Ocular Pathology Quiz

Pathology & Aging 3: Vascular Diseases & Neoplasia

• Vascular diseases involve the gradual deterioration of blood vessels
• Hyalinization is the accumulation of hyaline material in tissues, often as a response to chronic stress. This affects blood vessel walls.
• Hyalinization causes thickening, hardening of vessel walls, and reduced elasticity. It also impacts blood flow and increases the risk of ischemia.
• Voso-occlusive diseases disrupt blood flow and oxygen delivery.
• Atherosclerosis is a common cause, involving plaque buildup of cholesterol and fatty deposits within blood vessels.
• Risk factors for atherosclerosis include high cholesterol, hypertension, smoking, diabetes, and age.
• Thrombi and emboli (pieces of plaque) may form from atherosclerosis, potentially causing blood flow blockages.
• Different types of microvascular occlusions exist, including those caused by vascular diseases (e.g., hypertension, diabetes) and other systemic conditions (e.g., Lupus).
• Microvascular occlusions can result in microinfarction and tissue damage in the eye and other parts of the body.

Learning Objectives

• Students will understand hyalinization and its role in vascular pathology, and vaso-occlusive diseases such as atherosclerosis, and how they result in plaque formation and embolus formation.
• Description of microvascular occlusive conditions (cotton wool spots, exudates, microaneurysms, and retinal hemorrhages) and macrovascular occlusive conditions (central retinal vein occlusion, central retinal artery occlusion, ischemic optic neuropathy).
• Students will learn about neoplasia in ocular tissues, including pathogenesis, pre-malignancy, and tumor spread.
• Categorization of benign epithelial tumors affecting the eye and periocular area.
• Identification and clinical description of various ocular tumors like hamartomas, nevi, choristomas, and teratomas
• Categorization of malignant epithelial tumors as well as neural and vascular tumors, including their clinical features and roles in ocular pathology
• Students will describe how metastatic tumors can arise from different body tissues, their processes in the eye, and their presentation.
• Differentiating between benign and malignant conditions/tumors
• Review of various types of ocular tumors and the processes that can influence their development.

Terminology

• Thrombus: A blood clot forming within a blood vessel
• Coagulation: A biochemical process to stop bleeding from injured blood vessels
• Infarction: Damage or death of tissue due to lack of blood supply
• Fundus: The inner surface of the posterior eye, including the retina, optic nerve, and blood vessels
• Arteriole: A small branch of an artery
• Etiology: The study of causes of disease and conditions
• Arteritic: Relating to inflammation of an artery
• Cutaneous: Relating to or affecting the skin
• Periocular: The area surrounding the eye
• Pathogenesis: Process of disease development
• Congenital: Present at birth
• Embryogenesis: Formation of tissues and organs during embryonic development
• Totipotent Germ Cells: Cells with potential to differentiate into any cell type needed for organism development
• Sebum: Oily substance produced by sebaceous glands
• Telangiectasia: Dilation of small blood vessels
• Infiltrates: Substances that enter a tissue not normally found there
• Biopsy: Tissue sample examined microscopically

Terminology Cont.

• Periocular: Area around the eye.
• Pathogenesis: Process of disease development.
• Congenital: Traits or conditions present at birth.
• Embryogenesis: The formation of tissues and organs during embryonic development.
• Totipotent Germ Cells: The ability of certain cells to develop into any cell type in the body.
• Sebum: An oily substance produced by sebaceous glands.
• Telangiectasia: Dilation of small blood vessels, often near the skin's surface.
• Infiltrates: The entry of substances into a tissue that are not usually present at the same concentration.
• Biopsy: Procedure to remove a tissue sample for microscopic examination.

Degenerative Vascular Disease

• Degenerative vascular diseases involve gradual deterioration of blood vessels.
• Changes often impact the normal function of blood vessels and can affect the eyes.
• Aging process and conditions like diabetes and hypertension can contribute to these changes.
• Hyalinization, vaso-occlusive disease, microvascular occlusion, macrovascular occlusion, are examples of degenerative processes.

Hyalinization

• Accumulation of hyaline material in tissues, especially blood vessel walls, in response to chronic stress.
• Age-related wear and tear, repeated injury to blood vessels, and altered metabolism of vascular components (e.g., diabetes) can cause hyalinization.
• Consequences include thickening, hardening of vessel walls, reduced elasticity, impaired blood flow, and increased risk of ischemia.

Vaso-Occlusive Diseases

• Conditions that cause blockages in blood vessels, leading to impaired blood flow and oxygen delivery (ischemia).
• Examples include atherosclerosis, a condition in which plaques of cholesterol and fats form in artery walls.
• Risk factors for these diseases include hypertension, high cholesterol, smoking, age, and diabetes.

Atherosclerosis Progression

• Fatty streaks: Accumulation of lipids in the vascular endothelium.
• Plaque development: Lipid-rich deposits agglomerate.
• Fibrous cap formation: Fibrous tissue forms over plaque, forming an atheroma.
• Plaque rupture: Vulnerable plaque can rupture and cause embolisation.
• Thrombosis: Blood clot formation at the rupture site.

Embolus Formation from Plaque

• Unstable plaque can break apart or fragments separate from an atheroma, forming an embolus.
• Embolus travels through the bloodstream and gets lodged in smaller blood vessels, causing a blockage.

Thrombus Formation

• Blood vessel lining damage leads to platelet adhesion and aggregation.
• Activated platelets, using chemical signals, attract more platelets, forming a platelet plug
• A coagulation cascade series of reactions forms a clot blocking the blood flow.
• Thrombi can embolize, lodge in other vessels, and create blockages.

Impact on Ocular Health

• Emboli, including thrombi, travel in the bloodstream and can block the vessels in the eye.
• This can lead to various retinal vascular occlusive disorders depending on the blocked vessel.

Microvascular Occlusion

• Microvascular occlusion is localized capillary occlusion interrupting blood flow and causing ischemia.
• Vascular diseases, hypertension, diabetes, and other systemic conditions, such as lupus, are possible causes.
• May result in microinfarction causing tissue damage.
• Initial manifestations include edema due to disruptions in the axoplasmic flow in the damaged neurons.
• Tissues may eventually experience atrophy due to cell death.

Cotton Wool Spot

• Result from localized nerve fiber layer infarcts affecting retinal capillaries.
• Damage to retinal capillaries and small vessels reducing blood flow to localized areas, causing tissue hypoxia can cause nerve fiber layer infarctions and RNFL swelling.
• Clinical appearance is soft, cotton-like, white or grayish color, usually found near blood vessels.

Exudates

• Feature of microvascular diseases affecting the retina.
• Microvessel damage, caused by high blood sugar or other factors leads to leakage.
• Substances inside the blood can escape and accumulate lipid accumulation causing clustering of fats to create exudates.
• Clinical appearance includes yellowish or white spots in the retina.

Microaneurysm

• Tiny, localized bulges in the walls of retinal capillaries.
• Result of vessel weakness caused by microvascular diseases such as diabetic retinopathy over time
• Leakage of fluids into surrounding retinal tissue causes bulging of the weakened capillary wall, forming a microaneurysm.
• Clinically appear as small, round, red spots on the retina.

Retinal Hemorrhages

• Abnormal bleeding within the retinal layers due to damage to retinal blood vessels.
• Vessel damage by microvascular diseases causes rupture, allowing blood to leak into surrounding retina.
• Different types exist (flame, dot, or blot) depending on location/extent of vessel damage or bleeding.

Types of Retinal Hemorrhages

• Flame hemorrhage
• Dot and blot hemorrhages

Neovascularization

• Retinal cells detect oxygen deprivation, leading to the release of factors such as VEGF to stimulate new blood vessel formation.
• Newly formed vessels are often in the deeper retinal layers and grow toward the vitreous.
• Fragile vessels leading to leakages, and various complications.

Macrovascular Occlusion

• Obstruction, affecting blood vessels equal to or greater than medium sized arterioles.
• Possible causes include embolus from atherosclerosis or vascular changes from hypertension

Hypertensive Retinopathy Signs

• Arteriolar narrowing of retinal arterioles due to hypertension.
• Arteriovenous nicking (cross-compression of veins at crossings)
• Flame hemorrhages (irregularly shaped flame-like hemorrhages along arterioles)
• Dot and blot hemorrhages (small dot-like and larger blot-shaped hemorrhages).
• Cotton wool spots (white, fluffy lesions) due to nerve fiber layer infarcts.
• Exudates (lipid or protein deposits around damaged blood vessels).
• Macular edema (swelling of macula) and optic disc edema (swelling of optic nerve head).

Central Retinal Vein Occlusion (CRVO)

• Blockage or constriction of the central retinal vein.
• Thrombus formation, compression by surrounding vessels, or other factors leading to impeded blood flow.
• Hemorrhage and edema are possible results of impaired venous outflow.
• Clinical presentation includes sudden vision changes, painless vision loss/distortion, retinal hemorrhages, and macular edema.

Central Retinal Artery Occlusion (CRAO)

• Sudden blockage of the central retinal artery, often from plaque embolus or other compressing factors.
• Clinical presentation for CRAO includes abrupt blockage, vision loss, and a pale appearance of the retina.
• Key features include sudden vision loss, retinal edema, a pale retina, and in some cases a cherry-red spot within the macula.

Ischemic Optic Neuropathy (ION)

• Reduced blood supply to the optic nerve due to damage of optic nerve fibers.
• Possible causes include non-arteritic (NAION), most common (typically affects individuals over 50 and is often associated with diabetes, hypertension), and arteritic ION (less common, but more severe) which is often associated with severe systemic conditions.
• Symptoms may include sudden painless loss of vision, visual field defects, and pain

Neoplasia

• Unregulated proliferation of cells forming a tumor, potentially benign or malignant growth.
• Benign tumors are well-circumscribed and encapsulated, often slow-growing.
• Malignant tumors have irregular borders, capable of rapid growth and invasion of surrounding tissues; may also metastasize..

Nomenclature in Neoplasia

• Tumor naming utilizing the suffix "oma" related type of tissue.
• Common examples include adenoma (glandular origin), lipoma (fat cells), and carcinoma (epithelial tissue).

Neoplasia in Ocular Tissues

• Ocular tumors present different behaviors from non-ocular counterparts.
• Immune-privileged nature of the eye contributes to the differences in behavior of intraocular compared to periocular tumors.
• Important for diagnosis and differentiating from other conditions.

Pre-Malignancy

• Abnormal tissue changes that have the potential to progress to cancer may occur in specific locations like a colon polyp.
• Genetic mutations in cellular DNA stemming from exposure to various agents, like UV radiation, chemicals, or viruses, and chronic inflammation are contributing factors to pre-malignant cell growth.

Pathogenesis

• Uncontrolled cell growth and division, normal regulatory signals loss by affected cells can transform into pre-malignant and malignant lesions.
• Dysplasia (abnormal cell changes) is often present in pre-malignant lesions.
• Proliferation/accumulation of pre-malignant cells raises the risk for further genetic mutations.
• Changes in microenvironment (including inflammation and angiogenesis) can support tumor progression by providing blood flow and nutrients.

Conjunctival Intra-epithelial Neoplasia (CIN)

• Abnormal conjunctival epithelial cell growth with potential for becoming invasive conjunctival carcinoma.
• UV exposure, HPV infection, and chronic irritation are contributing factors to CIN.
• Often presents with characteristic conjunctival raised/flat lesions, and varying appearance (whitish or gel-like) with inflammation.

Carcinogenesis

• Process of normal cells transforming into cancerous cells, this process involves oncogenes and tumor suppressor genes.
• Oncogenes promote cell growth while tumor suppressor genes regulate and prevent cell division.
• Genetic mutations due to carcinogenic factors (exposure to chemicals, radiation, or viruses) can lead to uncontrolled cell proliferation and disrupt the function of both types of genes.
• These factors influence cell proliferation, and the development of cancer.

Tumor Suppressor Genes

• Genes that regulate cell division and prevent tumor formation.
• Examples include TP53, BRCA1/2, RB, mutations in these genes contribute to an increased risk of certain cancers.
• Loss of function of tumor suppressor genes can lead to an increased risk of malignancies.

Carcinogenesis Steps

• Initiation: DNA damage from carcinogens.
• Promotion: Initiated cell proliferation.
• Progression: Development to invasive properties and potential for metastases to other areas of the body.

Tumor Spread and Metastasis

• Tumor spread involves cells invading adjacent tissues, and initiating secondary tumors in distant organs.
• Different routes exist for spread, including local invasion of tissues.
• Lymphatic or hematogenous spread via the lymphatic or blood vessels.
• Spreading along natural body passages is also a means.

Hamartoma

• Benign growths consisting of cells and tissues that are normally found in a specific organ or location, but they exhibit an aberrant organization, not a cancerous origin.
• Hamartomas are not cancerous and typically do not have the potential for malignancy.

Capillary Hemangioma

• Benign tumors composed of capillaries, often appearing as raised, reddish/purplish lumps.
• Often present at birth and typically regress spontaneously, without intervention.
• May present complications (e.g., airway compression or eye problems) if located near vital structures.

Cavernous Hemangioma

• Benign tumors of dilated vascular spaces lined with endothelium, resembling a mulberry or raspberry.
• Potential for complications, due to leakage and hemorrhage into adjacent tissues and compression of adjacent structures, as the tumor expands.

Nevi

• Common benign growths of melanocytes which are non-cancerous and typically do not cause any malignancy.
• Occur in diverse eye areas like eyelid, iris, and choroid.

Iris Nevi

• Benign collections of melanocytes in the Iris.
• They commonly exhibit varying sizes and colors, may be flat or raised, and generally do not cause any eye issues or change its architecture.

Choroidal Nevi

• Benign melanocytic growths originating in the choroid, which is the middle layer of the eye wall.
• Typically dark brown or gray, they can be elevated or flat, situated beneath the retina.
• Routinely monitored for any changes in appearance or size

Choristomas

• Benign, non-cancerous growths with congenital origin consisting of tissues that are not typically found in a particular location (ectopic tissues).
• Commonly involve dermoid (can contain skin appendages like hair, and sweat glands) or phakomatous (contain lens tissue).

Ocular Choristoma

• Occur in various parts of the eyes, such as the cornea, limbus, and conjunctiva.
• Appearance as white or yellowish, nodular lesions, and may potentially contain hair-like structures.

Teratomas

• Rare congenital tumors arising from totipotent cells
• Abnormal mix of tissues (ectoderm, mesoderm, and endoderm) during embryonic development.
• Ocular location can be the orbit, causing potential for vision loss when located around the optic nerve.

Benign Epithelial Tumors

• Non-cancerous growths originating in epithelial cells.
• They typically grow slowly and remain confined to a region, they don't invade surrounding tissues or metastasize.

Benign Epithelial Tumors in the Eye

• Several benign epithelial tumors can occur in the eye and its adjacent structures.
• Common types include acrochordon (skin tag), papilloma, and seborrheic keratosis.

Seborrheic Keratosis

• Benign skin tumors that can affect the eyelids and periocular skin.
• Often present as brown or black, waxy, "stuck-on" growths.

Benign Tumors of Adnexal Glands

• Non-cancerous growths from adnexal glands, (lacrimal, sebaceous glands, etc).
• Common types include sebaceous adenoma (tumors of sebaceous glands and generally slow-growing presenting as yellowish or skin-colored nodules on the eyelids.) and epidermoid cysts (masses arising from epidermal tissue, often presenting as mobile lumps).
• Sudoriferous Cyst (Hidrocystoma) derives from eccrine sweat glands and presents as a translucent, dome-shaped cyst on eyelids.

Malignant Epithelial Tumors

• Cancerous growths that arise from epithelial cells lining ocular tissues.
• Types include basal cell carcinoma (BCC), squamous cell carcinoma, and melanoma.

Types of Malignant Epithelial Tumors

• Basal cell carcinoma
• Squamous cell carcinoma

Basal Cell Carcinoma (BCC)

• Most frequent type of skin cancer, often affecting eyelids and periocular skin.
• Typically slow-growing, rarely metastasizing.
• Characteristic appearance includes slow-growing, pearly nodules or ulcerations, and telangiectasia.

Squamous Cell Carcinoma (SCC)

• Originates in epidermal keratinocytes.
• More aggressive than BCC, more likely to metastasize, more quickly growing and frequently invades surrounding tissue.
• Commonly presents as nodular lesions, ulcers, or plaques.

Melanoma

• Cancerous growths originating from melanocytes within ocular tissues, affecting eyelids, conjunctiva, iris, and choroid.
• Often associated with sun exposure, but also genetic factors.
• Categorized by key characteristics like asymmetry, border irregularity, color variegation, diameter, and evolution.
• Can present as various forms in the eye.

Conjunctival Melanoma

• Melanoma originating from melanocytes on the conjunctival surface.
• Often raised, pigmented with feeder vessels, and irregular borders.

Iris Melanoma

• Melanoma originating from melanocytes in the iris.
• Varies in size and color (light brown to black).
• Can cause changes in iris architecture (shape, color, or pupil distortion), and are generally slower-growing than other forms of melanoma.

Choroidal Melanoma

• Originating in melanocytes within the choroid.
• Often dark or light brown, elevated dome-shaped growth underneath the retina and can be associated with fluid or lipofuscin.

Neural Tumors

• Originating in nerve tissues within the eye and adjacent tissues.
• Can affect eyelids, retina, and optic nerve.
• Forms like neurofibroma/schwannoma (benign) or malignant peripheral nerve sheath tumors (MPNST).
• Clinically present with visual disturbances, proptosis, pain, or neurological deficits.

Retinoblastoma

• Childhood cancer originating from embryonal retinal cells.
• Often presents with leukocoria (white pupil) due to a large, smooth-surfaced white mass in the retina.
• May spread to the brain.

Tumors Derived from Muscle

• Rare in the eye and periocular areas.
• Types like leiomyoma (benign, smooth muscle of iris and ciliary body) and malignant tumors such as leiomyosarcoma and rhabdomyosarcoma..

Vascular Tumors

• Originating from blood vessels, commonly include hemangiomas.
• Malignant tumors such as Kaposi sarcoma which typically presents as purplish-red nodules and is often associated with viral infections, including the human herpesvirus 8 (HHV-8).

Lymphoid Tumors

• Originating from lymphoid tissues, possible locations in the eye and adnexa.
• Examples include non-Hodgkin lymphoma and leukemia.
• Typically present as painless masses with potential for both localized and systemic involvement.

Lacrimal Gland Tumors

• Most common, such as pleomorphic adenoma, benign mixed tumors, and slow-growing , painless mass characteristics.
• Adenoid cystic carcinoma is a rarer, aggressive type having potential to invade nerves and surrounding tissues.

Metastatic Tumors

• Secondary tumors originating in other parts of the body, potentially affecting the eye.
• Commonly originated from various primary cancers (including breast, lung, etc).
• Various ocular sites are affected.

Disorders Misdiagnosed as Neoplasms

• Conditions sharing clinical features with neoplasms but without malignant potential.
• Key factors include growth rate, border definition, invasion, and possible metastasis.
• Other potential conditions that could be misdiagnosed include inclusion cysts, hidrocystoma, sebaceous cysts, xanthelasma, or orbital inflammatory conditions.