NEOPLASIANEOPLASIA

DR.ROOPADR.ROOPA

PathophysiologyPathophysiology

Premed 3Premed 3

NeoplasiaNeoplasia

Means new growth.Means new growth. Is the uncontrolled, disorderly proliferation Is the uncontrolled, disorderly proliferation

of cells, resulting in a benign or malignant of cells, resulting in a benign or malignant tumor or neoplasm.tumor or neoplasm.

A neoplasm , as defined by Willis , isA neoplasm , as defined by Willis , is ““an abnormal mass of tissue the growth of an abnormal mass of tissue the growth of

which exceeds and is uncordinated with which exceeds and is uncordinated with that of the normal tissues and persists in that of the normal tissues and persists in the same manner after the cessation of the same manner after the cessation of the stimuli which evoked the change”.the stimuli which evoked the change”.

Dysplasia- is a reversible change.Dysplasia- is a reversible change.Often precedes malignancy.Often precedes malignancy.Morphologically manifests by disorderly Morphologically manifests by disorderly

maturation and spatial arrangement of maturation and spatial arrangement of cells, marked variability in nuclear size and cells, marked variability in nuclear size and shape and increased, often abnormal , shape and increased, often abnormal , mitosis .mitosis .

nomenclaturenomenclature

A neoplasm is often referred to as a tumor, A neoplasm is often referred to as a tumor, and the study of tumors is called oncology.and the study of tumors is called oncology.

Oncos – tumor, logos –study ofOncos – tumor, logos –study of

Types Types Benign tumorBenign tumorMalignant tumor( cancer)Malignant tumor( cancer)

Benign tumors: In Benign tumors: In general , benign general , benign tumors are tumors are designated by designated by attaching the suffix –attaching the suffix –oma to the cell type oma to the cell type from which the tumor from which the tumor arises.arises.

Eg.fibrous tissue Eg.fibrous tissue tumor is a fibroma.tumor is a fibroma.

Malignant tumors:Malignant tumors: Mesenchymal tissue Mesenchymal tissue

or its derivatives are or its derivatives are called sarcomas.called sarcomas.

Eg fibrosarcomaEg fibrosarcoma Epithelial tissue Epithelial tissue

origuin are called origuin are called carcinoma.carcinoma.

Eg:adenocarcinomaEg:adenocarcinoma

Malignant vs BenignMalignant vs Benign

(+) invasion: spread (+) invasion: spread to nearby structuresto nearby structures

(+)metastasis: spread (+)metastasis: spread to distant structuresto distant structures

(+)anaplasia :(+)anaplasia :

cells are very different cells are very different from the normal cells from the normal cells

(poorly differentiated)(poorly differentiated)

(-) invasion(-) invasion (+) capsule(+) capsule (-)metastasis(-)metastasis Resemble the tissue Resemble the tissue

of origin (well of origin (well differentiated)differentiated)

Tumor characteristicsTumor characteristics

Differentiation and anaplasiaDifferentiation and anaplasiaRate of growthRate of growthLocal invasionLocal invasionmetastasismetastasis

AnaplasiaAnaplasia

A state of complete un differentiationA state of complete un differentiation Anaplastic cells show:Anaplastic cells show: PleomorphismPleomorphism Hyperchromatism (dark nuclei)Hyperchromatism (dark nuclei) Increased nuclear-cytoplasm ratioIncreased nuclear-cytoplasm ratio Abnormal mitosisAbnormal mitosis Prominent nucleoliProminent nucleoli

Basic underlying cause of Basic underlying cause of cancercancer

4 kinds of genes are damaged:4 kinds of genes are damaged:Genes that promote growthGenes that promote growthGenes that inhibit growthGenes that inhibit growthGenes that regulate apoptosisGenes that regulate apoptosisGenes involved in DNA repairGenes involved in DNA repair

Cancers develop in multiple steps.Cancers develop in multiple steps.

““cancer genes “cause bad cancer genes “cause bad things in cellsthings in cells

Autonomous growthAutonomous growth Insensitivity to growth – inhibitory signalsInsensitivity to growth – inhibitory signalsEvasion of apoptosisEvasion of apoptosisLimitless replicationLimitless replicationSustained angiogenesisSustained angiogenesis Invasion and metastasisInvasion and metastasis

Forms of Malignant tumorsForms of Malignant tumors Carcinoma: malignant tumor of epithelial originCarcinoma: malignant tumor of epithelial origin

1. squamous cell carcinoma1. squamous cell carcinomacancer of the skincancer of the skincancer of the esophaguscancer of the esophagus

2. adenocarcinoma: glands2. adenocarcinoma: glandscancer of the breastcancer of the breastcancer of the pancreascancer of the pancreas

3. transitional cell carcinoma3. transitional cell carcinomacancer of the bladdercancer of the bladder

Forms of Malignant tumorsForms of Malignant tumors Sarcoma: of mesenchymal originSarcoma: of mesenchymal origin

osteosarcomaosteosarcomarhabdomyosarcomarhabdomyosarcomaleiomyosarcomaleiomyosarcomaliposarcomaliposarcoma

Teratoma: from all 3 germ layersTeratoma: from all 3 germ layersskin, bone, cartilage, teeth,skin, bone, cartilage, teeth,ovaries and testis: most commonovaries and testis: most commonmay also be benignmay also be benign

teratomas consist of bits of teratomas consist of bits of bone,INTESTINAL epithelium, muscle, fat, bone,INTESTINAL epithelium, muscle, fat, nerve, tooth, etc.nerve, tooth, etc.

OsteosarcomaOsteosarcoma

LiposarcomaLiposarcoma

TeratomaTeratoma

Forms of Benign tumorsForms of Benign tumors

Papilloma: Adenoma: glandular epitheliumPapilloma: Adenoma: glandular epithelium

-ovary, breast-ovary, breastMesenchymal originMesenchymal origin

-leiomyoma, lipoma, fibroma, chondroma-leiomyoma, lipoma, fibroma, chondroma

PapillomaPapilloma

epithelium of skin, larynx and tongue; fingerlike epithelium of skin, larynx and tongue; fingerlike projectionsprojections

Properties of NeoplasmsProperties of Neoplasms

MonoclonalityMonoclonality

the neoplasm comes from a single the neoplasm comes from a single precursor cellprecursor cell

InvasionInvasion

enters the blood vessels and enters the blood vessels and lymphaticslymphatics

MetastasesMetastases

blood vessels: sarcomasblood vessels: sarcomas

lymphatic: carcinomalymphatic: carcinoma

Properties of NeoplasmsProperties of Neoplasms

Common sites of metastasesCommon sites of metastases

liver, lung, brain, liver, lung, brain,

adrenal glands, lymph nodes adrenal glands, lymph nodes

bone marrowbone marrow

Clinical signs of malignancyClinical signs of malignancy CachexiaCachexia

wasting, weakness, weight loss, wasting, weakness, weight loss, anemia, infectionanemia, infection.-.- Endocrine abnormalitiesEndocrine abnormalities

prolactinomaprolactinomaovarian tumorsovarian tumors

Paraneoplastic syndrome is a disease or symptom that is the Paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells.they commomnly due to the local presence of cancer cells.they commomnly presented with cancers of the lung, breast, ovaries or presented with cancers of the lung, breast, ovaries or lymphatic system.lymphatic system.

eg:ectopic production of hormoneseg:ectopic production of hormoneslung cancer : ACTHlung cancer : ACTH

summary :Risk factorssummary :Risk factors

Chemical agentsChemical agentsPhysical agentsPhysical agentsVirusesVirusesActivation of cancer-promoting genesActivation of cancer-promoting genes Inhibition of cancer-suppressing genesInhibition of cancer-suppressing genes

Carcinogenesis and carcinogensCarcinogenesis and carcinogens

Cigarette smoking : lung CA, laryngeal CACigarette smoking : lung CA, laryngeal CAExcessive sun: Skin CAExcessive sun: Skin CAAsbestos: MesotheliomaAsbestos: MesotheliomaNitrosamines: Gastric CANitrosamines: Gastric CAAlcohol: Esophageal CAAlcohol: Esophageal CALow-fiber diet: Colon CALow-fiber diet: Colon CA

Carcinogenesis and carcinogensCarcinogenesis and carcinogens

High-fat diet: Breast CAHigh-fat diet: Breast CAAniline dyes: bladder CaAniline dyes: bladder CaAflatoxin: liver CAAflatoxin: liver CAPVC: Angiosarcoma of the liverPVC: Angiosarcoma of the liverDES: Clear cell adenocarcinoma of the DES: Clear cell adenocarcinoma of the

vaginavaginaNickle, chromium, uranium: lung CA Nickle, chromium, uranium: lung CA

Carcinogenesis and carcinogensCarcinogenesis and carcinogens

HTLV – 1: Adult T cell leukemiaHTLV – 1: Adult T cell leukemiaHPV: cervical CAHPV: cervical CAEBV: Nasopharyngeal CA, Burkitts EBV: Nasopharyngeal CA, Burkitts

lymphomalymphomaHBV: Hepatocellular CAHBV: Hepatocellular CAHHV-8: Kaposi sarcomaHHV-8: Kaposi sarcomaHelicobacter pylori: Gastric CAHelicobacter pylori: Gastric CA

Cancer suppresor genesCancer suppresor genes(anti oncogene)(anti oncogene)

p53: “ guardian of the genome” ,gatekeeper genep53: “ guardian of the genome” ,gatekeeper gene mutated in 50% of all malignant tumorsmutated in 50% of all malignant tumors causes cell cycle arrest in G1, time for DNA repaircauses cell cycle arrest in G1, time for DNA repair unsuccessful repair: apoptosisunsuccessful repair: apoptosis LI-FRAUMENI SYNDROMELI-FRAUMENI SYNDROME

familial cancers of the breast, soft tissue familial cancers of the breast, soft tissue sarcomas, sarcomas, brain tumors, leukemiasbrain tumors, leukemias

Cancer suppresor genesCancer suppresor genes(anti oncogene)(anti oncogene)

WT-1 and WT-2: Wilms tumor( Wilms WT-1 and WT-2: Wilms tumor( Wilms tumour of the kidney)tumour of the kidney)

BRCA -1: breast and ovarian CABRCA -1: breast and ovarian CA *BRCA – 2: breast CA*BRCA – 2: breast CA RB codes for pRB protein, master brake on cell cycle RB codes for pRB protein, master brake on cell cycle

(retinoblastoma, bone, bladder, lung, and breast cancer) (retinoblastoma, bone, bladder, lung, and breast cancer)

Grading: degree of differentiation of the cellsGrading: degree of differentiation of the cells Staging: spread of the tumor or degree of Staging: spread of the tumor or degree of

localisationlocalisation

-uses the TNM system-uses the TNM system

Tumor sizeTumor size

Lymphonode involvementLymphonode involvement

MetastasisMetastasis

CANCER TREATMENTCANCER TREATMENT CHEMOTHERAPCHEMOTHERAPYY CYTOTOXIC DRUGS+BODY DEFENSESCYTOTOXIC DRUGS+BODY DEFENSES SINGLE AGENTSINGLE AGENT COMBINATION CHEMOTHERAPYCOMBINATION CHEMOTHERAPY _AVOIDS SINGLE AGENT RESISTANCE_AVOIDS SINGLE AGENT RESISTANCE CAN USE LOWER DOSECAN USE LOWER DOSE BETTER REMISSION AND CURE RATEBETTER REMISSION AND CURE RATE RADIATIONRADIATION TARGETS DNATARGETS DNA KILL TUMOR WITHOUT DAMAGE TO SURROUNDING KILL TUMOR WITHOUT DAMAGE TO SURROUNDING

TISSUESTISSUES TUMOR MUST BE ACCESSIBLETUMOR MUST BE ACCESSIBLE

SURGERYSURGERY METHOD OF CHOICE,CAN REMOVE ENTIRE METHOD OF CHOICE,CAN REMOVE ENTIRE

TUMOR,DEBULKINGTUMOR,DEBULKING ADJUVANT CHEMOTHERAPY OR RADIATIONADJUVANT CHEMOTHERAPY OR RADIATION IMMUNOTHERAPYIMMUNOTHERAPY .ELIMINATES CANCER CELLS ONLY.ELIMINATES CANCER CELLS ONLY .PROVIDES PROTECTION AGAINST RECURRENCE.PROVIDES PROTECTION AGAINST RECURRENCE .T_CELL BASED OR ANTIBODY RESPONSES.T_CELL BASED OR ANTIBODY RESPONSES .CONJUGATED ANTIBODIES.CONJUGATED ANTIBODIES .NONSPECIFIC ENHANCEMENT OF THE IMMUNE .NONSPECIFIC ENHANCEMENT OF THE IMMUNE

SYSTEMSYSTEM