18. Characteristic of tumours Flashcards
Different malignancies show varied growth rates. What are slow-growing tumours associated with?
Long survival
Different malignancies show varied growth rates. What are rapidly-growing tumours associated with?
Lethal within a short time
What is the definition of ‘differentiation’ in terms of tumours?
The extent that neoplastic cells resemble the corresponding normal parenchymal cells, morphologically and functionally
What are the characteristics of benign tumours in terms of differentiation?
- usually well-differentiated
- mitoses are rare
What are the characteristics of malignant neoplasms in terms of differentiation?
- wide range of parenchymal differentiation
- most exhibit morphologic alterations showing malignant nature
Do benign and malignant tumours look different histologically?
Well-differentiated malignant tumours and benign tumours can look very similar
What is anaplasia?
Poorly-differentiated cells
A condition whereby cells lose the morphological characteristics of mature cells
How are neoplasms comprised of poorly-differentiated cells described?
Anaplastic
What condition is a “telltale sign of malignancy”
Anaplasia
Neoplasms comprised of poorly-differentiated cells
What are some possible morphological changes in cells?
- pleomorphism
- abnormal nuclear morphology
- mitoses
- loss of polarity
- other changes
What is pleomorphism?
Describes variability in the size, shape and staining of cells and/or their nuclei. It is a feature characteristic of malignant neoplasms, and dysplasia
Give some examples of the huge differences shown in pleomorphism
- small cells with little differentiation
- large cells with one massive nucleus
- large cells with multinucleation
Cells can have abnormal nuclear morphology. Give some examples of this
- nuclei appear too large for the cell
- variability in nuclear shape
- chromatin distribution
- hyperchromatism
- abnormally large nucleoli
In abnormal nuclear morphology, nuclei may appear too large for the cell that they are in. What is normal?
Normal nuclear to cytoplasmic ratio = 1:4 or 1:6
When abnormal, it can reach 1:!
In abnormal nuclear morphology, there can be variability in nuclear shape. Give examples
- irregular
- making pictures (raisins, faces etc)
In abnormal nuclear morphology, there can be abnormal chromatin distribution. Give examples
- coarsely clumped
- along cell membrane
In abnormal nuclear morphology, there can be hyperchromatism. What does this look like?
Dark colour
What are mitoses an indication of and what are they seen in?
An indication of proliferation
Therefore seen in normal tissues with a rapid turnover and in hyperplasias
In malignancy, atypical bizzare mitotic figures are seen. Give examples
- tripolar division
- quadripolar division
- multiple spindles
etc
What occurs in loss of polarity in cells?
- orientation of cells disturbed
- disorganised growth
In summary, what are the main characteristics of well differentiated tissues?
- closely resembles normal tissue or origin
- little or no evidence of anaplasia
- benign and occasional malignant
In summary, what are the main characteristics of poorly differentiated tissues?
- little resemblance to tissue of origin
- highly anaplastic appearance
In summary, what are the main characteristics of undifferentiated/anaplastic tissues?
- cannot be identified by morphology alone
- need molecular techniques
What is ‘grade’ in terms of tumour classification?
- closely related to differentiation/clinical behaviour
well differentiated = low grade/grade 1
moderately differentiate = intermediate/grade 2
poorly differentiated = high grade/grade 3
What is ‘stage’ in terms of classification of tumours?
A measure of prognostication/therapeutic decisions
Better differentiation = ?
Better retention of normal function
How can benign and well-differentiated carcinomas of the endocrine glands be detected?
They frequently secrete hormones characteristic of origin
Increased levels in the blood can be used to detect and to follow up tumours
How can changes in function of tumours give clinical clues?
- some tumours express foetal proteins not seen in adults
- some express proteins only normally found in other adult cells
Change in function of tumours can lead to paraneoplastic syndromes. For example, in bronchogenic carcinomas, what is released which leads to secondary effects on the body?
- corticotropin
- parathyroid-like hormone
- insulin
- glucagon
- others
What are the general differences between cancer and benign tumours in terms of local invasion?
Cancer =
- infiltration
- invasion
- destruction
Benign =
- cohesive expansile masses
- localised to site of origin
- no capacity to infiltrate, invade or metastasise
Can benign tumours invade other areas of the body?
No, they are localised to their site of origin and cannot infiltrate, invade or metastasise
What is encapsulation? (in terms of benign tumours)
The tumour grows in a contained area usually surrounded by a fibrous connective tissue capsule
In encapsulation of benign tumours, ECM is deposited by stromal cells. How is this activated?
Activated by hypoxia from the pressure of the tumour
In benign tumours, what are the characteristics of the tissue plane?
Easy to identify because they are
- discrete, moveable
- easily palpable
- easily excised
The fibrous capsule around benign tumours consists of extracellular matrix (ECM). What is ECM deposited by?
Stromal cells
This process is activated by hypoxia from pressure of the tumour
Whereas you get encapsulation of benign tumours, what can sometimes occur in malignant tumours?
Pseudoencapsulation
Happens in the more slow-growing tumours
What is pseudoencapsulation?
Happens in slow-growing malignant tumours
Looks like encapsulation but microscopically there are actually rows of cells penetrating the margin
Do malignant tumours respect anatomical boundaries?
No
Penetration of organ surfaces and skin
Is surgical resection easy in malignant tumours?
No
Requires resection of adjacent macroscopically normal tissue (margin)
What is metastasis?
Spread of a tumour to sites physically discontinuous with the primary tumour
What does pathognomic mean?
Characteristic of a particular disease
What is metastasis pathognomic of?
Malignancy
If a tumour metastasises, it is NOT benign
What proportion of cancers metastasise?
30% of non-skin malignancies have metastasised at diagnosis
Metastasis is generally correlated which what features? (but with lots of exceptions)
- lack of differentiation
- local invasion
- rapid growth
- large size
What are the possible pathways for metastasis?
- direct seeding
- lymphatic spread
- haematogenous spread
What is direct seeding? (a pathway for metastasis)
The neoplasm penetrates a natural open field without physical barriers
Can remain confined to surface of peritoneal structures without penetrating eg. pseudomyxoma peritonea
In direct seeding, a neoplasm penetrates a natural open field without physical barriers. Give some examples of these
- peritoneal cavity
- pleural cavity
- pericardial space
- subarachnoid space
- joint spaces
What is the most common pathway for metastasis?
Lymphatic spread
Describe lymphatic spread
- tumours do not contain lymphatic channels
- lymphatic vessels at the tumour margins
- pattern of lymph node involvement follows the routes of lymphatic drainage
What is the pattern of lymphatic spread in breast cancers?
- most commonly presents in upper outer quadrant
- disseminate first to axillary nodes
- then infraclavicular and supraclavicular nodes become involved
What determines future course of disease and what therapy is most suitable for a patient with breast cancer?
Determination of axillary node status
What are sentinel nodes?
The first node in a regional lymphatic basin that receives lymph flow from the primary tumour
(the first few lymph nodes into which a tumour drains)
How are sentinel nodes identified?
Injection of radiolabelled tracers/coloured dyes
Despite being a passage of spread for tumours, how can regional nodes be beneficial?
Effective barriers to further tumour dissemination
Cells arrest within node and then can be destroyed by a tumour-specific immune response
Does every enlarged node next to a tumour have cancer in it?
No!
Drainage of tumour cell debris and tumour antigens induces a reactive change in nodes
What is haematogenous spread seen in?
Typical of sarcomas
But also seen in carcinomas!
Describe haematogenous spread
Bloodborne cells follow the venous flow drainage site of the neoplasm
Often come to rest in the first encountered capillary bed
In haematogneous spread, the cells often come to rest in the first encountered capillary bed, what is most frequently involved?
Liver (portal)
Lungs (caval)
In haemotogenous spread, why are veins involved?
They are more easily penetrated because they have thinner walls
What is the stroma?
Connective tissue framework that neoplastic cells are embedded in
What does the stroma provide?
- mechanical support
- intercellular signalling
- nutrition
What is a desmoplastic reaction?
Fibrous stroma formation due to induction of connective tissue fibroblast proliferation by growth factors from the tumour cells
What does the stroma contain? (in a desmoplastic reaction)
- cancer-associated fibroblasts
- myofibroblasts (see puckering of skin)
- blood vessels (blood to tumour)
- lymphatics
What are the clinical complications of tumours dependent on?
- location
- cell of origin
- behaviour
In what general classifications can effects of tumours be?
- local
- metabolic
- due to metastases
What are some LOCAL complications of tumours?
- compression
- destruction
Compression is a local complication of tumours. Describe this
Displacement of adjacent tissue
- benign eg. pituitary adenomas obliterate adjacent functioning pituitary tissue leading to hypopituitarism
Destruction is a local complication of tumours. Describe this
Invasion
Rapidly fatal is vital structures are invaded e.g. artery
Mucosal surfaces - ulceration eg. GI - anaemia
Describe tumour type-specific METABOLIC complications of tumours?
- well differentiated endocrine tumours can retain functional properties
- autonomous
- number of cells exceeds normal organ
- eg. thyrotoxicosis in thyroid adenoma
- if inappropriate (paraneoplastic) eg. ACTH/ADH in small cells lung cancer
Give some non-specific METABOLIC complications of tumours
- cachexia
- warburg effect
- neuropathies
- myopathies
- venous thrombosis
What is cachexia?
Profound weight-loss despite apparently adequate nutrition
Tumour-derived humoral effects that interfere with protein metabolism
What is the Warburg effect?
Produces energy by high rate of glycolysis with fermentation of lactic acid
Used in imagine - PET scanning (FDG uptake)
Observation seen in most cancer cells
