PROPERTI SEL TUMOR

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

DEPARTEMEN PATOLOGI ANATOMI FAKULTAS KEDOKTERAN UNIVERSITAS BATAM BATAM - 2012

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

Cellular Growth Control

Balance proliferation cell differentiation cell death Proliferation determined through cell cycle Cellular growth control by genetic : proto-oncogen supressor gen apoptosis and DNA repair in cell cycle

3/12/2014

Abnormal Growth
Atrophy : size of the cells decreased
Diffuse atrophy immobilitation 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
3/12/2014

 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)

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 through blood (called blood-borne or hematogenous) or through lymphatics (lymphogenous). - Cancer cells spread because they lose their molecular address where to go

 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

Karakteristik Neoplasma Jinak & Ganas

Neoplasma dapat dibedakan menjadi jinak / ganas, berdasarkan: Differensiasi & anaplasia Kecepatan pertumbuhan (rate of growth) Invasi lokal (local invasion) Metastasis (anak sebar)

1. Differensiasi & anaplasia

Differensiasi: derajat kemiripan sel neoplastik (sel parenkim tumor) dengan sel normal. Makin mirip makin baik differensiasinya. Well differentiated Moderately differentiated Poorly differentiated undifferentiated Semua tumor jinak --- tersusun dari sel neoplastik yang mirip dengan sel normal (well differentiated) Tumor ganas bisa: well differentiated s.d undifferentiated.

 Anaplasia --- menunjukkan pertumbuhan ke arah tingkatan lebih rendah atau hilangnya differensiasi struktural & fungsional suatu sel normal Anaplasia --- hallmark of malignant transformation (petanda tumor ganas)

 Ciri-ciri morfologik sel anaplastik Pleomorfik: ukuran & bentuk bervariasi (variation in size & shape). Sel bisa berukuran >> besar atau << kecil. Morfologi inti sel tidak normal Inti sel hiperkromatik (karena DNA >>) 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.

Sel anaplastik

 DYSPLASIA
Artinya: disordered growth Terutama pada sel epitelial, ditandai oleh hilangnya uniformitas individual sel & hilangnya orientasi arsitektur 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.

Dysplasia cervix

2. Kecepatan pertumbuhan (rate of growth)

Secara umum: Kebanyakan tumor jinak: tumbuh lambat tergantung hormon & supply darah contoh: leiomyoma uterus akan tumbuh cepat jika estrogen >> (kehamilan) Kebanyakan tumor ganas: tumbuh cepat. Secara umum, kecepatan pertumbuhan tumor berhubungan dengan derajat differensiasinya kebanyakan tumor ganas tumbuh lebih cepat daripada tumor jinak

3.Invasi lokal (local invasion)

Tumor jinak Tumbuh lokal & tidak mempunyai kemampuan untuk menginfiltrasi, menginvasi jaringan sekitarnya. Berbatas jelas dengan jaringan sekitar, mempunyai kapsul (simpai) ataupun pseudocapsul (simpai semu). Tidak metastasis (tidak beranak sebar) Pengecualian: hemangioma (tumor jinak pembuluh darah) tidak berkapsul & tumbuh seperti infiltratif dalam jaringan.

Leiomyoma uteri

 Tumor ganas: Tumbuh progresif, invasi & infiltrasi ke jaringan sekitarnya. Batas tidak jelas & tidak berkapsul Pengecualian: tumor ganas yang tumbuhnya lambat bisa terlihat berbatas jelas pada makroskopis, namun secara mikroskopis akan terlihat pertumbuhan yang infiltratif ke jaringan sekitar.

 Beberapa kanker dapat tumbuh dari suatu lesi preinvasif, disebut sebagai Carcinoma insitu. Biasanya terjadi pada cervix, kulit, mamma. Ca insitu menunjukkan gambaran sel ganas tetapi tidak menginvasi membran basal (basal membrane intak).

4. Metastasis
Adalah anak sebar ke jaringan yang jauh dari tumor asal. Merupakan petanda keganasan yang paling kuat diantara tanda lain: Tumor jinak --- tidak metastasis Tumor ganas --- metastasis Metastasis: Percontinuatum lewat rongga Limfogen Hematogen

 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 limfe mengikuti rute normal dari lymphatic drainage. contoh: Ca mamma - metastasis KGB axilla Ca paru metastasis ke KGB hilus Ca nasofaring metastasis KGB colli

 Metastases secara hematogen Terutama pada sarcoma Dapat juga terjadi pada carcinoma Renal cell ca --- vena renalis Penetrasi ke vena > arteri, karena arteri memiliki dinding > tebal lebih tahan Invasi pada vena --- sel tumor mengikuti aliran vena -- metastasis sering terjadi pada paru & hepar

Hepar yang mengandung metastasis kanker

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

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

Characteristics of cancer cells

1. 2. 3. 4.

Infiltration and destruction of surrounding tissues Loss of contact inhibition of growth Variation in shapes and sizes based on degree of differentiation 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

Cancer classification
Sporadic cancer:
Cancer without a family history; non-hereditary and not affecting off-springs - Mutations not present in the germline cells. - Colon cancer mostly sporadic

Hereditary cancer:
Mutations are present in the germline cells and predispose to inheritance towards developing cancer (familial). Breast cancer is an example

Properties of Cancer Cells

Unlimited Replicative Potential
Absence of Apoptosis

Absence of Telomere Shortening

Angiogenesis Metastasis

Unlimited Replicative Potential

Cancer Cells Escape Regulation of the Cell Cycle proto-oncogenes become oncogenes
ex: ras family of genes (mutated in lung, colon, and pancreatic cancers)

tumor suppression genes inactivated, or cell fails to respond

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 cell division uncontrolled

Cancer cells differently from normal cells

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

Absence of Telomere Shortening

telomerase allows cells to rebuild telomeres (prevents them from being used up gene for telomerase turned on in cancer cells

Angiogenesis

formation of new blood vessels vascular endothelial growth factor (VEGF) stimulates blood vessel growth Cancer cells release VEGF

Metastasis

Cancer cells produce proteinase enzymes that allow them to invade blood and lymphatic vessels and move about the body

Metastatic Cancer

Causes of Cancer

Heredity

Heredity

mutated tumor suppressor genes can be inherited ex: BRCA1 (breast cancer gene # 1) ex: mutated RB gene (retinoblastoma) causes eye tumors to develop some people may not be born with the mutated gene, but a predisposition for the gene to mutate when exposed to environmental carcinogens

Radiation

UV radiation of sunlight Radon nuclear fallout medical x-rays

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

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 of carcinogen: cigarette smoke, UV radiation, vinyl chloride may each derive from a different adduct some pollutants, I.e. dioxins suppress immune system cells

Age Specific Exposure

children tend to accumulate higher concentrations than adults children have higher metabolic rates, and a lot more hand to mouth activity breastfeeding can transfer large amounts from mother to infant

Cancer Process

initiation, promotion, progression some pollutants can do all three some do one process at one concentration and others as pollutant load increases dioxin: promoter at lower concentrations; complete carcinogen at high concentrations xenoestrogens (hormone disruptors that mimic estrogen) can be promoters

Adducts

polycyclic aromatic hydrocarbons (PAHs) caused 2-3x the rate of adducts in Silesias urban dwellers than in rural populations

Viruses linked to cancer

hepatitis B: liver cancer

Epstein-Barr: Burkitt lymphoma, nasopharyngeal cancer human papillomavirus: cervical cancer

Seven Warning Signs of Cancer

C hange in bowel or bladder habits A sore that does not heal U nusual bleeding or discharge T hickening or lump in breast or elsewhere I ndigestion or difficulty in swallowing O bvious change in wart or mole N agging cough or hoarseness

Routine Screening Tests

Pap Smear Breast Self Exam Mammography Testicle Self-Exam Digital Rectal Exam Colonoscopy

Traditional Cancer Therapies

Surgery Radiation Chemotherapy Bone Marrow Transplants: allows higher doses of radiation or chemotherapy

Future Cancer Therapies

Vaccines: Melacine against melanoma Monoclonal Antibodies: bind to cancer cell antigens (p53) Gene Therapy: use viruses to insert normal p53 genes and cause apoptosis Inhibitory drugs: antiangiogenesis (angiostatin) or anti metastasis

Actinic keratoses

10% risk of malignant transformation

Hypertrophic AKs

Cutaneous Horn

Bowens disease SCC-in-situ

SCC-in-situ Also called Erythroplasia of Queyrat

Leukoplakia

SCC-in-situ

Confirmed by biopsy

Invasive SCC

Dysplastic nevi

Precursors for melanoma Markers for melanoma

Clinical types- MM

Superficial spreading melanoma Lentigo maligna melanoma

Acral lentiginous melanoma

Nodular melanoma

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