8-6 Neoplasia Flashcards
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A: Neoplasia = New Monoclonal cellular growth that is Unregulated and caused by a series of acquired mutations
B: “Tumors” are what the abnormal growths of tissues are called
C: [Benign Neoplasms] Cellular growths that remain localized and DO NOT metastasize. These [Benign Neoplasms] can still cause deleterious effects depending on size & location
D: Malignant Tumors = referred to as “Cancers” and have the ability to metastasize and invade tissue
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What are the 2 components of the Neoplasm?
Parenchyma vs. Stroma
A: Parenchyma = the Actual Neoplastic cells that determine biological behavior and NAME of the tumor
B: Stroma = Supporting structures of the neoplasm that include connective tissue & blood vessels. Growth of Neoplasms depend on vascular supply from Stroma.
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There are different suffix identifications for neoplastic tissue types [benign vs. malignant]
Tissue: Mesenchyme [Fibrous tissue/blood vessels/muscle/chondroid/osteoid]
if benign: [ends in -oma ]
if MALIGNANT: [ENDS IN -SARCOMA ]
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There are different suffix identifications for neoplastic tissue type [benign vs. malignant]
Tissue: SPECIAL Mesenchyme [Lymphoid / Hematopoietic cells]
NEVER BENIGN
if MALIGNANT:
1. Lymphoid = Lymphoma
- Hematopoietic cells = Leukemia
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There are different suffix identifications for neoplastic tissue types [benign vs. malignant]
if benign: [ends in -oma ]
1. [Stratified Squamous] = [Stratified Squamous Papilloma]
- ## [Glandular Duct Epithelium] = [Adenoma]if MALIGNANT: [ENDS IN -CARCINOMA ]
- [Stratified Squamous] = Squamous Cell Carcinoma
- [Glandular Duct Epithelium] = Adenocarcinoma
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A: Mixed Tumors are tumors composed of more than 1 germ cell layer (i.e. gonads which come from totipotential germ cells)
B: Mixed Tumors are referred to as
-mature teratoma (benign )
and
-TERATOCARCINOMA (MALIGNANT)
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A: Tumor Differentiation = extent parenchymal CA cells look and function like their normal counterparts. [MORE Differentiated = MORE Normal]
B: Anaplasia = “backwards differentiation” = occurs when a neoplastic cell starts to function and look less and less like its normal counterpart
C: Pleomorphism= when neoplastic cells vary in size and shape. Anaplastic cells typically develop into pleomorphism
C2: Anaplasia and Pleomorphism (types of tumor morphology) are often Assessed by GRADING –>allows us to asses how “aggressive” the tumor is. Although GRADING IS GOOD…[TNM STAGING] IS A BETTER CLINICAL ASSESSMENT OF HOW PROGRESSED A TUMOR IS
C3: [TNM STAGING] = Assess the [Tumor Morphology-Size] / Node Spread / Metastasis of the tumor
D: Normal cells have a [nucleus-to-cytoplasm] ratio of 1:4 - 1:6 BUT MALIGNANT NEOPLASTIC CELLS CAN APPROACH 1:1 (CYTOPLASM SHRINKS AND NUCLEUS ENLARGES)
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Dysplasia is a potentially reversible process that involves cells altering their morphology, cell architecture, [nucleus-to-cytoplasm] ratio and become polymorphic in response to an injurious agent.
-They do NOT penetrate the basement membrane
-This is different from metaplasia because it involves DISORDERLY ARCHITECTURE and appears to be malignant but hasn’t invaded basement membrane yet
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B: [Carcinoma -in-situ] is what occurs when Dysplasia involves the FULL THICKNESS of the Epithelium and this is NOT REVERSIBLE
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B: Metastasis Dissemination can occur in 3 ways
1) Seeding (i.e. Ovarian CA) = CA sheds itself into the body cavity
2) Lymphatic Drainage (i.e. Carcinomas) = drain into the regional lymph nodes first
C: Epithelial Carcinomas consist of cells that were normally adhered together by [E-cadherins] but when these [E-cadherins] were down regulated, neoplastic cells attached to the laminin and destroyed the [Collagen 4 Basement Membrane] using a Collagenase drill—> Metastasis
C2: Neoplastic cells then attach to Fibronectin and use it to invade all of the extracellular matrix and spread locally
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benign vs. MALIGNANT
- benign *
1. Cell Morphology = very well differentiated = very normal in function and appearance
2. Rate of Growth = mostly slower
3. Metastasis = DOESN’T SPREAD. Is encapsulated and localized.
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benign vs. MALIGNANT
- MALIGNANT *
1. Cell Morphology = ºPLEOMORPHIC ºHYPERCHROMATIC NUCLEUS ºANAPLASTIC / DEDIFFERENTIATED ºMITOSIS
- Rate of Growth = HIGHLY VARIABLE AND DEPENDS ON HOW ANAPLASTIC CELLS ARE
- Metastasis = SPREADS AND INVADES LOCALLY
- Don’t forget that most tumors are monoclonal
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B: CA can be spread and inherited from a genetic familial level in 3 ways
1) Autosomal Dominant
2) Autosomal Recessive –> Defective DNA Repair
3) Unfamiliar Inheritance pattern
B2: Most CA is sporadic and not familial
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Carcinogenesis:
CA is a genetic disorder that comes from DNA mutations. The DNA mutations could be caused by sporadic somatic mutations inherited from the germline OR from environmental insult.
B: There are 4 genes tht are typically associated with CA
1) [proto-oncogenes] = promote cell growth. A mutation of a single allele in a [proto-oncogene] —-> Dangerous ONCOGENE = Genetically Dominant
2) tumor suppressor genes = inhibit cell growth
3) DNA repair genes
4) Cell Apoptosis Genes
C: Oncogene = mutant or over-expressed version of a [proto-oncogene] that acts autonomously to promote an uncontrolled rate of cell proliferation.
C2: “Gain of Function of oncogene” –> CA
D: Carcinogen = Any injurious agent that damages DNA [chemical vs. (microbial-viruses) vs. radiation]
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A: RAS is the most commonly mutated [proto-oncogene]. A single allele mutation of this [G-protein gene] causes it to lose GTP hydrolysis function.
B: RAS is a G-protein that sends receptor signals down to the cell nucleus and tells the cell to proliferate and grow. It only does this when bound to GTP / ACTIVE. It has an inherent hydrolase that chops off the [P] so that it can be quiescent again with a GDP
C: Mutated Ras [Oncogenic] loses its GTP hydrolysis capabilities and remains active with GTP bound. —> Uncontrolled cell growth
D: More common in Colon and Pancreatic adenocarcinomas
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A: [Tumor Suppressor genes] are genes that INHIBIT uncontrolled cell growth. They are genetically recessive which means you have to lose BOTH ALLELES in order to lose it function. = [Knudson’s 2-hit hypothesis]
A2: “Lost of Function of [Tumor Suppressor gene] = CA”
B: [Retinoblastoma gene] was the FIRST [Tumor Suppressor gene] discovered. It prevents uncontrolled cell growth by regulating the movement of cells from G1—> S during the cell cycle.
[Cyclin E] allows for the cell to move from G1—>S. [Cyclin E] comes from [E2F tx factor]. When Rb is hypOphosphorylated/ACTIVE it has “room” on its surface to bind to [E2F tx factor] and prevent it from transcribing for [Cyclin E].
C: Phosphorylation of Rb by [Cyclin-Dependent 4 Kinase] —> [E2F tx factor] being free to normally transcrbe for [Cyclin E] –> Cell proliferation.
D: DOUBLE MUTATION in Rb gene –> no functional Rb and allow [Cyclin E] to be produced uncontrollably. [Cyclin E] also has the capability to phosphorylate Rb so this leads to a vicious cycle of DeActivating normal [Rb proteins]
E: Germline Mutations of the [Rb gene] can —> [BILATERAL Retinoblastoma] OR Osteosarcomas
