Plenary Discussion

Blok 2.1 Mg. 2

Neoplasma
1. Adhiya Azni
2. Fadila Loviana
3. M. Irfan
4. M. Zarfan Suchyar
5. Rahmi Aldilla
6. Raihandi Putra
7. Riri Mulyanisa
8. Sri Rahmi Putri
9. Windy Asfarika
10. Zahara Bunga H.

1. Terminology
1. Vaginal bleeding : any vaginal bleeding unrelated to normal
menstruation.
2. Menopause : time in a woman's life when her periods
(menstruation) eventually stop. It is a natural event that
normally occurs in women age 45 - 55.
3. Breast Cancer : an uncontrolled growth of breast cells.
4. Lymphadenopathy : lymph nodes which are abnormal in size,
number or consistency and is often used as a synonym for
swollen or enlarged lymph nodes.
5. Ascites : a gastroenterological term for an accumulation of fluid
in the peritoneal cavity.
6. Curettage : the use of a curette (French, meaning scoop) to remove
tissue by scraping or scooping.

7. HTSOB : the removal of the uterus, cervix, fallopian tubes, and
ovaries.
8. Endometrial Adenocarcinoma : a cancer which arises from the
lining of the uterus, which is known as the endometrium
9. Pleomorphism : variability in the size and shape of cells and/or
their nuclei
10. Tumor : an abnormal mass of tissue which may be solid or fluid-
filled.
11. HPV Immunization : to protect against the virus that causes genital
warts and may lead to some kinds of cancer.
2. Problems
1. Why Mrs. Endar who was already menopause got a
vaginal bleeding?
2. What is the caused of menopause?
3. Why Mrs. Endar lost some weight and tired so
easily?
4. Is there any relation between Mrs. Endars condition
and her grandma who got breast cancer?
5. What is the interpretation of Mrs. Endars physical
examination?


6. Why the differential diagnosis of Mrs. Endar is an
Endometrial Adenocarcinoma?
7. Why did the doctor do some hystopathology
examination?
8. Why theres a white-red mass in Mrs. Endars uterus?
9. What is the effects when someone didnt have HPV
immunization?
3. Brainstorming
1. Mrs. Endars menopause : 54 yold late menopause
estrogen increased, progesteron (-) endometrium become
more thick uterus cant compensate vaginal bleeding

2. Germ cells in ovarium have limited number as we got older,
the number decreased (-) germ cells (-) month cycle , (-)
ovulation (-) estrogen , (-) corpus luteum menopause

3. Lost weight : people with cancer have TNF in their circulation
it reaches brain supress hunger center lost appetite
lost weight
4. Yes, theres. Tumors factors :
Gene Mrs. Endar got genes mutation from her grandma
Environment

5. (-) ikterik, sklera (-) hepar abnormality. (-) lymphadenopathy
(-) fluid accumulation

6. Hyperplasia Atipical : hyperchromatic nuclei, irregular, bigger
can continue to Endometrial Adenocarcinoma


7. Histopathology : to examine diseases based on histological
changing so we could know that nuclei becomes
hyperchromatic (cause by DNAs hyperactivity) & cells got
bigger

8. White mass because (-) vascularization. Tissues growth is
more rapid than angiogenesis.

9. HPV : disturbing gene uncontrolled cell proliferation
facilitate malignancy

4. Scheme
5. Learning Objectives (LO)
1. Cancer Epidemiology & Risk Factor
2. Classification & Terminology of Neoplasm
3. Histopathology of Neoplasm
4. Gene of Carcinogenesis
5. Cell Cycle Mechanism in Neoplasm
6. Invasion and Metastatic
7. Immunology of Neoplasm
8. Mechanism of Carcinogenesis
9. Prognosis and Predictive of Neoplasm
10. Epigenetic in Carcinogenesis


1. Cancer Epidemiology & Risk Factor
Cancer Epidemiology
Epidemiology is a study of distribution and
determinants of disease in human population.


Source of epidemiologic data in oncology:
1. Cancer registries
2. Death certificates
Methods of cancer epidemiology:
1. Descriptive studies
2. Analytic studies
A. Cohort
B. Case control

Sun exposure
Melanomas 6x incidence New Zealand vs. Iceland
Blacks have low incidence of melanoma, so do normally pigmented areas
like areolae on white people
Smoking and alcohol abuse
Body mass
Overweight = 50% increase in cancer
Viral exposure
Human papilloma virus (HPV) and cervical cancer
Hepatitis B virus (HBV) and liver cancer (Africa, Asia)
Epstein-Barr Virus (EBV) and lymphoma
Cancer Risk Factor
Environmental vs. racial factors
Japanese immigrants to USA
Age
Most cancers occur in persons 55 years
Childhood cancers
Leukemias & CNS neoplasms
Bone tumors
Genetic presdiposition
Familial cancer syndromes
Early age at onset
Two or more primary relatives with the cancer (soil theory)
Multiple or bilateral tumors
Polymorphisms that metabolize procarcinogens, e.g., nitrites

2. Classification & Terminology of Neoplasm
Definitions in Oncology. (Part 1)
Neoplasia: (Plasia = Cells)
Abnormal new cell proliferation of altered cells
Heritably Altered
Relative autonomous growth
Can be benign or malignant (See later)
Hyperplasia:
Abnormal proliferation of otherwise normal cells
Tumor:
Solid mass, usually cellular (but not necessarily)
Can be neoplastic, non-neoplastic, or even non-cellular
"Tumor" usually means a neoplasm in common usage
Some free cell neoplasms can be non-tumorous

Definitions in Oncology. (part 2)
Metaplasia:
Replacement of one type of normal adult differentiated cell
type that is normally present,
by another normal adult differentiated type that belongs
somewhere else.
Usually in response to injury or irritation
Reversible upon removal of the stimulus
See Reversible squamous metaplasia, next slide)
Dysplasia
Abnormal interaction of cells giving abnormal tissue
development
Can be pre-neoplastic


Definitions in Oncology. (part 3)
Anaplasia:
I rreversible loss of normal cell structure and function
Positional Anaplasia: Size, shape, arrangement, and overall
organization of cells in a tissue are altered
Cytological Anaplasia: Intra-cellular structures (mitochondria,
cytoskeletal elements, nuclear size and morphology) are altered
Cancer:
Mass of cells with potentially unlimited growth,
serves no useful function for the host,
deprives the host of nutrients necessary for survival,
expands locally by invasion and systemically by
lymphatic and hematogenous pathways,
untreated progresses to lethal condition in the host


Neoplasia
Definition:
is an abnormal mass of tissue,
the growth of which is uncoordinated with that of
normal tissues,
and that persists in the same excessive manner after the
cessation of the stimulus which evoked the change
With the loss of responsiveness to normal growth
controls

Different from hyperplasia, metaplasia and dysplasia.


Benign and Malignant Neoplasia
Benign Neoplasm
Generally Encapsulated
Non-invasive
Highly Differentiated
Few Mitotic Figures
Slow Growth or No Net
Growth
Little Anaplasia
Non-Metastatic (by
definition)
Malignant Neoplasm
Non-encapsulated
Invasive
Poorly Differentatied
Mitotic Figures Common
Can have rapid growth
Relatively Anaplastic
Metastatic or Capable of
becoming so
Neoplasia
All tumors have two basic components:
Parechyma: made up of neoplastic cells
Stroma: made up of non-neoplastic, host-derived
connective tissue and blood vessels
The parenchyma:
Determines the
biological behavior of
the tumor
From which the tumor
derives its name

The stroma:
Carries the blood
supply
Provides support for
the growth of the
parenchyma

Neoplasia
Nomenclature
Benign tumors:
prefix + suffix
Type of cell + (-oma)

Neoplasia
Examples:
Benign tumor arising in fibrous tissue:
Fibro + oma = Fibroma

Benign tumor arising in fatty tissue:
Lipo + oma = lipoma





Neoplasia
Benign tumor arising in cartilage
chondro + oma = chondroma
Benign tumor arising in smooth muscle
Leiomyo + oma = leiomyoma
Benign tumor arising in skeletal muscle
Rhabdomyo + oma = rhabdomyoma
Neoplasia
Adenoma : benign epithelial neoplasms
producing gland pattern.OR derived
from glands but not necessarily exhibiting
gland pattern

Papilloma : benign epithelial neoplasms
growing on any surface that produce
microscopic or macroscopic finger-like
pattern
Adenoma
Papilloma
Neoplasia
Polyp : a mass that projects above a
mucosal surface to form a
macroscopically visible structure.
e.g. - colonic polyp
- nasal polyp
Polyp
Neoplasia
Malignant tumors:
Malignant tumor arising in mesenchymal
tissue : SARCOMA
From fibrous tissue: Fibrosarcoma
From bone : Osteosarcoma
From cartilage : chondrosarcoma
Neoplasia
Malignant tumors arising from epithelial
origin : CARCINOMA
Squamous cell carcinoma
Renal cell adenocarcinoma
cholangiocarcinoma
3. Histopathology of Neoplasm
The cells image of neoplasm
Differensiation and anaplasia
Benigna : good differensiation, eg
lipoma , leiomioma uteri.
maligna : irreguler, anaplastic,
hiperkromatik , pleomorfic, mytotic
atypical.


benigna

malignant

4. Gene of Carcinogenesis
Gene of Carcinogenesis

Gen Of
Carcinogenesis
Oncogenes
Tumor
Supressor
Genes
Gene
Regulation of
Apoptosis
DNA Repair
Genes

1.Oncogen
is a gene that has the potential to cause cancer.
Proto-oncogenes Oncogenes
2. Tumor Supressor Genes
is known as antioncogenes. A gen that protects a cell
from one step on the path to cancer. When this gene
mutates to cause a loss or reduction in its function, the
cell can progress to cancer, usually in combination with
other genetic changes.
E.g : Retinoblastoma (Rb), p53, BRCA1 and BRCA2
3. Gene Regulatorion of Apoptosis
4. DNA Repair Genes
e.g : ATM, MLH1, PMS2

5. Cell Cycle Mechanism in Neoplasm

6. Invasion and Metastatic

INVASION
What is Invasion?
Ability of cells to break through basement
membrane and then spread.
Into surrounding tissue
In-Situ Carcinoma . Invasive Carcinoma
Characteristic of malignant cells

How Cells can be Invasion?
Complex mechanism involving various factors.
Malignant cells do not adhere (stick) to the same
extent as normal cells
Malignant cells show a change in their interaction
with surrounding stroma
Factors produced that help cells spread (scatter
factor)
Altered synthesis of enzymes that breakdown
basement membrane and stroma

Invasion mechanism:
Invasion mechanism:
Invasion mechanism:
Invasion mechanism:
Metastasis
What is Metastasis?
Ability of malignant cells to invade into
lymphatics, blood vessels and cavities
and spread to distant sites.
Cells must be able to invade out of
channels and grow at distant site.
Not all circulating cancer cells will settle at
a distant site and be able to grow.

Metastasis mechanism:
Why don't all malignant cells
Metastasis?
Cells may invade and circulate.
May get to distant site but environment
may not be appropriate for growth of
those cells.
Incorrect receptors
Metabolic factors
Failure of angiogenesis
Seed and Soil Hypothesis

Metastasis route :
Lymphatics
Blood Vessel
Coelemic spaces
7. Immunology of Neoplasm

8. Mechanism of Carcinogenesis
9. Prognosis and Predictive of Neoplasm

The growth and spread of tumors
Grading
Based on the degree of anaplasia are
shown.
Staging
Based on the size of the tumor, the
degree of local invasion, and degree of
metastasis.
Grading
Based on the differentiation / anaplasia
with cells of origin:
a) grade 1 = good differentiation (80-
70%)
b) grade 2 = medium differentiation (50-
60%)
c) grade 3 = poorly differentiation(30%)
d) grade 4 = anaplasia
Staging
Important stage of cancer is determined
after the diagnosis is made. Stadium will
affect prognosis and treatment
modalities used.
To be able to make a diagnosis of
cancer diagnostic action is required.
Diagnostic measures
1. Imaging
USG
X.rays
MRI
CT scans.
2. Biopsi :
a) Fine Needle Aspirate Biopsy.
b) Punch and Trephine biopsy.
c) Surgical biopsy.
1. insisional biopsi.
2. eksisional biopsi.
The classification stage is based on the
UICC (Union Internationale Contra Le
Cancer) or AJCC (American Joint
Committee on Cancer Staging and End
Resulls Reporting) from 2002 which has
been revised several times to get.
System to determine the stage
1. System TNM
T = Primary Tumor Size
T
o
= not found
T
1
= < 2 cm
T
2
= 2 5 cm
T
3
= > 5 cm
T
4
= infiltration/extensions on the cell
of origin


N= Nodes (Kelenjar Getah
Bening/KGB)
N
0
= no metastasis
N
1
= metastasis to lymph, mobilized
N
2
= metastasis to lymph , immobilized

M: distant metastases
M
0
: There were no distant metastases
M
1
: There is distant metastasis

2. System AJCC
Combining the TNM system into
several stages
Stadium 0 T 0 N 0 M 0
Stadium 1 T 1 N o M 0
Stadium 2 A T 0 N 1 M 0
T 1 N 1 M 0
T 2 N 0 M 0
Stadium 2 B T 2 N 1 M 0
T 3 N 0 M 0
Stadium 3 A T 0 N 2 M 0
T 1 N 2 M 0
T 2 N 2 M 0
T 3 N 1 M 0
T 3 N 2 M 0
Stadium 3 B T 4 N 0 M 0
T 4 N 1 M 0
T 4 N 2 M 0
Stadium 3 C TIAP T N 3 M 0
Stadium 4 TIAP T TIAP N M 1
Regrouping ( Grup Stadium)



























Regrouping ( Grup Stadium)

























Tumor cell markers
Remove a tumor cell marker (marker) in
the form of substance-specific antigen
that is secreted into the blood, urine, or
spinal fluid
The markers can be used for detection
of the presence of cancer followed
before, during, and after treatment
Examples of tumor cell marker:
- alfa fetoprotein = liver cancer
- PSA = prostate cancer
- CA-125 = ovarian cancer
10. Epigenetic in Carcinogenesis

Definition
Inactivation of tumour supressor
gene activity without DNA
mutation.
Mechanism
Metylation (CH
3
) activity in activating area of DNA
no stimulations received No
activation

Reverseable : no exposing towards Metyles agent
or given of antimetylation drug
Promotor agent : estrogen, drugs, smoke, alcohol.
Syukron