Pathology & Aging 3: Vascular Diseases & Neoplasia PDF

Pathology & Aging 3: Vascular Diseases & Neoplasia Renee Doss, OD, FAAO Learning Objectives 1. Understand the concept of hyalinization and its role in vascular pathology 2. Discuss vaso-occlusive diseases like atherosclerosis, and their role in plaque and embolus formation 3. Des...

Pathology & Aging 3: Vascular Diseases & Neoplasia Renee Doss, OD, FAAO Learning Objectives 1. Understand the concept of hyalinization and its role in vascular pathology 2. Discuss vaso-occlusive diseases like atherosclerosis, and their role in plaque and embolus formation 3. Describe microvascular occlusive conditions, including cotton wool spots, exudates, microaneurysms, and retinal hemorrhages 4. Describe macrovascular occlusive conditions, including central retinal vein occlusion, central retinal artery occlusion, and ischemic optic neuropathy 5. Discuss neoplasia in ocular tissues, including pathogenesis and pre-malignancy 6. Discuss carcinogenesis, focusing on oncogenes, tumor suppressor genes, and tumor spread 7. Identify various ocular tumors, including hamartomas, nevi, choristomas, and teratomas 8. Categorize benign epithelial tumors that affect the eye and periocular area 9. Categorize tumors of adnexal glands that affect the eye and periocular area 10. Discuss malignant epithelial tumors, including basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma and how they can affect the eye 11. Identify melanoma in ocular tissues and describe its clinical features 12. Discuss neural tumors, including retinoblastoma, and their role in ocular pathology 13. Categorize vascular tumors, lymphoid tumors, lacrimal gland tumors and their role in ocular pathology 14. Explain how metastatic tumors can present in the eye including the most common sites of origin 15. Differentiate between common forms of benign and malignant neoplasia Terminology Thrombus: A blood clot that forms within a blood vessel that can be triggered by various factors, including injury to blood vessel walls, changes in blood flow, and abnormalities in blood constituents Coagulation: A natural and complex biochemical process that helps the body stop bleeding when blood vessels are injured, aka blood clotting Infarction: Death or damage of tissue due to a lack of blood supply; it often occurs when a blood vessel supplying a specific area becomes blocked, leading to tissue ischemia (lack of oxygen) and cell death Fundus: The interior surface of the eye opposite the lens, it includes the retina, optic nerve head, and blood vessels Arteriole: A small branch of an artery Etiology: The study of the causes or origins of a disease or condition; it involves identifying factors that contribute to the development of a particular medical problem Arteritic: Arteritic relates to inflammation of the arteries Cutaneous: Cutaneous refers to anything related to the skin Terminology Cont. Periocular: The area around the eye or surrounding the eye Pathogenesis: The process or mechanism by which a disease or medical condition develops Congenital: Conditions or traits that are present at birth Embryogenesis: The process of development of an embryo from a fertilized egg, it involves the formation of tissues and organs Totipotent Germ Cells: Cells that have the potential to develop into any type of cell in the body, including those needed for the formation of a new organism during embryological development Sebum: An oily substance produced by the sebaceous glands in the skin Telangiectasia: Dilation of small blood vessels near the surface of the skin or mucous membranes Infiltrates: Substances that “infiltrate” into a tissue that are not usually found in that tissue or not found in that tissue at such a high level Biopsy: A medical procedure in which a sample of tissue or cells is removed from the body for examination under a microscope Degenerative Vascular Disease Degenerative vascular diseases are conditions that involve the gradual deterioration or changes in blood vessels over time These changes can impact the normal functioning of blood vessels and may affect various parts of the body, including the eyes They are often related to the aging process but are also increased in certain diseases such as diabetes and hypertension Degenerative processes include: hyalinization, vaso-occlusive disease, microvascular occlusion, and macrovascular occlusion Hyalinization Accumulation of hyaline material in tissues such as blood vessel walls that occurs as a response to chronic stress Causes and Mechanisms Age-related wear and tear Repeated injury/stress on blood vessel walls (e.g. high blood pressure from hypertension) Altered metabolism of vascular components (e.g. diabetes) Consequences of Hyalinization Gradual thickening and hardening of vessel walls Reduced vessel elasticity Impaired blood flow Increased risk of ischemia Vaso-Occlusive Diseases Conditions causing blockages in blood vessels which result in impaired blood flow and oxygen delivery (ischemia) Various causes and manifestations May be microvascular (capillaries) or macrovascular (larger blood vessels such as the central retinal artery) Atherosclerosis is a common cause Arterial plaque build up occurs in atherosclerosis due to the accumulation of cholesterol and fatty deposits inside of blood vessels Arteries progressively harden and narrow due to this plaque build up, as well as other factors such as hyalinization Risk factors: Hypertension, high cholesterol, smoking, age, poor diet, diabetes, etc.  Fatty Streak Formation: Accumulation of lipids on vascular endothelium Atherosclerosis Plaque Development: Lipid-rich deposits agglomerate Fibrous Cap Formation: Fibrous tissue forms over plaque becoming Progression an atheroma Plaque Rupture: Vulnerable plaque can rupture and embolize Thrombosis: Blood clot formation also possible at rupture site Embolus Formation from Plaque Embolus Formation: Unstable plaque can break apart or pieces can separate from an atheroma Broken plaque becomes an embolus in the bloodstream Blockage: Embolus gets stuck in smaller vessel, causing a blockage Plaque lodged in retinal vessel Thrombus Formation Endothelial Injury: Blood vessel lining (endothelium) is damaged due to trauma, inflammation, or other factors and exposes the underlying connective tissue or lipid deposit Platelet Adhesion and Aggregation: Platelets in the blood adhere to the exposed tissue at the injury site and become activated and change shape Activated platelets release chemical signals that attract more platelets to the injury site Platelets clump together, forming a platelet plug Coagulation Cascade: A series of enzymatic reactions (coagulation cascade) is initiated A clot forms around the area of rupture potentially impeding blood flow = thrombus The thrombus can embolize and become lodged in other vessels creating a blockage Impact on Ocular Health Embolic Events: Emboli, including thrombi and plaques, can travel through the bloodstream and end up in the eye They may block vessels within the eye, causing a variety of retinal vascular occlusive disorders depending on which vessel is occluded Microvascular Occlusion Microvascular occlusion is local capillary occlusion resulting in impaired blood flow and ischemia Causes: Vascular diseases Hypertension Diabetes Other systemic conditions Lupus May result in areas of microinfarction Loss of perfusion to a localized area results in tissue damage In the eye and brain this manifests first as edema due disruption and build of axoplasmic flow inside the damaged neurons Eventually tissues can atrophy due to cell death Cotton Wool Spot Cotton Wool Spots result from localized nerve fiber layer infarctions Process of Formation Microvascular Abnormalities: Damage to retinal capillaries and small vessels occurs Reduced Blood Flow: The damaged blood vessels may become narrowed or blocked, reducing the blood flow to localized areas of the retina resulting in tissue hypoxia Nerve Fiber Layer Infarctions: As a result, localized infarctions occur causing the RNFL to swell Clinical Appearance Soft, cotton-like appearance White or grayish color Commonly found near blood vessels Exudates Exudates are another feature of microvascular diseases affecting the retina Process of Formation Microvessel Damage: Due to factors like high blood sugar or pressure Leakage: Microvessels become leaky, allowing substances inside the blood to escape Lipid Accumulation: Lipids, including cholesterol, leak into retinal tissue from blood plasma Clustering: Lipids cluster and form exudates Clinical Appearance Yellowish or white spots or lesions in the retina May affect central vision if near the macula Microaneurysm Microaneurysms are tiny, localized outpouchings or bulges in the walls of retinal capillaries Formation Process: Vessel Weakness: Microvascular diseases, such as diabetic retinopathy, can weaken the walls of retinal capillaries over time Microvessel Leakage: As a result of this weakening, the capillaries become more permeable, allowing fluid to escape into the surrounding retinal tissue Localized Bulging: The increased pressure from the leaking fluid causes the weakened portion of the capillary wall to bulge outward, forming a microaneurysm Microaneurysm Appearance: Clinically, microaneurysms appear as small, round, red dots on the retina Retinal Hemorrhages Retinal hemorrhages are abnormal bleeding or leakage of blood within the layers of the retina They occur due to damage to retinal blood vessels, primarily capillaries Vessel Damage: Microvascular diseases weaken retinal blood vessels, making them prone to rupture Blood Leakage: Weakened vessels allow blood to leak into the surrounding retinal tissue Hemorrhage Appearance: The type of hemorrhage (flame, dot, or blot) depends on the location and extent of the vessel damage and bleeding  Types of Retinal Hemorrhages Flame Hemorrhage Appearance: Irregular, flame-shaped areas of hemorrhage Location: Typically found along the nerve fiber layer of the retina Clinical Significance: Often associated with hypertensive retinopathy and other vascular diseases Dot Hemorrhage Appearance: Small, round, pinpoint-sized areas of hemorrhage Location: Can occur in various retinal layers, including the inner nuclear layer Clinical Significance: Common in diabetic retinopathy and other microvascular diseases Blot Hemorrhage Appearance: Larger, irregularly shaped areas of hemorrhage with indistinct borders Location: Deeper layers of the retina, often obscuring underlying structures Clinical Significance: Often seen in diabetic retinopathy and other microvascular and macrovascular occlusive diseases Neovascularization When retinal cells sense oxygen deprivation (hypoxia), they release factors like vascular endothelial growth factor (VEGF) VEGF is a key signaling molecule that stimulates the formation of new blood vessels (angiogenesis) Neovascularization Process: These new vessels often form in the deeper layers of the retina and grow toward the vitreous They are fragile and prone to leakage, leading to various complications Macrovascular Branch Retinal Vein Occlusion Occlusion Obstruction of blood vessels of diameters equal to or greater than a medium-sized arteriole Includes occlusion from emboli from atherosclerosis as well as occlusion caused by vascular changes from hypertension Hypertensive Retinopathy Signs Arteriolar Narrowing: Hypertension can cause retinal arterioles to constrict or narrow Arteriovenous (AV) Nicking: Cross-compression of veins at arteriovenous 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 the macula, affecting central vision Optic Disc Edema: Swelling of the optic nerve head Central Retinal Vein Occlusion CRVO occurs when the central retinal vein becomes blocked or constricted Thrombus Formation: A clot (thrombus) in the vein can impede blood flow Compression by Arteries: Nearby retinal arteries can compress the vein when they are hardened, leading to occlusion Hemorrhage and Edema: Impaired venous outflow can cause retinal hemorrhages and macular edema Clinical Presentation Sudden Vision Changes: Patients often report sudden, painless vision loss or distortion Retinal Hemorrhages: Examination may reveal widespread retinal hemorrhages Macular Edema: Swelling in the macula can affect central vision Cotton Wool Spots: Nerve fiber layer infarcts can result in cotton wool spot formation Central Retinal Artery Occlusion CRAO is typically caused by a sudden blockage of the central retinal artery Most common etiology: Plaque embolus Other potential causes include vasculitis, thrombosis, or compression of the artery Clinical Presentation Sudden Vision Loss: Patients often describe an abrupt (faster than CRVO), painless loss of vision in one eye Pale Retina: Examination may reveal a pale appearance of the retina due to reduced blood flow Same etiology as with cotton wool spot (stasis of axoplasmic flow in retinal nerve cells and swelling due to ischemia) but on a much more widespread basis Cherry-Red Spot: In the macula, a “cherry-red spot” may be visible due to preserved choroidal circulation  Ischemic Optic Neuropathies Ischemic Optic Neuropathy (ION) is a condition characterized by reduced blood supply to the optic nerve, damaging optic nerve fibers This results in acute optic disc edema Arteritic vs. Non-Arteritic ION Non-Arteritic ION (NAION): Most common form of ION Typically occurs in patients over 50 Associated with risk factors like hypertension and diabetes Arteritic ION (AAION): Less common but more severe Often associated with Giant Cell Arteritis (GCA), a systemic inflammatory disease Arteritic Ischemic Patients may present with severe headache, jaw pain, and systemic symptoms Optic Neuropathy Clinical Presentation Sudden Vision Loss: Patients often experience abrupt, painless vision loss Visual Field Defects: Visual field testing reveals characteristic defects corresponding to the affected optic nerve Neoplasia Neoplasia refers to the abnormal, unregulated proliferation of cells These cells can form a mass of tissue known as a tumor Benign vs. Malignant Benign tumors are usually well circumscribed and may be encapsulated They are typically slow growing Malignant tumors have irregular borders that can grow rapidly and cause damage to surrounding tissue They can also spread (metastasize) to other parts of the body Nomenclature in Neoplasia Nomenclature involves naming and classifying neoplastic growths The suffix "oma" is commonly used in the names of tumors, added to the type of tissue the tumor is derived from Examples: Adenoma: A tumor of glandular origin (e.g., adenoma of the pituitary gland) Lipoma: A benign tumor composed of fat cells (e.g., lipoma in subcutaneous tissue) Carcinoma: A malignant tumor of epithelial tissue (e.g., carcinoma of the lung) Neoplasia in Ocular Tissues Neoplasia may result in tumors that behave differently in the eye than in non-ocular counterparts For example, choroidal melanomas have a clinical course that differs from cutaneous melanoma This may be due to the immune privileged nature of the eye resulting in a different immune response to growths in the eye vs. outside of the eye This is truer of intra-ocular tumors than periocular tumors Periocular growths generally do not exhibit distinct behavior as they are not immune-privileged areas Pre-malignancy A pre-malignant lesion is an abnormal tissue change that has the potential to transform into cancer For example, a benign neoplasm such as a colon polyp (an adenoma) may transform into colon cancer Pre-malignant lesions often begin with genetic mutations and alterations in cellular DNA These mutations may result from exposure to carcinogens, such as UV radiation, chemicals, and infectious agents including certain viruses Chronic inflammation can also play a role Pathogenesis Uncontrolled Cell Growth Genetic mutations can lead to uncontrolled cell growth and division Affected cells may lose the ability to respond to normal regulatory signals Dysplasia Dysplasia is a common feature of pre-malignant lesions It involves abnormal changes in cell size, shape, and organization within the affected tissue Dysplasia indicates that cells are undergoing transformation towards a malignant state Proliferation and Accumulation Pre-malignant cells continue to proliferate and accumulate within the lesion This proliferation increases the risk of further genetic mutations Microenvironment Changes The microenvironment surrounding pre-malignant lesions can change to support tumor progression Inflammation and angiogenesis provide blood flow and nutrients to the growing lesion Conjunctival Intra-epithelial Neoplasia CIN is an abnormal growth of conjunctival epithelial cells It is considered premalignant because it has the potential to develop into invasive conjunctival carcinoma Etiology UV exposure is a significant risk factor for CIN Other factors include human papillomavirus (HPV) infection and chronic irritation Clinical Features CIN often presents as a conjunctival lesion with the following characteristics: Raised or flat: Lesions may be elevated or flush with the conjunctiva Whitish or gel-like appearance: Lesions may appear white or gelatinous Conjunctival redness: Surrounding inflammation is common Irregular borders: Lesion margins may be ill-defined Carcinogenesis Carcinogenesis is the process by which normal cells transform into cancer cells This complex process involves the interplay of various factors, including mutation due to exposure to carcinogens, resulting in alterations to oncogenes and tumor suppressor genes Oncogenes Oncogenes are genes that promote cell growth and division when mutated or activated Mutations can turn proto-oncogenes into oncogenes, leading to uncontrolled cell proliferation Examples of oncogenes include: HER2 (Human Epidermal Growth Factor Receptor 2): Associated with breast cancer RAS: Mutations are common in various cancers EGFR (Epidermal Growth Factor Receptor): Implicated in lung cancer Tumor Suppressor Genes Tumor suppressor genes regulate cell division and prevent the formation of tumors Mutations in these genes can lead to loss of their inhibitory function Examples of tumor suppressor genes include: TP53 (p53): Known as the "guardian of the genome," mutations are common in many cancers BRCA1 and BRCA2: Mutations increase the risk of breast and ovarian cancers RB (Retinoblastoma): Mutations are associated with retinoblastoma and other cancers Carcinogenesis Steps Initiation: DNA damage or mutation occurs, often due to carcinogens These carcinogens may be chemical, radiation, viruses, or other agents Promotion: Proliferation of initiated cells Progression: Development of malignant features and the potential to invade nearby tissues and metastasize Tumor Spread and Metastasis Tumors spread when they invade other healthy tissues Metastasis occurs when cancer cells establish secondary tumors in distant organs Cancer cells may spread via several routes: Local invasion of normal tissue Lymphatic spread or hematogenous spread (through lymphatic vessels and blood vessels respectively) Intraepithelial spread (spread of cancerous cells within an epithelial tissue) Dissemination along natural passages (such as the colon) Hamartomas Hamartomas are benign growths composed of cells and tissues that are normally found in the specific organ or location where they occur Key Features of Hamartomas Non-Cancerous Nature Hamartomas are non-cancerous growths and do not have the potential to become malignant They result from an abnormal organization of tissue components in a specific area Normal Cell Types Hamartomas consist of normal cells that are native to the organ or tissue in which they develop In the case of capillary hemangiomas, they are made up of blood vessels, including capillaries Capillary hemangioma of the eyelid Capillary Hemangioma Capillary hemangiomas, also known as infantile hemangiomas, are benign tumors made up of capillaries They are often present at birth or develop during infancy Appearance Capillary hemangiomas typically appear as raised, reddish or purplish lumps on the skin or mucous membranes however they can also occur inside the eye They may grow rapidly during the first few months of life Spontaneous Regression Many capillary hemangiomas undergo spontaneous regression and gradually shrink over time Most resolve without the need for intervention Potential Complications While most capillary hemangiomas do not pose health risks, Retinal capillary hemangioma they can occasionally cause complications when located near vital structures (e.g., eyes, airway) Cavernous Hemangioma Cavernous hemangiomas are benign tumors made up of a malformation of venous cells arranged into “caverns” of dilated tissue saccules containing venous blood Appearance Dilated vascular spaces (caverns) form with a lining of endothelium resulting in a “mulberry” or “raspberry” like appearance Irregular endothelial cells lack tight junctions which results in leakiness Potential Complications Due to their tendency to leak, cavernous hemangiomas can result in chronic hemorrhaging into adjacent tissue They may also compress upon adjacent structures as they expand Retinal cavernous hemangioma Nevi Nevi (singular: nevus) are common benign growths composed of melanocytes They can develop in various parts of the eye, including the eyelid, iris, and choroid Key Features of Nevi Benign Nature Nevi are non-cancerous growths and do not have the potential to become malignant They are typically harmless and benign Melanocyte Origin Nevi are derived from melanocytes, cells responsible for producing melanin, which is why they typically occur in pigmented tissues such as skin Eyelid nevus Iris Nevi Iris nevi, also known as iris freckles or iris moles, are benign collections of melanocytes in the iris Appearance Iris nevi may vary in color and size, ranging from light brown to dark brown They can be flat or slightly raised on the surface of the iris Typically Asymptomatic Iris nevi are usually asymptomatic and do not affect vision They also do not alter normal iris architecture Choroidal Nevi Choroidal nevi are benign melanocytic growths located in the choroid Appearance Choroidal nevi are often dark brown or gray and are located beneath the retina They may be flat or slightly elevated Monitoring Choroidal nevi are typically monitored periodically to assess any changes in size or appearance Changes may prompt further evaluation to rule out malignancy, although true malignancy is rare Choristomas Choristomas are non-cancerous congenital growths that occur in various tissues composed of cells and tissues that are not normally found in the specific organ or location where they occur Two common types of choristomas are dermoid and phakomatous choristomas Key Features of Choristomas Non-Cancerous Choristomas are benign growths and do not have the potential to become malignant They are typically present at birth or develop early in life Ectopic Tissue Choristomas contain tissue types not typically found in the area where they are located (ectopic) They result from developmental anomalies during embryogenesis Ocular Choristomas Dermoid choristomas consist of ectopic skin appendages, including hair follicles, sweat glands, and sebaceous glands They are commonly located on the surface of the eye, such as the cornea, limbus, or conjunctiva Dermoid choristomas may appear as raised, white or yellowish, nodular lesions on the eye's surface They may contain hair or exhibit hair-like structures Phakomatous Choristoma Phakomatous choristomas contain lens tissue within ocular structures outside the lens capsule, such as the eyelid Limbal Dermoid Teratomas Teratomas are rare congenital tumors that arise from totipotent germ cells that can occur in various parts of the body In ocular tissues, teratomas are exceptionally rare findings, and their presentation can vary significantly Key Features of Teratomas Congenital Origin Teratomas originate during embryonic development and consist of tissues derived from multiple germ layers (ectoderm, mesoderm, and endoderm) Heterogeneous Composition Teratomas contain a mixture of different tissue types, including skin, hair, bone, cartilage, and more Their composition can vary widely, making each teratoma unique Ocular teratomas can present in various parts of the eye, such as the orbit which can result in marked proptosis Benign Epithelial Tumors Benign epithelial tumors are non-cancerous growths that develop from the epithelial cells lining various parts of the body, including the eye Key Features of Benign Epithelial Tumors Non-Cancerous Unlike malignant tumors, benign epithelial tumors do not invade nearby tissues or spread to distant parts of the body Slow Growth These tumors tend to grow slowly and are usually well-demarcated from surrounding healthy tissue Benign Epithelial Tumors in the Eye Several benign epithelial tumors can occur in the eye or its adnexal structures Common types include: Acrochordon (Skin Tag) Acrochordons are soft, pedunculated (growing from a stalk) growths that often occur in areas with skin-to-skin friction While they are more commonly found on the skin, they can occasionally develop on the eyelids Papilloma A papilloma is a small, benign growth that resembles a tiny wart It can develop on the conjunctiva or eyelids and may appear as raised, pinkish, or skin-colored lesions Eyelid papilloma  Seborrheic Keratosis Seborrheic keratosis is a benign skin tumor that can also affect the eyelids and periocular skin These tumors typically appear as brown or black, waxy, stuck-on growths Benign Tumors of Adnexal Glands Benign tumors of adnexal glands are non-cancerous growths originating from the accessory structures of the eye, including the glands that produce tears (lacrimal glands), sebaceous (oil) glands, and eccrine (sweat) glands Sebaceous Adenoma Sebaceous adenoma is a benign tumor arising from sebaceous glands It can appear as a painless, slow-growing, yellowish or skin-colored nodule on the eyelids It is derived from sebaceous gland cells (vs. sebum) Sebaceous Adenoma  Epidermoid Cyst Benign Tumors of Adnexal Glands Epidermoid Cyst Epidermoid cysts are benign, slow-growing masses originating from epidermal (skin) cells They can develop on the eyelids and present as painless, mobile lumps Sudoriferous Cyst aka Hidrocystoma Hidrocystoma is a cystic tumor originating from eccrine sweat glands It presents as a translucent, dome-shaped cyst on the eyelids, typically without symptoms Hidrocystoma Malignant Epithelial Tumors Malignant epithelial tumors are cancerous growths that arise from the surface or lining of ocular tissues These tumors can exhibit various levels of aggressiveness Types of Malignant Epithelial Tumors Basal Cell Carcinoma (BCC) BCC is the most common type of skin cancer In the eye it typically occurs on the eyelids and periocular skin BCC is often slow-growing and rarely metastasizes It may appear as a painless, pearly nodule with telangiectasia (dilated blood vessels) Squamous Cell Carcinoma (SCC) SCC is another type of skin cancer that can affect the eyelids and conjunctiva Unlike BCC, SCC has a higher potential for invasion and metastasis It may manifest as a scaly, ulcerated, or crusted lesion Sebaceous Gland Carcinoma Sebaceous gland carcinoma arises from the sebaceous (oil-producing) glands It most commonly affects the eyelids, originating in the meibomian glands This tumor can be aggressive and may present as a lump, thickening, or nodular lesion with potential for recurrence Basal Cell Carcinoma BCC is the most common malignant lid neoplasm (90% of all malignant lid neoplasms) It arises from the basal layer of the epidermis It is usually associated with sun exposure Key features: Slow growing Ulcerated appearance Alteration of normal lid architecture Madarosis (loss of lashes) May appear as a flesh-colored nodule that looks pearly or translucent with telangiectatic vessels Squamous Cell Carcinoma SCC arises from epidermal keratinocytes It grows more quickly than basal cell carcinoma It is also much more likely to metastasize Usually associated with sun exposure or chemicals/irritants Varied appearance vs BCC: May appear as a papule, plaque, or nodule Ulceration is common Also causes alteration of normal lid architecture May also cause madarosis Melanoma Malignant melanomas are cancerous growths that arise from melanocytes within ocular tissues These tumors can occur in various parts of the eye, including the eyelids, conjunctiva, iris, and choroid Melanoma Melanomas are often associated with sun exposure But there are genetic factors, especially in intraocular tumors They are the most malignant skin cancer and also the most likely to metastasize Key Features, remember “ABCDE” for cutaneous melanoma: Asymmetry Border irregularity Color variegation Diameter >6mm Evolution (growth and change over time) Eyelid melanoma Conjunctival Melanoma Conjunctival melanoma originates from melanocytes on the conjunctival surface They are usually pigmented but may also appear amelanotic (de-pigmented) Key Features Raised pigmented lesion with feeder vessels, usually unilateral Often has irregular borders May also cause alteration and damage to adjacent tissues Iris Melanoma Iris melanoma arises from melanocytes in the iris They can vary in size and color, from light brown to black Key Features The may cause changes in normal iris architectures such as iris color, shape, or pupil distortion They are typically slower growing compared to other melanomas Choroidal Melanoma Choroidal melanoma is the most common primary intraocular cancer in adults Choroidal melanoma is a cancer that originates from the melanocytes in the choroid It's important to note that melanoma in the eye is different from skin melanoma; they have distinct characteristics and behaviors Choroidal Melanoma Characteristics of Choroidal Melanoma: Choroidal melanomas can be pigmented (dark) or amelanotic (light) They often appear as elevated dome-shaped growths underneath the retina that increase in size over time They may be associated with fluid and lipofuscin build up Choroidal melanomas are much more likely to cause symptoms than benign choroidal nevi Neural Tumors Neural tumors in ocular pathology originate from nerve tissues within the eye and its surrounding tissues They can affect various structures, including the eyelids, retina, and optic nerve They may be benign or malignant Neural Tumors Cont. Neurofibroma and Schwannoma Neurofibroma and schwannoma are benign tumors that arise from Schwann cells from peripheral nerves They can occur as nodules on the skin, but can also occur near the optic nerve Clinical presentation may include visual disturbances or proptosis Malignant Peripheral Nerve Sheath Tumors Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies They can develop from pre-existing neurofibromas or on their own They often present with rapid growth, pain, or neurological deficits Patient with neurofibromatosis with many neurofibromas Retinoblastoma Retinoblastoma is a childhood cancer that originates from embryonal retinal cells It may be hereditary or sporadic and typically affects children under five Leukocoria (white pupil) is a hallmark sign due to the formation of a large smooth-surfaced white mass They can spread to the brain through the optic nerve sheath if the condition goes untreated Neural Tumors Cont. Astrocytic Hamartoma Astrocytic hamartoma is a noncancerous tumor composed of astrocytes Commonly found in the optic nerve head, it can lead to visual disturbances and vision loss Glioma A glioma is a type of brain tumor that arises from glial cells and may be benign or malignant Gliomas in the optic pathway, such as the optic nerve or chiasm, can cause vision loss Meningioma Meningiomas are typically benign tumors that arise from the meninges They can compress the optic nerve or other structures, also leading to visual deficits MRI showing optic nerve sheath meningioma Tumors Derived from Muscle Tumors derived from muscle tissue are relatively rare but can occur in ocular and periocular regions They can be either benign or malignant Leiomyoma A benign tumor arising from the smooth muscle of the iris and ciliary body Can become malignant Malignant tumors derived from muscle are classified into two primary types: leiomyosarcoma and rhabdomyosarcoma Tumors Derived from Muscle Cont. Leiomyosarcoma Leiomyosarcoma is a rare malignant tumor arising from the smooth muscle of the iris a ciliary body Clinical signs may include proptosis, pain, and visual disturbances/loss Rhabdomyosarcoma Rhabdomyosarcoma is a malignant tumor arising from skeletal muscle cells It can affect the orbit and adjacent tissues It is the most common orbital malignancy of childhood Symptoms may include proptosis, pain, and vision changes/loss Rhabdomyosarcoma Vascular Tumors Vascular tumors are a group of growths originating from blood vessels They can occur in various parts of the eye and periocular tissues They also include hemangiomas Kaposi Sarcoma A malignant vascular tumor Associated with human herpesvirus 8 (HHV-8) Most commonly affects the skin but can also occur in the conjunctiva Presents as purplish-red nodules Kaposi Sarcoma Lymphoid Tumors Lymphoid tumors originate from lymphoid tissues and can affect the eye or its adnexal structures Lymphocytes can be found in the conjunctiva but are not present behind the orbital septum Types of Lymphoid Tumors Lymphoma Non-Hodgkin lymphoma can occur in the orbit, conjunctiva, and lacrimal glands They presents as a painless mass with redness or swelling around the eye Diagnosis involves biopsy and histopathological examination Leukemia Rarely affects the eye directly but may infiltrate ocular structures May present with retinal hemorrhages, cotton-wool spots, or Conjunctival lymphoma leukemic infiltrates These ophthalmic findings can lead to a diagnosis of systemic leukemia Lacrimal Gland Tumors Tumors can affect both the lacrimal gland and lacrimal sac Types of Lacrimal Gland Tumors Pleomorphic Adenoma (Benign Mixed Tumor) Most common benign tumor of the lacrimal gland Slow-growing, painless mass Adenoid Cystic Carcinoma Rare, malignant tumor with slow growth Can invade nerves and surrounding tissues Adenoid Cystic Carcinoma  Metastatic Tumors Metastatic tumors in the eye are secondary cancerous growths originating from primary cancers elsewhere in the body Metastasis to the Eye Various primary cancers can metastasize to the eye, including breast, lung, and others Most common primary source for ocular metastases: Breast cancer Retinal metastatic tumor Metastatic Tumors Metastatic tumors can affect different ocular structures: Choroid: Most common site of ocular metastases Iris: Less common but can lead to visible changes in iris appearance and architecture Conjunctiva: Rare, but can Conjunctival metastatic tumor present as conjunctival nodules Disorders Misdiagnosed as Neoplasms Benign neoplasms and malignant tumors may share similar clinical features however they have key differences Benign neoplasms typically exhibit slow growth, have distinct borders, and do not invade or metastasize to other tissues Malignant tumors tend to grow rapidly, have indistinct borders, invade nearby tissues, and may metastasize Clinical evaluation, including imaging (e.g., ultrasound, MRI), and sometimes biopsy may be needed for diagnosis Disorders Misdiagnosed Hidrocystoma as Neoplasms Hidrocystoma Derived from sweat glands Typically present as painless, mobile, subcutaneous cysts Often translucent and may contain clear or yellowish fluid Epidermoid Cysts Arise from epidermal cells Appear as slow-growing, firm, often painless nodules Can contain keratinaceous material and may have a central pore Dermoid Cysts Embryonic remnants Contain skin appendages (hair, sebaceous glands) Present as slow-growing, non-tender masses, sometimes with hair  Sebaceous Cyst Disorders Misdiagnosed as Neoplasms Sebaceous Cyst Sebaceous cysts result from blocked sebaceous ducts and can occur on the eyelids and peri- ocular skin They appear as round, firm nodules Xanthelasma Xanthelasma is characterized by yellowish, cholesterol-filled deposits on the eyelids It is often associated with hyperlipidemia and may not require treatment unless it causes cosmetic concerns Xanthelasma  Conjunctival inclusion cyst Disorders Misdiagnosed as Neoplasms Inclusion Cysts Result from inclusion of epithelial cells Small, round, and usually painless cysts Commonly found on conjunctiva Lymphangiectasia Dilated lymphatic channels Appear as translucent, soft, painless swellings in a cluster May have a bluish tint due to lymph fluid Conjunctival lymphangiectasia Disorders Misdiagnosed as Pseudoepitheliomatous Hyperplasia Neoplasms Pseudoepitheliomatous Hyperplasia Reactive epithelial changes Can mimic malignancy but typically lacks invasion Idiopathic Orbital Inflammation Non-specific inflammation May mimic malignancy due to swelling, redness, pain, and proptosis Idiopathic Orbital Inflammation Conclusion Degenerative Vascular Disease Hyalinization, vaso-occlusive diseases, microvascular occlusion, macrovascular occlusion, and optic neuropathies are all aspects of vascular pathology that can impact ocular health Neoplasia Understanding various tumor types, including epithelial, neural, muscle- derived, vascular, and lymphoid tumors, is essential for diagnosis and management Differential Diagnosis Recognizing benign growths and distinguishing them from malignancies is crucial to ensure a patient receives treatment when needed (and doesn’t receive unnecessary treatment when not needed) Questions?