Week 5: Neoplasia Flashcards
In cancer cell growth is…..
Dysregulated
What is cancer?
Many different diseases
Characterised by dysregulated cell growth (increased proliferation and decreases apoptosis)
But can have different causative agents, aetiology and molecular profiles.
What are the key features of neoplastic cells?
Invade surrounding normal tissue
Metastasise
May kill host in which it originates.
Define neoplasia
Autonomous/idependent growth of abnormal cell or tissue, more rapid that normal and continues in the absence of the growth signal.
Genetic mutation in cell - survival and growth advantage resulting in excess proliferation
How do normal cells grow?
Highly regulated
Cell death is equal to cell division
Confined within a specific compartment and have a specific organisation within that compartment
What are the clinical questions that must be considered with cancer?
Is it cancer?
What type of cancer?
How will it behave? benign/malignant indolent/aggressive
How should the patient be treated
is the tumour completely removed?
Are there any associated diseases of relevance?
Are there any complications for relatives?
What features effect the pronosis of cancer diagnosis?
Bening or malignant
Tumour stage
Biological characteristics
What are the different tumour stages?
Carcinoma in situ
Invasvie
Metastatic
Define dysplasia
means disordered growth
Where several morphological changes occur in the cells
Architectural disarray and loss of orderly differentiation.
Reversible
Confined to the epithelium
What is the link between dysplasia and neoplasia?
Start with dysplasia
When the enitre epitheium is dysplastic and no normal epithelial cells are left is said to be neoplastic
What is meant by carcinoma in situ?
Severe dysplasia - now consider neoplasia.
No orderly differentiation of cell type.
Over the full thickness of the epithelium but is confined to the epithelium due to the intact basement membrane
Does not penetrate the basement membrane
What is invasive carcinoma?
Neoplastic cells that invade the basement membrane
Spread past the epithelial layer into the lamina propia and beyond
What are the growth features of benign tumours?
Slow
Expansive
Non-metastatic
non-invasive
Capsulated
What are the growth features of malignant tumours?
Fast
Invasive
Metastatic
destructuve
No capsule
What are the cellular features of benign tumours?
Uniform shape size and colour
Resembles normal cells
Normal nuclear to cytoplasmic ratio (1:4 to 1:6)
Low mitotic count (normal mitosis rate)
Adequate or normal amount of chromatin
What are the cellular features of malignant tumours?
Pleomorphic - varied, shape size and colour
Disorganised and haphazard appearance - does not resemble original tissue
Increased and disproportionately large nucleus (1:1 ratio with cytoplasm)
Low to high mitotic count - abnomrla apoptosis
Hyperchromatc (abundant DNA and dark stain)
Large nucleoli are often present
What are some gross features to differentiate between benign and malignant tumours?
Benign - clear borders, well circumscribed, Resembles tissue of origin
Malignant - disorganised appearance, no clear borders, does not resemble tissue of origin, may have infiltration into the surrounding tissue.
Define anaplastic
lack of differentiation - no longer resemebles the normal parenchymal cells
Neither morphologically or functionally.
Nucleus tends to vary in size and shape
Feature of malignant tumours
Define pleomorphic
Variation in size and shape
of both cells and nuclei
Feature of malignant tumour
What is meant by a hyperchromatic nuclei?
Dark staining nucleus
Contains abundant chromatin
Why do malignant tumours tend to have a higher nuclear to cytoplasmic ratio?
As dividing not functioning.
What is angiogenesis?
Why do cancer cells do this?
The growth of new blood vessels from the host vasculature
Aid metastic cascade, provide nutrients, provide oxygen, eliminate waste.
Define metastasis.
Spead of tumour from a primary organ to distant sites in the body
How does metastasis affect cancer prognosis?
Responsible for 90% of deaths in cancer
Difficult to treat (colonial expansion - more likely to have intratumor heterogenicity)
Needs more specific therapies
What ist he process of cancer development?
- Transformation from normal to abnormal cells - may be described as dysplasia and neoplasis
- Angiogenesis - provides the tumour which the nutrients needed to continue to proliferate and a potential mechanism to spread.
Will invade local tissue - Motility and invasion - undergoes a epithelial to mesenchymal transition (loss of E cadherin 3) as arrests and escapes into blood stream or other method to spread (requires retraction of endothelial cells)
- Evolved to survive as a singular cells in circulation
- Is arrested in emoboli and adheres to capillary bed, grow in emobli
- Invades target tissue (requires retraction of endothelial cells)
- Neovascularisation and proliferation of tumour cells will continue
- Has metastasis and the process repeats.
What is the difference between intravasation and extravasation in relation to cancer cells?
Intravasation - cancer cell penetrate bv or lymph vessels
Extraversion - escape from blood vessels or lymph
What are the different hypothesis behind where tumours spread during metastasis?
Seed and soil
Mechanical
What is the seed and soil mechanism of metastasis?
Certain tissues (soil) have an environment that is receptor to particular tumour cells (seeds)
- large number of cancer cells will circulate without finding a receptive environment so metastasis will not occur
What is the mechanical hypothesis of metastasis?
Metastatis is likley to occur at sites based on the pattern of blood flow from the primary organ
Where do these common cancers normally metastasise to?
Prostate
Colon
gastric
Breast
Melonama
Lung
(small cells)
(non- small cell)
Bone
Liver
Liver
Liver or Lung
Melanoma - Liver or Lung (lymph nodes, brain)
Liver
Loco-regional
What are the most common routes of tumour spread?
Blood vessels
Lympahatic system
Movement within body cavities
How do cancerous cells spread by direct extension?
Binding to ECM
Enzymatic lysis of the ECM
Grows into surrounding tissues
What are the key features of lymphatic spread?
Main type in early carcinoma
Step wise spread
In transit deposits can occur (melanomas)
Natural route to drainage
What are some common examples of lymphatic spread?
Breast carcinoma to axillary nodes
Lung carcinoma to mediastinal nodes
What are the barriers that metastasising cells face?
Must survive in vasculature (unattached to surfaces and subject to stress)
Must undergo epithelial to mesenchymal transition - acquire ability to invade, resist cell death and spread, this requires a certain microenvironment spread and change in adhesion molecules
What are the processes of extravasation?
Arrest
retraction of endothelial cells
invasion
What are the future improvements that are needed in cancer treatment/diagnosis?
Identification, prediction and treatment of precursor lesions
Increased accuracy of screening
Become minimally invasive in treatment
Target therapies
Point of care testing - to improve early diagnosis
Where might angiogenesis occur in health?
Development and growth
reproductive system (menstrual cycle in females)
Repair
When might angiogenesis occur in pathologica circumstances?
Vascular malformation
Chronic inflammatory disease
Malignant tumours
What is a biomaker?
A biological molecule found in blood or other body fluids that indicate a normal/abnormal process or disease/condition
What are the roles of a cancer biomarker?
Screening for cancer in the general population
Diagnosis
Classification: staging, localisation, estimate tumour volume
Efficacy of treatment/prognosis
Detection of disease recurrence/relpase
Prognostic indicators of disease progressions
** prognosis, diagnostic, predictive
What are the properties of an ideal biomarker?
Specific to the condition (absent in health)
Easy to detect (cheap and easy to quantify)
Higly sensitive (detectable in all cases)
early detectable
Proportional to the extent of tumour
Blood/saliva/urine found rather than by biopsy
What are some fetal biomakers fo cancer?
AFP Alpha-fetoprotein - teratomas and hepatomas
CEA carcinoembryoninc antigen- GI tumour
What are some examples of hormaonl biomakers for cancer?
HCG - teratomas, choriocarcinoma
What are some tumour assoaicted antigens that can be used as biomarkers of cancer?
CA125 - ovarian cancer
PSA - prostate cancer
How do tumour biomaker identification realte to tumour growth rate?
Aim to identify tumours are early as possible (sensitive to low levels of growth)
What stage of cancer progression is this? Dysplatic cells shown
Carcinoma in situ
What is shown in the image? How do you know?
Benign lipoma on surface of small intestine
Defined birder, mimics structure of origin
What is shown in the image? How do you know?
Small hepatic bending adenoma
Function maintained as green indicate bile production
Small clear boundaries and resembles tissue of origin
What is shown in the image? How do you know?
Hepatocellialr carcinoma in cirrhosis liver
Large
And normal appareacne
No clear boundary and infiltrate into surrounding tissue
How would you describe the tissue shown?
What are the key features circled?
Aplastic
Apoptosis
Abnormal tripolar spindle
Is this benign of malignant and how do you know?
Benign
Monomorphic nuclues resembles tissue of origin
Architecture preserved
Is this benign of malignant and how do you know?
Malignant
Pleomoprhic nuclei
What is the malignant feature in this image?
High nuclear to cytoplasmic ratio
Hyperchromatic nucleus
