Neoplasia Flashcards
What is a neoplasm? What are the different classifications?
Abnormal tissue mass who’s growth exceeds and is uncoordinated from normal tissue and persist after the healing and repair process (i.e. after damaging stimulus is removed)
Benign
Malignant= cancer
What is the difference between a driver mutation and a passenger mutation? How are these mutations involved in cancer development?
Driver= mutation with survival benefit for cell which promotes cancerous change
Passenger= biological inconsequential mutation
Driver and passenger mutations accumulation to produce a genetically heterogenous cancers with different subclones
What are the cytological features of cancer and why do they occur?
Increased nuclear cytoplasmic ratio i.e. large nuclei with little cytoplasm
Nuclear pleomorphism i.e. variation in nuclear size and shape
Nuclear hyperchromasia i.e. dark staining nuclei due to increase density of chromatin
Prominent nucleoli i.e. due to clusters of chromatin
Increased mitotic activity
How would you differentiate microscopically between benign and malignant neoplasms?
Benign: Normal nuclear size Small nucleoli Absent pleomorphism Infrequent mitosis Good differentiation
Malignant: Enlarged nuclear size Prominent nucleo Marked pleomorphism Frequent mitosis Variable differentiation
How would you differentiate between benign and malignant tumours macroscopically?
Benign; Well circumscribed Generally small Haemorrhage usual Ulceration unusual Necrosis unusual Lack of invasion into surround tissue No metastasis
Malignant: Irregular Generally larger Haemorrhage Ulceration Necrosis Invasion to local tissues Metastasis
Which cancer is commonly associated with seeding to the peritoneum?
Ovarian cancer
What processes are required for tumour cells to undergo invasion and metastasis? What enzymes are involved?
Loosening of cell junctions
- E-cadherin mutation
- epithelial-mesenchymal transition (EMT)
Degradation of ECM
- MMP (matrix metalloproteinases) to enable migration through stroma
- Cathepsin D
- Urokinase plasminogen activator
Migration of tumour cells
-actin cytoskeleton contracts to enable movement through stroma
What is involved in epithelial-mesenchymal transition?
Expression of cytoproteins lost= loss of epithelial architecture
Actin expressed= enables increased cell motility i.e. mesenchymal characteristic
What are the 3 types of cancer invasion? What are the implications of these types of invasion?
Stromal
-degradation of tissue
Perineural
- cancer-associated pain due to nerve irritation
- can cause problems with surgical resection due to neoplasm associated with the nerve not being able to be removed
Venous
-dissemination + spread to distant sites
What organs to cancers commonly metastasis to?
Liver
Lungs
Bones
Brain
What are the 3 main routes of metastatic spread? What are the consequences of cancer spreading via these routes?
Lymphatic spread (tumour spread to LN ) -LN invasion
Haematogenous (occurs later)
-widespread dissemination
Seeding in body cavities (local) i.e. peritoneum
-tumour cells break from mass and implant onto surface
I.e. omental cake
lymphatic spread is earliest pathway before haematogenous spread
Why does cancer spread to veins preferentially to arteries?
Veins have thinner walls
What is the difference in growth characteristics between benign and malignant?
Benign:
Slow growing
Spontaneous arrest common
Malignancy
Rapid growth
Spontaneous arrest rare
How would you differentiate between a malignant melanoma and a benign naevus (mole)?
Malignant melanoma: Large (20mm) Variable pigmentation Irregular border Partly flat and partly raised Asymmetrical
Benign naevus: Small (3mm) Uniform Well-defined border Polypoid Symmetrical
Which cancers are associated with bone mets? What are the different types of bone lesions and their implications?
Lung Breast Thyroid (follicular carcinoma) Prostate Kidney I.e. organs which are bi-lobular or have 2 components
Lytic lesions= destruction
Sclerotic= bone formation
Pain + fractures (can present before primary tumour site identified)
Where do the following cancers metastasis to? GIT cancer Lung Gall bladder/bile duct/salivary gland Renal cell carcinoma (RCC) Malignant melanoma
GIT cancer= liver via portal vein
Lung= adrenal gland and brain
Gall bladder/bile duct/salivary gland = perineural invasion
Renal cell carcinoma (RCC)= renal vein + lung
Malignant melanoma= satellite deposits on skin
What is the different staging system used for colorectal cancer? How is it used?
Duke’s
T1= submucosa T2= muscularis propria T3= subserosa T4= through peritoneal surface
N0= none N1= 2+ N2= 5+
M0= none M1= present
Which cancers are associated with inherited cancer syndromes?
Retinoblastoma + osteosarcoma = RB
Epithelial tumours= Cowden syndrome (PTEN defect)
Colon cancer= FAP (APC defect) or HNCC (MMR defect)
Multiple sites= Li-Fraumeni syndrome (p53)
Which environmental factors increase the risk of neoplasia? Which cancers are they associated with?
Smoking- lung Alcohol- UGI + liver Diet/obesity= CR Infection= hepatitis B + C i.e. risk factors for liver cancer Reproduction= breast Asbestos= mesothelioma
How is chronic inflammation linked to metaplasia?
Can cause epithelia metaplasia which is a risk factor for neoplastic transformation
What types of chronic inflammation are associated with neoplasia development?
H pylori gastritis
IBD
Viral hepatitis
What is the immune response to cancer? How can this be utilised in treatment?
Dendritic cells phagocytose tumour antigens and present to TC in lymph nodes
T-cells migrate to cancer site to attack tumour cell
PDL1 and CTLA4 inhibitors used in immunotherapies
What is dysplasia? What is the other term used?
Disordered cell growth due to accumulation of non-lethal mutations
Intraepithelial neoplasia
What differentiates malignant cells from cells undergoing dysplasia?
Dysplasia cells not yet invasive despite resembling malignant cells microscopically
