Chapter 7- Neoplasia Flashcards
What is neoplasia?
New, normally abnormal growth
What is a neoplasm?
An abnormal tissue mass caused by a cell growth disorder
What is another name for neoplasm?
Tumour
What are the two basic components of tumours?
- Parenchyma (neoplastic cells)
2. Stroma (supporting tissue)
What component is tumour classification based on?
The parenchyma
What is desmoplasia?
Abundant collagenous stroma stimulated by tumour parenchymal cells
What are scirrhous?
Stone hard desmoplastic tumours
What is a polyp?
A neoplasm that projects above the mucosal surface
How can benign tumours cause morbidity and mortality?
Pushing on surrounding structures
What are the characteristics of benign tumours?
Localized with well circumscribed/clear borders
Doesn’t spread
Homogenous cut surface
What suffix designated benign tumours?
-oma
What are choristomas?
Masses of normal tissue in abnormal locations
What are hamartomas?
Masses of disorganized tissue indigenous to the site in which they are found
What are the two types of malignant tumours and what cells do they involve?
Sarcomas- mesenchymal cells
Carcinomas- epithelial cells
How do mixed tumours form?
A single germ cell layer differentiates into more than one cell type
What cell types make up a pleomorphic adenoma?
Epithelial and stromal
What characterizes a teratoma?
Made up of more than one germ layer
What are tumours categorized based on?
Differentiation
Local invasion
Metastasis
Rate of growth
What is anaplasia?
Lack of differentiation
What is pleomorphism?
Variability in cell size and/or shape
What is dysplasia?
Non invasive growth (no penetration of basement membrane)
Carcinoma in situ
What is the difference in differentiation between malignant and benign tumours?
Benign- well differentiated, retain functional characteristics
Mal- pleomorphic, high N:C ratio, mitoses common, loss of polarity, tumour giant cells, necrosis
What is the difference in local invasion between malignant and benign tumours?
Benign- cohesive, remain localized, often capsulated
Mal- do not remain localized
What is metastasis?
Spread of tumour to sites physically discontinuous with the primary tumour
What is the most reliable feature for tumour differentiation?
Metastasis
What types of tumours does metastasis occur in?
Only malignant
What are the different ways cancer can be disseminated?
- Lymphatic spread
- Direct seeding of body cavities and surfaces (open space with no physical barriers)
- Hematogenous spread (veins invaded)
What type of tumours initially spread via lymphatics?
Carcinomas
What spaces are combining seeding during tumour dissemination?
Peritoneal, pleural, pericardial, subarachnoid, joint spaces
What are the most common sites of hematogenous tumour spread?
Lung and liver
How does growth rate differ between benign and malignant tumours?
Benign- slow and progressive
Mal- erratic
What different risk factors affect the development of cancer?
Environmental
Age
Acquired predisposing conditions
Genetic predisposition
What is the dominant risk factor for most cancers?
Environment
Why do most carcinomas occur later in life?
Accumulation of somatic mutations and decline in immune surveillance
What types of acquired predisposing conditions can lead to the development of cancer?
Chronic inflammation
Precursor lesions (eg. dysplasia)
Immunodeficiency states
Why is chronic inflammation associated with the development of cancer?
Produces a favourable environment
GF release, increases stem cells
ROS
Mediators cause cell survival
Metaplasia
What types of precursor lesions may lead to cancer?
Chronic inflammation with metaplasia
Noninflammatory hyperplasia
Benign neoplasms
What types of genetic predispositions can lead to the development of cancer?
Autosomal dominant mutations (tumour suppressor genes)
Defective DNA repair syndromes
Familial cancers
What is Lynch syndrome?
Inactivation of DNA mismatch repair gene
What does Lynch syndrome predispose a patient to?
Colon cancer
Endometrial cancer
What underlies carcinogenesis?
Non-lethal genetic damage
Cells continue to acquire mutations as they won’t die
What are the different classes of regulatory genes?
Proto-oncogenes- regulate cell growth and differentiation
Tumour suppressor genes- slow/stop cell division
Apoptotic regulating genes
DNA repair genes
What alterations are required for malignant transformation?
Self sufficiency in growth signals
Insensitivity to growth inhibitory signals
Evasion of apoptosis
Limitless replicative potential
Sustained angiogenesis
How is self sufficiency in growth signals achieved by cancer cells?
Proto-oncogene conversion to oncogene
Autocrine production of GFs
Constant activation of GF receptors
Signal transducing proteins are locked into signal transmission
Cyclins and CDK mutations result in a loss of cell cycle control
What mutations do tumour cells use to escape from senescence (become insensitive to inhibitory signals)?
RB mutations- cells bypass the G1/S checkpoint
P53 mutation- neither repair or apoptosis is activated
Adenomatous polyposis coli/beta catenin pathway mutations- growth signals in WNT pathway are no longer down regulated
What causes a germ line P53 mutation?
Li Fraumeni syndrome
Overexpression of what protein allows cancer cells to evade apoptosis?
BCL2
How does BCL2 prevent apoptosis?
Limits cytochrome C release from mitochondria
How is limitless replicative potential achieved by tumour cells?
Inappropriate telomerase activity allows cells to continuously divide
Why is angiogenesis required for malignant transformation?
Without blood vessel growth, tumours would only reach 1-2mm
Leaky vessels allow for metastatic potential
What is the major driving force in angiogenesis of malignant transformation?
Hypoxia
What normally prevents metastasis?
Cell detachment from E cadherin normally causes cell death
What mutations lead to genomic instability and increase the risk for carcinogenesis?
Mismatch repair- micro-satellite instability
Nucleotide excision repair
Recombination repair- hypersensitivity to agents that damage DNA
What type of mutation is hereditary nonpolyposis colon cancer syndrome associated with?
Mismatch repair
What is nucleotide excision repair responsible for?
Correct IV light pyrimidine dimer formation
What do defects on nucleotide excision repair lead to?
Skin cancer
What is the Warburg effect?
Tumours use glycolysis for energy even when adequate oxygen is available for oxidative phosphorylation
Results in required carbon intermediates
What can cause the dysregulation of cancer associated genes?
Chromosomal changes
Epigenetic changes
miRNA
How does Philadelphia chromosome (t(9:22)) affect the development of cancer?
Results in constitutive kinase activity
How are tumour cells recognized and destroyed by host defences?
MHC I cells present tumour Ags to and activate CD8 CTLs
How do tumour cells evade host defences?
Selective outgrowth of Ag negative variants
Loss/reduced expression of histocompatibility genes
Secretion of factors that suppress the immune response
How do inflammatory reactions modify the microenvironment to make it beneficial to cancer?
Release of GFs (promote proliferation)
Removal of growth suppressors (eg. proteases)
Enhanced resistance to cell death
Angiogenesis induction
Activation of invasion and metastasis
Evading immune destruction (immunosuppressive environment)
What is anoikis?
Epithelial cell detachment from the basement membrane resulting in cell death
What can prevent the anoikis of tumour cells?
Macrophages bound to the cells
What proteins remodel the ECM to activate invasion and metastasis?
Proteases
What are the three types of carcinogenic agents?
Chemical
Radiant energy
Oncogenic viruses and other microbes
How do chemical carcinogens exert their effects?
Initiation- irreversible genome changes
Promotion- tumour formation in previously initiated cells
What is the difference between direct and indirect chemical carcinogens?
Direct- reactive without metabolism
Indirect- require metabolic conversion
How does UV light lead to the development of skin cancer?
Dimer formation
How does radiant energy lead to the development of cancer?
Free radical generation
What type of UV light is associated with melanoma? Non-melanoma skin cancer?
Melanoma- intense intermittent light
Non-melanoma- cumulative
What are some examples of oncogenic viruses and the cancers they cause?
HTLV-1- T cell leukaemia/lymphoma (CD4)
HPV- cervical cancer via inhibition of RB, P53 and CDK inhibitors
EBV- Burkitt lymphoma, B cell and Hodgkin lymphoma, nasopharyngeal carcinoma
Hep C- hepatocellular carcinomas via P53 inactivation
H. pylori- gastric cancer and MALToma
What characteristics of tumours affect their morbidity and mortality?
Location and impingement on other structures
Functional activity
Bleeding and infection
Symptoms from rupture or infarction
Cachexia
Paraneoplastic syndrome
What is cachexia?
Loss of body fat and muscle (wasting away)
What is paraneoplastic syndrome?
Mimicry of metastatic disease
Symptoms can’t be explained by tumour location or hormones normally produced
What does grading determine?
Degree of differentiation
What is staging based on?
TNM system
T= primary tumour (size and structure)
N= lymph node involvement
M= metastases
What is used for the laboratory diagnosis of cancer?
Histo/cyto
IHC- cell surface markers
Flow cytometry- blood based
Molecular- FISH (chromosomal changes)
Tumour markers- screening
What is the most important component of lab diagnosis of cancer?
Histo/cyto
What types of cancer is IHC useful for?
Poorly differentiated (can determine site of origin)
What does FISH detect?
Chromosomal changes
What are some examples of tumour markers?
PSA- prostate
CEA- colon, pancreatic, stomach, breast
AFP- liver and testicular
