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Year 1 Semester 2 Pathological Processes > S8) Invasion, Metastasis and Effects of Neoplasms > Flashcards

S8) Invasion, Metastasis and Effects of Neoplasms Flashcards

1
Q

Explain why invasion and metastasis are the most lethal features of a malignant neoplasm

A
  • The ability of malignant cells to invade and spread to distant sites leads to a greatly increased tumour burden
  • Untreated, this results in vast numbers of “parasitic” malignant cells
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2
Q

Invasion and metastasis is a multi-step journey.

In three steps, explain what is necessary for malignant cells to get from a primary site to a secondary site?

A

⇒ Grow and invade at the primary site

⇒ Enter a transport system and lodge at a secondary site

⇒ Grow at the secondary site to form a new tumour (colonisation)

At all points the cells must evade destruction by immune cells

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3
Q

Invasion involves three important alterations.

What are they and what effect do they have?

A
  • Invasion into surrounding tissue by carcinoma cells requires altered adhesion, stromal proteolysis and motility
  • These changes create a carcinoma cell phenotype that appears more like a mesenchymal cell than an epithelial cell, hence this is called epithelial-to-mesenchymal transition (EMT)
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4
Q

Describe the changes which drive altered adhesion in the process of invasion for malignant cells

A
  • 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
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5
Q

Describe the changes which drive proteolysis in the process of invasion for malignant cells

A
  • The cells must degrade basement membrane and stroma to invade
  • This involves altered expression of proteases, notably matrix metalloproteinases (MMPs)
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6
Q

Explain the role and components of a cancer niche in the invasion of malignant cells

A
  • Malignant cells take advantage of nearby non-neoplastic cells, which together form a cancer niche
  • These normal cells provide some growth factors and proteases
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7
Q

Describe the changes which drive altered motility in the process of invasion for malignant cells

A
  • 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
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8
Q

Transport to distant sites is via three routes, what are they?

A

Malignant cells can enter:

  • Blood vessels via capillaries and venules
  • Lymphatic vessels
  • Coelomic spaces (transcoelemic spread – fluid in pleura, peritoneum, pericardium and brain ventricles)
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9
Q

Explain how malignant cells must grow at a secondary site to form a clinical metastasis and the consequences of this

A
  • Colonisation is when malignant cells successfully grow at a secondary site
  • Failed colonisation occurs with many malignant cells which lodge at secondary sites but die/fail to grow into clinically detectable tumours (greatest barrier to successful metastasis)
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10
Q

What are micrometastases?

A

Micometastases are surviving microscopic deposits which failed to grow at a secondary site

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11
Q

What is the significance of micrometastes?

A
  • An apparently disease-free person may harbour many micrometastases aka tumour dormancy
  • When a malignant neoplasm relapses years after an apparent cure it is typically due to one or more micrometastases starting to grow
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12
Q

What determines the site of a secondary tumour?

A
  • Regional drainage of blood, lymph or coelomic fluid
  • The “seed and soil” phenomenon
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13
Q

Explain how the regional drainage of blood, lymph or coelomic fluid determines the site of the secondary tumour

A
  • Lymphatic metastasis → regional lymph nodes
  • Transcoelomic spread → other areas in the coelomic space / adjacent organs
  • Blood-borne metastasis → next capillary bed that the cells encounter (lungs/liver)
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14
Q

Explain how the “seed and soil” phenomenon determines the site of the secondary tumour

A

The “seed and soil” phenomenon states that 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

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15
Q

How do carcinomas and sarcomas spread?

A
  • Carcinomas typically spread via lymphatic metastasis first and then to blood-borne distant sites
  • Sarcomas tend to spread via blood-borne metastasis
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16
Q

What are the common sites of blood borne metastasis?

A
  • Lung
  • Liver
  • Bone
  • Brain
17
Q

Identify the five neoplasms that most frequently spread to bone?

A
  • Breast
  • Bronchus
  • Kidney
  • Thyroid
  • Prostate
18
Q

Using two examples, explain how different malignant tumours have “personalities” in terms of metastasis

A
  • Some malignant neoplasms are more aggressive and metastasise very early in their course e.g. small cell bronchial carcinoma
  • Some malignant neoplasms almost never metastasise e.g. basal cell carcinoma of the skin
19
Q

What determines the likelihood of metastasis?

A

The likelihood of metastasis is related to the size of the primary neoplasm (basis of cancer staging)

20
Q

What are some of the effects of neoplasms?

A
  • Direct local effects
  • Indirect systemic effects (aka paraneoplastic syndromes)
21
Q

What are the causes behind the local effects of primary and secondary neoplasms?

A
  • Direct invasion and destruction of normal tissue
  • Ulceration at a surface leading to bleeding
  • Compression of adjacent structures
  • Blocking tubes and orifices
22
Q

Identify some systemic effects of neoplasms

A
  • Thrombosis
  • Reduced appetite and weight loss (cachexia)
  • Immunosuppression (also due to direct bone marrow destruction)
  • Malaise
23
Q

Differentiate between the systemic effects of benign and malignant neoplasms

A
  • Benign neoplasms of endocrine glands are well differentiated so typically produce hormone e.g. a thyroid adenoma produces thyroxine
  • -* Malignant neoplasms sometimes also produce hormone e.g. bronchial small cell carcinoma produces ACTH/ADH, bronchial squamous cell carcinoma produces a PTH-like hormone
24
Q

Identify some miscellaneous systemic effects of neoplasms

A
  • Neuropathies affecting the brain and peripheral nerves
  • Skin problems e.g. pruritis, abnormal pigmentation
  • Fever
  • Finger clubbing
  • Myositis
25
Q

Provide definitions for the following terms:

  • Oncology
  • Clonal
  • Scirrhous
A
  • Oncology: the study of tumours or neoplasms
  • Clonal: the entire population of cells within a tumour arises from a single cell, that has incurred genetic change
  • Scirrhous: stony hard tumours
26
Q

Provide definitions for the following terms:

  • Cystadenoma
  • Polyp
  • Meningioma
A
  • Cystadenoma: benign epithelial neoplasm that forms large cystic masses
  • Polyp: benign/malignant neoplasm producing macroscopically visible projection above a mucosal or skin surface and projecting into a lumen
  • Meningioma: benign tumour arising from the dura (one of the meninges)
27
Q

Provide definitions for the following terms:

  • Rhabdomyosarcoma
  • Haemangioma
  • Angiosarcoma
A
  • Rhabdomyosarcoma: malignant tumour of striated muscle
  • Haemangioma: benign tumour of blood vessels, often in the skin, may present as a birthmark
  • Angiosarcoma: malignant neoplasm arising from vascular endothelial cells
28
Q

Provide definitions for the following terms:

  • Mesothelioma
  • Rhabdomyoma
  • Hepatocellular carcinoma
A
  • Mesothelioma: malignant neoplasm of mesothelium
  • Rhabdomyoma: benign tumour of striated muscle
  • Hepatocellular carcinoma: malignant tumour derived from hepatocytes
29
Q

Provide definitions for the following terms:

  • Naevus
  • Malignant melanoma
  • Hamartoma
A
  • Naevus: a congenital growth/mark on the skin (mole – benign melanocytic tumour)
  • Malignant melanoma: malignant tumour of melanocytes, usually in the skin

- Hamartoma: mass of disorganised but mature specialised cells/tissue resembling the cells of its origin

30
Q

Provide definitions for the following terms:

  • Seminoma
  • Teratoma
  • Choriocarcinoma
A
  • Seminoma: malignant germ cell tumour, usually of the testis
  • Teratoma: germ cell tumor composed of multiple tissues (which can be derived from all three germ layers), malignant in the testes, benign dermoid cysts in the ovaries
  • Choriocarcinoma: malignant tumour derived from trophoblastic tissue that develops typically in the uterus following pregnancy, miscarriage or abortion
31
Q

Provide definitions for the following terms:

  • Astrocytoma
  • Papilloma
A
  • Astrocytoma: malignant tumour of the astrocytes of the CNS
  • Papilloma: benign epithelial neoplasm producing micro-/macroscopically visible finger-like/warty projections from the epithelial surface
32
Q

Hypercalcaemia can be due to both benign and malignant neoplasms, and the mechanisms generally differ between the two types.

Which benign tumours cause a high serum calcium and how?

A

Primary parathyroid adenomas produce hyperparathyroidism:

  • Raised serum ionised calcium and bone resorption
  • Hypophosphataemia
  • Increased excretion of calcium and phosphate in the urine
33
Q

What is paraneoplastic syndrome?

A

Paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells

34
Q

Hypercalcaemia can be due to both benign and malignant neoplasms, and the mechanisms generally differ between the two types.

Which malignant tumours cause high serum calcium and how?

A
  • Ectopic secretion of PTH-related protein in a paraneoplastic syndrome:

I. Mediated by humoral factors excreted by tumour cells / an immune response against the tumour

II. Carcinomas of the breast, kidney, ovary, lung e.g. squamous cell bronchogenic carcinoma

  • Destruction of bone tissue:

I. Primary tumours of bone e.g. multiple myeloma, leukaemia

II. Diffuse skeletal metastases e.g. breast cancer

35
Q

What are the symptoms of hypercalcaemia?

A
  • Painful bones (fractures)
  • Renal stones
  • Abdominal groans (constipation, peptic ulcers, pancreatitis, gallstones)
  • Psychiatric moans (depression, lethargy, seizures)
36
Q

Anaemia (low haemoglobin) can be either the presenting feature of a tumour or a major complication.

What types of anaemia can occur?

A
  • Microcytic anaemia due to chronic external haemorrhage
  • Anaemia of chronic disease secondary to cytokine production
  • Myelophthisic anaemia due to space occupying lesions that destroy bone marrow
  • Immunohaemolytic anaemia secondary to reaction to tumour/drugs
  • Aplastic anaemia secondary to irradiation or drugs
  • Megaloblastic anaemia secondary to folate acid antagonists
37
Q

Which tumours cause anaemia and how?

A
  • Chronic blood loss – gastric carcinoma, colonic carcinoma, renal or bladder tumours, uterine cancer
  • Anaemia of chronic disease – Hodgkin’s lymphoma, carcinomas of lung and breast
  • Myelophthisic anaemia – carcinomas of breast, lung and prostate
  • Immunohaemolytic anaemia – lymphomas and leukaemias
38
Q

Cachexia (severe weight loss and debility) is a common feature of malignancy.

What are the various factors which are involved in its aetiology and how do they exert their effects?

A
  • Increased expenditure of resting energy due to cytokines produced by the tumour e.g TNF, IL1, IL6, interferon gamma
  • Production of lipid and protein-mobilising factors
  • Anaemia and decreased food intake

Year 1 Semester 2 Pathological Processes (15 decks)

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