Neoplasia Flashcards
define neoplasm/neoplasia
An abnormal growth of cells that
persists after the initial stimulus is removed”.
For malignant neoplasms the definition needs extending: “an abnormal growth
of cells that persists after the initial stimulus is removed AND invades surrounding tissue with potential to spread to distant
sites”
what do tumour, cancer, dyspalsia, neoplasm mean
A tumour is any clinically detectable lump or swelling.
A neoplasm is just one type of tumour.
A cancer is any malignant neoplasm.
Dysplasia is a pre-neoplastic alteration in
which cells show disordered tissue organisation. It is not neoplastic because the change is reversible. it becomes malignant when it invades other tissues, such as past the basal layer of epilthelium
what is a metastatis
A metastasis is a malignant neoplasm that has spread
from its original site to a new non-contiguous site. The original location is the primary site and the place to which it has spread is a secondary site.
beningn vs malginant neoplasms
beningn are limited to site of growth
A benign neoplasm has cells that closely
resemble the parent tissue, i.e. they are well differentiated.
malignant have the ability to metastatise
Malignant neoplasms range from well to poorly differentiated - the more poorly differentiated the worse the grade and the worse the outlook
what 4 things will you see in a neoplastic group of cells that have a worsening level of diffrentation
note: this also applies to areas of dysplasia - as it is pre neoplastic
pleomorphism - varying size and shape of cell
hypercrhomasia - increased nuclear staining
mitotic figures present
increased nuclear/cytoplasmic ratio
what is the key difference between dysplasia and malignancy
dysplasia is a reversible state, malignancy is not
to what extent is cancer intrinsic vs extrinsic and inherited vs envriomental
studies on Japanese migrants imply that cancer is about 85% environmental and 15% familial genetic traits
intrisic factors are age, gender, genetics
extrinsic factors are enviroment and lifesytle - smoking, obesity, lack of exercise, alcohol
are neoplasms monocolonal ? what does this mean ?
neoplasms are monoclonal -they all originated from a single founding cell.
this fits the initiation and promotion concept
outline the basics of naming cancers
get the key ones, skin, blood, lymph not the random specific ones for now
Benign neoplasms ends in –oma.
Malignant ones end in – carcinoma if it is an epithelial malignant neoplasm, which
constitute 90% malignant tumours, or –sarcoma if it is a stromal malignant neoplasm.
Carcinomas can be in-situ (no invasion
through epithelial basement membrane) or invasive (penetrated through basement membrane).
Leukaemia is a malignant neoplasm of blood-forming cells arising in the bone marrow
lymphomas are malignant neoplasms of lymphocytes, mainly affecting lymph nodes.
Myeloma is a malignant neoplasm of
plasma cells.
Germ cell neoplasms arise from pluripotent cells,
mainly in the testis or ovary.
Neuroendocrine tumours arise
from cells distributed throughout the body.
Some neoplasms are called “-blastomas”, which occur mainly in children and are formed from immature precursor cells, e.g. nephroblastoma.
how does a malignant neoplasm metastasie
For malignant cells to get from a primary site to a secondary site they
must:
(1) grow and invade at the primary site;
(2) enter a transport system and lodge at a secondary site;
(3) grow at the secondary site to form a new tumour (colonisation).
At all points the cells must evade destruction by immune cells.
this requires a set of alterations
what alterations does a malignant neoplasm need to metastasie
and what is an EMT
Invasion into surrounding tissue by carcinoma cells requires: altered adhesion - Altered adhesion between malignant cells involves a reduction in E-cadherin and Integrin expression.
stromal proteolysis - The cells must degrade basement membrane and stroma to invade. This involves altered expression of proteases, notably matrix metalloproteinases (MMPs).
motility - Altered motility involves changes in the actin cytoskeleton.
Together, these three changes
create a carcinoma cell phenotype that sometimes appears more like a mesenchymal cell than an epithelial cell, hence this is called epithelial-to-mesenchymal transition (EMT)
explain the concept of a nice and seed and soil
Malignant cells take advantage of nearby non-neoplastic cells, which together form a
cancer niche. These normal cells provide some growth factors and proteases.
The “seed and soil” phenomenon, which may explain the seemingly unpredictable distribution of blood-borne metastases, is due to interactions between malignant cells and the local tumour environment (i.e. the niche) at the secondary site - ie why tumor may grow well at some sites
what are the mechanisms of spread of neoplasms
3 ways
how and where will neoplasms spread ?
Malignant cells can reach distant sites by entering:
(1) blood vessels via capillaries and venules;
(2) lymphatic vessels;
(3) fluid in body cavities (pleura, peritoneal, pericardial and brain ventricles), which is known as transcoelomic spread
For lymphatic metastasis this is very predictably to draining lymph nodes.
For transcoelomic spread this is predictably to other areas in the coelomic space or to adjacent organs.
For blood-borne metastasis this is sometimes (but not always) to the next capillary bed that the cells encounter - so most commonly the lungs and liver but can also spread to bone and brain
what neoplasms commonly spread to bone
The neoplasms that most frequently spread to
bone are breast, bronchus, kidney, thyroid and prostate.
what is different about how carcinomas and sarcomas spread ?
carcinomas typically spread first to draining lymph nodes and then to blood-borne distant
sites
sarcomas tend to spread via the blood stream
why do rates of metastaises for different cancers differ, give examples
Some malignant neoplasms are more aggressive and metastasise very early in their course, e.g. small cell bronchial carcinoma.
Others almost never metastasise, e.g. basal cell carcinoma of the skin.
outline the local and systemic effects that neoplasms can have genrally
the local effects of primary and secondary neoplasms are due to
(1) direct invasion and destruction of normal tissue;
(2) ulceration at a surface leading to bleeding / possible infection;
(3) compression of adjacent structures
(4) blocking tubes and orifices
SYSTEMIC EFFECTS OF NEOPLASMS:
Increasing tumour burden leads to a parasitic effect on the host.
Together with secreted
factors such as cytokines this contributes to reduced appetite and weight loss (cachexia), malaise,
immunosuppression and thrombosis also occur
Benign neoplasms of endocrine glands are well differentiated so typically produce hormones, e.g. a thyroid adenoma produces thyroxine.
Malignant tumours sometimes also produce
hormones; e.g. bronchial small cell carcinoma can produce ACTH or ADH
Miscellaneous systemic effects include neuropathies affecting the brain and peripheral nerves,
skin problems such as pruritis and myotosis.
what does carcinogenesis mean ?
the causes of cancer and the reasons that caused them
outline causes of carinogenesis and what that are categorised into
what are cigarettes
we have chemicals - often considered mutagens hence initiators and also promoters sometimes
ames test shows that initiators are mutagens
radiation such as UV to skin and x rays/gamma rays
these are initiators. they cause damage and mutations, they also generate free radicals, which causes further damage
cigarette smoke is considered a complete caringnogen which mean sit is both an initiator and a promoter
infections are also cacinogenic
what is a pro carcinogen ?
something that is not a carcinogen until it is converted to a carcinogen in the liver by cytochrome p450 enzymes
outline how and what infections are cacinogenic
Human Papilloma virus (HPV), which is strongly linked to cervical carcinoma, is a direct carcinogen because it expresses the E6 and E7 proteins that inhibit p53 and pRB protein function respectively, both of which are important in cell proliferation.
In contrast, Hepatitis B and C viruses are indirect carcinogens that cause chronic liver cell injury and regeneration. and hence promote mutations
what role do proto-oncogenes and tumour supressor genes play in cancer formation ?
what are the third set of genes involoved
Genes that inhibit neoplastic growth are known as tumour suppressor genes Because they act
like brakes on tumour growth, both alleles must be inactivated, which explains why they need two hits, i.e. one for each allele.
In contrast, genes that enhance neoplastic growth are known oncogenes and are abnormally activated versions of normal genes called proto-oncogenes.
Only one allele of each proto-oncogene needs to be activated to favour neoplastic growth.
think two person bike analogy
the third set of genes involved are called caretaker genes - involve protecting from mismatch repair, neucleotide excision repair and DNA double strand breaks - when inactivated they lead to genetic instability
what is progression ?
occurs after promotion
Most malignant tumours require alterations affecting a
combination of multiple TS genes and proto-oncogenes.
a general principle of step-wise
accumulation of mutations in malignant neoplasms. This steady accumulation of multiple mutations is called cancer progression.
what are the six hallmarks of cancer and the enabling factor ?
- cell immortalisation
- resistance to apoptosis
- self sufficient growth signals
- resistance to growth stop signals
- sustained ability to induce new blood vessels (angiogenesis)
- the ability to invade and
produce metastases.
enabling factor - genetic instability
