Dr. T.

Ibnu Alferraly, SpPA

Bagian Patologi Anatomi

Fakultas Kedokteran
Universitas Islam Sumatera Utara
2010

CANCER is a complex of diseases

which occurs when normal cells
mutate into abnormal cells that
take over normal tissue,
eventually harming and
destroying the host

A large group of diseases characterized

by:
Uncontrolled growth and spread of
abnormal cells
Proliferation (rapid reproduction by
cell division)
Metastasis (spread or transfer of
cancer cells from one organ or part to
another not directly connected)

Viruses
Chemical carcinogens
Physical stressors
Hormonal factors
Genetic factors

Metastasis
Metastasis: 3 stages
Invasion neoplastic cells from primary
tumor invade into surrounding tissue
with penetration of blood or lymph.
Spread tumor cells spread through
lymph or circulation or by direct
expansion
Establishment and growth tumor cells
are established and grow in secondary
site: lymph nodes or in organs from
venous circulation

Spread of Cancer
1. LYMPHATIC
Most common

2. HEMATOGENOUS
Blood-borne, commonly to Liver and Lungs

3. DIRECT SPREAD
Seeding of tumors

Body Defenses Against TUMOR

1. T cell System/ Cellular Immunity
Cytotoxic T cells kill tumor cells

2. B cell System/ Humoral immunity

B cells can produce antibody

3. Phagocytic cells
Macrophages can engulf cancer cell debris

Classification of Tumors
CARCINOMAS: EPITHELIAL TISSUE
BODY SURFACES, LINING OF BODY CAVITIES
ETC: (ADENOCARCINOMA)
SARCOMAS: CONNECTIVE TISSUE
STRIATED MUSCLE, BONE, ETC
(OSTEOSARCOMA)
LYMPHOMAS AND LEUKEMIAS
HEMATOPOIETIC SYSTEM
NERVOUS TISSUE TUMORS
EX. NERVE CELLS-NEUROBLASTOMA
MYELOMA
Develops in the plasma cells of bone marrow

Effects of Cancer
Disruption of Function- can be due to
obstruction or pressure
Hematologic Alterations: can impair
function of blood cells
Hemorrhage: tumor erosion, bleeding,
severe anemia
Anorexia-Cachexia Syndrome: wasted
appearance of client

Effects of Cancer
Paraneoplastic Syndromes: ectopic
sites with excess hormone production
Parathyroid hormone
hypercalcemia
secretion of insulin hypoglycemia
Antidiuretic hormone (ADH) fluid
retention, HTN & peripheral edema
Adrenocorticotropic hormone
(ACTH): cause excessive secretion of
cortisone (ie: fluid retention,
glucose levels)

Effects of Cancer
Pain: major concern of clients and
families associated with cancer
Physical Stress: body tries to respond
and destroy neoplasm

ASSESSMENT
Nursing History
Health History chief complaint and
history of present illness (onset,
course, duration, location,
precipitating and alleviating factors)
Cancer signs: CAUTION US!

CAUTION US!
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickenings or lumps
Indigestion or difficulty in swallowing
Obvious change in a wart or mole
Nagging or persistent cough or
hoarseness
Unexplained anemia
Sudden unexplained weight loss

Change in bowel or bladder habits

A person with colon cancer may have
diarrhea or constipation, or he may
notice that the stool has become
smaller in diameter
A person with bladder or kidney
cancer

A sore that does not heal

Small, scaly patches on the skin that
bleed or do not heal may be a sign of
skin cancer
A sore in the mouth that does not heal
can indicate oral cancer

 Unusual bleeding or discharge

Blood in the stool is often the first sign
of colon cancer
Similarly, blood in the urine is usually
the first sign of bladder or kidney
cancer
Postmenopausal bleeding (bleeding
after menopause) may be a sign of
uterine cancer

 Thickenings or lumps
Enlargement of the lymph nodes or
glands (such as the thyroid gland) can
be an early sign of cancer
Breast and testicular cancers may
also present as a lump

 Indigestion or difficulty in
swallowing
Cancers of the digestive system,
including those of the esophagus,
stomach, and pancreas, may cause
indigestion, heartburn, or difficulty
swallowing

 Obvious change in a wart or mole

Moles or other skin lesions that
change in shape, size, or color should
be reported

 Nagging or persistent cough or

hoarseness
Cancers of the respiratory tract,
including lung cancer and laryngeal
cancer, may cause a cough that does
not go away or a hoarse (rough) voice

 Unexplained anemia
Sudden unexplained weight loss

 Inspection skin and mucus

membranes for lesions, bleeding,
petechiae, and irritation
Assess stools, urine, sputum, vomitus
for acute or occult bleeding
Scalp noting hair texture and hair loss
Palpation
Abdomen for any masses, bulges or
abnormalities
Lymph nodes for enlargement
Auscultation of lung sounds,
heart sounds and bowel sounds

Laboratory & Diagnostic

Tests Cancer detection examination
Laboratory tests
Complete blood cell count (CBC)
Tumor markers identify substance
(specific proteins) in the blood that are
made by the tumor
PSA (Prostatic-specific antigen): prostate
cancer
CEA (Carcinoembryonic antigen): colon
cancer
Alkaline Phosphatase: bone metastasis
Biopsy

Diagnostic Tests
Determine location of cancer:
X-rays
Computed tomography
Ultrasounds
Magnetic resonance imaging
Nuclear imaging
Angiography

 Diagnosis of cell type:

Tissue samples: from biopsies,
shedded cells (e.g. Papanicolaou (PAP)
smear), & washings
Cytologic Examination: tissue
examined under microscope

 Direct Visualization:
Sigmoidoscopy
Cystoscopy
Endoscopy
Bronchoscopy
Exploratory surgery; lymph node
biopsies to determine metastases

At tissue level

At cellular level

Anaplasia
Pleomorphism
Hyperchromatism
Nucleus/cytoplasm
Nucleolus/nucleus
Abnormal mitoses
(i.e.qualitative)
Increased mitosis
(i.e.quantitative)
Abnormal function

Altered organization, loss

of:
Normal stratification
Polarity
Tubules & acini
irregular form
Destructive invasion tissue
Distant metastasis
Necrosis (from ischaemia)
Stimulation of non-septic
inflammatory reaction
(lymphocytic &
fibroplastic)
Abnormal function

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Hilangnya differensiasi, fungsi spesifik &

organisasi yang normal ( Ewing )

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1. Pleomorphism (variation in size and shape of cells

and nuclei)
2. Hyperchromatism (nuclei contain abundance of darkstaining chromatin)
3. Enlarged nucleoli
4. Increased mitosis with abnormal mitotic figures
5. Formation of tumor giant cells (in some instances)

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A, Low-power,
Seluruh ketebalan epitel digantikan oleh sel
displasia atipik, diferensiasi sel skuamous
tidak dijumpai. Basal membran intact,
tumor pada stroma subepitel tidak dijumpai

B, High-power
Tidak dijumpai diferensiasi epitel
normal, Sel & inti pleomorfik,
mitosis (+).

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CARCINOGENESIS

Refers to the process by which a normal cell is

transformed into a malignant cell and repeatedly
divides to become a cancer.

A chemical which can initiate this process is

called a chemical carcinogen.

Some chemicals which are non-carcinogenic or

only weakly carcinogenic can greatly enhance the
effectiveness of carcinogenic chemicals.
Such "helpers" are called co-carcinogens.
They may act by altering uptake or
metabolism of carcinogens by cells.

May take as long as 15-25 years in humans and in

several animal models has been shown to involve
two stages, initiation and promotion.

o In general, carcinogens are mutagens indicating that they

have the potential to interact with DNA.
o Patients with DNA repair defects, such as xeroderma
pigmentosum (defect in repair of damage induced by
UV and bulky aromatic chemicals), have increased
incidence of
cancer.

Carcinogenesis: Pathogenesis of cancer

Carcinogen -

agent causing cancer.

Oncogen -

agent causing neoplasm.

Mutagen -

agent causing mutation.

Oncogenes

p-onc, v-onc

genes causing cancer

Proto/viral/ - naming of
oncogenes.

 These factors can be divided into three main

groups:

Environmental Toxins
chemical
physical (e.g. radiation)

Dietary
natural products found in spices, etc.
additives (rarely)

Lifestyle
hormonally-mediated
other

Chemicals Generally Recognized as Carcinogenic in Humans

Industrial Exposures
Benzidine

Urinary Bladder

Vinyl Chloride

Liver

Certain tars

Skin and

Asbestos
smoking)

Peritoneum (lungs when combined with cigarette

Benzene

Lymphoid Tissue

Other Exposures
Diethylstilbestrol

VaginaI

Arsenic Compounds

Skin cancer

Cigarette Smoke

Lungs, urinary tract

Betal Nut

Buccal Mucosa

Diets play important roles in the

development of tumors.

The following factors should be considered.

Natural Foods May Contain Carcinogens:
MushroomsHydrazine
Betal NutHydrocarbons
Food contaminants:
Aflatoxin B1Peanuts
NitrosaminesBeer, Wine, Pickled Vegetables
Food Processing:
Barbecued MeatPolycyclic Hydrocarbons
Heat Processing of Protein-Rich
FoodsHeterocyclic Aromatic compounds
Dietary Fat:
Saturated Fatty Acids
Polyunsaturated Fatty Acids: Corn oil, Safflower oil

Natural Foods May Contain

AnticarcinogensVitamins, Antioxidants

Carcinogens
Chemicals
Viruses
Radiation
Hereditary causes- Genetic
defects.
Combination common.

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Oncogene

Viruses contribute to the pathogenesis of human

malignancies through the integration of viral genetic
elements into the host DNA. These new genes are
expressed by the host; they may affect cell growth or
division, or disrupt normal host genes required for
control of cell growth and division. Alternatively, viral
infection may result in immune dysfunction, leading to
decreased immune surveillance for early tumors.
Insertion of viral nucleic acids mutation
Alterations in Oncogenes, cancer suppressor genes
and genes regulating DNA repair resulting in upregulation of cell division Carcinogenesis.
Human Papilloma Virus
Cervical neoplasia warts, papilloma, ca cx
Epstein-Barr virus
Burkitts Lymphoma, Nasopharyngeal ca.
Hepatitis B & C virus
Hepatocellular carcinoma.

Ionizing radiation develop from 2 different mechanisms;

1. Direct ionization damages DNA and other molecules
can cause direct somatic mutations
2. Secondary effectors such as oxygen radicals can be
formed by ionizing radiation. Oxygen free radicals can
damage and kill cells and also induce mutations.

X Ray workers Leukemia

Radio-isotopes Thyroid carcinoma

Atomic explosion Skin cancer, Leukemia

Initiation
DNA damage eg.Benzpyrene

Promotion
Histologic change eg.
Turpentine (co-carcinogens)

Malignant transformation:
Visible tumor formation
further DNA damage.

Initiation - point at which an irreversible alteration,

usually genetic, is introduced into a target cell.
(genotoxicity)=Interaction with DNA
May involve conversion of proto-oncogen to
oncogen
Initiation:
(1) is essentially irreversible
(2) caused only by carcinogenic compounds
(3) occurs rapidly after carcinogen exposure
(4) alone does not result in tumor formation
Several exposures to an initiator may result in
tumor without presence of a promoter.

Promotion is the process whereby an initiated

tissue or organ develop focal proliferations and it
requires the presence of continuous stimulation.
A promotor: is a substance which doesn't damage
DNA but enhance growth of tumor induced by
genotoxic carcinogens e.g.: skin cancer in mice
can be induced by application of benzo [ ]
pyrene ( initiator) followed by phorbol ester from
cotton oil ( promoter).
Promotion
(1) reversible
(2) acts only after exposure to an initiating agent
(3) requires repeated administration of a
promoter
(4) is not carcinogenic in itself

In general, chemical carcinogens are electrophiles

or can be metabolically converted to
electrophiles. (by metabolic activation ) These
electrophiles can react with nucleophilic centers
(predominantly N and O and to some extent S) in
cellular macromolecules such as DNA, RNA and
protein.

Genotoxic
Act directly on DNA or expression of DNA
during translation.
DNA replication errors.
Point mutations.
Chromosomal aberration.
Epigenetic
Non-DNA reactive.
Potentiators.
Ex.: hormone, immune function modifiers

Chemical capable of producing cancer by directly

altering the genetic material of target cells.
1- Direct carcinogens (no metabolic activation).
Alkylating agents.
2-Indirect carcinogens (metabolic activation).
Polycyclic aromatic hydrocarbons.
Aromatic amines.
Nitrosamines.
Natural substances.
3 Inorganic carcinogens.
4- Ni, Cr, Cd, As.

Cytotoxic carcinogens.
Nitrillotriacetate, BHA, BHT.
Tumor promotors.
DDT, Dioxin
Hormones.
Estradiol, DES
Immunosuppressants.
Cyclosporin A
Particulates.
Asbestos.

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Departemen Patologi Anatomi FKUSU

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Berkaitan dengan
mutasi gen supresor
kanker pada germ-line
yang diturunkan

Cendrung terjadi
bilateral & timbul
lebih cepat drpd
sporadik

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