Thomas V Widiyatno

sinonyms
Tumor
Geschwlst (Deutsch)
Blastoma
Tumbuh ganda (bahasa indonesia)

Definition
Willys
Tumor (swelling)
Crab/ cancer
Development of tumor : a stepwise process

*
*
*
*

potencially preneoplastic changes :

hyperplasia
hypertrophy
metaplasia
dysplasia

Sir Ruppert A Willys (1967)

A

tumor is an abnormal mass of

tissue, the growth of which
exceeds and is uncoordinated
with that of the normal tissues
and persists in the same
excessive manner after cessation
of the stimuli which evoked the
change .

Nomenclature
Histogenesis

the tumor must be named by the specific

tissue or cell
type from which it arose and of which it is
composed
eg : Sertoli cell tumor, Leydig cell tumor

Nomenclature (contd.)
Behaviour

is an assessment of whether the tumor is

relatively harmless or a dangerous, lifethreatening lesion. Tumors that are confined,
slow-growing and non invasive are called
benign and carry the suffix -oma. Tumors that
are invasive, rapidly growing, and dangerous
are called malignant and carry the suffix
sarcoma if derived from mesenchymal tissues,
or the suffix carcinoma if derived from
epithelial tissues.

Characteristics of benign and

malignant tumors
benign
malignant
1. Structure

Well differentiated,
typical

Imperfectly
differentiated and
atypical

2. Mode of growth

Expansive and
circumscribed

Infiltrative, expansive
and not circumscribed

3. Rate of growth

Slow, scanty mitotic

figures

Rapid, many mitotic

figures

4. End of growth

Rarely ceases
growing

5. Metastasis

absent

Frequently present

6. Clinical result

Dangerous because of
:
-Position
- accidental
complication
-Production of excess

Dangerous also
because of
progressive
infiltrative growth and
metastasis

Cell Cycle
Cell cycle consists of :
State
Quiescent/senesc
ent
Interphase
Cell Division

Phase

Abbreviation

Gap 0

G0

Gap 1

G1

Synthesis

Gap 2

G2

Mitosis

Cell-cycle landmarks. The figure shows the cell-cycle phases (G0, G1,G2,
S, and M), the location of the G1 restriction point, and the G1/S and G2/M
cell-cycle checkpoints. Cells from labile tissues such as the epidermis and
the gastrointestinal tract may cycle continuously; stable cells such as
hepatocytes are quiescent but can enter the cell cycle; permanent cells
such as neurons and cardiac myocytes have lost the capacity to
proliferate. (Modified from Pollard TD and Earnshaw WC: Cell Biology.
Philadelphia, Saunders, 2002.)
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 17 January 2007 02:57 AM)
2007 Elsevier

Proliferation
Cell proliferation controlled by signals (soluble or contact-

dependent) from the microenvironment

- stimulate
- inhibit
Accelerated growth can be accomplished by :
- excess stimulator
- deficiency inhibitor
- shortening cell cycle *
- conversion of resting or quiescent cells into
proliferating cells by making the cells enter the cell
cycle *
*) require stimulating signals to overcome normal
physiologic blocs to cell proliferation

Cell proliferation can be stimulated

under both physiologic and

pathologic conditions

Differentiation
Differentiation also impacts the size of cell

population and its proliferative potential

Terminally differentiated cells : cardiac

myocytes, neurons, bone marrow, skin, gut

Quiescent differentiated cells :
hepatocytes, kidney cells

Apoptosis
Physiologic

or pathologic
Death factors ( FasL and TNF )
P53
CTL and NKcells
Cytochrom c
The final effector :
Caspases

Tumor Growth
Latent period : clinically undetectable
Smallest detectable mass : 1 gm or 109cells

10 doublings

1012 cells ( 1 kg)

Biology of Tumor Growth

Mitotic index
The number of cells in

microscopic field that

contain condensed
chromosome and
lack of nuclear membranes

Proliferative potential
The growth of tumor is not completely

exponential. A proportion of tumor cells is lost

from replicative pool because of irreversible
cell cycle arrest, differentiation or death

Schematic of tumor growth as cell pop. expands, progressively

higher percentage of tumor cells leaves the replicative pool by
reversion G0 , diff & death

19

telomerase
Many neoplastic cells regain the ability to

produce telomerase and thus to replicate

their telomeres
tumor cell immortality
(end of part 1 )

Thomas V Widiyatno

TUMOR EVOLUTION
Neoplasms develop as the result of multiple

genetic and epigenetic changes that occur over

a relatively long time course.
E.g :
*

Squamous cell carcinoma :

- epidermal hyperplasia
- carcinoma in situ
- invasive carcinoma

initiation
Introduction of irreversible genetic change.
Initiators are chemical or physical carcinogens

that damage DNA

Initiated cells appear morphologically normal
and may remain quiescent for many years and
may respond more vigorously to mitogenic
signals or be more resistant to apoptosisinducing stimuli

promotion
The second stage of tumor development
Promotion refers to the outgrowth of initiated

cells in response to selective stimuli. These

selective stimuli termed promoting agents or
promoters, drive proliferation
Promoter is not mutagenic
reversible
E.g : croton oil
The end of promotion phase : a benign
tumor

progression
The final stage
Malignant conversion : an irreversible change
Progression is a complex and poorly

understood process involving both genetic

and epigenetic changes

TUMOR SPREAD
Metastasis is the single most reliable

hallmark of malignancy
Cancer may metastasize by seeding of the
body cavities and surfaces (transcoelomic),
by lymphatic or by hematogenous spread

trancoelomic
When cancers arise on the surface of an

abdominal or thoracic cavities, they encounter

a few anatomic barriers to spread.
Mesotheliomas may be confined to the
abdominal or pleural cavities, but the tumor
cells readily to cover all visceral and parietal
surfaces.
Another example of transcoelomic spread :
ovarian adenocarcinoma

lymphatic
The lymph nodes closest to the tumor are

usually colonized earliest and the largest

metastatic tumor masses.
Regional lymph nodes actually represented a
mechanical barrier to the spread of cancer.
Mostly carcinomas

hematogenous
Tumors generally invade veins rather than

do arteries because arterial walls are much

thicker and more difficult to penetrate
Tumors that enter veins ultimately enter the
vena cava and lodge in the lungs or enter
the portal system and lodge in the liver
Sarcomas more frequently than carcinomas
use the hematogenous route

MECHANISM OF
METASTASIS
A complex process of metastasis :
- Invasion of extracellular matrix (ECM)
- Entry into blood vascular or lymphatic vessels
- Extravasation of tumor cells
- Colonization of the metastatic site

Detachment from the main

tumor mass
Loss of cadherin

or catenin function
tumor cells separate from each other
Contact with ECM components such as :
fibronectin, laminin, collagen through their
receptors

Invasion and migration

In malignant tumor the neoplastic epithelial

cells penetrate the basement membrane to

invade surrounding tissue. Degradation of
basement membrane and ECMcomponents
by secreting proteolytic enzymes (proteases)
Tumor cell migration is stimulated by
autocrine growth factor

Metastasis suppression
Metastatic potential is probably the

cummulative effect of many differen

genetic alteration.
On the other hand, a small number of genes
have been identified that seem to function to
suppress metastasis effectively
Eg : gene encoding E-cadherin (metastasis
suppressor gene)

The role of p53-gene

papilloma

papilloma

squamous cell carcinoma

sqaumous cell carcinoma

papilloma

papilloma

squamous cell carcinoma

basal cell tumor

heavily pigmented multiplebasal cell tumor

basal cell tumor with medussa head

solid basal cell tumor

baso-squamous tumor

trichoepihelioma

sebaceous adenoma

sebaceous adenoma

sebaceous adenoma with closely packed reserve cells

with squamous metaplasia

Hepatoid adenoma

hepatoid /perianal adenoma

hepatoid adenocarcinoma

sweat gland cyst adenoma

sweat gland adenoma

sweat gland adenocarcinoma

multiple malignant melanoma

malignant melanoma

fibroma vulva

fibrosarcoma

equine sarcoid

equin sarcoid