L61, L62: Neoplasia Flashcards
Definition of neoplasia
Abnormal mass of tissue, growth EXCEEDS and UNCOORDINATED compared with normal tissues and PERSISTS in the same excessive manner after cessation of the stimuli which evoked the change
Neoplasia vs hyperplasia
Hyperplasia:
- Occurs under influence of physiological factor e.g. growth factors and ceases after removal of such factors
- Similar to normal tissue but occasionally occur alongside hypertrophy
Neoplasia:
- Uncoordinated proliferation of cells despite the absence/removal of stimuli
- Characterised by dysplasia (abnormality of development of cells) or anaplasia (loss of cellular differentiation)
What is malignant neoplasm
Neoplasm that shows
- Invasion into surround tissues
- Metastasise to distant sites
Benign vs malignant neoplasms In terms of 1. Mode of growth 2. Rate of growth 3. Gross appearance 4. Microscopic appearance 5. Metastasis 6. Clinical effects 7. Outcome
Benign vs Malignant:
1. Mode of growth:
Expansive, limited by BM
Infiltrative, Invasion beyond BM
- Rate of growth
Slow and may cease
Rapid and outgrow blood supply —> necrosis - Gross appearance:
Circumscribed/encapsulated
Poorly defined margins - Microscopic appearance
Well-differentiated, resemblance of tissue of origin (morphologically and functionally)
Low NC ratio
Normochromatic nuclei
Absent or scanty mitotic figures
Maintained polarity (apical-basal polarity)
VS
Pleomorphism (variation in size and shape)
High NC ratio / prominent nucleoli
Hyperchromatic nuclei
Abnormal and increased mitosis (tripolar/multipolar spindles)
Loss of polarity
- Metastasis:
Absent vs present - Clinical effects:
Mechanical/hormonal
Mechanical/hormonal & destructive and systemic effects caused by cytokines - Outcome:
Rarely fatal vs usually fatal
Name for benign and malignant tumours of epithelium
Benign: Papilloma
Malignant: Carcinoma
Name for benign and malignant tumours of glandular epithelium
Benign: Adenoma
Malignant: Adenocarcinoma
Definition of dysplasia
- Disorderly proliferation of cells
- Loss in uniformity and polarity
- Mild, moderate and severe
- A process which can ultimately lead to pre-invasive neoplasm (carcinoma-in-situ).
- Mild to moderate dysplasia may be reversible
Intrinsic control mechanisms of tumour growth
- Proliferation rate
- Death rate (apoptosis)
- Differentiation rate (become mature, non-dividing cells)
Extrinsic control mechanisms of tumour growth
- Immune response
- Blood and nutrient supply
- Hormonal and growth factors
10 common biological properties of cancer
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Evading immune destruction
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Genome instability and mutation
- Deregulating cellular metabolism
- Tumour-promoting inflammation
5 types of spread of a tumour
- Local invasion (type 4 collagenase cleaves the collagen)
- Metastasis (via lymphatics and blood)
- Transcoelomic spread (penetrating surfaces such as peritoneal, pleural, pericardial/subarachnoid space)
- Perineural spread
- Implantation (by surgical instruments)
Definition of metastasis
Discontinuous spread of a tumour / formation of new sites of growth at non-contiguous site
Some cancer cells have organ trophism
Common sites of metastasis (記 LLLBB):
- LN
- Lungs (Breast, Colon)
- Liver (Esophageal, Stomach, Pancreatic, Lung, Breast, Kidney, Skin)
- Bone (TBLPK: Thyroid, Breast, Lung, Prostate, Kidney)
- Brain
4 effects of tumour
- Local effects
- Non-specific systemic effects
- Hormonal effects
- Paraneoplastic syndrome
Definition of clonality of tumours
Tumours cells arising from mitotic division of the same single somatic cell
Definition of heterogeneity of tumours
Tumour cells which have distinct morphological and phenotypic profiles with different characteristics such as ability to invade, metastasise etc.
Describe the process of carcinogenesis
- Mutations within the DNA of a cell
- Clonal expansion of cell
- Cells able to develop heterogeneity
- Overcome selection pressure
- Accumulation of different mutations/heterogeneity
- No longer responds to regulatory signals
- Better adapt at survival, growth, invasion, metastasis
- Tumour become more aggressive and less responsive to treatment
Cause of growth autonomy
- Activation of proto-oncogene —> oncogene (Dominant gene)
- Code for growth factors etc.
- Promoter insertion
- Adjacent enhancer insertion
- Chromosomal rearrangement
- Point mutation - Inhibition of tumour suppressor gene —> anti-oncogene (Recessive gene)
- Inheritable, e.g. loss of 1 Rb allele in familial retinoblastoma
- Deletion
- Point mutation
- Promoter methylation - Alteration of genes regulating apoptosis
Cause of Carcinogenesis
- Hereditary factors
- Autosomal dominant cancer
- Autosomal recessive cancer - Ethnical
- Chemical
- long latent period
- great individual variation due to SNPs which gives varying degree of susceptibility
- Initiator (electrophilic and mutagenic, causing rapid irreversible DNA changes e.g. alkylation agents, aromatic hydrocarbons)
- Promoter (stimulate proliferation of cell without altering DNA e.g. estrogen hormone) - Radiation (Initiator)
- Viruses (viral DNA integration —> viral oncoprotein which modify function of cellular proteins)
- Epstein-barr virus: Nasopharyngeal carcinoma, Burkitt lymphoma
- Human papilloma virus: Cervical cancer
- Hepatitis B virus: Hepatocellular carcinoma - Hormonal and drugs
- Chronic irritation
- Immunodeficiency
Examples of autosomal dominant cancer
- Familial adenomatous polyposis (FAP)
- germline mutation in adenomatous polyposis coli (APC) gene in chromosome 5
- APC gene: tumour suppressor gene
- 2nd copy of APC gene if inactivated will lead to excessive cell proliferation - Hereditary non-polyposis colon cancer syndrome (HNPCC)
- DNA mismatch repair gene mutation
- failure to repair replication errors in microsatellites
- somatic mutation inactivate the remaining copy of MMR gene —> inability to repair
Example of autosomal recessive cancer
Xeroderma pigmentosa
Most common tumours in adult and children
Adult: carcinoma (84%)
Children: leukaemia/ lymphoma (46%), CNS malignancy
Most common cancer in Hong Kong (male and female)
Male:
Lung, colorectal, liver, stomach, prostate
Female:
Lung, colorectal, breast, liver, pancreatic
