Pathology Lecture - Neoplasia
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“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
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Pathology of
NeoplasiaDr. Venkatesh M. Shashidhar.
A/Prof. & Head of Pathology
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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 *
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Neoplasia
Cell population / Growth Control:• Proliferation Differentiation Apoptosis * Normal
Stem cell
Apoptosis
Organ / Tissue
Neoplasia Benign - Malignant
C
CarcinogenInitiator + Promotor
Inflam
1.Proto-Oncogenes (growth factors) 2.Growth/Tumor suppressor genes. 3.Genes controlling Apoptosis.4.Genes controlling DNA Repair.
RASRbMYCp53
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Neoplasia
Non neoplastic Neoplastic (Polyclonal) (Monoclonal)
Growth Disorders:
Normal Adaptation Benign Malignant
HyperplasiaHypertrophyAplasiaAtrophyMetaplasiaDysplasia
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Neoplasia
Cell division Control - Carcinogenesis*
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Growth Control, Oncogenes & Therapy
You know this (Review)
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The mind is everything. What you think you become! -- Buddha
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Neoplasia
Clinical Pathology• Etiology (Carcinogenesis)• Pathogenesis • Morphology• Clinical Features
(Cancer Biology)
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Neoplasia
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.
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Neoplasia
Neoplasms Nomenclature:
Benign Malignant
• Adenoma - Adencarcinoma• Papilloma - Squamous cell ca.
• Fibroma - Fibrosarcoma• Osteoma - Osteosarcoma• Chondroma Chondrosarcoma• Lipoma Liposarcoma• Leiomyoma Leiomyosarcoma• Rhabdomyoma Rhabdomyosarcoma
Oma - TumourCarcin-oma – Hard TumourSarc-oma - Soft Tumour
Cell of Origin
• Gland. Epithelium• Lining. Epithelium
• Fibroblast• Osteoblast• Chondrocyte• Lipocyte• Smooth muscle• Skeletal muscle
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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?
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The searching out and thorough investigation of truth ought to be the primary study of man.
-- Cicero
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Cancer Clinical Features
Cancer Biology
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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
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• Tumors are clonal (one parent)• But have different mutations
different shapes & features.• Each new mutation adds a new
feature.
Malignant cells
Normalcell
Fourth orlater
mutation
Thirdmutation
Secondmutation
Firstmutation
More new mutations with time.
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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...!
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Neoplasia
Neoplasia:
Embryo Cancer
Self growth auto regulation
Limitless potentialAngiogenesis
Evade apoptosisInvasion & infiltration
Retrograde evolution…!
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Neoplasia
19
Pathogenesis of Lung Cancer.
K-RasC-myc
p53
Irritation Carcinogens Initiation Promotion Ca.
Smoke
Anaplasia
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Neoplasia
Colon: Normal Adenoma Carcinoma
Colon Cancer: Common type - 80%
Carcinogenesis)
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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)
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Neoplasia
Prostate Ca : Gleason Grading:
22
Low G
radeH
igh Grade
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“Beware of this world, for it is sweet and tempting.”
Control your desires.
— alsunna
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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 +
Based on - ANATOMY & LYMPHATICS
T1
T4
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Neoplasia
Staging of Colon cancer:
Pre-Cancer
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Neoplasia
26
Prostate Cancer Staging
Cancer
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Neoplasia
Metastasis: Lymphatic, Hematogenous, Direct.
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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.
28What chemical mediators are involved?
• E-Cadherin, β-catenin• Matrix Metalloproteinases (MMP)• Collagenase (not in benign)• Actin Cytoskeleton, chemokine
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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
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“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
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“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
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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