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
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
Stem cell
Apoptosis
Neoplasia
Benign - Malignant
Organ / Tissue
Carcinogen
Initiator + Promotor
Inflam
1.Proto-Oncogenes (growth factors)
2.Growth/Tumor suppressor genes.
3.Genes controlling Apoptosis.
4.Genes controlling DNA Repair.
RAS
Rb
MYC
p53

5. Neoplasia
Growth Disorders:
Non neoplastic Neoplastic
(Polyclonal) (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
Necrosis
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BENIGN
• Well differentiated
• Slow growth
• Cohesive,
• expansile
• Capsule
• No invasion/infiltration
MALIGNANT
• Poorly differentiated
• Rapid growth
• Non Cohesive,
• No capsule
• invasion/infiltration
• Metastases.

11. Neoplasia
Neoplasms Nomenclature:
Oma - Tumour
Carcin-oma – Hard Tumour
Sarc-oma - Soft Tumour
Benign Malignant
• Adenoma - Adencarcinoma
• Papilloma - Squamous cell ca.
• Fibroma - Fibrosarcoma
• Osteoma - Osteosarcoma
• Chondroma Chondrosarcoma
• Lipoma Liposarcoma
• Leiomyoma Leiomyosarcoma
• Rhabdomyoma Rhabdomyosarcoma
Cell of Origin
• Gland. Epithelium
• Lining. Epithelium
• 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.
Malignant cells
Normal
cell
Fourth or
Third
mutation
later mutation
Second
mutation
First
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…!
Embryo Cancer
Self growth
auto regulation
Limitless potential
Angiogenesis
Evade apoptosis
Invasion & infiltration

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

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:
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Low Grade High Grade

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 +
T1
T4
Based on - ANATOMY & LYMPHATICS

25. Neoplasia
Staging of Colon cancer:
Pre-Cancer

26. Neoplasia
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Cancer
Prostate Cancer Staging

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.
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• E-Cadherin, β-catenin
• Matrix Metalloproteinases (MMP)
• Collagenase (not in benign)
• Actin Cytoskeleton, chemokine
What chemical mediators are involved?

29. Neoplasia
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