Neoplasia characterization Flashcards
Localized neoplasm
-Frequently benign
-Minimal effects
-examples: lipoma, histocytoma, sebaceous adenoma
-Cant cause invasion
-Clone and subclones proliferate at a greater rate
-angiogenesis minimal
Angiogenesis
Growth of new blood vessels in response to VEGF and b-FGF
Localized neoplasm interaction with ECM
Minimal, stick to eachother tightly, cadherins and adhesins often normal
Effects of localized neoplasm
-Largely locally
-Can compress adjacent tissues an organs
-Small ones normally non critical
-Minimal systemic effects
Outcome of localized neoplasms
-Remain static for a long time
-Can get spontaneous regression
-Usually remove surgically
Locally invasive neoplasm
-Can be malignant or benign
-Affect variable depending on cell type
-Ex: Hemngiopercytoma, fibrosarcoma, mast cell tumor
-Capable of local invasion
-Subclones have additional mutations
-Adequate angiogenesis, can get growth that exceeds this and leads to necrosis
Locally invasive neoplasms and ECM
Interactions extensive, less adhesion cel-to-cell
-Decreased cadherins
-Increased expression of receptors for laminin, fibronectin, and collagen
Locally invasive Epithelial neoplasms
Seperated by basement membrane to ECM. Have to penetrate this making it malignant
Locally invasive mesenchymal neoplasms
Already in ECM harder to determine if it is malignant
Effects of locally invasive neoplasm
-Largely local
-Can infiltrate normal tissues and organs
-Can get loss of function of tissue
-Systemic effects may occur because of damaged tissue
Outcome of locally invasive neoplasms
-Some grow to a certain size then remain static
-May continue to grow until damaged
-Surgical removal often followed by local reoccurence
-Malignancy and can metastasize
Metastatic neoplasm
-ALways malignant
-Always significant and ultimately fatal
-Ex: hemangiosarcoma, osteosarcoma, mammary adenocarcinoma
-Local and systemic invasion
-greater number of subclones with additional mutations
Pathogenesis of metastatic neoplasm
-Angiogenesis at the site of primary neoplasm, can serve as route of entry into circulation
-Angiogenesis is very important at site of secondary ones so they can survive
Metastatic interaction with ECM
Extensive. Similar to locally extensive neoplasms
What is required for metastasis
Intravasuclar invasion and has to penetrate the vascular basement membrane. Usually use collagenase
Carcinomas spread through
Lymphatic vessels
Sarcomas spread through
Blood vessels
Outcome of intravascular neoplastic emboli
Usually die or are killed by host defenses
Criteria for successful metastasis
-Adhere to endothelium
-Migrate out of vessel
-Local extravascular environment where they can grow
How do they adhere to endothelium
Receptor mediated binding (CD44). More prominent in arease with slow moving blood
Migrating out of vessel
Have to break through basement membrane
Local extravascular environment for neoplastic growth
-Need adequate vascularity
-Appropriate nutrients and microenvironment
Significance of metastatic neoplasms
-Local and systemic
-Primary and secondary ones infiltrate and destroy tissues and organs
-Cytokines and products of neoplastic cells disrupt homeostasis
Outcomes of metastatic neoplasm
-Invariably fatal
-Time course and progression variable depending on tumor
Local effects of neoplasia
-Destroy and replace normal tissue
-Compression
-Interfere with normal function
-metatstatic sites cause localized damage
-Vascular erosion and hemorrhage
Systemic effects of neoplasia
-Dyshomeostasis brom products of normal and neoplastic cells such as TNF, IL 1, IL6, prostaglandins
-Cachexia and fever
Paraneoplastic disorders
Systemic effects induced by tumor cell products
Paraneoplastic syndromes
Hypercalcemia
-Hypo or hyperglycemia
-Leukocytosis/leukopenia
-Neuropathy
-Myelofibrosis
-Thrombocytosis/penia
Recognition of neoplastic cells
-Tumor specific antigens (class I MHC molecules)
-Tumor-associated antigens
-Humoral and cell-mediated responses
Responses to neoplastic cells
-T cell mediated cytotoxicity
-Type II hypersensitivity reaction
-Innate responses by NK cells and activated macrophages
Tumor-specific antigens
May be products of normal genes that aren’t normally expressed or from mutated genes that are now present
Tumor associated antigens
Always present at low levels, but get up regulated when undergoes transformation
