Pathology Lecture - Neoplasia

Pathology of Neoplasia. Lecture for medical students. Pre clinical basic science lecture.

1. “The world in which you were born is just one model of reality. Other cultures are not failed attempts at being you; they are unique manifestations of the human spirit, Just like you!” -- Wade Davis Antrhopologist

2. Pathology of Neoplasia Dr. Venkatesh M. Shashidhar. A/Prof. & Head of Pathology

3. Neoplasia : Neo + Plasia  New + Growth. Tumour  Swelling  any swelling* Clinically tumour = neoplasm (technically incorrect..!) Willis definition: “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists in the same manner after cessation of the stimuli which evoked the change” “Cell division without control” Irreversible DNA damage , resulting in autonomous growth of abnormal cells *

4. Cell population / Growth Control : Proliferation  Differentiation  Apoptosis * Normal Stem cell Apoptosis Organ / Tissue Neoplasia Benign - Malignant C Carcinogen Initiator + Promotor Inflam Proto-Oncogenes (growth factors) Growth/ Tumor suppressor genes. Genes controlling Apoptosis. Genes controlling DNA Repair. RAS Rb MYC p53

5. Non neoplastic Neoplastic (Polyclonal) (Monoclonal) Growth Disorders: Normal Adaptation Benign Malignant Hyperplasia Hypertrophy Aplasia Atrophy Metaplasia Dysplasia

6. Cell division Control - Carcinogenesis*

7. Growth Control, Oncogenes & Therapy You know this (Review)

8. The mind is everything. What you think you become!   -- Buddha

9. Neoplasia Clinical Pathology Etiology (Carcinogenesis) Pathogenesis Morphology Clinical Features (Cancer Biology )

10. Benign - Malignant 10 Necrosis BENIGN Well differentiated Slow growth Cohesive, expansile Capsule No invasion/infiltration MALIGNANT Poorly differentiated Rapid growth Non Cohesive, No capsule invasion/infiltration Metastases.

11. Neoplasms Nomenclature : Benign Malignant Adenoma - Adencarcinoma Papilloma - Squamous cell ca. Fibro ma - Fibro sarcoma Osteo ma - Osteo sarcoma Chondro ma Chondro sarcoma Lipo ma Lipo sarcoma Leiomyo ma Leiomyo sarcoma Rhabdo myoma Rhabdo myosarcoma Oma - Tumour Carcin-oma – Hard Tumour Sarc-oma - Soft Tumour Cell of Origin Gland. Epithelium Lining. Epithelium Fibroblast Osteoblast Chondrocyte Lipocyte Smooth muscle Skeletal muscle

12. Nomenclature : exceptions Teratoma – Tumour of Germ cell – multiple tissues. Benign (mature) or malignant (immature) Melanoma ( Melano -carcinoma ) – Malignancy of melanocytes . Seminoma ( Seminal carcinoma ) –carcinoma of Testes . Leukemia – white blood – Ca. of Haemopoietic stem cells. Lymphoma ( Lymphosarcoma )– Malignancy of lymphocytes. Mixed Tumours : Both epithelial & connective tissue components. Pleomorphic adenoma (Salivary gland) & Carcinosarcoma (breast/uterus) What is a Granuloma, Hamartoma & Choristoma ?

13. The searching out and thorough investigation of truth ought to be the primary study of man. -- Cicero

14. Cancer Clinical Features Cancer Biology

15. Cancer Biology: Structure: Parenchyma – Neoplastic cells. Stroma : Non neoplastic - normal DNA Features: Differentiation – Maturation of cells. Rate of Growth – Mitotic rate / Ki 67 Local invasion – Hemorrhage, necrosis, destruction Metastasis – Distant Spread. 15

16. Tumors are clonal (one parent) But have different mutations  different shapes & features. Each new mutation adds a new feature. Malignant cells Normal cell Fourth or later mutation Third mutation Second mutation First mutation More new mutations with time.

17. 6 Features of Cancer cells : Clinically each patient’s cancer has a different mix of features depending on quality & quantity of mutations & changes with time...!

18. Neoplasia: Embryo Cancer Self growth a uto regulation Limitless potential Angiogenesis Evade apoptosis Invasion & infiltration Retrograde evolution…!

19. 19 Pathogenesis of Lung Cancer. K-Ras C-myc p53 Irritation  Carcinogens  Initiation  Promotion  Ca. Smoke Anaplasia

20. Colon : Normal  Adenoma  Carcinoma Colon Cancer: Common type - 80% Carcinogenesis)

21. Stage & Grade of Cancer: Staging : Progression or spread in the body. Grading : Cell differentiation & Rate of growth – Microscopy. Well differentiated (low grade) Adenocarcinoma Grade Undiff . (high grade)

22. Prostate Ca : Gleason Grading: 22 Low Grade High Grade

23. “Beware of this world, for it is sweet and tempting.”  Control your desires . —   alsunna

24. TNM : Staging of tumor : Lung Ca Stage - Features T0 In-situ T1 Primary site T2 Sec. Anat. site T3 Tertiary site T4 Adjacent region N0 No LN mets . N1 Primary LN N2 Seondary LN N3 Tertiary LN M0 No metastases M1 Metastases + Based on - ANATOMY & LYMPHATICS T1 T4

25. Staging of Colon cancer: Pre-Cancer

26. 26 Prostate Cancer Staging Cancer

27. Metastasis : Lymphatic, Hematogenous , Direct.

28. Metastasis: Pathogenesis: Cell loosening BM degradation Invasion Locomotion BV adhesion Intra- vasation Tumour embolus Adhesion Extra- vasation Angiogenesis Growth. 28 What chemical mediators are involved? E-Cadherin, β -catenin Matrix Metalloproteinases (MMP) Collagenase (not in benign) Actin Cytoskeleton, chemokine

29. Cancer Diagnosis: e.g. Lung Cancer. Cell of origin Rate of growth Differentiation Local Invasion Metastasis Bronchial Epith . Mitotic rate – grade. Low, Intermediate, high Maturation of cells Well – Mod – Poor – Un diff. Tumour Stage.. 1,2,3,4. Distant Spread.. DIAGNOSIS: (Lung cancer) Bronchogenic Squamous cell Carcinoma, high grade, Stage T2 , N1, M1, Liver+ LN++ ( in.. patient details..). Grade Stage

30. “ Our character is but the stamp on our souls of the free choices of good and evil we have made through life. --  John C. Geikie

31. “Good & Evil, Happiness and Misery, Merit and sin depend on our actions. As is the action, so is the result. It is easy & fun to indulge in sinful deeds but it is extremely painful to bear the results they yield” Karma - You reap what you sow!  -- Baba

32. If diversity is a source of wonder, its opposite..! “Cultural supremacy, indeed, is a fire burning over the earth, taking with it plants and animals, cultures, languages, ancient skills and visionary wisdom. Quelling this flame, and re-inventing the poetry of diversity is perhaps the most important challenge of our times.” ― Wade Davis