Neoplasia Flashcards
What does neoplasm mean
‘new growth’
What is a tumour
Neoplasm
Abnormal mass of tissue
Growth is unco-ordinated and exceeds that of normal tissues
Persists after removal of the stimuli that initiated the change
In what tissue do neoplasms usually occur
Epithelial – lining/covering/glandular tissue
Connective tissue
Other tissues
What are the types of tumours
Benign
Malignant
What are the differences between the growth of benign and malugnant tumours
BENIGN
-expansion
-may be encapsulated
-localised
-slow
MALIGNANT
-Invasion/Infiltration
-No capsule
-matastasis (outwith normal area)
-rapid variable
What are the clinical effects of benign tumours
Lump/pressure/obstruction depending on site and size
+/- hormone secretion
Treates by local excision
What are the possible clinical effects of a malignant tumour
-Local pressure, infiltration and destruction, distant metastasis
-+/- hormone secretion
-local excision and chemotherapy or radiation if metastasis presents
What are the epithelium origins of both benign and malignant epithelial tumours
BENIGN
squamous epithelium - papilloma
Glandular epithelium - adenoma
MALIGNANT
squamous epithelium - squamous cell carcinoma
Glandular epithelium - adenocarcinoma
How do we name tissues originating in the connective tissue
Smooth = Leiomyoma - Leiomyosarcoma
Fibrous = Fibroma - Fibrosarcoma
Bone = Osteoma - Osteosarcoma
Cartilage = Chondroma - Chondrosarcoma
Fat = Lipoma - Liposarcoma
Blood vessel = Angioma - Angiosarcoma
What causes papilloma
Variety of HPV (16, 18)
What coes carcinoma indicate
Epithelial tumour
Where do lymphoma and leukaemia originate
Lymphoid and haemopoietic
What tumours are found in melanocytes
naevus (mole)
melanoma
What tumours could be found within germ cells
Benign teratoma
Malignant teratoma
What is a carcinogen
Any substance or agent with the potential to cause cancer
What are some chemical carcinogens
Smoking polycyclic hydrocarbons including tars
Diet, drugs, alcohol
Asbestos
What are the two stages of chemical carcinogenesis
- Initiation – permanent DNA damage (mutations)
- Promotion – agent promotes proliferation
What is the latent period
Time from promotion to clinical tumour
What is involved in the initiation step of carcinogenesis
When a carcinogen induces a genetic change resulting in a neoplastic potential
What is promotion and progression of carcinogenesis
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 examples of physical carcinogenesis
Ionising radiation
damages DNA, causing mutations
radioactive metals and gases
radium - bone and bone marrow tumours
Ultraviolet light
Damages DNA
skin cancer
What makes a tissue sensitive to radiation
The speed at which cells are renewed (more rapid, more sensitive)
List the tissues from most to least sensitive to radiation
embryonic tissues
haematopoietic organs (spleen, bone marrow)
gonads
epidermis
intestinal mucous membranes (variable)
connective tissue
muscle tissue and nerve tissue
What are the classifications of viruses
DNA viruses
-more common
-viral DNA inserted into host DNA
RNA viruses
-reverse transcribed and then inserted
What viruses causes tumours
Epstein-Barr virus - Burkitt’s lymphoma
nasopharyngeal carcinoma
Hepatitis B/C - hepatocellular carcinoma
Human papillomavirus - cervical and oropharyngeal carcinoma
What is the epidemiology of cancer
20% of deaths
2nd most frequent cause of death
30% of population will develop cancer
highest in elderly
type
90% carcinoma
10% lymphoma or sarcoma (more in young)
What is the most common form of cancer
Carcinoma
What is the aetiology of oral cancer
multifactorial
tobacco - smoking or smokeless tobacco
betel quid (chewing habits)
alcohol
diet and nutrition
oral hygiene
viruses HPV EBV HHV-8
Immunodeficiency
Socioeconomic factors
GORD
What is leukoplakia
White patch that cannot be rubbed off or attributed to any other cause (oral cancer)
Why is it important to identify dysplasia and get it checked
Tissue that shows dysplasia:
HAS THE POTENTIAL TO BECOME MALIGNANT
Abnormality confined to epithelium; underlying tissue not affected.
Not all become malignant-may regress.
Dysplasia (histopathology) is the gold standard for assessing this (at present)
What epithelial tissues does dysplasia affect
Squamous eg. oral, cervix - the basis of cervical screening
Glandular eg Barrett’s oesophagus, colonic polyps
Transitional eg bladder
What are the accelerator genes in carcinogenesis
Oncogenes
Which genes act as the brakes
Tumour suppressor genes
What is an epigenetic mutation
No change to the DNA itself
Groups attach to the DNA and influence expression of the genes ex silence or increase activity
What do oncogenes do
Regulate cell division
What are the proteins that oncogenes code for called
Oncoproteins
What do oncogenes do to accelarate uncontrolled division
tight regulation may be lost 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
How does TP53 act in response to damages DNA
stops the cell cycle to allow DNA repair
apoptosis (if repair not possible)
What gene is often inactivated in cancer
TP53 - mutation/deletion
What is the two hit hypothesis
Oncogene - 1 cell deleted
Tumour suppressor - both must be deleted
Before the cell begins to become malignant
At what point does cell division stop and DNA checked
Restriction points
How many cases of head and neck cancer show deletion or mutation of the TP53 gene
50%
What are some inherited cancer syndromes
Retinoblastoma
Some colon cancers
What causes familial cancer
family clusters
gene(s) and pattern of inheritance not clear
-Breast, ovary, colon
What are the modes of spread of cancer
local spread
lymphatic spread
blood spread (haematogenous)
transcoelomic spread
Intraepithelial spread ( Paget’s disease of the breast)
What is metastasis
spread of the malignant cells to distant organs forming secondary tumours
What are the patterns of spread of sarcomas and carcinomas
carcinomas
-lymphatic
-blood (often later)
sarcomas
-blood (lymphatic spread rare)
predictable patterns of spread
-lung to local nodes, liver, bone and brain
-tongue to neck nodes, later lung and spine
What are the 6 hallmarks of cancer
Evading apoptosis
Insensitivity to anti-growth signals
Self-sufficiency in growth signals
Sustained angiogenesis
Tissue invasion & metastasis
Limitless replicative potential
What does the grading of a tumour mean
Biological nature of the tumour
(hitsopathology)
What is the stage of a tumour
Extent of spread
How can we determine the grade of a tumour
Histological assessment of :
Invasion into underlying tissue
Cellular atypia : abnormal mitotic activity, nuclear pleomorphism, differentiation, necrosis
Various methods
-numerical grades (1,2,3 etc)
-low, intermediate, high
-degree of differentiation (squamous cell carcinoma
What is staging
The extent or severity of a person’s cancer
How can staging be determined
Physical exams, imaging procedures, laboratory tests, pathology and surgical reports - determine staging
What staging system is used for oral cancer
TNM
Tumour size
Lymph node involvement
Presence of metastases
What is the immune response to tumours
Immune surveillance.
Can suppress or enhance carcinogenesis
Elimination - equilibrium - escape
How can the immune system recognise tumour cells
Products of mutated genes
Overexpressed proteins (tyrosinase)
Viral proteins (HPV,EBV)
Oncofetal antigens (carcinoembryonic antigen)
What is the elimination response
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.
How can tumour cells evade the immune response
Cells may acquire molecular changes such as:
-Alter tumour antigen expression regularly, 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 immunotherapy
Use the patient’s own immune response to control and destroy malignant cells
What are the methods 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.
What is the equilibrium stage
Cancer cells evade detection and lie dormount in the body for a period of time until escape of the immune system due to activation
What are the 3 Es
Elimination
Equilibrium
Escape
