What is a Neoplasm? Invasion, Metastasis and Effects

Question 1

What is a neoplasm and what is a malignant neoplasm?

Answer 1

An abnormal growth of cells that persists after the initial stimuli is removed. A malignant neoplasm invades surrounding tissue with the potential to spread to distant sites.

Question 2

What is a tumour?

Answer 2

A tumour is any clinically detectable lump/swelling (neoplasm is one type, but there’s also non neoplastic e.g. Cyst, haematoma).

Question 3

What is cancer and what is a metastasis?

Answer 3

A cancer is any malignant neoplasm. A metastasis is a cancer that has spread from its original site to a new, non-contiguous site. The regional location is primary and the place to which it has spread is the secondary site.

Question 4

What is dysplasia?

Answer 4

Dysplasia is a pre-neoplastic alteration in which cells show disordered tissue organisation, but it is not neoplastic, as the change is reversible.

Question 5

What is the difference between benign and malignant neoplasms?

Answer 5

Benign neoplasms remain contained at the site of origin and do not produce metastases, whereas malignant neoplasms (cancers), have to potential to metastasise.

Question 6

Why are benign tumours rarely dangerous?

Answer 6

Benign tumours grow in a confined local area, so they have a pushing outer margin and are hence, rarely dangerous.

Question 7

What might a malignant tumour look like?

Answer 7

Malignant tumours have irregular outer margins and shapes - they may show areas of ulceration and necrosis if on a surface.

Question 8

Varying degrees of neoplasm differentiation are seen microscopically, how might benign and malignant neoplasms be differentiated?

Answer 8

Benign neoplasms have cells that closely resemble the parent tissue (well differentiated), but malignant neoplasms can range from well to poorly differentiated.

Question 9

What do you call cells that have no resemblance to any tissue?

Answer 9

Anaplastic.

Question 10

What may be seen cellularly, with poorly differentiated cells?

Answer 10

Worsening differentiation brings increased nuclear size and nuclear to cytoplasm ratio, hyperchromasia (increased nuclear staining), more mitotic figures and increased variation in size and shape of cells and nuclei, known as pleomorphism.

Question 11

When clinicians use the term ‘grade’, what are they talking about?

Answer 11

High grade is poorly differentiated, correlating with more aggressive tissue,ours (G1,2,3 based on tubules, mitosis and nuclear pleomorphism).

Question 12

What does dysplasia describe?

Answer 12

Dysplasia also describes altered differentiation (worsening from mild to moderate to severe). While dysplasia is reversible, the next step of carcinoma in situ isn’t and it will lead to invasive carcinoma.

Question 13

What is the cause of neoplasia?

Answer 13

Accumulated mutations in somatic cells (cells of the body, not germ line cells).

Question 14

What are the 2 things mutations are caused by?

Answer 14

Initiators (mutagenic agents) and promoters (cause cell proliferation). In combination, initiators and promoters result in an expanded monoclonal population of mutant cells.

Question 15

Approximately 85% of cancer risk is environmental/extrinsic factors. What are the main initiators?

Answer 15

The main initiators (mutagenic agents) are chemicals, infection and radiation, with some also acting as promoters.

Question 16

In some neoplasms, mutations are not from external mutagenic agents, where instead?

Answer 16

They are inherited.

Question 17

How does a neoplasm emerge from a monoclonal population after initiators and promoters have done their work?

Answer 17

By a process of progression, characterised by the accumulation of more mutations (sub clones emerge).

Question 18

What makes a collection of cells monoclonal?

Answer 18

If they all came from a single, founding cell.

Question 19

Describe a study showing that neoplasms are monoclonal.

Answer 19

The study of an X-linked gene for glucose-6-phosphate dehydrogenase (G6PD) in tumours of different women gave evidence that neoplasms were monoclonal, as several alleles encode different isoenzymes. Lyonisation occurs in early female embryogenesis where 1 allele is inactivated. Heterozygous women end up with a patchwork of each type (heat stable and heat labile isoenzymes), but neoplastic cells express only 1, indicating a monoclonal group.

Question 20

Genetic alterations affecting which genes may favour neoplasm formation?

Answer 20

Those affecting proto-oncogenes and tumour suppressor genes. Proto-oncogenes become oncogenes when abnormally activates, favouring neoplasm formation. TSGs (which normally suppress neoplasm formation) become inactivated (2 alleles each).

Question 21

Part of naming neoplasms is by an organised system, taking into account the site of origin, benign/malignant, type of tissue the tumour forms and sometimes the gross morphology (cyst/papilloma). How do names end to show if a tumour is benign or malignant?

Answer 21

Benign neoplasms end in ‘Oma’ and malignant neoplasms end in ‘carcinoma’ if it’s epithelial malignant neoplasm or ‘sarcoma’ if it’s a stromal malignant neoplasm.

Question 22

Carcinomas constitute ____% of malignant tumours and may be ___ ______ (no invasion through epithelial basement membrane) or __________ (penetrated).

Answer 22

90
In situ
Invasive

Question 23

What is leukaemia and what are lymphomas?

Answer 23

Leukaemia is a malignant neoplasm of blood forming cells arising from the bone marrow and lymphomas are malignant neoplasms of lymphocytes, mainly affecting the lymph nodes.

Question 24

What is a myeloma?

Answer 24

A myeloma is a malignant neoplasm of plasma cells.

Question 25

Germ cell neoplasms arise from _________________ cells (mainly in the testes/ovaries). ____________________ tumours arise from cells distributed throughout the whole body. Some neoplasms are termed ‘blastomas’ - mainly in __________, they are formed from immature, ___________ cells.

Answer 25

Pluripotent
Neuroendocrine
Children
Precursor

Question 26

Invasion and metastasis are the most lethal features of ____________ neoplasms. The ability to spread to distant sites leads to a greatly increased __________ ________ - untreated leads to vast numbers of ‘___________’ malignant.

Answer 26

Malignant
Tumour burden
Malignant

Question 27

What is stage used for when describing neoplasms?

Answer 27

Stage is a measurement of tumour burden (I-IV with worsening prognosis).

Question 28

For malignant cells to get from a primary to a secondary sites, what 3 requirements are there?

Answer 28

1. Grow and invade at the primary site. 2. Enter a transport system and lodge at the secondary site. 3. Grow at the secondary site to form a new tumour (colonisation).
   At all steps they must evade destruction by immune cells.

Question 29

The process of malignant cells moving from a primary to secondary site is inefficient, give one reason why?

Answer 29

Mainly because cells in blood vessels are sheared by mechanical trauma.

Question 30

For carcinomas, what 3 alterations are involved in invasion and what does it create?

Answer 30

Altered adhesion, stromal proteolysis and motility. These create a carcinoma cell phenotype - sometimes appears more like a mesenchymal than an epithelial cell, so called an EMT (epithelial-to-mesenchymal transition).

Question 31

What does altered adhesion of malignant cells involve?

Answer 31

Altered adhesion between malignant cells involves a reduction in E-cadherin expression and between malignant and stromal proteins, it involves changes in Integrin expression.

Question 32

Cells must degrade the basement membrane and stroma to invade, what does this involve?

Answer 32

Altered expression of proteases - notably matrix metalloproteinases (MMPs).

Question 33

For neoplasm invasion, nearby non-neoplastic cells are taken advantage of by malignant cells to together form a cancer niche. What do the normal cells provide?

Answer 33

The normal cells provide some growth factors and proteases.

Question 34

Altered motility involves changes in the _______ (cyto)skeleton. Signalling through ________ is important and occurs via small ___ __________ e.g. Members of the Rho family.

Answer 34

Actin
Integrins
G proteins

Question 35

Malignant cells can reach distant sites by entering transport systems, describe the 3.

Answer 35

1. Blood vessels via capillaries and venules.
2. Lymphatic vessels.
3. Fluid in body cavities - known as transcoelomic spread.

Question 36

What is colonisation and its significance in the success of metastases?

Answer 36

Colonisation is where malignant cells grow at secondary sites. Failed colonisation is the greatest barrier to successful metastasis formation, as many tiny clusters of malignant cells lodged at the secondary site die/fail to grow into clinically detectable tumours.

Question 37

What are micrometastases and what is tumour dormancy?

Answer 37

Micrometastases are surviving microscopic deposits of malignant cells that fail to grow. An apparently disease-free person may harbour many, known as tumour dormancy. When a malignant neoplasm relapses years later, it is typically from the growth of one or more micrometastases.

Question 38

What does the site of the secondary neoplasm depend on?

Answer 38

1. Regional blood/lymph/coelomic fluid drainage (e.g. Lymphatic metastases often drain to lymph nodes, transcoelomic spread often to other areas in the coelomic space/adjacent organs and bloodborne metastases sometimes to the next capillary bed - liver/lung). 2. ‘Seed and soil’ phenomenon - hence seemingly unpredictable bloodborne spread, due to interactions between malignant cells and the local tumour environment (niche) at the secondary site.

Question 39

Carcinomas typically spread first to draining lymph nodes and then onto blood-borne distant sites. Sarcomas tend to spread via the blood stream. Name some common sites of blood-borne metastases.

Answer 39

Lung, bone, liver and brain.

Question 40

Which neoplasms most frequently spread to the bone?

Answer 40

Breast, bronchus, kidney, thyroid and prostate.

Question 41

Some malignant tumours are very aggressive and metastasise early in their course and others never metastasise; give examples of each.

Answer 41

Aggressive - small cell bronchial carcinoma.

Never metastasise - basal cell carcinoma of the skin.

Question 42

What is the basis of cancer staging?

Answer 42

The size of the primary neoplasm is related to the likelihood of any metastases.

Question 43

What are the different ways a neoplasm can affect the host and which are most relevant for benign neoplasms?

Answer 43

Direct local effects - may be due to primary and/or secondary neoplasms and those due to indirect systemic effects (including the effects of tumour burden, secreted hormones and/or miscellaneous effects) - sometimes described as paraneoplastic syndromes.
For benign neoplasms, local effects from the primary and hormonal effects are the most relevant.

Question 44

What are the local effects of primary and secondary neoplasms due to? (4)

Answer 44

1. Direct invasion and destruction of normal tissue.
2. Ulceration at a surface leading to bleeding.
3. Compression of adjacent structures.
4. Blocking tubes and orifices.

Question 45

How do the systemic effects of a neoplasm lead to some of the recognisable symptoms of cancer?

Answer 45

Systemic effects of a neoplasm: increased tumour burden leading to a parasitic effect on the host - together with secreted factors e.g. Cytokines, contributing to reduced appetite and cachexia, malaise, immunosuppression (also due to direct bone marrow destruction) and thrombosis.

Question 46

What type of neoplasms are likely to produce hormones?

Answer 46

Benign neoplasms of endocrine glands are often well differentiated, so produce hormones e.g. Thyroid adenoma produces thyroxine. Malignant tumours may also (sometimes) produce hormones e.g. Bronchial small cell carcinoma may produce ACTH or ADH while bronchial squamous cell carcinoma can make a PTH-like hormone.

Question 47

List some miscellaneous systemic effects of neoplasms.

Answer 47

Neuropathies affecting the brain and peripheral nerves, skin problems such as pruritus (itching) and abnormal pigmentation, fever, finger clubbing and myositis (muscle pain and weakness). Many other signs/symptoms can occur with poorly understood pathogenesis.