neoplasia Flashcards
What is a neoplasm?
Abnormal mass of tissue
Growth is excessive, uncoordinated w normal tissue, persists after stimulus is removed and is clonal
What does clonal mean?
Originates from a single cell
What does cytology mean?
Features of individual cells
What does differentiation and anaplasia mean?
How much do neoplasms resemble normal cells/tissue
Anaplastic (looks nothing like it)
What does invasion mean?
Unconfined growth into underlying tissues
What does metastasis mean?
Spread distant from primary lesion
How are neoplasms classified?
Clinical behaviour- benign/malignant
By histogenesis- tissue of origin
~epithelial- lining/glandular
~mesenchymal- various types
What is the difference between benign and malignant?
BENIGN ~expansion, encapsulated, localised ~slow ~resembles histogenesis ~uniform cell/nuclear shape and size ~few mitoses ~local pressure ~excision cures
MALIGNANT ~invasion, no capsule, metastasis ~more rapid but variable ~variable resemblance to histogenesis ~cellular/nuclear pleomorphism ~many mitoses ~infiltration and spread ~local pressure ~excision may not cure
What is the pathology of benign neoplasms?
Expansile growth pattern of neoplastic cells, supporting c. tissue (stroma) and usually encapsulated
What is neurofibromatosis?
Genetic
Massive no of small benign tumours
All over skin
Internally also
What are the problems w benign neoplasms?
Pressure on structures
Lumen may become obstructed
May have a function- excessive hormone secretion
What is the pathology of malignant neoplasms?
Irregular growth pattern of cytologically abnormal neoplastic cells of varying differentiation that invade underlying tissues
Have c. tissue (stroma) and immune response
What is the cytology of malignant neoplasms?
- Large no of irregularly shaped dividing cells
- Large variably shaped nucleus
- Small cytoplasmic vol compared to nuclei
- Variation in cell size/shape
- Loss of normal specialised features
- Disorganised arrangement
- Poor defined tumour boundary
How do you name neoplasms?
90% EPITHELIAL Benign ~lining=papilloma ~glandular=adenoma Malignant ~lining=carcinoma ~glandular=(adeno)carcinoma
MESENCHYMAL
Benign
~eg. Fibroma, osteoma, lipoma, myoma, chondroma
Malignant
~sarcoma eg. Osteosarcoma, leio/rhabdomyosarcoma (smooth/skeletal muscle)
ODDITIES
Melanoma- malignant melonocytes
Lymphoma- many ranging from benign—>malignant
Leukaemia- malignant bone marrow
Teratoma- germ cell tumours, most in testes, most malignant (ovaries tend to be benign)- can mimic ANY tissue
What is a polyp?
Colonic adenoma
Why do neoplasms arise?
Benign- little known, many inherited factors
Malignant- inherited/environmental factors
What is carcinogenesis?
Multi step process from a normal cell to a cancerous cell
Initiation- carcinogen causes genetic change
Promotion- cell is primed to multiply
Transformation- genetic change into malignant cell
Progression- genetic change into malignant tumour
What are inherited factors of cancer?
Genetic susceptibility
- inherited cancer syndromes- single mutant genes, often TSGs (eg retinoblastoma, some colon cancers)
- familial cancer- family clusters, genes and pattern of inheritance not clear (eg breast, ovary, colon)
- defective DNA repair- increased sensitivity to carcinogens/general risk
Up to 10% breast/ovarian cancer is hereditary (mutations BRCA1 and BRCA2)
What are environmental factors of cancer?
Chemical agents
Physical agents
Viruses
Why are chemical carcinogens?
Two stage process
-intitiation- permanent DNA damage
-promotion- may be reversible (promotes proliferation)
~latent period- time from initiation to clinical lesion
Important concepts
- pro-carcinogen- often metabolised to ultimate carcinogen
- co-carcinogen
What is a direct chemical carcinogen?
Neoplasm arises at site of carcinogen application
Eg. Smoking and lung cancer
What is an indirect chemical carcinogen?
Neoplasm arises at different site form carcinogen application
Eg. Aromatic amines from industrial exposure
~inhaled in lungs
~bladder carcinoma (bladder enzymes release aminophenol)
What are some chemic carcinogens?
Smoking- polycyclic, hydrocarbons
Diet- burnt hydrocarbons
Asbestos- fibrous silicates- inhaled (fibrosis, mesothelioma)
Synergy in smokers w asbestos
What are physical carcinogens?
Ionising radiation- damages DNA causing mutations (X-rays, radioactive metals and gases*, atomic bombs)
Radium- bone/marrow tumours
Radon- lung cancer
UV light- damages DNA (squamous cell carcinoma, nasal cell carcinoma and melanoma)
xeroderma pigmentosum
What is radiation sensitivity?
Most sensitive- labile (rapidly renewed)
Most to least- ~embryonic tissue ~haematopoietic organs (spleen, bone marrow) ~gonads ~epidermis ~intestinal mucous membranes ~c. tissue ~muscle/nerve tissue
What are viral carcinogens?
DNA viruses-
~more common
~viral DNA inserted into host DNA
RNA viruses ~reverse transcribed then inserted into host ~may contain oncogenes ~importance not certain ~act w other factors
Epstein-Barr virus- Burkitts lymphoma (change in c-myc protein)
Human papilloma virus- cervical/oropharyngeal carcinoma (sexually transmitted, viral protein binds to and inactivates tumour suppressors p53 and pRb)
Hep B/C- hepatocellular carcinoma
What are other influences?
Often act as promoters
Hormones (breast cancer, prostate cancer)
Drugs, inc alcohol
Inflammation (long term, chronic- increased risk, esp. stomach [chronic gastritis], in oral cavity oral lichenplanus- higher risk)
Why is the combination of alcohol and smoking more carcinogenic?
Alcohol itself- not carcinogenic, when ethanol is metabolised can grt some metabolites (acetaldehyde) which causes DNA damage
Together-
- Ethanol acts as solvent
- Increases permeability of oral mucosa to larger numbers of carcinogens in smoke
What are some neoplasm names?
Glandular epithelium-
Adenoma, adenocarcinoma
Cartilage-
Chondroma, chrondrosarcoma
Smooth muscle
Leiomyoma, leiomyosarcoma
Surface epithelium
Papilloma, carcinoma
What is the epidemiology of cancer?
9.5M deaths (1 in 6) 2nd most common cause of death 30% population will have cancer Caries by geography, age, race etc 90% carcinoma, 10% lymphoma/sarcoma
How do cancers develop?
de novo-
salivary gland neoplasm
Benign neoplasm- adenocarcinoma of colon
Premalignant lesion- HNSCC
What is premalignancy?
Changes in cells and tissue architecture before invasion
Disorganisation of tissue- dysplasia
Abnormalities- increased risk of cancer
Basis of cancer screening (cervical smears, oral cancer)
What is oral leukoplakia?
White patch in mouth- increased risk of developing cancer
How does cancer affect patients?
Invasion (local spread) ~pressure/obstruction ~destruction and loss of function Metastasis Non-metastatic effects- ~25% will die from cancer related cachexia
What are the modes of spread?
Invasion- path of least resistance, tissue destruction, perineural spread
Metastasis-
~lymphatic spread- invasion of vessels (embolism/permeation) and spread to draining lymph nodes
~haematogenous spread- invasion of veins spreading to organs (liver, lung, bone, brain)
~seeding in body cavities- spread across serous cavities eg. Abdominal cavities
What are the mechanisms of spread?
Neoplastic cells interact w cells and molecules in the local environment New abilities- ~motility enhanced ~alter adhesion molecules ~make poor basement membrane ~increase protease production/reduce inhibitors ~alter ECM Happens throughout ‘metastatic cascade’
What are the patterns of spread?
Carcinomas- lymphatic then blood later
Sarcomas- blood (rarely lymphatic)
Lung cancer to local nodes in hilum, to liver, bone, brain
Tongue cancer to neck nodes then lungs and spine
Prostate cancer to bones
Melanoma to lungs
Colorectal cancer to liver
What are the effects of neoplastic spread?
Pressure and obstruction Destruction Haemorrhage Infection Pain (esp bone) Anaemia (colonisation of marrow)
What are non-metastatic effects?
Paraneoplastic syndrome
~often caused by biochem substances released by tumour cells eg. TNF-alpha
Fever, anorexia, weight loss/cachexia
Endocrine syndromes (Cushings, metabolic effects eg. Hypocalcaemia)
Neuro problems eg. Neuropathy
Haematological syndrome eg. Erythrocytosis
How do you grade a cancer?
Histological assessment
~Well differentiated- looks like tissue it arose from- not as bad
~Poorly differentiated- looks nothing like tissue it arose from- much more aggressive
Linked to prognosis
Various methods-
~numerical grades 1,2,3
~low, intermediate, high
~well, moderate, poor
How is cancer staged?
Defines clinical extent of tumour
Done by radiologist first
Then done by pathologist after surgery
TNM system (WHO) Tumour (size), nodes (regional), metastasis (distant)
T 1-4
N 0-3
M 0 or 1 (present/absent)
COLORECTAL CARCINOMA Early stage cancer Stage 1- small tumour w/o metastasis Stage 2- larger tumour w/o metastasis Later stage cancer Stage 3- tumour w regional metastasis Stage 4- tumour w distant metastasis
What are the rough 5 year survival rates for patients w melanoma?
Stage 1- 90%
Stage 2- 65%
Stage 3- 15%
What do cancer bio markers show?
Prognostic- likely? Diagnostic- type? Predictive- optimal drug? Pharmacodynamics- optimal dose? Recurrence- return?
How is cancer diagnosed?
Biopsy
Cytology (Fine Needle Aspirates)
Imaging- CT/MR/PET scanning
Molecular analysis (assess genetic changes)
How is cancer treated?
Surgery Radiotherapy Chemotherapy Biological (immune) therapy Supportive care
What are side effects of radiotherapy?
Tiredness Feeling sick Difficult eating/drinking Skin reaction Hair loss Haematological changes Possible long term side effects
Affecting rapidly dividing cells?
What is IMRT?
Intensity modulated radiotherapy allows you to reduce area of dose to make sure it directly targets tumour
What are the types of drugs used in chemo therapy?
Conventional agents (cytotoxic) ~targets DNA structure or segregation of DNA as chromosomes in mitosis (targets every cell undergoing cell division)
Targeted agents
~small molecules interact w molecular target maintaining malignancy/selectively expressed by tumour
Hormonal therapies
~target biochem pathways of oestrogen and androgen function
Biological therapies
~macromolecules w particular target/ability to regulate immune response to kill
What are side effects of chemotherapy?
Generally cytotoxic
Mucositis Nausea/vomiting Diarrhoea Cystisis Sterility Myalgia Neuropathy Alopecia Pulmonary fibrosis Cardio toxicity Local reaction Renal failure Myelosuppression Phlebitis
What are oral problems in cancer management?
Dry mouth
Immunocompromised
Difficulty in maintaining oral hygiene
Therefore- ~oral mucosal disease ~dental disease ~discomfort ~social embarrassment
