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Pathology Lecture - Neoplasia

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

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Pathology Lecture - Neoplasia

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  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 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. Neoplasia Cell population / Growth Control: • Proliferation  Differentiation  Apoptosis * Normal Neoplasia Benign - Malignant Stem cell Carcinogen Initiator + Promotor Inflam Organ / Tissue 1.Proto-Oncogenes (growth factors) 2.Growth/Tumor suppressor genes. 3.Genes controlling Apoptosis. 4.Genes controlling DNA Repair. RAS Rb MYC p53 Apoptosis

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

  6. Neoplasia Cell division Control - Carcinogenesis*

  7. Growth Control, Oncogenes & Therapy

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

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

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

  11. Neoplasia Neoplasms Nomenclature: Oma - Tumour Carcin-oma – Hard Tumour Sarc-oma - Soft Tumour Cell of Origin Benign Malignant • Adenoma - • Papilloma - Adencarcinoma Squamous cell ca. • Gland. Epithelium • Lining. Epithelium • Fibroma - • Osteoma - • Chondroma • Lipoma • Leiomyoma • Rhabdomyoma Rhabdomyosarcoma Fibrosarcoma Osteosarcoma Chondrosarcoma Liposarcoma Leiomyosarcoma • Fibroblast • Osteoblast • Chondrocyte • Lipocyte • Smooth muscle • Skeletal muscle

  12. Neoplasia 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. Neoplasia 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. Normal cell First mutation Second mutation Third mutation Malignant cells Fourth or later mutation More new mutations with time.

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

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

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

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

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

  24. Neoplasia 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 + T4 T1 Based on - ANATOMY & LYMPHATICS

  25. Neoplasia Staging of Colon cancer: Pre-Cancer

  26. Neoplasia Cancer Prostate Cancer Staging 26

  27. Neoplasia Metastasis: Lymphatic, Hematogenous, Direct.

  28. Metastasis: Pathogenesis: 1. Cell loosening 2. BM degradation 3. Invasion 4. Locomotion 5. BV adhesion 6. Intra-vasation 7. Tumour embolus 8. Adhesion 9. Extra-vasation 10. Angiogenesis 11. Growth. E-Cadherin, β-catenin Matrix Metalloproteinases (MMP) Collagenase (not in benign) Actin Cytoskeleton, chemokine • • • • What chemical mediators are involved? 28

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

  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

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