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Thomas V Widiyatno
sinonymsTumorGeschwlst (Deutsch)BlastomaTumbuh ganda (bahasa indonesia)
DefinitionWillysTumor (swelling)Crab/ cancerDevelopment of tumor : a stepwise process potencially preneoplastic changes : * hyperplasia * hypertrophy * metaplasia * dysplasia
Sir Ruppert A Willys (1967)A tumor is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change .
NomenclatureHistogenesis the tumor must be named by the specific tissue or cell type from which it arose and of which it is composed eg : Sertoli cell tumor, Leydig cell tumor
Nomenclature (contd.)Behaviour is an assessment of whether the tumor is relatively harmless or a dangerous, life-threatening lesion. Tumors that are confined, slow-growing and non invasive are called benign and carry the suffix -oma. Tumors that are invasive, rapidly growing, and dangerous are called malignant and carry the suffix sarcoma if derived from mesenchymal tissues, or the suffix carcinoma if derived from epithelial tissues.
Characteristics of benign and malignant tumors
benignmalignant1. StructureWell differentiated, typicalImperfectly differentiated and atypical2. Mode of growthExpansive and circumscribedInfiltrative, expansive and not circumscribed3. Rate of growthSlow, scanty mitotic figuresRapid, many mitotic figures4. End of growth+Rarely ceases growing5. MetastasisabsentFrequently present6. Clinical resultDangerous because of :Position accidental complicationProduction of excess hormoneDangerous also because of progressive infiltrative growth and metastasis
Cell CycleCell cycle consists of :
StatePhaseAbbreviationQuiescent/senescentGap 0G0InterphaseGap 1G1SynthesisSGap 2G2Cell DivisionMitosisM
Cell-cycle landmarks. The figure shows the cell-cycle phases (G0, G1,G2, S, and M), the location of the G1 restriction point, and the G1/S and G2/M cell-cycle checkpoints. Cells from labile tissues such as the epidermis and the gastrointestinal tract may cycle continuously; stable cells such as hepatocytes are quiescent but can enter the cell cycle; permanent cells such as neurons and cardiac myocytes have lost the capacity to proliferate. (Modified from Pollard TD and Earnshaw WC: Cell Biology. Philadelphia, Saunders, 2002.)Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 17 January 2007 02:57 AM) 2007 Elsevier
ProliferationCell proliferation controlled by signals (soluble or contact-dependent) from the microenvironment - stimulate - inhibitAccelerated growth can be accomplished by : - excess stimulator - deficiency inhibitor - shortening cell cycle * - conversion of resting or quiescent cells into proliferating cells by making the cells enter the cell cycle **) require stimulating signals to overcome normal physiologic blocs to cell proliferation
Cell proliferation can be stimulated under both physiologic and pathologic conditions
DifferentiationDifferentiation also impacts the size of cell population and its proliferative potential
Terminally differentiated cells : cardiac myocytes, neurons, bone marrow, skin, gutQuiescent differentiated cells : hepatocytes, kidney cells
ApoptosisPhysiologic or pathologicDeath factors ( FasL and TNF )P53 CTL and NKcellsCytochrom cThe final effector : Caspases
Tumor GrowthLatent period : clinically undetectableSmallest detectable mass : 1 gm or 109cells
10 doublings
1012 cells ( 1 kg)
Biology of Tumor Growth
Mitotic indexThe number of cells in microscopic field that contain condensed chromosome and lack of nuclear membranes
Proliferative potentialThe growth of tumor is not completely exponential. A proportion of tumor cells is lost from replicative pool because of irreversible cell cycle arrest, differentiation or death
*Schematic of tumor growth as cell pop. expands, progressively higher percentage of tumor cells leaves the replicative pool by reversion G0 , diff & death
telomeraseMany neoplastic cells regain the ability to produce telomerase and thus to replicate their telomeres tumor cell immortality (end of part 1 )
Thomas V Widiyatno
TUMOR EVOLUTIONNeoplasms develop as the result of multiple genetic and epigenetic changes that occur over a relatively long time course.
E.g : * Squamous cell carcinoma : - epidermal hyperplasia - carcinoma in situ - invasive carcinoma
initiationIntroduction of irreversible genetic change.Initiators are chemical or physical carcinogens that damage DNAInitiated cells appear morphologically normal and may remain quiescent for many years and may respond more vigorously to mitogenic signals or be more resistant to apoptosis-inducing stimuli
promotionThe second stage of tumor developmentPromotion refers to the outgrowth of initiated cells in response to selective stimuli. These selective stimuli termed promoting agents or promoters, drive proliferationPromoter is not mutagenic reversibleE.g : croton oilThe end of promotion phase : a benign tumor
progressionThe final stageMalignant conversion : an irreversible changeProgression is a complex and poorly understood process involving both genetic and epigenetic changes
TUMOR SPREADMetastasis is the single most reliable hallmark of malignancyCancer may metastasize by seeding of the body cavities and surfaces (transcoelomic), by lymphatic or by hematogenous spread
trancoelomicWhen cancers arise on the surface of an abdominal or thoracic cavities, they encounter a few anatomic barriers to spread.Mesotheliomas may be confined to the abdominal or pleural cavities, but the tumor cells readily to cover all visceral and parietal surfaces.Another example of transcoelomic spread : ovarian adenocarcinoma
lymphaticThe lymph nodes closest to the tumor are usually colonized earliest and the largest metastatic tumor masses.Regional lymph nodes actually represented a mechanical barrier to the spread of cancer.Mostly carcinomas
hematogenousTumors generally invade veins rather than do arteries because arterial walls are much thicker and more difficult to penetrateTumors that enter veins ultimately enter the vena cava and lodge in the lungs or enter the portal system and lodge in the liverSarcomas more frequently than carcinomas use the hematogenous route
MECHANISM OF METASTASISA complex process of metastasis :Invasion of extracellular matrix (ECM)Entry into blood vascular or lymphatic vesselsExtravasation of tumor cellsColonization of the metastatic site
Detachment from the main tumor massLoss of cadherin or catenin function tumor cells separate from each otherContact with ECM components such as : fibronectin, laminin, collagen through their receptors
Invasion and migrationIn malignant tumor the neoplastic epithelial cells penetrate the basement membrane to invade surrounding tissue. Degradation of basement membrane and ECMcomponents by secreting proteolytic enzymes (proteases)Tumor cell migration is stimulated by autocrine growth factor
Metastasis suppressionMetastatic potential is probably the cummulative effect of many differen genetic alteration.On the other hand, a small number of genes have been identified that seem to function to suppress metastasis effectivelyEg : gene encoding E-cadherin (metastasis suppressor gene)
The role of p53-gene
papilloma
papilloma
squamous cell carcinoma
sqaumous cell carcinoma
papilloma
papilloma
squamous cell carcinoma
basal cell tumor
heavily pigmented multiplebasal cell tumor
basal cell tumor with medussa head
solid basal cell tumor
baso-squamous tumor
trichoepihelioma
sebaceous adenoma
sebaceous adenoma
sebaceous adenoma with closely packed reserve cells with squamous metaplasia
Hepatoid adenoma
hepatoid /perianal adenoma
hepatoid adenocarcinoma
sweat gland cyst adenoma
sweat gland adenoma
sweat gland adenocarcinoma
multiple malignant melanoma
malignant melanoma
fibroma vulva
fibrosarcoma
equine sarcoid
equin sarcoid
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