Neoplasia 2. Lecture 9. Pathology and Clinical Science 1 (BIOC211) Department of Bioscience. endeavour.edu.au

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1 Neoplasia 2 Lecture 9 Pathology and Clinical Science 1 (BIOC211) Department of Bioscience Text Reference: Grossman, S.C. & Porth, C.M. (2014). Porth s Pathophysiology: concepts of altered health states, (9th ed.). Philadelphia, U.S.A. Walters Kluwer Health - Lippincott, Williams & Wilkins. endeavour.edu.au

2 Session Learning Outcomes This session aims to understand and discuss: o Identify characteristic of benign and malignant tumours o Local and systemic effects of tumour o Metastasis o Identify progressive cellular changes to produce a malignant tumour o Staging of cancer o General management principles for cancer Endeavour College of Natural Health endeavour.edu.au 2

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4 Benign and Malignant Tumours o Benign are less serious than malignant o Both can cause problems through compression or obstruction, alteration of hormone synthesis, bleeding and infections o Benign: o Malignant: Comparison: Benign vs. Malignant Endeavour College of Natural Health endeavour.edu.au 4

5 Characteristic of Benign and Malignant Tumours BENIGN o Usually consist of differentiated cells that reproduce at a slightly faster rate than normal o Often encapsulated o Expands but does not spread o Tissue damage results from compression of adjacent structures such as blood vessels o Not life threatening unless in delicate location such as brain where compression could cause serious damage MALIGNANT o Cells are undifferentiated and non-functional cells o Cells are varied in size and shape o Cells reproduce much more rapidly than normal o Tumour cells infiltrate or spread to surrounding tissue o Generally not encapsulated o Tumour cells detach or break off and spread to other organs and tissues - metastasise- spread to other parts of the body via the blood and lymphatics Endeavour College of Natural Health endeavour.edu.au 5

6 Leiomyoma (benign) Leiomyosarcoma (malignant) From Basic Pathology. (6 th ed., p. 141), by V. Kumar & S. Robbins 1997, Philadelphia, W B Saunders Company Endeavour College of Natural Health endeavour.edu.au 6

7 Local Effects of Tumours o Pain Absence of pain in early formation, presence in advanced stages Severity of pain depends on tumour location o Potential causes of pain Direct pressure on nerves Stretching of a visceral capsule Infection Ischemia Bleeding Irritation of nerve endings by chemical mediators Endeavour College of Natural Health endeavour.edu.au 7

8 Local Effects of Tumours o Obstruction compression of duct or passageway Blood supply or lymphatic flow leading to ulceration or oedema Air flow o Tissue necrosis and ulceration Lack of blood supply o Infection Opportunistic As a result of ulceration and cell death Endeavour College of Natural Health endeavour.edu.au 8

9 Systemic Effects of Tumours o Cachexia Contributed by anorexia, fatigue, stress Altered carbohydrate and protein metabolism Cachexic factors produced by macrophages. This leads to added fatigue, weakness and tissue breakdown o Anaemia Decreased haemoglobin as a result of anorexia Bleeding and blood loss Depression of bone marrow o Infections Increase as general immunity declines Frequent infections. Endeavour College of Natural Health endeavour.edu.au 9

10 Systemic Effects of Tumours o Bleeding tumour cells may erode blood vessels or cause tissue ulceration Chronic blood loss leads to iron deficiency anaemia o Paraneoplastic syndromes Additional problems associated with certain tumours Substances that are released from the tumour can have other effects such as: Affect neurological function Blood clotting Hormone secretion o Metastasis Endeavour College of Natural Health endeavour.edu.au 10

11 Metastasis is: Metastasis o Spreading to distant sites by blood and lymph o Cancer cells move along in a vein, lodge in a hospitable environment and cause secondary tumours o Common sites for secondary tumour development: - Lungs - Liver - Bones - Brain Endeavour College of Natural Health endeavour.edu.au 11

12 Metastatic Cascade Sequential steps involved in the hematogenous spread of a tumour From Basic Pathology. (6 th ed., p. 162), by V. Kumar & S. Robbins 1997, Philadelphia, W B Saunders Company Endeavour College of Natural Health endeavour.edu.au 12

13 Metastasis o Defined as the spread of the tumour to distant sites by the blood and lymphatics o Leads to the development of secondary implants (metastases) at distant locations o Only a few tumour cells survive but only one surviving cell can start a secondary tumour o One or more methods of spread depending on the characteristics of the specific tumour Endeavour College of Natural Health endeavour.edu.au 13

14 Mechanisms of Metastasis o Invasion- Local spread to adjacent tissues o Metastasis- spread to distant sites via blood or lymphatics o Seeding- Spread of cancer cells along membranes, usually in body cavities Can lead to the development of multiple tumours Endeavour College of Natural Health endeavour.edu.au 14

15 Liver metastases From Basic Pathology. (6 th ed., p. 139), by V. Kumar & S. Robbins 1997, Philadelphia, W B Saunders Company Endeavour College of Natural Health endeavour.edu.au 15

16 Staging of Cancer o Describes the extent of the disease & affects the corresponding potential for treatment and prognosis o Staging systems are based on the: Size of the tumour Extent of involvement of regional lymph nodes Evidence of metastatic spread Endeavour College of Natural Health endeavour.edu.au 16

17 Staging of Cancer Staging: Breast Cancer o Stage I- tumour 2 cm or less in diameter o Stage II- tumour less than 5 cm in diameter o Stage III- tumour larger than 5 cm in diameter o Stage IV- tumour of any size but fixed to chest wall or skin Endeavour College of Natural Health endeavour.edu.au 17

18 T 0 N 0 Staging of Cancer Local tissue Local tissue Local tissue organ organ organ 1 2 Local tissue organ M 0 1 B ones lungs liver B ones lungs liver B ones lungs liver Dr Kunjal Dave Endeavour College of Natural Health endeavour.edu.au 18

19 Grading and Staging of Tumours o Grade l - Cells are well differentiated o Grade ll - Less differentiation o Grade lll - Poor resemblance to normal tissue - Greater nuclear pleomorphism - Increased mitotic activity From Pathology. )2 nd ed., p. 88), by A. Stevens & J. Lowe. 2000, London. Mosby, Harcourt Publishers Ltd. Endeavour College of Natural Health endeavour.edu.au 19

20 Immune Role & Host Defence o Immuno-surveillance not very successful as the tumour cells express self antigens. Cytotoxic T cells and NK cells can lyse some tumour cells if recognised Obstacles to Success o Poor immunogenicity: some tumours do not express novel proteins or peptides so immune cells see the tumour as a normal part of the body. Also, there is a lack of adhesion molecules and costimulatory molecules, which are required to activate the cytotoxic cells to kill. Endeavour College of Natural Health endeavour.edu.au 20

21 Immune Role & Host Defence Obstacles to Success o Antigen variation: Changing cell surface expression: many tumours change what is expressed on their cell surface and/ or down-regulate MHC molecules to evade detection. o Immunosuppression: some tumours produce cytokines that suppress immune function Co-morbidities. i.e., HIV o Availability: Solid tumours- difficult for the immune cells to reach all the cells Endeavour College of Natural Health endeavour.edu.au 21

22 Epidemiology o Cancer epidemiology can contribute important information about the risk factors for the development of cancer o The association of smoking with lung cancer was derived from epidemiological studies o The association of high dietary fat and low dietary fibre with colon cancer Endeavour College of Natural Health endeavour.edu.au 22

23 Occupational Risks for Cancers AGENT CANCER OCCURRENCE Arsenic lung, skin metal melting alloys, electrical devices Asbestos lung,(mesothelioma) brake linings, heat resistant material Benzene Leukemia Hodgkin lymphoma light oil, solvents, dry cleaning Cadmium Prostate solders, batteries Vinyl chloride liver refrigerant, plastics Endeavour College of Natural Health endeavour.edu.au 23

24 Cancer Risk Factors & Prevention Risk Factors o Genetic factors - Brca-1 & Brca-2 oncogenes in breast cancer o Virus exposure Human Papilloma Virus in cervical cancer o Radiation UV in Melanoma, radioactive material in Leukaemia (certain types) o Chemicals Asbestos in mesothelioma, benzene in bladder cancer o Biological factors chronic irritation and inflammation in colon cancer, age & hormones in breast & uterine cancer o Diet - additives, processing methods ie. sodium nitrate in gastric cancer o Immunodeficiency HIV and Karposi s sarcoma Endeavour College of Natural Health endeavour.edu.au 24

25 Cancer Risk Factors & Prevention Prevention o Limit sun exposure o Reducing fat intake especially heated unsaturated fats (trans FA) o Increase anti-oxidant levels - protect against free radicals o Avoid carcinogens o All of the above are preventative health measures Endeavour College of Natural Health endeavour.edu.au 25

26 Tumour Markers Early Detection Endeavour College of Natural Health endeavour.edu.au 26

27 Treatment Surgery Used for the removal of solid tumours Aims to remove the boundaries and margins of the tumour Sometimes the complete removal of the tumour is impossible Removal of surrounding lymph nodes Often combined with chemotherapy and/or radiotherapy Endeavour College of Natural Health endeavour.edu.au 27

28 Treatment Chemotherapy & Radiation o Administered repeatedly at intervals that maximise tumour killing and minimise damage to normal tissue o Not all cancer cells are destroyed in one treatment o Not all cancer types are susceptible to this type of treatment o Treatment is usually long term whether curative or palliative o Serious side effects are common Combination Therapy o Treatment may aim at being either: Curative Palliative Endeavour College of Natural Health endeavour.edu.au 28

29 Treatment Chemotherapy - Management of metastases - Rounds of treatment Radiotherapy - Management of primary tumour or larger metastases - Management of obstructing or compressing tumours - Management of inoperable tumours - 5 days per week for 5-6 weeks Endeavour College of Natural Health endeavour.edu.au 29

30 Side Effect Chemotherapy Chemotherapeutic agents target rapidly dividing cells, so adverse effects will present in tissues containing rapidly dividing cells: o Depression of bone marrow and dangerously low blood counts may require transfusion o Thrombocytopenia- haemorrhage o Leukopenia- severe infection potential o Vomiting effect of the drug, damage to the GIT o Vomiting effect of the drug, damage to the GIT o Vomiting effect of the drug, damage to the GIT o Individual drug related pathologies Endeavour College of Natural Health endeavour.edu.au 30

31 Side Effect Radiation Therapy o Depression of bone marrow therefore decreased leukocytes o Infection risk is greatly increased o Bleeding from decreased platelets o Burns to the skin o Alopecia o Damage to digestive tract involving nausea and vomiting, diarrhoea, malnutrition, inflammation and ulceration, bleeding. Ulceration to oral mucosa can occur with head and neck radiation o Sterility if radiation to abdominopelvic region o Fatigue and lethargy o Inflammation, necrosis and scar tissue formation along the path of radiation and at the tumour site Endeavour College of Natural Health endeavour.edu.au 31

32 Immunotherapy Oncogenic virus injected Tumour develops Tumour excised Tumour cells extracted Tumour cells injected into 2 nd mouse Tumour develops in 2 nd mouse Two outcomes Tumour excised from 2 nd mouse Original tumour cells reinjected Mouse rejects tumour transplanted cells and survives Untreated mouse dies From Essential Pathology. (3rd ed., p. 115) by E. Rubin Philadelphia. Lippincott, Williams & Wilkins Endeavour College of Natural Health endeavour.edu.au 32

33 Prognosis & Care o Cure - defined as 5 year survival with no return of symptoms o Remission and exacerbations are common o Early diagnosis and treatment often limit the extent of the illness o Can get remissions just prior to the disease becoming terminal o Death rates for different cancers vary greatly Important aspects and principles of palliative care including: o Pain management o Psychological support o Spiritual counselling o Management of symptoms o Nutrition Endeavour College of Natural Health endeavour.edu.au 33

34 Hepatocellular Carcinoma From Liver Tumor Center. Johns Hopkins University. Retrieved from Endeavour College of Natural Health endeavour.edu.au 34

35 Liver Cancer Hepatocellular Carcinoma Secondary Liver Cancer Endeavour College of Natural Health endeavour.edu.au 35

36 Readings and Resources Resources: o o Set Textbooks: Colledge, N.R., Walker, B.R. & Ralston S.H. (2014). Davidson s Principles and Practice of Medicine, (22nd ed.). Edinburgh. Churchill Livingstone. Grossman, S.C. & Porth, C.M. (2014). Porth s Pathophysiology: concepts of altered health states, (9th ed.). Philadelphia, U.S.A. Walters Kluwer Health - Lippincott, Williams & Wilkins. Additional textbooks: Davies, A. & Moores, C. (2010). The respiratory system: basic science and clinical conditions, (2 nd ed.). Edinburgh. Churchill, Livingstone, Elsevier. Field, M., Pollock, C., Harris, D. (2010). Systems of the Body: The Renal System; Basic Science and Clinical Conditions. (2 nd ed.). United Kingdom: Churchill Livingstone. Jamison, J.R. (2006) Differential Diagnosis for Primary Care: a handbook for health care practitioners. (2 nd ed.). Edinburgh. Churchill Livingstone. Lee, G. & Bishop, P. (2013). Microbiology and Infection Control for Health Professionals, (5th ed.). Frenchs Forest, NSW. Pearson Education. McCance, K.L. & Huether, S.E. (2014). Pathophysiology: the biological basis for disease in adults and children, (7 th ed.). St. Louis, MO. Elsevier. Murphy, K. (2011). Janeway s immunobiology, (8 th ed.). New York. Garland Science. Noble, A., Johnson, R. & Bass, P. (2010). The cardiovascular system: basic science and clinical conditions, (2 nd ed.). Edinburgh. Churchill, Livingstone, Elsevier. Pagana, K.D. & Pagana, T.J. (2013). Mosby s diagnostic and laboratory test reference, (11 th ed.). St. Louis, MO. Elsevier. Smith, M.E. & Morton, D.G. (2010). The digestive system: basic science and clinical conditions, (2 nd ed.). Edinburgh. Churchill, Livingstone, Elsevier. VanMeter, K.C. & Hubert, R. (2014). Gould s pathophysiology for health professions, (5 th ed.). St. Louis, MO. Elsevier. Endeavour College of Natural Health endeavour.edu.au 36

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