Define neoplasm?
Lesion resulting from the autonomous growth or relatively autonomous abnormal growth of cells that persists in the absence of the initiating stimulus
Define histogenesis?
The differentiation of cells into specialised tissues and organs during growth from undifferentiated cells (the 3 primary germ layers)
Tumours arising from epithelial cells are known as what?
Carcinomas
Tumours arising from connective tissues are known as what?
Sarcomas
Tumours arising from lymphoid/haematopoietic organs are known as what?
Lymphomas/leukaemias
What 2 factors contribute to the geographic variation in specific cancers?
1) Exposure to environmental carcinogens
2) Screening programmes
What has been the pattern of cancer incidence from 1975-2009?
Was increasing and has begun to plateau
What has been the pattern in mortality from cancers from the 70’s to now?
Decrease in mortality from cancer, however it is still one of the leading causes of death
What are the 3 most common cancers in males?
1) Prostate
2) Lung
3) Colon and rectum
What are the 3 most common cancers in females?
1) Breast
2) Lung
3) Colon and rectum
What 4 factors enable you to distinguish between benign and malignant tumours?
1) Differentiation
2) Rate of growth
3) Local invasion
4) Metastasis
What is meant by the differentiation of a tumour?
The extent to which neoplastic cells resemble the corresponding normal parenchymal cells, morphologically and functionally
Are benign tumours usually well-differentiated or not?
Benign tumours are usually well differentiated and mitoses are rare
Are malignant tumours usually well or poorly differentiated?
Malignant neoplasms exhibit a wide range of parenchymal differentiation, most exhibit morphological alterations showing malignant nature
What is meant by anaplastic tumours?
Neoplasms consisting of poorly differentiated cells are described as anaplastic, this is a tell tale sign of malignancy
What is meant by pleomorphism?
Made up of cells which vary in shape and size
What 4 morphological changes can be seen in malignant tumours?
1) Pleomorphism
2) Abnormal nuclear morphology
3) Mitoses
4) Loss of polarity
What 4 changes can be seen in the cells of a malignant tumour showing abnormal nuclear morphology?
1) Nuclei appear too large for the cell that they are in: nuclear to cytoplasmic ratio can reach 1:1 rather than the usual 1:4/6
2) Variability in nuclear shape: irregular, ‘making pictures’
3) Chromatin distribution: coarsely clumped, along cell membrane
4) Hyperchromatism: dark colour
5) Abnormally large nucleoli
Mitoses can be seen in the cells of malignant tumours, what is meant by this?
An indication of proliferation. Therefore seen in normal tissues with a rapid turnover and in hyperplasia. Atypical, bizarre mitotic figures seen in malignancy (tripolar, quadripolar, multipolar spindles)
What is meant by loss of polarity of cells of malignant tumours?
The orientation of cells is disturbed and you get disordered growth
What are the features of well differentiated tumours?
1) Closely resembles the normal tissue of origin
2) Little or no evidence of anaplasia
3) Benign and occasionally malignant
What are the features of poorly differentiated tumours?
Bear little resemblance to the tissue of origin, highly anaplastic appearance
What are the features of undifferentiated/anaplastic tumours?
Cannot be identified by morphology alone, have to use molecular techniques
How are grades applied to tumours according to their differentiation?
Well differentiated = low grade/grade 1
Moderately differentiated = intermediate/grade 2
Poorly differentiated = high grade/grade 3
How does the extent of differentiation affect function?
Better differentiation = better retention of normal function
What kind of tumours of endocrine glands display retention of function and how can this be useful in treatment?
Benign and well differentiated carcinomas of endocrine glands frequently secrete hormones characteristic of origin, increased levels in the blood can be used to detect and follow up tumours
Aswell as producing products of the tissue of origin, what other products can be produced by tumours which provide clinical clues?
Some tumours express foetal proteins not seen in adults
Some tumours express proteins only normally found in other adult cells
What is meant by paraneoplastic syndromes?
Syndromes that occur alongside the cancer
What is the difference in local invasion between a malignant tumour and a benign tumour?
Malignant tumour - infiltrates, invades and destroys local tissue
Benign tumour - appears as a cohesive, expansile mass, localised to sight of origin, no capacity to infiltrate, invade or metastasise
What is meant by the statement that ‘benign tumours are encapsulated’?
Benign tumours have a rim of compressed fibrous tissue, has an ECM deposited by stromal cells activated by hypoxia from pressure of tumour, this all gives a benign tumour a clear tissue plane and thus benign tumours tend to be discrete, moveable, easily palpable and easily excised
Pseudoencapsulation can occur in malignant tumours, which kind does it tend to occur in and how can it be distinguished from true encapsulation microscopically?
Usually occurs in slow growing tumours
Microscopically a row of cell penetrating margin can be seen
How does the local invasion of malignant tumours affect surgical resection?
Have penetration of organ surfaces and skin
This makes surgical resection very difficult
Requires resection of adjacent macroscopically normal tissue (margin)
What percentage of non skin malignancies have metastasised at diagnosis?
30%
What is meant by metastasis?
Spread of tumour to sites physically discontinuous with the primary tumour
How does the presence of metastasis affect prognosis?
Reduces life expectancy significantly
Metastasis is generally correlated with tumours with what 4 qualities?
1) Lack of differentiation
2) Local invasion
3) Rapid growth
4) Large size
What are the 3 pathways of metastasis?
1) Direct seeding
2) Lymphatic spread
3) Haematogenous spread
What is meant by direct seeding pathway of metastasis?
Neoplasm penetrates a natural open field without physical barriers
eg. peritoneal cavity, pleural, pericardial, subarachnoid, joint spaces
Can remain confined to surface of peritoneal structures without penetrating eg. Pseudomyxoma peritonei
What is the most common pathway of metastasis?
Lymphatic spread
By which lymphatic vessels do metastatic tumours initially spread?
Tumours do not contain lymphatic channels, travles by lymphatic vessels at the tumour margins
Give the common lymph node involvement in breast cancer metastases?
Most commonly present in the upper outer quadrant, disseminate first to axillary nodes, then infraclavicular and supraclavicular nodes become involved, determination of axillary node status determines future course of disease and what therapy is most suitable
What is meant by sentinel nodes?
The first node in a regional lymphatic basin which receives lymph flow from the primary tumour
How are sentinel nodes identified?
Injection of radio labelled tracer’s/coloured dyes
Frozen section during surgery can guide surgeon to the appropriate therapy
How can regional nodes be used to stop further spread?
They are effective barriers to tumour dissemination, cells arrest within the node and then can be destroyed by a tumour specific immune response
What is important to note about enlarged nodes in metastatic spread?
Not every enlarged node has cancer in it, drainage of tumour cell debris and tumour antigens induces reactive changes in nodes
Haematogenous spread is typical of what kind of cancers?
Sarcomas - although can occur in carcinomas too!
By which type of blood vessel does haematogenous spread occur, how and why?
By veins - these are more easily penetrated as have thinner walls
Bloodborne cells follow the venous draining site of the neoplasm, often come to rest in the first encountered capillary bed - liver (portal) and lungs (caval) most frequently involved
What is stroma and what 3 functions does it have?
Stroma = connective tissue framework that neoplastic cells are embedded in
Provides mechanical support, intercellular signalling and nutrition
What is meant by the term desmoplastic reaction?
Fibrous stroma formation due to induction of connective tissue fibroblast proliferation by growth factors from the tumour cells
What does the desmoplastic reaction lead to stroma containing? 4
1) Cancer-associated fibroblasts
2) Myofibroblasts
3) Blood vessels
4) Lymphocytic infiltrate
Clinical complications of tumours are dependent on location and occur in both benign and malignant tumours, what are the possible local complications? 2
Compression - displacement of adjacent tissues, can happen in benign eg. pituitary
Destruction - invasion, rapidly if vital structures are invaded eg. arteries and mucosal surfaces
What are the 5 non-specific metabolic clinical complications of tumours?
1) Cachexia - profound weight loss despite apparent adequate nutrition due to tumour derived hormonal effects which interfere with protein metabolism
2) Warburg effect - produces energy by high rate of glycolysis with fermentation of lactic acid, can be identified used imaging - PET scanning
3) Neuropathies
4) Myopathies
5) Venous thrombosis
