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Conjunctiva

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Macroscopic Overview – Normal Conjunctiva

Conjunctiva covers the surface of the globe (except cornea) and posterior eyelids. It is divided into bulbar, forniceal and palpebral sections. It also includes some unique zones such as the Plica Semilunaris. It contains many goblet cells, blood vessels, and immune cells.

Nick’s Tips: The conjunctival surface is nonkeratinized, stratified squamous epithelium about 2-5 cells thick with goblet cells (generally very easily recognizable) present in normal and many pathological states. Look for the goblet cells in the epithelium and lack of keratin to distinguish from corneal epithelium and lids, respectively. By observing the key cellular features, the conjunctival should be easy to recognize. Remember, however, that there are some pathological states that may have a reduction in goblet cells or acanthosis (epithelial thickening), or may have surface keratinization (Examples: severe Sjogren’s, chemical burns, Stevens-Johnson disease, Ocular cicatricial pemphigoid, severe trachoma and severe ocular surface disease).

8.01 Low Magnification view of conjunctiva

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8.02 Medium magnification view of forniceal conjunctiva

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8.03 Higher magnification of forniceal conjunctiva

Limbal dermoid

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8.04 External Photo of limbal dermal choristoma

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8.05 Limbal dermal choristoma

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8.06 Limbal dermal choristoma

Nick’s Tips: epibulbar dermoids are a choristoma – benign collection of fully differentiated tissue located in an abnormal anatomic location (example: cartilage in the conjunctiva). Look for normal tissue elements in an abnormal location. Also look for syndromes such as Goldenhar Syndrome and Linear nevus sebaceous syndrome. Be careful if excising – the lesion may extend full thickness through the cornea – should have corneal graft available. Be careful – there are multiple structures in ocular pathology called dermoids.

Avoid confusion – Structures with dermoid in the name:

Epibulbar limbal dermoids

Lipodermoid

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8.07 Lipodermoid

Ectopic lacrimal gland

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8.08 Lacrimal gland (plus cartilage) as conjunctiva

Episcleral osseous choristoma

Complex choristoma

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8.09 Multiple choristoma types together in one lesion such as dermoid with bone.

Capillary hemangioma

Nick’s tips – look for many red blood cells in thin walled vessels in the substantia propria. Non-keratinized epithelium shows that this hemangioma is not located in lid or orbit.

Papillary conjunctivitis

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8.10 Central vascular core seen in papillary conjunctivitis

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8.11 Central vascular core in papillary conjunctivitis

Nick’s Tips: note that the surface is flat with crypts. In higher magnification, look for cell types associated with allergy (eosinophils [link], plasma cells [link], mast cells [link]). Typically highly vascular with central blood vessel tuft.

Follicular conjunctivitis

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8.12 Cobblestone appearance of follicular reaction

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8.13 Follicle with lymphoid tissue and vessels around the edges

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8.14 Large benign lymphocytes in a follicle

Nick’s Tips: follicles are clearer on their surface, papillae are redder on the surface. Follicles are usually avascular. Look for subepithelial germinal center consisting of a center of proliferating immature lymphocytes and a peripheral ring of plasma cells and mature lymphocytes.

Granulomatous conjunctivitis

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8.15 Sarcoidosis

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8.16 Foreign Body

Causes:

Infectious conjunctivitis

Nick’s Tips: consider the appropriate stains for each type: Bacteria (gram stain), Chlamydia (Giemsa), Mycobacteria (Ziehl Nielssen stain – acid fast), Fungi (periodic acid Schiff (PAS), Gomori methenamine silver (GMS), Mycobacteria spores (modified trichrome stains), viruses (viruses are too small to be seen in light microscopy – can see results of virus or use PCR (polymerase chain reaction)).

Conjunctival membranes in Conjunctivitis:

True Membranes – tightly adherent, bleed when peeled. Associated with:

Pseudomembranes do not bleed when peeled. Associated with:

Some special cases of conjunctivitis:

 Trachoma – Infectious conjunctivitis caused by the atypical bacteria Chlamydia trachomatous. Uncommon in the USA, but a major cause of blindness historically and worldwide.

Vernal Keratoconjunctivitis:

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8.17 Limbal vernal conjunctivitis

Giant Papillary Conjunctivitis

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8.18 Giant Papillary Conjunctivitis

Phlyctenular Conjunctivitis

Parinaud’s oculoglandular syndrome:

Ligneous Conjunctivitis:

Nick’s Tips: Woody material is massive fibrin deposits – appears as granulomatous inflammation with sheets of very eosinophilic acellular material.

Ocular cicatricial pemphigoid

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8.19 Ocular cicatricial pemphigoid

Nick’s Tips: Look for immunofluorescence specimens showing complement or immunoglobulins in the region of the basement membrane

Stevens-Johnson Syndrome / Erythema Multiforme

Pemphigus Vulgaris

Pyogenic granuloma

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8.20 Pyogenic granuloma

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8.21 Granulation tissue in pyogenic granuloma

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8.22 Pyogenic granuloma

Nick’s Tips: look for spoke like pattern of blood vessels and history of surgical or accidental trauma or chalazion. Not a true “pyogenic granuloma” as defined by dermatologist, but more accurately described as exuberant granulation tissue.

Pinguecula

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8.23 Pinguecula

Nick’s Tips: look for elastoic degeneration and basophilic changes.

Pterygium

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8.24 Pterygium – crosses the limbus

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8.25 Pterygium, a subepithelial disease with solar elastosis, basophilic degeneration, and thinning of the epithelium

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8.26 Calcium may be present in a pterygium

Nick’s Tips: look for elastoic degeneration – Verhoeff van Gieson stain will stain degenerated collagen. Look for basophilic degeneration.

Amyloidosis

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8.27 Congo red staining in amyloidosis

Nick’s Tips: Apple green birefringence with polarized light and Congo red staining is a hallmark of amyloid. Can also stain with crystal violet or thioflavin T.

Epithelial inclusion cyst

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8.28 Epithelial inclusion cyst may transilluminate on examination

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8.29 Lining of epithelial inclusion cyst – goblet cells within the stratified squamous epithelium lining

Squamous papilloma

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8.30 Squamous papilloma

Nick’s Tips: Must biopsy – cannot distinguish visually from papillomatous squamous cell carcinoma in situ or carcinoma – need histopathological diagnosis.

Ocular surface squamous neoplasia (OSSN)

Actinic keratosis:

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8.31 Actinic keratosis with CIN with marked dysplasia

Conjunctival Intraepithelial Neoplasia

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8.32 Thickening is epithelial, not subepithelial in CIN

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8.33 Thickening is epithelial, not subepithelial in CIN

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8.34 Intact basement membrane seen in CIN

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8.35 Severe CIN with nucleoli extending greater than 2/3 of the way through the epithelium

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8.36 CIN with marked dysplasia

Nick’s Tips: Look for thickened epithelium (up to 10 X normal thickness), look for abnormal cells at the basal epithelium first. Abnormal cells may appear spindle shaped with very little epithelium or epidermoid with lots of eosinophilic cytoplasm. Mitotic figures may be common or extend to areas beyond the basal layer.

Squamous carcinoma in situ

Invasive squamous cell carcinoma

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8.37 Squamous cell carcinoma is more likely to arise from the limbus than CIN

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8.38 Disrupted basement membrane seen in SCC

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8.39 Invasive SCC with keratin pearls

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8.40 Higher magnification of keratin pearls seen in SCC

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8.41 Invasive SCC growing into the sclera

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8.42 SCC can spread along a nerve to metastasize

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8.43 Another example of SCC growing along a nerve

Hereditary Benign Intraepithelial Dyskeratosis (HBID)

Melanotic Lesions of the conjunctiva

Melanotic lesion                      Age begins       Appearance         Location                 Malignant potential

Freckle (ephelides)                 youth                  small                        conjunctiva                                 zero

Racial melanosis                       youth                  diffuse                    conjunctiva                                 zero

Benign acquired melanosis    adult                  diffuse                  conjunctiva                                  zero

Conjunctival Nevis                   youth                small                     conjunctiva                                  low

Ocular melanocytosis             congenital        diffuse                  sub-conjunctiva                          yes (uveal)

PAM                                           middle age       diffuse                  conjunctiva                                      yes

Ephelides (freckles):

Racial Melanosis:

Conjunctival nevus (multiple types)

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8.44 Nevus

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8.45 Epithelial lined cysts may be seen when removing a nevus, which indicates that the nevus has likely been present for years

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8.46 Epithelial lined cysts may be seen when removing a nevus, which indicates that the nevus has likely been present for years

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8.47 Junctional Nevus

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8.48 Compound nevus

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8.49 Subepithelial (dermal in other areas of the body) nevus

Nick’s Tips: If nevus located in palpebral conjunctiva, then probably needs a biopsy as these are usually PAM or melanoma.

Nevus of Ota (congenital oculodermal melanocytosis or oculocutaneous melanosis):

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8.50 Pigment seen superficially and deep to the sclera

Nick’s Tips: If unsure, anesthetize the eye and see if the pigmented lesion moves with the conjunctiva – if so, then the lesion is in the conjunctiva, not in the underlying tissue and therefore is one of the other melanocytic lesions, not oculodermal melanocytosis.

Primary acquired melanosis (PAM)

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8.51 Superficial pigment in PAM without atypia

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8.52 PAM without atypia – pigmented melanocytes seen along the basement membrane

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8.53 Higher magnification view showing no atypia in this example of PAM

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8.54 PAM with atypia – pigmentation may appear more substantial on exam

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8.55 PAM with atypia – the melanocytes are contained within the basement membrane but have an atypical appearance.

Conjunctival Melanoma

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8.56 Scarring secondary to removal of PAM with atypia plus pigment seen in the fornix, which should be considered melanoma until proven otherwise

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8.57 Melanocytes extending through the basement membrane in melanoma

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8.58 Malignant melanoma secondary to PAM

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8.59 Immunoperoxidase staining will indicate whether cells are melanocytes but not necessarily determine malignancy.

Nick’s Tips: Conjunctival melanoma more closely resembles skin melanoma than choroidal melanoma

Lymphoid tumors of the conjunctiva:

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8.60 Conjunctival lymphoma is classically salmon colored on gross exam

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8.61 Sheets of lymphocytes seen in lymphoma

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8.62 Immunoperoxidase stain of lymphoma. Typically these are of B-cell origin

Nick’s Tips: If suspect lymphoma, please send fresh specimen for flow cytometry analysis along with fixed specimen. Formaldehyde and paraffin processing destroy light chains and other markers.

Oncocytoma