Developmental anomaly

Developmental anomalies are structural or functional anomalies that develop in utero or during early childhood, as the body is developing. They may be detected prenatally, at birth, or later in life. Developmental anomalies usually involve abnormalities in size, location, organization, or amount of tissue, such as congenital hypertrophy of the retinal pigment epithelium or eyelid coloboma. Often, they may be classified as choristomas or hamartomas. A choristoma consists of normal, mature tissue (1 or 2 embryonic germ layers) at an abnormal location. An epibulbar dermoid is classified as a choristoma because it consists of normal, mature skin structures at an atypical location, the limbus. In contrast, hamartoma describes hypertrophy and hyperplasia (abnormal amount) of mature tissue in a normal location. An orbital cavernous hemangioma is an example of a hamartoma, as it is an encapsulated mass of mature venous channels in the orbit. A tumor made up of tissue derived from all 3 embryonic germ layers is called a teratoma (Fig 1-1).

Inflammation

Inflammation can be classified in several ways: for example, as acute or chronic in regard to onset; focal or diffuse regarding location; infectious or noninfectious with respect to etiology; and granulomatous or nongranulomatous regarding predominant cell type (see Table 1-1). A bacterial corneal ulcer, for instance, is generally an acute, focal, nongranulomatous inflammatory process, whereas sympathetic ophthalmia is a chronic, diffuse, granulomatous inflammatory disease.

In the early phases of the inflammatory process, polymorphonuclear leukocytes, which include neutrophils, eosinophils, and basophils, typically predominate and can be found in tissues (Fig 1-2). Neutrophils typify the acute inflammatory response and can be recognized by their multisegmented nuclei and intracytoplasmic granules (Fig 1-3). They are often associated with bacterial infections and may be found in blood vessel walls in some forms of vasculitis. Eosinophils are commonly found in allergic reactions but may also be present in chronic inflammatory processes such as sympathetic ophthalmia. They have bilobed nuclei and prominent intracytoplasmic eosinophilic granules (Fig 1-4). Basophils contain basophilic intracytoplasmic granules; when found in tissues, they are referred to as mast cells (Fig 1-5).

Inflammatory cells that are characteristic of a chronic inflammatory response include lymphocytes, plasma cells, and monocytes (see Fig 1-2B). Lymphocytes are small cells with round, hyperchromatic nuclei and scant cytoplasm (Fig 1-6). Lymphocytes mature either in the thymus (T cells) or the bone marrow (B cells). To distinguish T cells from B cells in tissue sections, specific immunohistochemical stains are required, as it is not possible to distinguish between B and T lymphocytes with routine histologic stains. T cells can be classified into several subtypes based on their surface markers, with each subtype having a different function. B cells can differentiate into plasma cells that produce immunoglobulins. Plasma cells are characterized by eccentric nuclei with a “cartwheel” or “clock-face” chromatin pattern and a perinuclear halo corresponding to the Golgi apparatus (Fig 1-7A, B). These cells may become completely distended with immunoglobulin and form Russell bodies (Fig 1-7C). See BCSC Section 9, Uveitis and Ocular Inflammation, for in-depth discussion of the mechanisms involved in inflammatory processes.

Monocytes consist primarily of histiocytes (also known as macrophages) when they migrate from the intravascular space into tissue (Fig 1-8). Histiocytes have eccentrically located, indented nuclei and abundant eosinophilic cytoplasm (see Fig 1-8C). Histiocytes activated by an antigen are referred to as epithelioid histiocytes because of their resemblance to epithelial cells. Epithelioid histiocytes are the hallmark of granulomatous inflammation and may aggregate into a spheroid formation known as a granuloma. Granulomas may consist completely of viable epithelioid histiocytes (“hard” tubercles; Fig 1-9A), or they may exhibit necrotic centers (“caseating” granulomas; Fig 1-9B). Epithelioid histiocytes may coalesce to form a multinucleatedgiant cell, of which there are several varieties:

• Langhans cells, characterized by a horseshoe arrangement of the nuclei (Fig 1-10A)

• Touton giant cells, characterized by an annulus of nuclei surrounded by a foamy, lipid-filled pale zone (Fig 1-10B)

• foreign body giant cells, characterized by haphazardly arranged nuclei (Fig 1-10C)

For more on cells that are part of the inflammatory response, see Activity 1-2.

ACTIVITY 1-2 Identify the cell type.

Developed by Vivian Lee, MD.

Degeneration and dystrophy

Degeneration refers to a wide variety of changes that may occur in tissue over time. It is usually characterized by accumulation of acellular material or loss of tissue mass rather than proliferation of cells. Extracellular deposits may result from cellular overproduction of normal material or metabolically abnormal material. These findings may occur in response to injury or inflammation or as part of a systemic process. Examples include calcification of the lens in congenital cataract (developmental anomaly) and corneal amyloid deposition in trachoma (inflammatory process). As used in this book, the concept of degeneration encompasses a wide range of tissue alterations in order to streamline the discussion and avoid using multiple subcategories, such as aging, trauma, and vasculopathies.

Dystrophies are defined as bilateral, often symmetric, inherited conditions that appear to have little or no relationship to environmental or systemic factors. Dystrophies affecting the eye typically involve abnormal deposition of material in ocular tissues or characteristic patterns of degeneration.

Degeneration of the eye The globe can undergo a unique range of tissue alterations secondary to trauma and chronic disease processes. Phthisis bulbi is defined as atrophy, shrinkage, and disorganization of the eye and intraocular contents. Not all eyes rendered sightless by trauma become phthisical. If the nutritional status of the eye and near-normal intraocular pressure (IOP) are maintained during the repair process, the globe will remain clinically stable. However, blind eyes are at high risk for repeated trauma, with cumulative destructive effects. Slow, progressive functional decompensation may also prevail.

STAGES OF OCULAR DEGENERATION Many blind eyes pass through several stages of atrophy and disorganization before progressing to the end stage of phthisis bulbi:

• Atrophia bulbi without shrinkage. In this initial stage, the size and shape of the eye are maintained despite the atrophy of intraocular tissues. The following structures are most sensitive to loss of nutrition: the lens, which becomes cataractous; the retina, which atrophies and becomes separated from the retinal pigment epithelium (RPE) by serous fluid accumulation; and the aqueous outflow tract, where anterior and posterior synechiae develop.

• Atrophia bulbi with shrinkage. In this stage, the eye becomes soft because of ciliary body dysfunction and progressive reduction of IOP. The globe becomes smaller and assumes a squared-off configuration as a result of the influence of the 4 rectus muscles. The anterior chamber collapses. Associated corneal endothelial cell damage initially results in corneal edema, followed by opacification with degenerative pannus, stromal scarring, and vascularization. Most of the remaining internal structures of the eye will be atrophic but recognizable histologically.

• Phthisis bulbi (Fig 1-11). In this end stage, the size of the globe shrinks from a normal average diameter of 23–25 mm to an average diameter of 16–19 mm. Most of the ocular contents become disorganized. In areas of preserved uvea the RPE proliferates, and nodular drusen may develop. In addition, extensive dystrophic calcification of the Bowman layer, lens, retina, and drusen usually occurs. Osseous metaplasia of the RPE with bone formation may be a prominent feature. Finally, the sclera becomes markedly thickened, particularly posteriorly.

Neoplasia

A neoplasm is a new, often monotonous, growth of a specific tissue phenotype and can be either benign or malignant. General histologic signs of malignancy include nuclear hyperchromatism and pleomorphism; prominent nucleoli; necrosis; hemorrhage; and increased, sometimes atypical, mitoses. Some neoplastic proliferations are called borderline or indeterminate because they exhibit both malignant and nonmalignant characteristics. Many examples in this book are presented as definitively benign or malignant, but for some cases in clinical practice, the diagnosis is less certain or may evolve over time. Table 1-2 summarizes the origin and general classification of neoplasms and includes clinical examples of neoplasms found in various tissues. See Figure 1-12 for illustrations of neoplastic growth patterns.

Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.