Neoplasm 2

Question 1

What are the most lethal features of a malignant neoplasm?

Answer 1

INVASION AND METASTASIS ARE THE MOST LETHAL FEATURES OF A MALIGNANT NEOPLASM: The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden. Untreated, this results in a vast numbers of “parasitic” malignant.

Question 2

What are the steps of invasion and metastasis?

Answer 2

INVASION AND METASTASIS IS A MULTI-STEP JOURNEY: 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.
The whole process is inefficient. The steps have been studied mainly with carcinomas rather than other types of malignant neoplasms.

Question 3

What are stage I II III IV melanoma

Answer 3

I: tumour
II: bigger but no metastasis
III: spread through lymphatic first
IV: disband spread via blood vessels

Question 4

What are 3 important alterations in invasion?

Answer 4

3 INVASION INVOLVES THREE IMPORTANT ALTERATIONS: Invasion into surrounding tissue by carcinoma cells requires: altered adhesion, stromal proteolysis and motility. 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)

Question 5

Di benign tumours metastasise?

Answer 5

No

Question 6

What does altered adhesion between malignant cells cause?

Answer 6

Altered adhesion between malignant cells involves a reduction in E-cadherin expression. Altered adhesion between malignant cells and stromal proteins involves changes in Integrin expression. The cells must degrade basement membrane and stroma to invade. This involves altered expression of proteases, notably matrix metalloproteinases (MMPs).

Question 7

What happened when malignant cells take advantage of non neo plastic cells?

Answer 7

Malignant cells take advantage of nearby non-neoplastic cells, which together form a cancer niche. These normal cells provide some growth factors and proteases. Altered motility involves changes in the actin cytoskeleton. Signalling through integrins is important and occurs via small G proteins such as members of Rho family.

Question 8

Why is metastasis inefficient

Answer 8

Damages in arteries, sheared in capillaries, growing at the secondary site is hard - cells lodge at distant sites but dont end up growing

Question 9

What are the 3 routes of transport to distant sites

Answer 9

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.

Question 10

What does the niche comprise

Answer 10

Stream, fibroblasts, endothelial cells, inflammatory cells
Dynamoc relationship between cancer cell and niche
Cancer cells can make the niche cells do things
Niche can be harsh on cancer cell

Question 11

What is clinical metastasis

Answer 11

MALIGNANT CELLS MUST GROW AT A SECONDARY SITE TO FORM A CLINICAL METASTASIS

Question 12

What is colonisation

Answer 12

At a secondary site malignant cells must grow. This is called colonisation. Failed colonisation is considered to be the greatest barrier to successful formation of metastasis because many malignant cells lodge at secondary sites but these tiny cell clusters either die or fail to grow into clinically detectable tumours.

Question 13

What are mictometastases?

Answer 13

Surviving microscopic deposits that fail to grow are called micrometastases

Question 14

What this tumour dormancy

Answer 14

An apparently disease-free person may harbour many micrometastases, a phenomenon known as tumour dormancy. When a malignant neoplasm relapses years after an apparent cure it is typically due to one or more micrometastases starting to grow.

Question 15

What determines the site of a second tumour

Answer 15

The site of
(1) Regional drainage of blood, lymph or coelomic fluid. 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. (2) 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
a secondary neoplasm depends on:

Question 16

Where are common sites of metastasis

Answer 16

Lymphatic - regional lymph node
Coelom e.g. pleurae- elsewhere in the coelomic space
Blood - lung and liver = first capillary bed

Question 17

Where do carcinomas typically spread first?

Answer 17

2.7 CARCINOMAS TYPICALLY SPREAD VIA LYMPHATICS FIRST. SARCOMAS TEND TO SPREAD VIA BLOOD STREAM: Carcinomas typically spread first to draining lymph nodes and then to blood-borne distant sites. Common sites of blood borne metastasis are lung, bone, liver and brain. The neoplasms that most frequently spread to bone are breast, bronchus, kidney, thyroid and prostate.

Question 18

How are malignant cells different in how/when they metastasis?

Answer 18

MALIGNANT TUMOURS HAVE “PERSONALITIES”: 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. The likelihood of metastasis is related to the size of the primary neoplasm. This is the basis of cancer staging (see Mechs Lecture 11)

Question 19

What are the effects of neoplasms

Answer 19

NEOPLASMS CAN HAVE MANY EFFECTS: The effects a neoplasm on the host can classified as those that are due to the direct local effects, which can be due to the primary neoplasm and/or the secondary neoplasm(s), and those due the indirect systemic effects. The latter include effects of increasing tumour burden, secreted hormones and/or miscellaneous effects. These are sometimes referred to as paraneoplastic syndromes. For benign neoplasms, local effects from the primary and hormonal effects are most relevant

Question 20

Classify the effects o neoplasms

Answer 20

Local - primary or secondary

Systemic - burden, hormones, miscellaneous

Question 21

What are the local effects of neoplasms

Answer 21

LOCAL EFFECTS OF NEOPLASMS: 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; (3) compression of adjacent structures and (4) blocking tubes and orifices

Question 22

In terms of systemic effects, what does increasing tumour burden result in?

Answer 22

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 (can also be due to direct bone marrow destruction) and thrombosis.

Question 23

In terms of systemic effects, what do neoplasms of endocrine glands do

Answer 23

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 while bronchial squamous cell carcinoma can produce a PTH-like hormone.

Question 24

What are miscellaneous systemic effects/

Answer 24

Miscellaneous systemic effects include neuropathies affecting the brain and peripheral nerves, skin problems such as pruritis and abnormal pigmentation, fever, finger clubbing and myositis. Many other signs and symptoms can also occur and the pathogenesis is poorly understood