Anatomy - Lung cancer Flashcards
What does neoplasia mean?
What is a neoplasm?
Tumours
Abnormal tissue mass with exceeded and uncoordinated growth than normal and persist after cessation of stimulus
What is differentiation?
Describes how close in appearance cells of a tumour are to cell type they were derived from, predicting tumour behaviour
What is a well-differentiated tumour?
Composed of cells which closely resemble cell of origin
What is a poorly differentiated tumour?
Composed of cells which bear little resemblance to cells of origin, but enough to identify original cell
What is an undifferentiated tumour?
Composed of cells which are so undifferentiated that cell of origin is unknown
What are the two ways to classify a tumour?
Via histogenesis
Furthee classified into benign or malignant
What are the properties of benign tumours?
- Grow by expansion
- Compress adjacent tissue
- Do not infiltrate
- Stay at site of origin and don’t spread
What are the properties of malignant tumours?
- Grow by expansion and infiltration
- Compress and invade adjacent tissue
- Infiltrate
- Can spread to distant sites - metastasis
What are the 2 names and types of benign epithelial tumours?
Adenoma –> tumour of glandular epithelium
Papilloma –> tumour of squamous and transitional epithelium
What are the 3 types of malignant epithelial tumours?
(Carcinoma)
Squamous cell carcinoma
Transitional cell carcinoma
Adenocarcinoma (glandular cell origin)
What is the suffix for benign mesenchymal tumours and the 5 different types?
What is the suffix for malignant mesenchymal tumours and the 5 different types?
-OSARCOMA
Bone = osteosarcoma
Adipose tissue = liposarcoma
Cartilage = chondrosarcoma
Smooth muscle = leiomyosarcoma
Striated muscle = rhabdomyosarcoma
What are germ cell tumours?
Tumours derived from germ cells in ovary and testes
What are teratomas?
Tumours derived from germ cells, containing representatives from all 3 germ layers
What are embryonal tumours?
Tumours derived from embryonic blast tissue
What are gliomas?
Tumours derived from glial cells of the CNS
What are melanomas?
Tumours of melanocytes, usually in skin
What is lymphoma?
Tumour of lymphoid tissue
What is leukaemia?
Tumour of haemopoietic cells in bone marrow
What is neuroendocrine tumour?
Tumours derived from neuroendocrine cells, scattered in many sites
What are the properties of benign tumours in solid organs?
- Compress adjacent tissue
- Grow evenly
- Spherical
What are the properties of benign tumours on epithelial surfaces?
- Form papillary outgrowths
- Papillomas as they have papillary shape
What are the properties of malignant tumours?
- Expand but infiltrate and invade adjacent tissue
- Irregular outline
- No distinct edges
What is the cytology of malignant tumours?
- Differentiation varies
- Pleomorphism – cellular/nuclear
- High nucleus to cytoplasm ratio
- Nuclear hyperchromatism
- High mitotic count
- Abnormal mitoses
What is cellular pleomorphism?
Variation in size and shape of cells in tumour
What is nuclear pleomorphism?
Variation in size and shape of nuclei in tumour cells
What is nuclear hyperchromatism?
What is high mitotic count?
+ cells in mitosis, including abnormal mitosis forms
What does poor differentiation look like?
What does pleomorphism and abnormal mitosis look like?
What does high mitotic count, nuclear hyperchromatism and high nucleus to cytoplasmic ratio look like?
What is dysplasia and causes?
Abnormal cell structure
- Loss of differentiation
- Pleomorphism
- Nuclear hyperchromatism
- High nucleus/cytoplasm ratio
- High mitotic activity
What is carcinoma-in-situ?
Epithelium with cytological characteristics of malignancy but no evidence of invasion
What are the 3 ways malignant tumours spread?
- Lymphatics
- Blood vessel
- Serosal surfaces
What happens during malignant lymphatic spread?
- Invades lumen on lymphatic vessel
- Bits break off and pass into lymph nodes
- Bits in lymph nodes get trapped in subcapsular sinus
- Tumour cells proliferate until whole node is tumour
What happens during malignant blood vessel spread?
- Tumour invades wall of a small vessel
- Breaks off and passes into circulation
- Tunour grows where vessel becomes too small for it to pass
- Distant metastasis produced
What are the 4 common sites of blood-borne metastasis?
- Breast
- Bronchus/lung
- Kidney
- Thyroid
Where do liver mets often arise from?
- GI tract
- Pancreas
- Breast
- Lung/bronchus
- Kidney
What are the effects of benign tumours?
- Bleeding e.g. gut, bladder
- Pressure on adjacent vital structures e.g. in brain
- Obstruction e.g. in brain, bronchus
- Hormone secretion e.g. pituitary adenoma
- Conversion to a malignant tumour
What is tumour grade?
Biology of the tumour
What is tumour stage?
The size of a primary tumour, the degree to which it has locally invaded, the extent to which it has spread by distant metastasis
What are the 5 steps for tumour diagnosis?
- Symptoms: clinical history
- Signs: physical examination
- Imaging
- Tumour markers - i.e. blood in urine
- Biopsy: tissue sampling - use imaging as an aid
What are the 3 tumour markers?
- HCG – human chorionic gonadotrophin from tumours with trophoblast elements
- AFP - alpha fetoprotein. Liver cancer, germ cell tumours.
- PSA – prostate-specific antigen from carcinoma of the prostate
What are the 3 steps of a biopsy?
- Fix in formalin solution for routine histology, special stains and immunohistochemistry.
- Fix in glutaraldehyde for electron microscopy.
- Send fresh for cytogenetics, tumour genetics.
What do the dark purple areas represent?
Suspected tumour area
What are the properties of diagnostic cytology?
- Examination of cells in tissue fluids or exfoliated from surfaces
- May give a diagnosis of malignancy
- Useful for screening – main example is cervical cytology programme
What are the 2 assessments made of a discovered tumour?
Analysis of degree of differentiation and tumour growth pattern
Evaluation of how far it has spread
What are the difference between low-grade and high-grade tumours?
Low = slow growing and have good prognosis
High = fast growing and poor prognosis
What are the properties of tumour grade?
- The degree of differentiation of tumour cells relative to normal tissue of origin
- Variation in size and shape of constituent cells of the tumour (pleomorphism)
- The proportion of cells containing mitotic figures (mitotic index)
What are the 3 cancer assessments for a tumour?
- Tubule formation
- Nuclear pleomorphism
- Mitotic counts
What are the grades of breast cancer?
What is the TNM breast cancer staging?
What is Dukes colorectal carcinoma staging?
What is the table for Dukes cancer staging?
What are the tumour therapy options?
- Three main modes of therapy for neoplastic disease
- Surgery
- Radiotherapy
- Chemotherapy
- Multimodal therapy is common
- Pathology is pivotal in deciding on appropriate therapy
What are the 4 main prognoses?
- Remission
- Disease –free survival
- Five-year survival
- Ten-year survival
What type of tumours have excellent prognosis?
Thyroid
What type of tumours have moderate prognosis?
Kidney
Breast
Prostate
Cervix
What type of tumours have poor prognosis?
Pancreas
Brajn
Oesophagus
What are the different types of neck imaging?
- Bones: Plain film and CT
- Spinal cord and nerves: MRI
- Soft tissue (glands, lymph nodes, muscles): Ultrasound, CT and MRI
- Vessels: Ultrasound, CT and MRI
What are the different types of thorax imaging?
- Lungs: Plain film and CT
- Heart: MRI
- Bones: Plain film and CT
- Spinal cord and nerves: MRI
- Vessels: CT
What are the different types of benign growths?
- Hyperplasia- over proliferation of cells that appear otherwise normal.
- Metaplasia – normal appearance but in wrong place, usually from an adjacent tissue layer
- Dysplasia – cells that appear abnormal; often increased nuclear to cytoplasmic ratio and loss of features of differentiation.
- Adenomas/polyps/warts – larger growths of dysplastic cells.
What is a malignant tumour?
Invading other tissue, usually by breaking through basement membrane of epithelium.
What are the main 5 properties of cancer?
- Proliferation: grow independently of signals
- Immortality: avoid senescence/telomere shortening
- Avoiding cell death: apoptosis, they don’t do it
- Angiogenesis: they must be fed
- Metastasis: many activities needed
What are the properties of carcinogens and mutations?
- Carcinogens lead to a high rate of mutation
- Most mutations not in genes or don’t affect gene function
- Most that affect gene function do not affect features of cell that would lead to cancer
- Need to identify those mutations that DO affect function of genes that regulate proliferation, apoptosis, immortality etc – these are ‘driver’ mutations
- All other mutations that are no relevant to the promotion of cancer are ‘passenger’ mutations
What are the 2 gene classes targeted for mutations?
What are the 2 tumour growth restrictions?
Senescence - cells in G0 don’t proliferate
Apoptosis - programmed cell death
What are the key points about senescence?
- Metabolically active, irreversibly lost ability to re-enter cell cycle
- Normal cells have finite proliferative capacity (Hayflick limit), stop dividing and go into replicative senescence
- Cancers must avoid senescence if they are to keep growing
When do cells reach crisis and what are its consequences?
- If tumour suppressors, such as P53, are inactivated
- Occurs due to shortened telomeres
- Telomere loss = chromosome instability
What happens during crisis?
- Damage to the chromosomes will eventually make the cell unviable.
- Cells undergo apoptosis if they can.
- ‘genetic catastrophe’ is so severe it triggers apoptosis even in the absence of p53.
What do tumours induce and what does this lead to?
Angiogenesis
O2 and nutrient supplied by blood vessels
What is the function of VEGF?
- Produced by many cancers
- Induces new vessel growth and production of endothelial precursor cells in bone marrow
What is the process leading to metastasis? (picture)
What mutations lead to a gain-of-function?
- Overexpression: amplification/ regulatory regions change
- Point mutations/fusions
What mutations lead to loss of function?
- Point mutation
- Deletion-frameshift
- Loss of allele
How do you identify key cancer genes?
- Cellular and biochemical studies of normal cells and tumours
- Find genes with damage in cancers
- Now best approach is whole genome analyses
What are the 3 family syndromes?
- Retinoblastoma
- Colon cancer
- Breast cancer
What are the properties of retinoblastoma?
- Unilateral = sporadic cases
- Bilateral = familial cases
- Rb = retinoblastoma gene
What is the Knudson 2-hit hypothesis?
Sporadic = requrie 2 random somatic events
- Phenotype of the mutant Rb allele is dominant at the level of the whole organism
- However - the phenotype of the mutant allele is recessive at the cellular level
- Characteristic of tumor suppressor genes
What is the function of the P53 gene?
Can trigger cell to enter apoptosis
What is the function of TS proteins?
Detect errors, mediate repair, inhibit replication or mediate entry to apoptosis
What happens when an error is spotted and repaired?
Proliferation
What happens when an error is spotted and not repaired?
Apoptosis
What are the properties of oncogenes?
- Undergo dominant activating mutations in tumours
- Rarely in inherited forms
- Amplification
- Deletion and point mutation = cell undergoes proliferation
What are the 3 main causes of cancer?
- Carcinogens - react with free radicals, mechanism of mutation (adducts, cross links, breaks), increase rate of mutation, leads to errors
- Infectious agents - inflammation, inflammation and genes HBV), oncogenes E6 and E7 (HPV), oncogene (EBV), immune suppression (HIV)
- Inherited predisposition - inherited mutation in a gene, causing defects leading to genome damage (BRCA1)
What are the 4 cancer screening programmes?
- Breast –47-73yrs
- Colon – 60-74yrs –> fecal blood test, colonoscopy (+ effective)
- Prostate – 50 plus
- Cervical 25-65yrs
What are the properties of radiotherapy?
- X-rays or radioisotopes
- Equivalent to placing cancer cells less than 2km from the epicentre of the nuclear bombs dropped on Hiroshima or Nagasaki
- To damage cells to such an extent that they cannot survive. If this radiation was experienced body-wide this would kill us, but therapy targets the tumour
- Often ‘fractionated’ or ‘brachytherapy’ used
What is mitotic catastrophe?
- Dividing cells, most initially survive, but continue to progress through the cell cycle despite the breaks in their DNA.
- Genome becomes progressively more damaged until it is insufficiently intact to continue, and they die from ‘mitotic catastrophe
What are targeted cancer therapies examples?
- Antibodies to specific antigens eg. Herceptin, EGFR, breast cancer
- Small molecule inhibitors eg …, Abl, leukaemias; …, BRAF, melanoma.
- Angiogenesis inhibitors eg. Avastin, VEGF, colon cancer
- Immune system booster, vaccines etc.
What are the cancer prevention methods?
- Lifestyle – smoking, UV, processed meat
- Immunization – HPV, Hepatitis
- Prenatal genetic Diagnosis
What are the clinical features of oesophageal carcinoma?
- Dysphagia
- Mild food regurgitation
- Weight loss
What are the most common type of oesophageal carcinomas?
Squamous carcinoma - as oesophagus has squamous epithelium
Where does adenocarcinoma (oesophageal carcinoma) arise?
In metaplastic epithelium
How does oesophageal carcinoma spread?
- Local extension
- Nodal spread
- Vascular spread
What are the symptoms of stomach carcinoma?
- Indigestion
- Weight loss
- Loss of appetite
- Repeated vomiting
What type of carcinoma is stomach carcinoma?
Adenocarcinoma
What are the histological features of poorly differentiated adenocarcinoma?
Singet ring cell pattern
What is a common complication of stomach cancer?
Metastasis to the liver
What type of carcinoma is colon cancer?
Adenocarcinoma
Where do colon carcinomas commonly present and why?
Right side (caecum)
Due to bleeding with anaemia
Where does colon carcinoma spread to?
Lymph nodes and liver (by blood)
What type of carcinoma is rectal cance4r?
Adenocarcinoma
What are the clinical features of rectal cancer?
- Bleeding
- Obstruction
What is the prognosis for rectal cancer?
Curative if resected at its early stages
What type of carcinoma is lung cancer related to smoking and where does it arise?
Squamous cell carcinoma
Arises in metaplastic epithelium
What are the clinical features of lung cancer?
- Cough
- Haemoptysis
- Ulceration
How do you diagnose lung cancer?
Sputum cytology
Biopsy
What type of carcinoma is lung cancer not related to smoking?
Adenocarcinoma
What are the clinical features of lung cancer not related to smoking?
Pleural effusion
How do you diagnose lung cancer not related to smoking?
Image-guided biopsy
What treatment is appropriate for localised, non-smoking related lung cancer?
Surgery
What is the worse type of smoking related carcinoma and its derivative?
Small cell carcinoma
Derived from pulmonary neuroendocrine cells
How do you diagnose small cell carcinoma of lung?
Cytology and biopsy
What is the prognosis for small cell carcinoma of the lung?
Terrible - would have spread at time of diagnosis
