Neoplasia including classification of tumours Flashcards
What is a neoplasm?
An abnormal mass of tissue, growth of which is excessive and is unco-ordinated with that of normal tissues. It persists after the provoking stimulus is removed
Define invasion
Uncontrolled growth into CT - defining feature of malignant tumours
Define metastasis
Spread distant from primary tumour
Define differentiation
The extent of resemblance of normal cells/ tissue is very variable
Define cytology
Features of individual cells - often very abnormal
Classification of neoplasms
By clinical behaviour -benign -malignant By histogenesis (tissue of origin) -epithelial - lining or glandular -mesenchymal - various types
Growth pattern of benign or malignant tumours
Benign: expansion, encapsulated, localised
Malignant: invasion, no capsule, metastasis
Growth rate of benign and malignant tumours
Benign: slow
Malignant: more rapid, but variable
Histology of benign and malignant tumours
Benign: resembles tissue of origin, uniform cell/ nuclear shape and size, few mitoses
Malignant: variable resemblance to tissue of origin, cellular and nuclear polymorphism, many mitoses, abnormal
Clinical effects of benign and malignant tumours
Benign: localised, local pressure, excision cures
Malignant: infiltration and spread, local pressure, excision may not cure
Components of benign tumour
Tumour cells Stroma (supporting CT) including fibroblasts and BVs Capsule -most, but not all tumours -may be incomplete
Effects of benign tumours
Pressure Obstruction Function - especially hormone secretion -these vary by site and tumour -effect is not always 'benign'
Pathology of malignant tumours
Tumour cells -invade, underlying tissues -cytologically abnormal -differentiation varies (well, moderate, poor; anaplasia) Stroma -angiogenesis -immune response
Cytology of malignant cells
> no. of irregularly shaped dividing cells > variable shaped nuclei < cytoplasmic vol. relative to nuclei Variation in cell size and shape Loss of normal specialised cell features Disorganised arrangement of cells Poorly defined tumour boundary
Classification of epithelial neoplasms
90% of neoplasms BENIGN Lining: papilloma Glandular: adenoma MALIGNANT Lining: Carcinoma Glandular: Adenocarcinoma
Classification of mesenchymal neoplasms
BENIGN Depends on tissue -e.g. fibroma, osteoma, lipoma, myoma, chondroma -skeletal muscle: rabdomyoma MALIGNANT Sarcoma, depends on tissue -osteo, -leiyomyo
Classification of neoplasms: oddities
Melanoma (melanocytes - malignant)
Lymphoma (arise from WBC)
Leukaemia (arise from bone marrow precursor cells)
Terratoma (germ cell tumours)
-most in testes, most malignant (ovarian tend to be benign)
-can mimic any tissue incl. teeth!
Why do benign tumours arise?
Little known, may be due to inherited factors
Carcinogenesis is multi-step process
Inherited factors: genetic susceptibility to cancer
Inherited cancer syndromes -single mutant genes, often tumour suppressor genes -retinoblastoma, some colon cancers -likelihood of developing cancer extremely high Familial -family clusters of cancers (e.g. BRCA1) -e.g. breast and ovarian cancer -pattern of inheritance unclear -lots of other contributing factors -not only one single gene gives risk Defective DNA repair -> sensitivity to carcinogens -DNA damage isn't repaired -e.g. skin cancer at very young age
Why do malignant tumours arise?
Inherited factors Environmental factors -chemical agents -physical agents -viruses
Two stages of chemical carcinogenesis
- initaition: permanent DNA damage
- promotion: may be reversible, promotes proliferation
Important concepts of chemical carcinogenesis
Pro-carcinogen often metabolised to ultimate carcinogen
Co-carcinogens
Latent period of chemical carcinogenesis
Time from promotion to clinical tumour
Direct chemical carcignogens
Tumour arises at site of carcinogen application
-e.g. smoking and lung cancer
Indirect chemical carcinogens
Tumour arises at different site from carcinogen application
E.g. aromatic amines - industrial exposure
-inhaled - lungs
-metabolised in liver, excreted by kidney
-bladder enzymes release aminophenol
result is bladder carcinoma
Examples of chemical carcinogens
Smoking -polycylic -hydrocarbons -including tars Diet -burnt hydrocarbons Asbestos -fibrous silicates -inhaled (fibrosis, mesothelioma) -synergy in smokers
Physical carcinogenesis
Ionising radiation -damages DNA, causing mutations -X-rays -radioactive metals and gases (radium: bone and bone marrow tumours, radon: lung cancer) -atomic bomb UV light -damages DNA -skin (squamous cell & basal cell carcinoma, malignant melanoma) -xeroderma pigmentosum
Radiation sensitivity
Most sensitive tissues are where cells rapidly renewed. Most to least sensitive:
- embryonic tissues
- haematopoietic organs (spleen, bone marrow)
- gonads
- epidermis
- intestinal mucous membranes (variable)
- CT
- muscle tissue and nerve tissue
Viral carcinogenesis
DNA viruses -> common -viral DNA inserted into host DNA RNA viruses -reverse transcribed and then inserted -may contain 'oncogenes' -importance in many tumours not certain -act with other factors
Virus –> tumour (act with other factors)
Epstein-Barr virus –> Burkitt’s lymphoma, nasopharyngeal carcinoma
Hep B/ C –> hepatocellular carcinoma
HPV –> cervical carcinoma
HPV and cancer
HPV sexually transmitted Some genotypes cause -cervical cancer -oro-pharyngeal cancer Viral protein binds to and inactivates tumour-suppressor, p53
Other influences on cancer
Often act as 'promoters' Hormones -breast cancer: hormonal dependence, ovary and adrenal -prostate cancer: testosterone Drugs, including alcohol Inflammation
Epidemiology of cancer
20% of deaths 2nd most frequent cause of death 30% of pop. will develop cancer Highest in elderly Type -90% carcinoma -10% lymphoma or sarcoma (more in young)
How does cancer develop?
De novo - salivary gland tumours
Via benign tumour - adenocarcinoma of colon
Via premalignant lesion - HNSCC (in some cases)
Premalignancy
Some of changes in cells & tissue architecture are seen before invasion occurs
This disorganisation of tissue is called dysplasia
Basis of cancer screening
Cancer screening
Detection of ‘premaligcancy’
- identification of changes in cells before invasion occurs
- cervical smears
- oral cancer?
