“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

Pathology of

NeoplasiaDr. Venkatesh M. Shashidhar.

A/Prof. & Head of Pathology

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 *

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

Neoplasia

Non neoplastic Neoplastic (Polyclonal) (Monoclonal)

Growth Disorders:

Normal Adaptation Benign Malignant

HyperplasiaHypertrophyAplasiaAtrophyMetaplasiaDysplasia

Neoplasia

Cell division Control - Carcinogenesis*

Growth Control, Oncogenes & Therapy

You know this (Review)

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

Neoplasia

Clinical Pathology• Etiology (Carcinogenesis)• Pathogenesis • Morphology• Clinical Features

(Cancer Biology)

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.

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

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?

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

-- Cicero

Cancer Clinical Features

Cancer Biology

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.

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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.

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...!

Neoplasia

Neoplasia:

Embryo Cancer

Self growth auto regulation

Limitless potentialAngiogenesis

Evade apoptosisInvasion & infiltration

Retrograde evolution…!

Neoplasia

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Pathogenesis of Lung Cancer.

K-RasC-myc

p53

Irritation Carcinogens Initiation Promotion Ca.

Smoke

Anaplasia

Neoplasia

Colon: Normal Adenoma Carcinoma

Colon Cancer: Common type - 80%

Carcinogenesis)

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)

Neoplasia

Prostate Ca : Gleason Grading:

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Low G

radeH

igh Grade

“Beware of this world, for it is sweet and tempting.” 

Control your desires.

—  alsunna

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

Neoplasia

Staging of Colon cancer:

Pre-Cancer

Neoplasia

26

Prostate Cancer Staging

Cancer

Neoplasia

Metastasis: Lymphatic, Hematogenous, Direct.

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

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

“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

“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

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