Neoplasia I: Definition & Classification

Question 1

What is neoplasia?

Answer 1

Abnormal mass of tissue, the growth of which is uncoordinated with that of normal tissues and persists after the stimulus is removed.

Question 2

What is a tumour?

Answer 2

Swelling, generally without inflammation, caused by an abnormal growth of tissue whether benign or malignant.

Question 3

What are the major categories for cell types of origin for tumours?

Answer 3

-Epithelium
-Connective tissue
-Lymphoid/haematopoietic tissue
-Germ cells

Question 4

What is tumour differentiation?

Answer 4

Tumour differentiation refers to how well the tumour resembles its normal counterpart, both morphologically & functionally.

Question 5

Are well differentiated lesions more or less proliferative than the poorly differentiated ones?

Answer 5

Generally, well-differentiated lesions are less proliferative & less aggressive, with less potential for metastatic spread than their poorly differentiated counterparts.

There are exceptions

Question 6

What are the different grades of tumours?

Answer 6

Grade 1/well differentiated
Grade 2/moderately differentiated
Grade 3/poorly differentiated

Question 7

What are some important definitions regarding abnormalities of growth & can you give examples of each one

Answer 7

Hyperplasia: Increase in the number of cells in a tissue.
Eg: Bone marrow cells in people living at high altitudes

Hypertrophy: Increased in the size of cells in a tissue eg: Bodybuilders/athletes

Atrophy: Reduction in the size of cells in a tissue. Eg: Muscle atrophy in a dis-used limb

Involution: Breast tissue on cessation of breastfeeding

Metaplasia: A change from one to another normal differentiated cell type within a tissue. Eg: Barrett’s oesophagus

Dysplasia: A state in some tissues which denotes an increased risk of
malignant change. Eg: Cervical screening

Question 8

How do you differentiate benign neoplasia from malignant neoplasia?

Answer 8

Benign:
-Well differentiated, likely to resemble tissue of origin
-Slow growth
-Mitotic figures rare and normal
-Well demarcated
-Expansible growth
-Do not metastasise

Malignant:
-Spectrum of differentiation from well to poorly differentiated
-Growth rate variable and less predicable
-Mitotic figures may be numerous and atypical
-Poorly demarcated
-Locally invasive
-Regional and distant metastasis

Metastasise = Spread to other parts of the body

Question 9

Which tumours are more common?

Answer 9

epithelial

Question 10

What are the general rules for tumour nomenclature ?

Answer 10

Generally speaking for epithelial tumours, if the suffix is carcinoma it’s malignant and if it’s papilloma or adenoma, it’s benign

For mesenchymal tumours, if the suffix is sarcoma, it’s malignant and if it’s just -oma, then it’s benign

The prefix of the tumour will always refer to the type of tissue of origin e.g. osteoma (osteo meaning bone)

Question 11

What are some individual tumour names we should be familiar with?

Answer 11

Lymphoma- malignant tumours of the lymphoid system

Melanoma- malignant tumour of melanocytes

Leukaemia- malignant tumour of bone marrow cells

Teratoma- a tumour which includes elements of all 3 embryonic germ layers

Hamartoma- a developmental anomaly (not actually a tumour)

Question 12

What can cause tumours?

Answer 12

Genetic predisposition, surrounding tissues e.g. inflammation, environmental/social/infectious factors

Some cancers can also be caused by viruses and infection

Question 13

what cancer is caused by a virus?

Answer 13

Cervical, oropharyngeal and anal squamous cell carcinoma: high risk
HPV
“Oropharyngeal HPV associated squamous cell carcinoma”

Nasopharyngeal carcinoma and Burkitts lymphoma: EBV

Kaposi sarcoma: HHV-8 (human herpes virus 8

Question 14

what cancers are associated with infections and inflammation?

Answer 14

Hepatitis and liver cancer (hepatocellular carcinoma)

H pylori and gastric cancer (adenocarcinoma)

Pancreatitis and pancreatic cancer (adenocarcinoma)

Question 15

What are the different ways that malignant tumours spread?

Answer 15

Direct- local infiltration

Lymphatic- to regional lymph nodes

Haematogenous- lungs, liver, bone

Peri-neural- salivary tumours

Trans-coelomic- pleura, pericardium, peritoneal

Question 16

What forms the lining of the oral mucosa?

Answer 16

Squamous epithelium

Question 17

How do squamous cells infiltrate & become malignant cells?

Answer 17

They undergo genetic changes & lose those tight attachments to each other

They disrupt/dissolve the basement membrane & then they gain the ability to enter connective tissues and acquire mobility

Question 18

What are the sequence of events that makes it go from a primary to a metastatic tumour?

Answer 18

Tumour cells secrete vascular growth factors- encourages angiogenesis (formation of new blood vessels)

Well vascularised tumour has good supply of nutrients & oxygen so can keep growing at an abnormal rate

Large sheets of tumour cells detach by downregulating proteins that normally mediate their connections

Then, invasion of connective tissues towards blood vessels & lymphatic channels happens and this involves acquiring mobility

Evasion of host defences follows

Then, migration through vessel wall & a formation of a tumour embolus happens as well as further evasion of host defences

Next we have adhesion to vessel wall, and they can utilise processes very similar to inflammatory cell extravasation to gain access to the tissues

Finally, there is invasion of new host tissue & angiogenesis again

Question 19

What are some non-malignant effects of tumours?

Answer 19

Increased tendency to thrombosis

Cellular overactivity

Paraneoplastic phenomenon - set signs and symptoms that are a consequence of the presence of the tumour but not directly attributable to it.

Question 20

What are some factors that affect prognosis of tumours?

Answer 20

-Tumour type
-Site and size; resectability
-Differentiation
-Degree of cellular atypia (cellular state of not being typical)
-Depth and extent of invasion
-Mitotic index and degree of mitotic atypia
-Regional lymph node involvement
-Distant metastasis

Question 21

What prognostic index is used for colorectal cancer?

Answer 21

Dukes staging:

Dukes A being confined to the bowel wall whereas Dukes D is distant metastases

Question 22

What prognostic index is used for melanoma?

Answer 22

Clark Levels (level 1 being the least invasive and level 5 being the most)

Question 23

What prognostic index can we use for histological images?

Answer 23

Mitotic count,

Question 24

How do you diagnose a tumour?

Answer 24

You need a tissue sample for diagnosis of presence of a tumour and also to sub-type it

Radiology can help to define size, extent and structures involved and might give some clues as to the tumour type Tissue:

-Fine needle aspirate (FNA)
-Histology (biopsy)

Question 25

What is screening?

Answer 25

The systematic search for cancer in people who have no signs or symptoms of cancer.

Question 26

What are a couple of issues with screening?

Answer 26

False positives

Over diagnosis e.g some people with papillary thyroid cancer are not affected at all during their lifetime.

Question 27

Why is screening common for cervical, breast, & colorectal cancer but not for lung, thyroid, & prostate cancer?

Answer 27

Lung: CT screening 70-90% patients had 1 false positive result– remember radiological examination does not diagnose cancer and consider the radiation dose for a CT chest

Prostate: PSA screening 25-30% of patients had 1 false positive result – equally a simple blood test cannot differentiate a hyperplastic prostate from a malignant one

Question 28

What is the difference between staging and grading?

Answer 28

Grading is tumour differentiation (well, moderate, poor)

Staging uses a T N M classification (T-tumour; N-lymph nodes; M-metastasis) and it’s all about prognosis