NEOPLASIANEOPLASIA

DR.ROOPADR.ROOPA

PathophysiologyPathophysiology

Premed 2Premed 2

NeoplasiaNeoplasia

Neoplasm is an abnormal mass of tissue Neoplasm is an abnormal mass of tissue as a result of neoplasia.as a result of neoplasia.

Uncontrollable or abnormal proliferation of Uncontrollable or abnormal proliferation of cells.cells.

TypesTypesA neoplasm can be A neoplasm can be benign, potentially , potentially

malignant (malignant (pre-cancer), or malignant (), or malignant (cancer). ).

Benign neoplasms include Benign neoplasms include uterine fibroids and and melanocytic nevi (skin moles). They (skin moles). They do not transform into do not transform into cancer. .

Potentially malignant neoplasms include Potentially malignant neoplasms include carcinoma in situ. They do not invade and . They do not invade and destroy but, given enough time, will destroy but, given enough time, will transform into a transform into a cancer. .

Malignant neoplasms are commonly called Malignant neoplasms are commonly called cancer. They invade and destroy the . They invade and destroy the surrounding tissue, may form surrounding tissue, may form metastases and eventually kill the host. and eventually kill the host.

MetastasisMetastasis sometimes abbreviated sometimes abbreviated metsmets, , is the spread of a is the spread of a disease from one from one organ or part to another non-adjacent organ or or part to another non-adjacent organ or part.part.

cancer cells can break away, leak, or spill can break away, leak, or spill from a from a primary tumor, enter , enter lymphatic and and blood vessels, circulate through the , circulate through the bloodstream, and be deposited within , and be deposited within normal normal tissue elsewhere in the body. elsewhere in the body.

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)

AnaplasiaAnaplasia PleomorphismPleomorphism Hyperchromatism (dark nuclei)Hyperchromatism (dark nuclei) Increased nuclear-cytoplasm ratioIncreased nuclear-cytoplasm ratio Abnormal mitosisAbnormal mitosis Prominent nucleoliProminent nucleoli

The more anaplastic, the more aggressive the The more anaplastic, the more aggressive the cancercancer

The more anaplastic, the more responsive to The more anaplastic, the more responsive to chemo and radiotherapychemo and radiotherapy

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

osteosarcomaosteosarcomarhabdosarcomarhabdosarcomaleiomyosarcomaleiomyosarcomaliposarcomaliposarcoma

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

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 marrow.bone marrow.

Clinical signs of malignancyClinical signs of malignancy CachexiaCachexia

wasting, weakness, weight loss, wasting, weakness, weight loss, anemia, anemia, infectioninfection

cause: CACHECTINcause: CACHECTIN Endocrine abnormalitiesEndocrine abnormalities

prolactinomaprolactinomaovarian tumorsovarian tumors

Paraneoplastic syndromesParaneoplastic syndromesectopic production of hormonesectopic production of hormoneslung cancer : ACTHlung cancer : ACTH

Carcinogenesis and carcinogensCarcinogenesis and carcinogens

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

An An oncogeneoncogene is a gene that, when is a gene that, when mutated or expressed at high levels, helps mutated or expressed at high levels, helps turn a normal cell into a tumor cell.turn a normal cell into a tumor cell.

OncogenesOncogenes

bcl-2: inhibits apoptosisbcl-2: inhibits apoptosis

Follicular lymphomaFollicular lymphoma

c-myc : Burkitts lymphomac-myc : Burkitts lymphoma

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

A A tumor suppressor genetumor suppressor gene, or , or anti-oncogeneanti-oncogene, is a , is a

gene that protects a cell from one step on the path to gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.usually in combination with other genetic changes.

p53: “ guardian of the genome” p53: “ guardian of the genome” 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 SYNDROMEfamilial cancers of the breast, soft familial cancers of the breast, soft

tissue sarcomas, tissue sarcomas, brain tumors, brain tumors, leukemias.leukemias.

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

WT-1 and WT-2: Wilms tumorWT-1 and WT-2: Wilms tumorBRCA -1: breast and ovarian CABRCA -1: breast and ovarian CABRCA – 2: breast CABRCA – 2: breast CA

The The stagestage of a cancer is a descriptor of a cancer is a descriptor (usually numbers I to IV) of how much the (usually numbers I to IV) of how much the cancer has spread.cancer has spread.

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

-uses the TNM system-uses the TNM system

TNM staging systemTNM staging system Cancer staging can be divided into a Cancer staging can be divided into a clinical clinical

stagestage and a and a pathologic stagepathologic stage. In the TNM . In the TNM (Tumor, Node, Metastasis)(Tumor, Node, Metastasis)

system, clinical stage and pathologic stage system, clinical stage and pathologic stage are denoted by a small "c" or "p" before are denoted by a small "c" or "p" before the stage.the stage.

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