Neoplasia Flashcards
What is a neoplasm?
An abnormal mass of tissue
Growth is unco-ordinated and exceeds that of normal tissues
Persists after removal of the stimuli that initiated the change
What is oncology?
study of malignant tumours
What kind of disorder is neoplasm?
genetic disorder of cell growth by acquired/inherited mutations affecting a single cell and its clonal progeny
What are the two clinical classifications of neoplasm?
benign
malignant
What are the histological classifications of neoplasm?
Growth can occur in
Epithelial – lining/covering/glandular tissue
Connective tissue
Other tissues
What is the growth pattern of benign tumours vs malignant tumours?
benign tumours expand, may be encapsulated and are localised
malignant tumours invade, have no capsule and metastasis
What is metastasis?
to travel to other organs and other sites in the body and form tumours there
What is the growth rate of benign vs malignant tumours?
benign = slow
malignant = fast but variable
What is the microscopic appearance of benign vs malignant tumours?
benign
resembles tissue of origin in differentiation
uniform cell/nuclear shape and size
few mitoses (dividing cells)
malignant
variable resemblance to tissue of origin
nuclear and cellular pleomorphism
many abnormal mitoses
What are the clinical presentations of benign vs malignant tumours?
benign
lump/pressure/obstruction depending on site and size
+/-hormone secretion
treat by local excision
malignant
local pressure
infiltration and destruction
distant metastases
+/-hormone secretion
local excision and chemotherapy or radiation if metastases present
What are the effects of benign tumours dependant on?
Depend on site, size and tumour
What happens if the tumour is in endocrine gland?
it can increase or decrease hormone dosage
What are the effects of benign tumours?
Palpable lump
Pressure
Obstruction
Function – esp hormone secretion
What is an example of a benign tumour?
Benign salivary gland tumour
pleomorphic adenoma
What is an example of a malignant tumour?
squamous cell carcinoma
What are the two components tumours are composed of?
neoplastic cells that make the parenchyma
stroma (connective tissue, blood vessels, lymphatic vessels, and nerves.)
What is a malignant type of squamous and glandular epithelium tumour?
squamous = squamous cell carcinoma
glandular = adenocarcinoma
What added to the end of a connective tissue word usually indicates if the tumour is malignant or benign
saroma = malignant
oma = benign
What are tissues that cannot form benign tumours usually?
lymphoid
haemopoietic (fluid blood)
What is a teratoma?
germ cell tumour (usually found benign in the ovaries)
What is a potentially malignant disorder found in the oral mucosa?
leukoplakia - white patch that cannot be rubbed off or attributed to any other cause
If the dysplasia occurs in epithelium, what usually occurs?
does not extend to underlying connective tissue such as lamina propria and submucosa
What is a type of glandular dysplasia?
barrets oesophagus
What are the causes of oral cancer?
tobacco
betal quid chewing
alcohol
diet + nutrition
oral hygiene
viruses (HPV)
immunodeficiency
socioeconmic factors
GORD
What types of hpv cause cancer?
HPV-16 + HPV-18
What types of cancer do HPV cause?
oropharyngeal
cervical
What carcinogens cause malignant tumours?
chemical
physical
viruses
What are the steps of the multi-step theory of carcinogenesis?
intiation
promotion
progression
What does each step include?
Initiation: When a carcinogen induces a genetic change resulting in a neoplastic potential.
Promotion: Another factor stimulates the initiated cell for division. (clonal proliferation). Does not act on non-initiated cells.
Progression; Additional mutations resulting in malignancy.
What are driver mutations?
genes that build up during development of cancer and induce characteristics that are necessary for cancer cell development
What are examples of chemical carcinogens?
smoking polycyclic hydrocarbons (tar)
diet, drugs, alcohol
asbestos
What are physical carcinogens?
ionising radiation
UV light (natural, sunbeds)
What does ionising radiation cause and what are types?
– damages DNA, causing mutations
– radioactive metals and gases
What tumours can radium cause?
bone and bone marrow tumours
What are the most sensitive tissues and what are the least sensistive tissues?
Most - embryonic tissues, haematopoietic organs (spleen, bone marrow)
Least - connective tissue, muscle tissue and nerve tissue
What does UV light cause?
damage to DNA
What are the viruse types that can cause cancer?
- DNA viruses
– more common
– viral DNA inserted into host DNA - RNA viruses
– reverse transcribed and then inserted
What cancer does epistein-barr virus cause?
Burkitt’s lymphoma nasopharyngeal carcinoma
What cancer does hepatatis B/C cause?
hepatocellular carcinoma
What are the important genes in carcinogenesis?
- Oncogenes (“accelerators”)
- tumour suppressor genes (“brakes”)
- DNA repair genes
- miRNAs
- Chromosomal aberrations
- Epigenetic mutations
What are proto-oncogenes?
normal genes which regulate cell divison
What do proto-oncogenes control?
– growth factors
– growth factor receptors
– signal transducers
– control of gene expression
What are abnormal versions of protoco-oncogenes called?
oncogenes
produce Onco-proteins
What do onco-genes cause?
– mutation
* increases activity of product
– excess normal product
* duplication of the gene
* viral product
– enhanced transcription
* translocation
* chromosome rearrangement
What do tumour suppressor genes do?
Act to inhibit cell division and suppress growth
What are tumour suppressor genes described as?
anti-oncogenes
What tumour suppressor gene is usually lost and what must happen to cause retinoblastoma cancer?
retinoblastoma gene (RB)
both alleles must be lost (Knudson’s “two-hit” hypothesis)
What are functions of tp53? and where does it act?
acts just before the Restriction Point (cell cycle)
in response to damaged DNA
– stops the cell cycle to allow DNA repair
– apoptosis (if repair not possible)
What are genetic susceptibilites to cancer and what are cancer examples of each?
- inherited cancer syndromes
– single mutant genes, often tumour suppressor genes
– retinoblastoma, some colon cancers. - familial cancer
– family clusters
– gene(s) and pattern of inheritance not clear
– breast, ovary, colon - defective DNA repair
– increased sensitivity to carcinogens and general increased cancer risk
– Xeroderma pigmentosum
What are the effects of cancer on other mechanisms?
- other cell division controls
- DNA repair mechanisms
- apoptosis inhibited
- stimulation of blood vessel formation
- destructive enzymes activated
- cell motility increased
What are the hallmarks of cancer?
tissue invasion/ metastasis
evading apoptosis
sustained angiogenesis
insensitivity to anti-growth signals
limitless replicative potential
self-sufficieny in growth signals
What are the modes of spread of malignant tumours?
- local spread
- lymphatic spread
- blood spread (haematogenous)
- transcoelomic spread (through cavity)
- Intraepithelial spread ( Paget’s disease of the breast)
What is the difference between sarcoma and carcinoma?
sarcomas are cancers of connective tissue (fat, blood vessels, nerves, bones, muscles, deep skin tissues and cartilage)
carcinomas are cancers of epithelial tissue
How do carcinomas spread?
via lymphatics first and blood secondly
How do sarcomas spread?
usually through blood mostly
What are the predicatable patterns of spread?
– lung to local nodes, liver, bone and brain
– tongue to neck nodes, later lung and spine
What is the grade and stage of a tumour?
grade -how normal or abnormal cancer cells look under a microscope. (histopathology)
stage - extent of spread (imaging)
What is the grading meant to assess?
- Invasion into underlying tissue
- Cellular atypia : abnormal mitotic activity, nuclear pleomorphism, differentiation, necrosis
What are the methods of grading?
– numerical grades (1,2,3 etc)
– low, intermediate, high
– degree of differentiation (squamous cell carcinoma)
What are assessments used to determine the stage of cancer?
Physical exams, imaging procedures, laboratory tests, pathology and surgical reports
What system is used to clinically stage oral cancers?
- TNM system is used for oral cancer
- Tumour size (T)
- Lymph node involvement (N)
- Presence of metastases (M)
What antigens allow recognition of tumour cells?
tumour-associated antigens
(neoantigens)
What are examples of tumour-associated antigens?
- Products of mutated genes
- Overexpressed proteins (tyrosinase)
- Viral proteins (HPV,EBV)
- Oncofetal antigens (carcinoembryonic antigen)
What is the tumour immunology reaction?
Elimination-Equilibrium-Escape
What is elimination?
Cell mediated immune response
* Cytotoxic T-lymphocytes (CD8+)
* Natural killer cells. First line of defence against tumour cells.
* Macrophages.
Mechanisms similar to anti-microbial killing.
What response is largely decreased in immuno-deficient individuals?
elimination
How do tumour cells evade (escape) immune system?
Cells may acquire molecular changes such as:
* Alter tumour antigen expression . Lack of T-cell recognition
* Activation of immunoregulatory pathways leading to T-cell unresponsiveness and apoptosis.
* Immunosuppressive factors eg. cytokines (TGF-β). Inhibit T-cell response
What is equilibrium in tumour cells?
involves the continuous elimination of tumor cells and the production of resistant variants
may last years
What is immunotherapy?
Use the patient’s own immune response to control and destroy malignant cells
What are examples of immunotherapy?
Active immunisation.(HPV, Hep B)
Reversal of immunosuppression
Adopted cell transfer (ACT)
Tumour- infiltrating lymphocytes (TILs)
CAR T-cell therapy- haematological malignancies
Strengthening natural immune responses-research still needed.
