithelium
Prognostic factors
Case reports
Clinical images

Contributed by Pia Mendoza, M.D.

Conjunctival lesion in the limbus extending to the cornea

Limbal leukoplakic appearing lesion with feeder vessels

Diffuse lesion

Pigmented carcinoma in situ

Contributed by Frederick A. Jakobiec, M.D., D.Sc.

Papilliform lesion at the limbus

Gross description
  • Gelatinous, translucent or granular appearance of conjunctiva
Microscopic (histologic) description
Architectural features:
  • Thickened epithelium (acanthosis); increased cellularity
  • Loss of normal maturation sequence; disorganization
  • Dysplasia begins in basal layers and extends toward surface
  • Noninvasive; epithelial basement membrane is intact
  • May have sharp demarcation between normal and abnormal epithelium
  • Chronic inflammatory infiltrate in underlying stroma may be present
  • Can have surface keratinization
  • Papillary configuration with intralesional vessels and fibrovascular cores occasionally seen
  • Intratumoral pigmented dendritic melanocytes can give rise to pigmented lesions resembling melanoma (Ophthalmology 2008;115:1673)

Varieties (Can J Ophthalmol 1995;30:312):
  • Actinic keratosis variety:
    • Arises in epithelial covered areas of solar elastosis
    • Usually leukoplakic due to surface keratinization
    • Focal and well delineated
  • Diffuse variety:
    • Arises in non sun exposed epithelium
    • Usually gelatinous
    • Diffuse and poorly delineated
Microscopic (histologic) images

Contributed by Pia Mendoza, M.D.

Grade 3 / severe dysplasia

Grade 2 / moderate dysplasia

Carcinoma in situ

Actinic keratosis carcinoma in situ

Contributed by Frederick A. Jakobiec, M.D., D.Sc.

Grade 3 / severe dysplasia

Contributed by Deepali Jain, M.D.

Carcinoma in situ

Conjunctival intraepithelial neoplasia

Cytology description
  • Increased nuclear:cytoplasmic ratio
  • Nuclear hyperchromasia
  • Pleomorphism
  • May have mitotic figures above the basal layer
  • May have dyskeratosis
  • Rarely have HPV related / koilocytic changes
Positive stains
Negative stains
Molecular / cytogenetics description
  • No specific molecular findings
Differential diagnosis
  • Conjunctival squamous papilloma:
    • Prominent well formed fibrovascular cores; cells with banal nuclei or mild dysplastic changes
    • CK7+; PAS+ in numerous goblet cells
  • Pterygium:
    • Wing-like fleshy conjunctival lesion
    • Epithelium without dysplasia
    • Underlying stromal fibrovascular tissue with solar elastosis
  • Pyogenic granuloma:
    • Lobulated capillary proliferation with acute and chronic inflammation
  • Sebaceous gland carcinoma:
    • Primarily an eyelid tumor with extension into the conjunctiva
    • Large anaplastic cells with finely vacuolated cytoplasm spreading in pagetoid fashion to the conjunctiva
    • Adipophilin+
Board review style question #1
66 year old Caucasian male construction worker presents with the lesion shown. Biopsy reveals the following histopathology. What is the likely diagnosis?

  1. Conjunctival intraepithelial neoplasia grade 3
  2. Primary acquired melanosis
  3. Pterygium
  4. Squamous cell carcinoma
Board review style answer #1
A. Conjunctival intraepithelial neoplasia grade 3

The patient is an older, light skinned male likely with significant UV exposure, putting him at higher risk for the conditions listed in the choices. The clinical image shows a gelatinous conjunctival lesion with feeder vessels at the limbus in the interpalpebral zone. The biopsy shows thickened conjunctival epithelium with loss of the normal maturation sequence. There is a proliferation of dysplastic squamous cells with high nuclear:cytoplasmic ratios, mitotic activity, hyperchromatic ad pleomorphic nuclei involving > 2/3 of the epithelial thickness (conjunctival intraepithelial neoplasia 3 / severe dysplasia). The basement membrane is intact.

Primary acquired melanosis (choice B) is a proliferation of intraepithelial melanocytes that typically grow in a nested pattern.

Pterygium (choice C) would present clinically as a wing-like fleshy conjunctival lesion. Histopathology would show thin epithelium without dysplasia and underlying stromal fibrovascular tissue with solar elastosis.

Conjunctival intraepithelial neoplasia is a precursor of squamous cell carcinoma (choice D). In squamous cell carcinoma, dysplastic cells invade beyond the basement membrane.

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