Neoplastic and Non-neoplastic Disorders of the Conjunctiva and Eyelid

Conjunctivitis (Infectious and Non-Infectious)

Conjunctivitis is an inflammation of the conjunctiva that can manifest in both an acute and chronic form (persisting for 4 weeks or more). The etiology of the inflammation can include allergic, infectious (bacterial, viral, protozoal, parasitic), autoimmune, or autoreactive.

Histologic Features

A conjunctival biopsy is often not needed but can be useful in characterizing conjunctivitis and distinguishing it from neoplastic disorders. As with any inflammatory process the density, composition, and proportion of the inflammatory cells (lymphocytes, neutrophils, eosinophils, histiocytes, plasma cells) varies depending on the time course (early versus late), activity (acute versus chronic) and nature of the process (allergic versus infectious versus other). A suppurative neutrophil-rich infiltrate is typical of an acute bacterial infection, but lymphocytes and plasma cells are commonly seen in chronic conjunctivitis ( Fig. 19-1 ). Chronic irritated lesions often display squamous metaplasia of the surface mucosa ( Fig. 19-2 ). On occasion, a conjunctivolith may be seen in the mucosa ( Fig. 19-3 ). A high number of eosinophils suggest an allergic hypersensitivity reaction. Except for the identification of an infectious organism, foreign body, or ruptured cyst, the cause of conjunctivitis can usually not be deduced from the histologic findings and depends on clinical correlation.

Foreign Body Granuloma or Chalazion

Conjunctival foreign bodies can elicit focal inflammation. Similarly, a chalazion is a discrete granulomatous inflammatory lesion resulting from retained sebaceous material secreted from meibomian glands along the eyelid edge. It is also referred to as “lipogranuloma.”

Clinical Findings

Foreign body granulomas present as an elevated erythematous nodule that can incite circumscribing inflammatory reaction. Similarly, a chalazion is a discrete nontender nodule with overlying erythema and typically located close to the eyelid margin. An inspissated meibomian gland may be visualized ( Fig. 19-4 ).

Histologic Features

The pathology of a chalazion usually shows a nodular mixed inflammatory cell infiltrate, typically with a prominent lymphogranulomatous component reaction, but neutrophils and plasma cells may also be present ( Fig. 19-5 ). It later stages, there may be associated fibrosis.

Connective Tissue Disease (Wegener's Granulomatosis)

The conjunctiva is an uncommon site of involvement for connective tissue disease, occurring in approximately 5% to 15% of Wegener's granulomatosis cases.

Clinical Findings

In Wegener's granulomatosis, the palpebral conjunctiva and tarsus of the upper eyelid are common sites of disease. In its inflammatory stage, the conjunctiva appears hyperemic with granulomatous or ulcerative changes. The lesion may become necrotic with an avascular appearance and surrounding conjunctival injection and may progress to a fibrovascular proliferation and fibrous scar tissue. A concomitant episcleritis or scleritis is possible. Peripheral ulcerative keratitis may also occur, with dilated perilimbal vessels, peripheral cornea thinning, and epithelial defect ( Fig. 19-6 ). Cicatricial changes can lead to alterations in eyelid architecture, including ectropion and entropion.

Histologic Features

The histologic changes associated with Wegener's granulomatosis of the conjunctiva usually involve a lymphoid infiltrate admixed with plasma cells, histiocytes, and eosinophils ( Fig. 19-7 ). There may or may not be evidence of vascular damage. A necrotizing vasculitis is rarely seen.

Degenerative (Solar Elastosis)

Prolonged exposure to ultraviolet (UV) light can result in solar damage to the conjunctiva, known as solar elastosis (and akin to actinic keratosis of the skin). Because of its predisposition from cumulative sun exposure, it is more common in individuals of advancing age.

Histologic Features

Solar elastosis is characterized by loss of pink material and fibers on routine sections and their replacement by homogeneous grayish material ( Fig. 19-8 ).

Pingueculae and Pterygium

Both pingueculae and pterygium occur with advancing years and result from elastotic degeneration due to prolonged UV exposure ( Fig. 19-9 ).

Clinical Findings

Both pingueculae and pterygium occur in the intrapalpebral space adjacent to the limbus. They typically develop over many years. They are not neoplasms but degenerative tissue alterations related to chronic sun damage. Pingueculae appear as small yellow-gray-white nodules with either an atrophic or thickened overlying epithelium. Pterygium crosses over the limbus and impinges onto the cornea in a winglike, triangular expansion ( Fig. 19-10 ). It has a thickened, fibrovascular appearance.

Amyloid

Conjunctival deposition of amyloid protein is a common process in healthy young and middle-aged adults without systemic amyloidosis. It is typically a primary localized entity but can less commonly result from prolonged, antecedent inflammation. It can also occur as an ophthalmic manifestation of systemic disease, such as multiple myeloma or lymphoma.

Clinical Findings

Amyloid deposition presents as a nodular or diffuse rubbery, waxy thickening of the conjunctiva ( Fig. 19-11 ). It has a yellow-orange appearance and clings in a perivascular fashion. Whereas palpebral deposits usually signify a localized pathology, eyelid involvement is more commonly a systemic manifestation.

Histologic Features

Amyloid material manifests on routine sections as hyaline amorphous pink material ( Fig. 19-12 ).

Cysts

Retention cysts of the conjunctiva are common and asymptomatic and previous surgery can be a predisposing feature.

Clinical Findings

Cysts appear as thin-walled, clear fluid-filled elevations more commonly on the palpebral conjunctiva ( Fig. 19-13 ). They can form large solitary lesions or small cysts may form confluent clusters.

Histologic Features

Conjunctival cysts are lined by conjunctival-type mucosa, including columnar epithelium and goblet cells. Squamous metaplasia may be present. They usually appear as cystic invaginations of the surface mucosa in the superficial subepithelial stroma ( Fig. 19-14 ).

Squamous Papilloma

Histologic Features

Lesions are characterized by papillomatous epithelial hyperplasia. Multiple branching fronds may emanate from a fibrovascular core ( Fig. 19-15 ). Pedunculated lesions have a narrow stalk, sessile lesions, and a broad base. The epithelium is usually composed of nonkeratinizing squamous epithelium with variable number of admixed goblet cells. The fibrous cores are usually hypervascular with many ectatic vessels. Cytologic atypia is usually absent. HPV cytopathic changes (koilocytes, binucleated cells, raisinoid nuclei) may or may not be present.

Ocular Surface Squamous Neoplasia

Ocular surface squamous neoplasia consists of corneal/conjunctival intraepithelial neoplasia (CCIN) and squamous cell carcinoma (SCC). Its incidence is between 0.2 and 20 cases per million and varies geographically, with some of the highest rates in Africa. The incidence in the United States is approximately 1/10 ⁶ . Risk factors include older age, UV or toxin exposure, immunosuppression, HPV infection, male gender, and fair skin.