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8/12/2019 Properti Sel Tumor

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PROPERTI SEL TUMOR

Dr. HUMAIRAH MEDINA LIZA LUBIS, M. Ked .(PA), Sp.PA

DEPARTEMEN PATOLOGI ANATOMI

FAKULTAS KEDOKTERAN

UNIVERSITAS BATAM

BATAM - 2012


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Normal Cells

Attach to each other by various cell junctions so that they are

fixed in place

Communicate with each other via Growth Factors

Stimulatory growth factors turn on genes called

protooncogenes

Inhibitory growth factors turn on Tumor Suppressor Genes


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Cellular Growth Control

Balance proliferationcell differentiationcell death

Proliferation determined through cell cycle

Cellular growth control by genetic : proto-oncogen

supressor gen

apoptosis and

DNA repair in cell cycle


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Abnormal Growth

Atrophy: size of the cells decreased

Diffuse atrophyimmobilitation

Denervation atrophy : poliomyelitis

Loss of Trophic hormon : Breast, endometrium atrophy

Lack of nutrition : Kwashiorkhor

Senile atrophy : Brain atrophy

Hypertrophy: size of the cells increased

Physiologic hypertrophy


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Hyperplasia: Means too much cell proliferation or mitosis.

This is abnormal but not cancer

Dysplasia: A cell is not only proliferating excessively, but

attains abnormal and orientation; Pre-cancerous

Neoplasia: New aggressive growth of cells and tissues

putting pressure on neighboring tissues (Causing

abnormal swelling or tumor) or invading neighboring

tissues (cancer)


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More TERMS:

Metaplasia: conversion of one cell type into another, such as, stratified

oesophagus or lung tissues (due to acidity or cigarette).The process is reversible

and is not cancer, but may lead to cancer.

Metastasis: Spreading to distant sites.

- First site where cancer is detected is called primary site and the second

site, secondary site.

- Small clumps of cancer cells (emboli) Spread by migration throughblood (called blood-borne or hematogenous) or through lymphatics

(lymphogenous).

- Cancer cells spread because they lose their molecular address where to

go


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Anaplasia: Primitive undifferentiated state of cell growth

Aplasia: A loss of normal appearance and

disorganizations of tissues

In situ cancer: abnormal growth at a particular site but no

invasion of neighboring tissues

Invasive cancer: Lethal and malignant as neighboring

tissues are invaded


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Karakteristik NeoplasmaJinak Ganas

Neoplasma dapat dibedakan menjadi jinak / ganas,berdasarkan:

Differensiasi & anaplasia Kecepatan pertumbuhan (rate of growth)

Invasi lokal (local invasion)

Metastasis (anak sebar)


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1. Differensiasi & anaplasia

Differensiasi:derajat kemiripan sel neoplastik (selparenkim tumor) dengan sel normal. Makin mirip makin baik differensiasinya.

Well differentiated Moderately differentiated Poorly differentiated undifferentiated

Semua tumor jinak --- tersusun dari sel neoplastikyang mirip dengan sel normal (well differentiated) Tumor ganas bisa: well differentiated s.d

undifferentiated.


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Anaplasia--- menunjukkan pertumbuhan ke arahtingkatan lebih rendah atau hilangnya differensiasi

struktural & fungsional suatu sel normal Anaplasia --- hallmark of malignant transformation

(petanda tumor ganas)


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Ciri-ciri morfologik sel anaplastik Pleomorfik: ukuran & bentuk bervariasi (variation in

size & shape). Sel bisa berukuran >> besar atau >) Rasio inti : sitoplasma (N/C ratio) (hampir 1:1)

(normalnya N/C ratio 1:4 atau 1:6) Butiran kromatin kasar Nukleoli (anak inti) nyata/ prominent

Mitosis: jumlah > & didapatkan mitosis atipik. Hilangnya polaritas: gangguan orientasi susunan

sel dalam jaringan.


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Sel anaplastik


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DYSPLASIA

Artinya: disordered growth Terutama pada sel epitelial, ditandai oleh hilangnya

uniformitas individual sel & hilangnya orientasiarsitektur normal sel dalam jaringan

Morfologi: Pleomorfisme (+)

Inti hiperkromatik (+)

Mitosis meningkat

Derajat dysplasia Displasia ringan (mild dysplasia)

Displasia sedang (moderate dysplasia)

Displasia berat (severe dysplasia) = Carsinoma insitu.


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Dysplasia cervix


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2. Kecepatan pertumbuhan

(rate of growth) Secara umum:

Kebanyakan tumor jinak: tumbuh lambat

tergantung hormon & supply darah

contoh: leiomyoma uterus akan tumbuh cepat jikaestrogen >> (kehamilan)

Kebanyakan tumor ganas: tumbuh cepat.

Secara umum, kecepatan pertumbuhan tumorberhubungan dengan derajat differensiasinya

kebanyakan tumor ganas tumbuh lebih cepat

daripada tumor jinak


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3.Invasi lokal (local invasion)

Tumor jinak

Tumbuh lokal& tidak mempunyai kemampuan untukmenginfiltrasi, menginvasi jaringan sekitarnya.

Berbatas jelasdengan jaringan sekitar, mempunyaikapsul(simpai) ataupun pseudocapsul(simpai semu).

Tidak metastasis(tidak beranak sebar)

Pengecualian: hemangioma (tumor jinak pembuluh

darah)tidak berkapsul & tumbuh seperti

infiltratif dalam jaringan.


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Leiomyoma uteri


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Tumor ganas:

Tumbuh progresif, invasi & infiltrasike jaringansekitarnya.

Batas tidak jelas & tidak berkapsul

Pengecualian: tumor ganas yang tumbuhnya lambat

bisa terlihat berbatas jelas pada makroskopis,namun secara mikroskopis akan terlihatpertumbuhan yang infiltratif ke jaringan sekitar.


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Beberapa kanker dapat tumbuh dari suatu lesipreinvasif, disebut sebagai Carcinoma insitu.

Biasanya terjadi pada cervix, kulit, mamma.

Ca insitu menunjukkan gambaran sel ganas tetapitidak menginvasi membran basal (basal membraneintak).


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4. Metastasis

Adalah anak sebar ke jaringan yang jauh dari tumorasal.

Merupakan petanda keganasan yang paling kuatdiantara tanda lain:

Tumorjinak --- tidak metastasis

Tumor ganas --- metastasis

Metastasis:

Percontinuatum

lewat rongga Limfogen

Hematogen


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Metastasis per continuatum: Lewat rongga tubuh (body cavity)

Contoh: Ca ovarium --- ke peritoneum

Ca colon --- ke cavum peritoneum

Ca paru --- ke cavum pleura

Metastasis secara limfogen:

Terutama pada carcinoma

Pola penyebaran metastasis kelenjar limfemengikuti rute normal dari lymphatic drainage.

contoh: Ca mamma - metastasis KGB axilla

Ca paru metastasis ke KGB hilus

Ca nasofaringmetastasis KGB colli


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Metastases secara hematogen

Terutama pada sarcoma

Dapat juga terjadi pada carcinoma Renal cell ca --- vena renalis

Penetrasi ke vena > arteri, karena arteri memilikidinding > tebal lebih tahan

Invasi pada vena --- sel tumor mengikuti aliran vena --- metastasis sering terjadi pada paru & hepar


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Hepar yang mengandung metastasis kanker

P b di t t ji k &


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Perbandingan antara tumor jinak & ganas(contoh: leiomyoma >< leiomyosarcoma)


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Classification:

Carcinoma: cancer of epithelial tissues

Adenocarcinoma: cancer of glandular tissue; spread through lymphatics

Sarcoma: cancer of stromal or mesenchymal layers of organs; spread via blood

Carcinosarcoma: mixtures of cancer cells from both epithelia and mesenchma

Teratoma: cancer of stem cells

Undifferentiated neoplasms: poorly undifferentiated


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Characteristics of cancer cells

1. Infiltration and destruction of surrounding tissues

2. Loss of contact inhibition of growth

3. Variation in shapes and sizes based on degree of differentiation4. Uncontrolled mitosis or cell proliferation or growth rate. Less

dependent on growth factors

5. Often migration to distant sites and loss of similarity with parent

tissues


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Cancer classification

Sporadic cancer:

Cancer without a family

history; non-hereditary andnot affecting off-springs

- Mutations not present inthe germline cells.

- Colon cancer mostlysporadic

Hereditary cancer:

Mutations are present in

the germline cells and

predispose to

inheritance towards

developing cancer

(familial).

Breast cancer is an

example


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Properties of Cancer Cells

Unlimited Replicative Potential

Absence of Apoptosis

Absence of Telomere Shortening

Angiogenesis

Metastasis


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Unlimited Replicative Potential

Cancer Cells Escape Regulation of the Cell Cycle

proto-oncogenes become oncogenes

ex: ras family of genes (mutated in lung, colon, andpancreatic cancers)

tumor suppression genes inactivated, or cell fails torespond

ex: RB tumor suppressor gene fails to function (breast,prostate, bladder, and other cancers)

ex: mutated p21 gene product no longer binds to cyclin,thus cyclin-dependent kinase uninhibited and celldivision uncontrolled


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Cancer cells differently from

normal cells


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Absence of Apoptosis

most often caused by damage to p53 gene that triggers

apoptosis

cells do not respond to normal triggers of apoptosis such

as metabolic stress or oxygen deprivation


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Absence of Telomere Shortening

telomerase allows cells to rebuild telomeres (prevents them

from being used up

gene for telomerase turned on in cancer cells


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Angiogenesis

formation of new blood vessels

vascular endothelial growth factor (VEGF) stimulatesblood vessel growth

Cancer cells release VEGF


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Metastasis

Cancer cells produce proteinase enzymes that allow them to

invade blood and lymphatic vessels and move about the body


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Metastatic Cancer


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Causes of Cancer

Heredity


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Heredity

mutated tumor suppressor genes can beinherited

ex: BRCA1 (breast cancer gene # 1)

ex: mutated RB gene (retinoblastoma)causes eye tumors to develop

some people may not be born with themutated gene, but a predisposition for the

gene to mutate when exposed toenvironmental carcinogens


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Radiation

UV radiation of sunlight

Radon

nuclear fallout

medical x-rays


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Organic Chemicals

benzene, carbon tetrachloride, vinyl chloride, asbestos fibers,pesticides, dioxins


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Body Burden

Steingraber: 177 different organochlorine residues

detectable in the body of the average middle age man

mutations of p53 can be distinguished by the type ofcarcinogen: cigarette smoke, UV radiation, vinyl chloride

may each derive from a different adduct

some pollutants, I.e. dioxins suppress immune system cells


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Age Specific Exposure

children tend to accumulate higher concentrations than

adults

children have higher metabolic rates, and a lot more handto mouth activity

breastfeeding can transfer large amounts from mother to

infant


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Cancer Process

initiation, promotion, progression

some pollutants can do all three

some do one process at one concentration and others aspollutant load increases

dioxin: promoter at lower concentrations; complete

carcinogen at high concentrations

xenoestrogens (hormone disruptors that mimic estrogen)can be promoters


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Adducts

polycyclic aromatic hydrocarbons (PAHs) caused 2-3x the rate

of adducts in Silesias urban dwellers than in rural populations


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Viruses linked to cancer

hepatitis B: liver cancer

Epstein-Barr: Burkitt lymphoma, nasopharyngeal cancer

human papillomavirus: cervical cancer


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Seven Warning Signs of Cancer

Change in bowel or bladder habits

Asore that does not heal

Unusual bleeding or discharge

Thickening or lump in breast or elsewhere

Indigestion or difficulty in swallowing

Obvious change in wart or mole

Nagging cough or hoarseness


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Routine Screening Tests

Pap Smear

Breast Self Exam

Mammography Testicle Self-Exam

Digital Rectal Exam

Colonoscopy

di i l h i


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Traditional Cancer Therapies

Surgery

Radiation

Chemotherapy

Bone Marrow Transplants: allows higher doses of

radiation or chemotherapy

F C Th i


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Future Cancer Therapies

Vaccines: Melacine against melanoma

Monoclonal Antibodies: bind to cancer cell antigens

(p53) Gene Therapy: use viruses to insert normal p53genes and cause apoptosis

Inhibitory drugs: antiangiogenesis (angiostatin) or anti

metastasis


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A ti i k t


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Actinic keratoses

10% risk of malignant transformation

H t hi AK


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Hypertrophic AKs

C t H


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Cutaneous Horn


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Bowens disease SCC-in-situ


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SCC-in-situ

Also called

Erythroplasiaof Queyrat


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Leukoplakia


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SCC-in-situ

Confirmed by biopsy


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Invasive SCC


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Dysplastic nevi

Precursors for

melanoma

Markers for

melanoma


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Clinical types- MM

Superficial spreading melanoma

Lentigo maligna melanoma

Acral lentiginous melanoma Nodular melanoma

THANK YOU


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THANK YOU

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