Neoplasia

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Incidence

Back 1

number of NEW cases/year

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Prevalence

Back 2

number of existing cases at any moment in time

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Deadliest Cancer in NA

Back 3

LUNG, then prostate/breast, colon, rectal

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Oncology

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Study of neoplasms

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Neoplasm

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uncontrolled growth of new cells, benign or malignant

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Benign neoplasms

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- arenot capable of metastasizing and usually do not cause death.

- are defined by behaviour not by appearance.

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Adenoma

Back 7

benign neoplasm of gland

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Malignant neoplasm

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- capableof metastasizing and causing death.

- defined by behaviour not by appearance.

- ie. Cancer

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Tumour

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- amass, this term is sometimes used instead of neoplasm. However not all tumoursare masses

- e.g. leukaemias, the white cells are in the blood and bone marrowbut not in masses.

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The biological capabilitiesof neoplasia

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1. Self-sufficiencyof growth (OUT OF CONTROL)

2. Evasionof growth suppression signals (NOBRAKES)

3. Cells divide indefinitely (UNLIMITEDREPRODUCTION)

4. Avoidapoptosis (LIVEFOREVER)

5. Makenew blood vessel supply to increase nutrients (OVER FEED)

6. Invadenearby tissue and spread to distant site (FAME IS SPREADING - MALIGNANTNEOPLASMS only).

7. Evadeimmune surveillance, the cancer detection and destruction system in the healthybody (POLICEAND ARMY CORRUPTED)

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Carcinoma

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malignant neoplasm of epithelial cells (e.g. breast,prostate, bronchus)

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Sarcoma

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malignant neoplasm of mesenchymal cells (e.g. bonecartilage, fat, muscle or fibrous tissue).

Front 13

Tumour naming

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Origin + Benign or Malignant

i.e. Fibrous tumour that is benign = Fibroma

i.e. Blood vessel tumour that is malignant = Haemangiosarcoma

Blood cells: Granulocytes and Lymphocytes = Malignant and called Leukaemia in blood or Lymphoma in lymph or organs.

Names are not always consistent: Melanoma is malignant tumour of melanocytes, nevus is the name for benign.

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Molecular basis of neoplasms

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· Damaged DNA is the cause of all neoplasms. [this may not be entirely true, perhaps the problemis lack of the ability to efficiently remove damaged DNA]

· Neoplasmsrequire nutrients and an adequate blood supply.

· Neoplasmstake many years to grow to a clinically detectable size.

· Thetransformation of cells from benign to malignant is slow.

· Malignantcells have a distinctive appearance and behaviour.

· Malignantcells do not spread unless they can invade the blood vessels or the lymphsystem.

· Malignantcells spread best in clusters. Alone they die.

· The immune system plays an important rolein (some) cancer prevention.

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Mutations

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Almostall leading to cancer are defects in somatic cells. Themutations are the result of age, viruses, chemicals or radiation and are notheritable.

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Oncogenes

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- mutated forms ofnormal genes called proto-oncogenes. These genes code for proteins thatregulate normal cellular growth processes such as proliferation,differentiation and programmed cell death. There are five major groups: growth factors, growth factor receptors,signal transducers, transcription factors and programmed cell death regulators.

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Most common gene that is mutated in cancer is called?

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- p53

- normally causes natural cell death, apoptosis of cells with damaged DNA

Front 18

Aneuploid

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- In healthy cellsthere is one set of normal chromosomes but in tumours the nucleus can containmore than one set.

- Thenucleus is enlarged and dark coloured because of the increased amount of DNA.

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Carcinogenesis

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Canceris caused by a transformation of a cell, followinginjury that damages DNA, mutagenesis.

Front 20

Tumour Suppressor Gene

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- genesthat are the “off” or “stop” switches.

- They lead to the production of proteins that inhibitcell division.

- If a tumour suppressor gene is damaged then cell growth isuninhibited e.g. the RB gene defect that leads to familial retinoblastoma ininfants is a growth suppressor gene

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Proto-oncogenes

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Allcells contain genes that function as “on” or “off” switches for cell growth. Usuallythere is a balance. Theses are the “on” genes. Theycause the production of proteins that promote growth and stimulate normal celldivision.

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Two pathways to cancer

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1) Chronic Inflammation: Barrett oesophagitis caused by GERD

2) Abnormal epigenetic regulation: BRCA genes

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Polyp

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lump sticking out, common tumour shape.

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Papilloma

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tumour growing in a fern-like pattern (like broccoli)

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Cystic

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tumour with a hollow centre

Front 26

Hyperchromatism

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Malignanttumours have nuclei that are large and dark from the excess DNA present.

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Atypia/anaplasia

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degreeto which the individual nuclei are different from normal nuclei.

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Mitotic figures

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tumouris growing rapidly then cells may be seen to be rapidly dividing.

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Premalignant states and the evolution of cancer

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1. Dysplasia – large dark nuclei. May not progress tocancer but is a concern if seen.

2. Carcinomain situ – fully malignantcancer. The basement membrane is intact in epithelial cancers. E.g. colonicpolyp. This stage is always curable.

3. Earlyinvasive carcinoma - themalignant cells have broken the basement membrane but have not yet got into thelymphatic or vascular system.

4. Invasionof blood vessels or lymphatics with metastasis – distant metastases will result.

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Some diseases predispose to cancer – premalignant conditions. Someexamples:

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· Human papilloma virus (HPV) infection causes almost alldysplasia, carcinoma in situ and invasive carcinoma of the cervix. Only 3 of 15HPV types actually cause cancer. Encouraging the growth of the other HPV typesmay be the most effective control of the malignant three.

· Chronic atrophic gastritis may cause gastric carcinoma.

· Barrett’s metaplasia of the oesophagus may cause oesophageal cancer.

· Adenomatous polyps and ulcerativecolitis may go on to colon cancer.

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Well differentiated

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like normal cells (benign tumours)

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Poorly differentiated

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Malignant, unlike normal.

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Clones of cells

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Tumour cells are sets of identical cells that descend from a clone.

All tumours are MONOCLONAL.

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Tumour growth fraction

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- ~30generations (doubling) for a tumour mass to grow to a size that may be seen orfelt (the size of a grape).

- How rapidly a tumour grows depends on the number of cells that aredividing at the sampling time.

- Leukaemia and lymphomas do so at a high rate.

Front 35

Angioneogenesis

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Tumours develop their own blood supply.

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Tumour cell variation

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- as tumours grow they may diverge into cell lines withdifferent characteristics. Each cell line has a different mutation – tumourcell heterogeneity.

- In therapy the more normal cell lines may perish and themost malignant ones survive.

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Spread of neoplasia - Invasiveness

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- ability of aneoplasm to invade tissue. The invasion could lead to an obstruction as inbronchial carcinoma but the most common property is metastasis.

- This may be byseeding, travelling in fluids from one place to another in the body.

- Sarcomas generallyspread to the blood and invade widely.

- Carcinomas invadelymphatics first and spread to local lymph nodes. These can be surgicallyremoved.

Front 38

Immune Surveillance

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Asneoplasms grow they become less and less like the cells of “self” and so theimmune system can attack them.

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Signs and symptoms of cancer

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· Change in bowel habit – colon or bladder cancer.

· A sore that does not heal – malignant melanoma.

· Unusual bleeding or discharge – breast, intestinal,cervical or uterine cancer.

· Thickening or a lump – breast and others.

· Indigestion of difficulty swallowing – throat oroesophageal cancer.

· Obvious change in a wart or mole – malignant melanoma.

· Nagging cough or hoarseness – lung or laryngealcancer.

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Paraneoplastic syndrome

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- sometimes neoplasms have systemic effects

- This is due to hormones produced by thetumour. The hormone could be the usual one produced by the tissue e.g.pheochromocytoma, or it could be a hormone not usually produced by the tissuee.g. some lung cancers.

- Tumoursmost commonly causing paraneoplastic syndrome are carcinoma of the lung, renalcell carcinoma and tumours of the endocrine glands.

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Cachexia

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- muscle and body fat wasting

- common in cancer

- likely due to high metabolic rate induced by tumour

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Cancer grading

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- microscopic assessment of degree of cell differentiation

- staged I-IV or I-III (Gleason score for prostate cancer)

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Cancer staging

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- clinically basedfrom size and spread of the cancer as assessed by history, physicalexamination, pathology and diagnostic imaging.

- Staging is betterthan grading for making decisions about therapy or prognosis.

- A common clinicalstaging system is the TNM system. T is the size of the primary tumour, N is forthe local lymph node involvement and M is for distant metastases.

Front 44

Gleason grades/score

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1. Thetissue is quite similar in appearance to healthy tissue. This is the leastaggressive grade.

2. Thetissue is a little different from normal tissue.

3. Thetissue is moderately different from normal tissue.

4. Thetissue is abnormally shaped and quite irregular.

5. Thetissue is very different from normal tissue; this is the most aggressive grade.

- Because the prostate gland tissue israrely homogenous, the cancer may be more aggressive in some areas than others.Two areas are looked at and the total of the 2 grades is known as the score.

Front 45

Duke system

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Stages Colorectal Cancer

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Ann Arbor System

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Stages Hodgkin and Non-Hodgkin lymphomas