Dr. T.

Ibnu Alferraly, SpPA

Bagian Patologi Anatomi
Fakultas Kedokteran
Universitas Islam Sumatera Utara
2010

Within every nucleus of every one of the

human body's 30 trillion cells exists DNA,
the substance that contains the information
needed to make and control every cell
within the body. Here is a close-up view of a
tiny fragment of DNA.

This piece of DNA is an exact copy of the DNA

from which it came. When the parent cell divided
to create two cells, the cell's DNA also divided,
creating two identical copies of the original DNA.

Here is the same section of DNA but from another cell.

If you can imagine that DNA is a twisted ladder, then
each rung of the ladder is a pair of joined molecules, or
a base pair. With this section of DNA, one of the base
pairs is different from the original.
This DNA has suffered a mutation, either through miscopying (when its parent cell divided), or through the
damaging effects of exposure to radiation or a chemical
carcinogen.

Body cells replicate through mitosis, they

respond to their surrounding cells and replicate
only to replace other cells. Sometimes a genetic
mutation will cause a cell and its descendants
to reproduce even though replacement cells are
not needed.
The DNA of the cell highlighted above has a
mutation that causes the cell to replicate even
though this tissue doesn't need replacement
cells at this time or at this place.

The genetically altered cells have, over time, reproduced

unchecked, crowding out the surrounding normal cells.
The growth may contain one million cells and be the size
of a pinhead. At this point the cells continue to look the
same as the surrounding healthy cells.
After about a million divisions, there's a good chance
that one of the new cells will have mutated further. This
cell, now carrying two mutant genes, could have an
altered appearance and be even more prone to
reproduce unchecked.

Not all mutations that lead to cancerous cells result in the

cells reproducing at a faster, more uncontrolled rate. For
example, a mutation may simply cause a cell to keep from
self-destructing. All normal cells have surveillance
mechanisms that look for damage or for problems with their
own control systems. If such problems are found, the cell
destroys itself.
Over time and after many cell divisions, a third mutation may
arise. If the mutation gives the cell some further advantage,
that cell will grow more vigorously than its predecessors and
thus speed up the growth of the tumour.

The new type of cells grow rapidly,

allowing for more opportunities for
mutations. The next mutation paves the
way for the development of an even more
aggressive cancer.
At this point the tumour is still contained.

The newer, wilder cells created by another

mutation are able to push their way through the
epithelial tissue's basement membrane, which is
a meshwork of protein that normally creates a
barrier. The invasive cells in this tumour are no
longer contained.
At this point the cancer is still too small to be
detected.

Often during the development of earlier stages of the

tumour, or perhaps by the time the tumour has broken
through the basement membrane (as pictured above),
angiogenesis takes place. Angiogenesis is the
recruitment of blood vessels from the network of
neighbouring vessels.
Without blood and the nutrients it carries, a tumour
would be unable to continue growing. With the new
blood supply, however, the growth of the tumour
accelerates; it soon contains thousand million cells
and, now the size of a small grape, is large enough to
be detected as a lump

The tumour has now invaded the tissue beyond

the basement membrane.
Individual cells from the tumour enter into the
network of newly formed blood vessels, using
these vessels as highways by which they can
move to other parts of the body. A tumour as
small as a gram can send out a million tumour
cells into blood vessels a day.

What makes most

tumours so lethal is
their ability to
metastasize -- that
is, establish new
tumour sites at other
locations throughout
the body.
Secondary tumours.

Metastasis is now
underway, as tumour
cells from the
original cancer
growth travel
throughout the body.
Most of these cells
will die soon after
entering the blood or
lymph circulation.

To form a secondary tumour, a tumour cell needs

to leave the vessel system and invade tissue. The
cell must attach itself to a vessel's wall. Once this
is done, it can work its way through the vessel
and enter the tissue.
Although perhaps less than one in 10,000 tumour
cells will survive long enough to establish a new
tumour site, a few survivors can escape and
initiate new colonies of the cancer.

Patterns of cell Proliferation

Hyperplasia
Dysplasia
Metaplasia
Anaplasia
Neoplasia

Patterns of cell Proliferation

Metaplasia
conversion of one type of cell in a tissue to
another type not normal for that tissue
Anaplasia
change in the DNA cell structure and orientation
to one another, characterized by loss of
differentiation and a return to a more primitive
form.
Neoplasia
uncontrolled cell growth, either benign or
malignant

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

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

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

Gambaran Patologi
Neoplasma Maligna
Pada Beberapa Organ

NEOPLASMA KULIT

TABEL 61-4

> Lesi Kulit Premaligna

Actinic Keratosis
- Akibat ultraviolet
- Lesi eritomatous kasar, atau papula2 kecil
- HTPL : displasia dermis, degenerasi kolagen dermis ( solar elastosis )
kecendrungan menjadi ganas tergantung : tingkat displasia epitel

> Neoplasma Maligna

Bowens Disease ( carcinoma in situ )
- Dapat pada kulit yg terkena matahari atau vulva, mukosa mulut, glans penis
- Lesi : bercak eritema yg tumbuh lambat
- HTPL : perubahan displastik ( carcinoma in situ ), invasi membrana basalis (-)

Basal Cell Carcinoma ( Basal Cell Epithelioma )

- Sering terjadi, usia > 40 thn, daerah kulit yg terpapar sinar matahari ( wajah ).
- Jarang : Multiple Basal Cell Carcinoma ; pada bayi, congenital, dgn abnormalitas pd
tulang, syaraf, mata.
- Lesi : papula berlilin, telengiectasis pblh darah pd permukaan, nekrosis pd bagian
tengah ( Rodent Ulcer )
- HTPL : berasal dari lapisan basal epidermis yg menyusup ke dermis membentuk
gambaran seperti sarang. Sel2 basal membentu palisade pd bagian tepi
tumor
- Bersifat agresif, dapat invasi lebih dalam ke tulang dan otot, metastasis (-)
- Diperlukan operasi lesi meluas, batas operasi dengan Frozen Section

Basal Cell Carcinoma

N : nodular
T : Trabecular
C : cystic

Squamous Carcinoma
- Sering pd orang tua, akibat terpapar sinar matahari
- agresif, matatasis 1%
- sering bersamaan dengan chronic ulcers, burn scars, infeksi sinus
- lesi : dengan batas yang meninggi
- HTPL : sel2 poligonal besar (+) dengan sitoplasma berwarna pink
gambaran atipia, pleomorfik, dan mitotik bervariasi antara well differentiated
ke poor differentiated
- Bila dgn metastatik : perlu diseksi lymph node

Squamous Cell carcinoma

K : Keratin
D : Dermis
C : Cartilage

Dermatofibrosarcoma

EPIDEMIOLOGY the most common

malignancy of women after cervix cancer.

PATHOGENESIS :
- Genetic Factor history of breast ca in
first line degree relatives
(mother,sister,daughter).

Mutations of p53 tumor suppressor gene;

BRCA 1 gene (breast ca 1) located at
chromosome 17 (17q21) and BRCA 2 gene
located on chromosome 13q.

Hormonal status early menarch, late

menopause and older age at first term
pregnancy increased risk.

Environmental Influences high fat

intake.
Radiation.
Fibrocystic Change.
Previous cancer.
Viruses.
Genomic alterations gene amplification,
overexpression & allelic deletion.

INTRADUCTAL CARCINOMA IN SITU:

- COMEDOCARCINOMA
- NON COMEDO INTRADUCTAL CA

LOBULAR CARCINOMA IN SITU.

PAPILLARY CARCINOMA IN SITU.

1. DUCTAL CARCINOMA.
- The most common form Breast ca.
- Hard, fixed mass(often referred as
scirrhous ca).
- Gross: firm with irregular margin, pale
gray,gritty & flecked yellow chalky
streaks.
- Micros: irregular nests epitheloid cell
within dense fibrous stroma.

Variant ductal caPaget Disease of nipple.

2.LOBULAR CARCINOMA
Micros: single strands of malignant cells
infiltrating between stromal fiber
INDIAN FILING.
+ Signet Ring Caintracelluler mucin
compress nucleus to one side.
+ Pleomorphic Lobular Camarked
nuclear pleomorphism.

3.Colloid
carcinoma
composed of small
clusters of
epithelial cells
forming glands,
floating in pools of
extracell mucin.

4. Tubular
Carcinoma
Well differentiated
ca composed of
infiltrating, wellformed small ducts
consist one/two
layers of small
regular cells.

5. Medullary
Carcinoma
circumscribed
mass with lacks
calcifications.
Composed sheets
of cells, highly
pleomorphic &
high mitotic index.

6. Metaplastic Carcinoma
a rare invasive variant malignant
epithelium partially differentiation into
either another type of epithelium or
mesenchymal tissue tumor may show
areas of malignant squamous, fibrous,
cartilaginous or bony tissue, admixed with
malignant glandular component.

< 1% ALL CASES OF BREAST CA.

LESS FAT IN BREAST INVASION OF CHEST

WALL MUSCLES MORE FREQUENT.

MUTATION IN BRCA 2 GENE INCREASE THE

RISK OF THIS TUMOR.

MAMMOGRAM

LABORATORY FINDINGS
1. Biopsy procedures
2. Mammography

MAMOGRAFI

Kanker duktus invasif

( manipulasi dukun )

Melanoma Malignan

Metastase kanker ke kulit

Kanker Py stadium lanjut

Kanker Py stadium lanjut

OPERASI CA PAYUDARA

PASKA
OPERASI

Gastrointestinal
ESOFAGUS

markedly
thickened

extensive
mucosal erosion

barium enema technique

adenocarcinoma

adenocarcinoma

Adenocarcinoma
Kelenjar mukosa yang normal

Muskularis

Adenoca

Aflatoxin

Mutation in p53
gene

Produce by Aspergillus
flavus
In peanuts, rice,
soybeans, corn and wheat

Estrogen &
protein building
steroid

HCC

Immunosuppressive

Hepatic adenoma

Hereditary Hemochromatosis

Hereditary
Tyrosinemia

+ HBV infection

HCC

Cirrhosis

Alpha 1 antitrypsin

Normal

Metastatic Adenocarcinoma Hepar

Hepato Celluler Carcinoma

PRIMARY LUNG CA
ANOTHER LUNG NEOPLASMA
- BENIGN
- MALIGNANT
SECONDARY LUNG NEOPLASMA

RCC ( Renal Cell Carcinoma )

Kanker Pada
Alat Kelamin
Wanita

Karsinoma Endometrium :
- massa menonjol ke kavum uteri
- invasi ke lapisan myometrium

Leiomyoma Uterus :
- nodul2 dgn berbagai ukuran

NEOPLASMA SERVIKS
1 . Kondiloma Akuminata
- HPV ok STD
2 . Adenokarsinoma Endoserviks
- 10 15 % kanker cervix

Sexual Exposure
HPV Infection
Cervical Transformation Zone
Squamous Ep

Columnar Ep

High Risk Types (16,18)

Low Risk-6,11

Smoking, Hormone, Oral contr. parity,

Altered immune response etc.

Squamous Ca

Adeno Ca

NORMAL SERVIX

CANCER SERVIX

CONDILOMA
SERVIX

Karsinoma Skuamus Serviks

PAPS SMEAR

Karsinoma Skuamus Vulva

Kondiloma Akuminata Vulva

NEOPLASMA

CNS

Neoplasma Otak Kematian, Cacat fisik/mental

dpt di diagnosa dgn :

CT- Scan
Stereotatic Radiosurgery / MicroNeurosurgery
MRI / MRIA
Endoscopy/Minimal Invasive / Gamma Knife

Insidens : Pada umumnya laki2 dg wanita tdk ada perbedaan

Weel Diff. Astrocitoma

Glioblastoma Multiform

Ependymoma

Meningioma

Metastatic Melanoma

Seorang wanita 27 tahun, kesadaran menurun, sebelumnya menderita

sakit kepala dan tiba-tiba kejang serta tidak sadarkan diri. MRS dengan
keadaan koma.
Head CT scan tampak 3 buah tumor besar intracranial.
Dilakukan operasi :
a. emergency
b. elektif