Neoplasia Flashcards
Neoplasm definition and distinguishing features:
Abnormal growth of cells which persists after initialising stimulus removed
Distinguishing features:
- Differentiation
- Rate of growth (malignant fast growing, benign slow growing)
- Local invasion
- Metastasis
Benign vs malignant
Malignant: A neoplasm with potentially lethal, abnormal characteristics which has the ability to invade metastasise
Benign: A neoplasm which does not have the above ability
What is differentiation, and what is meant by well/poor/undifferentiated differentiation?
The extent to which neoplastic tissues resemble their normal tissue of origin
Well differentiated:
- Closley resembles tissue of origin
- E.g Benign tumours
Poorly differentiated:
- Little resemblance of tissue of origin
- Variation in nuclear shape/size
- E.g Malignant tumours
Undifferentiated: Cannot be identified without molecular techniques
Benign and malignant suffixes for epithelial tumours:
Benign - OMA:
- Adenoma (glandular tissue)
- Papilloma (cell type)
- Identified by cell type and glandular tissue (e.g. squamous cell papilloma / colonic adenoma)
Malignant - Carcinomas:
- Adenocarcinoma (glandular tissue/degree of differentiation)
- Carcinoma (cell type)
Benign and malignant suffixes for mesenchymal tumours:
Benign - OMA (examples):
- Bones - osteoma
- Fat tissue - lipoma
Malignant - Sarcoma:
- All types have this suffix
- E.g fat tissue = liposarcoma
Hamartomas and choristomas
Hamartoma: Non-neoplastic disordered overgrowth of normal tissue, NORMAL to the site of occurrence
Choristoma: Benign normal tissue seen in ABNORMAL location
Teratomas
Originate in germ cells
Teratoma cells contain all three germ cell layers:
- Endoderm
- Mesoderm
- Ectoderm
Melanoma vs melanocytic naevus:
Melanoma: Malignancy of melanocytes
Melanocytic naevus: Benign proliferation of melanocytes
Haematological malignancies based on cell of origin
Lymphoma:
- Malignancy of B or T cells, usually in lymph nodes
Myeloma:
- Malignancy of plasma cells
Leukaemia:
- Malignancy of WBC beginning in bone marrow
Metastasis definition:
The spread of tumour to a site discontinuous from the source organ / tissue
Dysplasia and carncinoma in-situ
Dysplasia:
- Neoplastic change confined within basement membrane
- Cytomorphological features of malignancy
Carcinoma in-situ:
- Severe dysplasia
- Cytomorphological features of malignancy but without invasion (basement membrane not penetrated)
- NOT malignant
Hallmarks of cancer
- Avoids immune destruction
- Evades growth suppressors
- Enabling replicative immortality
- Resisting cell death
What is clonality?
Proliferation of genetically unstable cells producing tumour cell variants
How do cells become immortal?
Autocrine growth stimulation:
- Abnormal expression of oncogenes
- Inactivation do tumour suppressor genes
Reduced apoptosis:
- Abnormal expression of gene that inhibits apoptosis
Telomerase:
- Prevents shortening of telomeres
What are tumour suppressor genes and their role?
Genes that inhibit neoplasticism growth:
- E.g TP53 (encodes for p53)
p53:
- Both caretaker (DNA repair) and gatekeeper (stops damaged cells dividing) function
- Missense and nonsense mutations can cause it to lose function
Oncogenes
Genes which drive the neoplastic behaviour of cells
Can be viral or can be genes that exist in normal cells
Five groups of oncogene / oncoprotein
•Growth factors
•Receptors for growth factors
•DNA binding transcription factors
•Signalling mediator with tyrosine kinase activity
•Signalling mediator with nucleotide binding activity
Different types of carcinogens:
Chemical:
- Smoking
- Rubber/dye industry
- Cured meats
- PVC manufacture
Oncogenes virus:
- Human papilloma virus
- Epstein-Barr virus
How do carcinogens (HPV and EBV) act on cells?
HPV:
- E6 acts on TP53
- E7 viral oncoprotein acts on RB (tumour suppressor)
- Neoplasticism cells with integrated viral gene keeps replicating
EBV:
- Drives B cells to proliferate
- Inactivates p16/CDKN2A and TGFBR2 leading to malignant transformation
Predisposing factors:
Radiation:
- UV causes skin cancer, melanoma
- Ionising radiation (x-ray, gamma)
Bacteria (release toxins that activate oncoproteins) /Fungi
Hormones (excess oestrogen/growth hormones)
Lifestyle:
- Age
- Diet (obesity/processed meats)
- Alcohol
Inherited:
- BRCA1/2 genes (breast, ovarian)
- MEN gene (endocrine)
What makes tumours behave badly (become invasive)?
Decreased cellular adhesion
Secretion of proteolytic enzymes:
- Damages surrounding tissue
Abnormal/increased cellular mobility
How do tumours metastasise and what routes can they takes?
Steps:
1. Detachment
2. Invasion of surrounding tissue
3. Intravasation into vessels
4. Evasion of defences
5. Adherence to endothelium elsewhere
6. Extravasation of cells from vessel into surrounding tissue
Routes:
- Haematogenous (blood)
- Lymphatic
- Transcoelomic (across body cavity)
