Session 8 ILO's Neoplasia 1

Question 1

Neoplasm

Answer 1

Neoplasm = abnormal growth of cells that persists after the initial stimulus is removed (irreversible)

Question 2

Dysplasia

Answer 2

Dysplasia = pre-neoplastic alteration in which cells show a disordered tissue organisation (technically reversible)

Question 3

Tumour

Answer 3

Tumour = a swelling i.e. any clinically detectable lump or swelling

Question 4

Cancer

Answer 4

Cancer = colloquial term for a malignant neoplasm which is: abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with the potential to spread to distant sites

Question 5

Metastasis

Answer 5

Metastasis = a malignant neoplasm that has spread from its original site to a new, non-contiguous site

Question 6

Anaplasia

Answer 6

Anaplasia = cells with no resemblance to any tissue; cells appear primitive and lack specialization along any particular cell line

Question 7

Pleomorphism

Answer 7

Pleomorphism = variety in cell size or shape (i.e. a large hyper chromatic nucleus with a high nucleus to cytoplasm ratio)

Question 8

Progression

Answer 8

Progression = process by which a neoplasm arises from monoclonal cells, followed by the accumulation of yet more mutations

Question 9

Differentiation

Answer 9

Differentiation = the process of becoming different by growth or development

Question 10

In situ

Answer 10

In situ = no invasion through epithelial basement membrane

Question 11

Understand, explain and define the terms: neoplasm, dysplasia, tumour, cancer, metastasis, anaplasia, pleomorphism, progression, differentiation and in situ.

Answer 11

Neoplasm = abnormal growth of cells that persists after the initial stimulus is removed (irreversible)

Dysplasia = pre-neoplastic alteration in which cells show a disordered tissue organisation (technically reversible)

Tumour = a swelling i.e. any clinically detectable lump or swelling

Cancer = colloquial term for a malignant neoplasm which is: abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with the potential to spread to distant sites

Metastasis = a malignant neoplasm that has spread from its original site to a new, non-contiguous site

Anaplasia = cells with no resemblance to any tissue; cells appear primitive and lack specialization along any particular cell line

Pleomorphism = variety in cell size or shape (i.e. a large hyper chromatic nucleus with a high nucleus to cytoplasm ratio)

Progression = process by which a neoplasm arises from monoclonal cells, followed by the accumulation of yet more mutations

Differentiation = the process of becoming different by growth or development

In situ = no invasion through epithelial basement membrane

Question 12

Describe and understand the difference between in-situ and invasive malignancy.

Answer 12

In-situ = showing all the features of malignancy but no invasion through epithelial basement membrane

Invasive = penetrated through epithelial basement membrane and spreading to non-contiguous sites

Question 13

Explain how proto-oncogenes are involved in the development of neoplasms (7)

Answer 13

• A proto-oncogene is a normal gene that is found in a cell
• They’re are loads of them and they have multiple different functions
• All these functions participate in some way in the signalling pathways that drive proliferation (growth promoting genes)
• If a mutation occurs in one of these, it can be permanently and abnormally tuned on (even when it is not supposed to be)
• This promotes an excessive increase in its normal function ie growth
• Sometimes a mutation can impart a completely new function on the affected gene
• These are known as gain-of-function mutations
• These changes favour neoplasm formation

Question 14

Describe the science behind how porto-oncogenes work

Answer 14

• We have a proto-oncogene
• We get a mutation in it
• That forms an oncogene
• That oncogene will encode proteins, known as oncoproteins
• It is those oncoproteins that have the ability to continually promote cell growth in the absence of our normal cell growth promoting signals
• You only need 1 allele to be affected with that mutation for you to have that growth promotion (as oncogenes are dominant over their normal counterparts thus they can transform cells despite a normal copy of the same gene)

Question 15

Example of Proto-Oncogene mutation

Answer 15

BRAF (v600e) mutation

Question 16

Describe the normal function of tumour suppressor genes (3)

Answer 16

• Stop cell proliferation
• Help encourage repair damage to cellular DNA
• Cause damaged cells to undergo apoptosis

Question 17

Explain how tumour suppressor genes are involved in the development of neoplasms

Answer 17

• Normal function is to stop cell proliferation and thus suppress neoplasm formation
• When they become altered or inactivated as a result of mutation, it leads to failure of growth inhibition in cells
• Cells also stop undergoing apoptosis (programmed cell death)
• Tumor supressor genes tend to be recessive, so both alleles have to be damaged in order for the transformation to occur

Question 18

Explain how proto-oncogenes and tumour suppressor genes are involved in the development of neoplasms

Answer 18

Genetic alterations affect proto-oncogenes and tumour suppressor genes.

Proto-oncogenes become abnormally activated (when they are then called oncogenes), favouring neoplasm formation.

Tumour suppressor genes, which normally suppress neoplasm formation, become inactivated.

Question 19

Describe and understand the difference between benign and malignant tumours including macroscopic and microscopic features and biological behaviour.

Answer 19

Macroscopic/Microscopic differences:

Benign: (5)

• Cells are uniform throughout tumour
• Normal or mild increase in nuclear to cytoplasmic ratio
• Few mitoses
• Well differentiated (closely resemble parent cell/tissue)
• They have a pushing outer margin

Malignant: (5)

• Cells/nuclei vary in size and shape (pleomorphism)
• High nuclear to cytoplasmic ratio
• Many mitoses including abnormal forms
• Range from well to poorly differentiated(depends on proximity to origin) but in general, failure to differentiate fully
• Irregular outer margin and shape

Biological behaviour :

Benign Tumours: (4)
•Grow in a confined local area 
•Do not produce metastases 
•Rarely dangerous (location) 
•Retained functions of their cells of origin

Malignant tumours: (5)
•Expansive and invasive
•Potential to metastasise 
•May have ulcerations and necrosis 
•Infiltrative 
•Less likely to retain functions of cells of origin and may sometimes acquire unexpected functions due to derangements in differentiation

Question 20

Understand the reasoning behind the nomenclature given to benign and malignant neoplasms and the exceptions to this rule

Answer 20

Benign - end in ‘oma’ regardless of cell type
Malignant - ends in ‘carcinoma’ (if epithelial) or ‘sarcoma’ (if stromal)

Testicular neoplasms are the exceptions

A malignant tumours of the testis = all end in ‘Oma’
e.g. teratoma and seminoma = malignant

In the ovary, a teratoma is benign (ie dermoid cyst) so rule is not exception in ovaries

Question 21

Identify the types of cancers that most commonly arise in certain organs and why

• Bladder
• Oesophagus
• Stomach/Bowel
• Skin
• Lung
• Breast/Prostate
• Brain
• Thyroid/Pancreas/Uterus
• Cervix

FIND OUT WHY

Answer 21

• Bladder – transitional cell carcinoma
• Oesophagus – squamous cell carcinoma, adenocarcinoma
• Stomach/Bowel – adenocarcinoma
• Skin – squamous cell carcinoma, malignant melanoma,
  basal cell carcinoma
• Lung – adenocarcinoma, squamous cell carcinoma, small cell carcinoma
• Breast/Prostate – adenocarcinoma
• Brain –astrocytoma
• Thyroid/Pancreas/Uterus – adenocarcinoma
• Cervix – squamous cell carcinoma

Question 22

Explain the concept of clonality of neoplasm

Answer 22

Clonality: the concept that a collection of cells is monoclonal if they all originated from a single founding cell.

Neoplastic cells tend to be monoclonal.

Neoplasia is caused by accumulated mutations in somatic cells; mutations are caused by initiators (mutagenic agents) and promoters (cause cell proliferation). Together, initiators and promoters result in an expanded, monoclonal population of mutant cells.

Question 23

Hall Marks of Malignancy

Answer 23

With worsening differentiation the individual cells have:

• Increasing nuclear size
• Increased nuclear to cytoplasmic size
• Increased nuclear staining (hyperchromasia)
• Increased numbers of mitotic figures
• Abnormal mitotic figures (Mercedes Benz)
• Variation in size and shape of cells and nuclei (pleomorphism)

Question 24

Recognise the histological characteristics of certain common neoplasms e.g. squamous cell carcinoma, adenocarcinoma, melanoma.

COME BACK TO WHEN IPAD PENCIL WORKS

Answer 25

• We have a proto-oncogene
• We get a mutation in it
• That forms an oncogene
• That oncogene will encode proteins, known as oncoproteins
• It is those oncoproteins that have the ability to continually promote cell growth in the absence of our normal cell growth promoting signals
• You only need 1 allele to be affected with that mutation for you to have that growth promotion (as oncogenes are dominant over their normal counterparts thus they can transform cells despite a normal copy of the same gene)