DEFINITATION

NEOPLASIA is a "new growth" composed of cells, origianally

derived from normal tissues, that relatively unresponsive to normal
growth controls and to expand beyond their normal anatomic
boundaries.

Describe their clinical appearance or behavior:

Tumor (swelling)
Cancer (crab)
Benign or malignant growths

Oncology is the study of neoplasia; the term is derived from the

Greek word oncos (tumor)
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 .”
Benign tumors do not invade surrounding tissue or spread to new

anatomic locations within the body; thus these tumors are usually

curable and are rarely responsible for the death of the host.

Malignant tumors, invade locally, and may spread by metastasis

(change of place), and will ultimately kill the host.

Tumor development is a stepwise process, potentially
preneoplastic changes have assumed new diagnostic and
clinical significance.

These changes include :

Metaplasia (transformation of one differentiated cell type

into another)

Dysplasia (abnormal pattern of tissue growth)

 Nomenclature/classification

 Most tumors appear to consist of a single cell type, and the

name of the neoplasm reflects the cell type (mesenchymal or
epithelial) from which the tumor is presumed to arise.
 MESENCHYMAL TUMORS

 Mesenchymal tumors arise in cells of embryonic mesodermal

origin.
 Benign tumors adding the suffIx -oma to the name of the cell of
origin (lipoma, and fibroma).
 A malignant tumor adding the suffIx sarcoma (Liposarcoma and a
fibrosarcoma.
 The cells comprising the hematopoietic system are mesenchymal.
Tumors arising from circulating blood cells or their precursors are
termed leukemias ("white blood")
 neoplastic hematopoietic cells are usually found in large numbers
in the blood stream, although they may also form solid tumor
masses.
 EPITHELIAL TUMORS

 Benign tumors that arise from glandular or tubular (renal tubular)

epithelium are called adenomas

 Papilloma refers to a benign exophytic growth arising from an

epithelial surface, whereas a polyp is a grossly visible, benign
epithelial tumor projecting from a mucosal surface.
UNDIFFERENTIATED TUMORS

 The appearance of some malignant tumors gives no

clue to their cell of origin; thus they are termed
undifferentiated neoplasms.
MIXED TUMORS

 Mixed tumors contain multiple cell types derived from a single

or multiple germ layers.
 Mixed tumors are believed to arise from a single pluripotential
or totipotential cell capable of differentiating into a variety of
more mature cell types.
 Teratomas and teratocarcinomas arise from totipotential germ
cells; thus they contain tissue derived from all embryonic cell
layers and consist of a bizarre mixture of adult and embryonic
tissue types.
 The mixed mammary gland tumor of dogs is generally
considered a mixed tumor. A mixed mamary tumor is composed
of a variable admixture of neoplastic epithelial elements (luminal
epithelium and myoepithelium) and mesenchymal elements
(fibrous connective tissue, fat, cartilage, and bone)
TUMORLIKE LESIONS

 Disorganized but mature mesenchymal or epithelial tissues

found in their normal anatomic location (hamarotomas)

 Hamartomas identified in animals consist of abnormal

proliferations of blood vessels.

 Choristomas are composed of normal mature tissue located at

an ectopic site (dermoid ; mature skin found at unussual site ex.
Cornea)
Veterinary nomenclature

 The terms used by veterinary pathologists to describe tumors in animals

may differ from the terms used by medical pathologists to describe
human tumors.

 A significant difference between veterinary and human nomenclature is

that a benign tumor arising from melanocytes is termed a "benign
melanoma" or "melanocytoma" and malignant melanomas
TUMOR CHARACTERISTICS
BENIGN

Vs
MALIGNANT TUMORS
Characteristics of benign and malignant tumors
benign malignant

1. Structure Well differentiated, Imperfectly differentiated

typical and atypical
2. Mode of growth Expansive and Infiltrative, expansive
circumscribed and not circumscribed
3. Rate of growth Slow, scanty mitotic Rapid, many mitotic
figures figures
4. End of growth + Rarely ceases growing

5. Metastasis absent Frequently present

6. Clinical result Dangerous because of : Dangerous also

-Position because of progressive
- accidental complication infiltrative growth and
-Production of excess metastasis
hormone
 TUMOR CHARACTERISTICS

The most important distinction between benign and malignant

tumors is that malignant tumors are able to invade locally and
metastasize systemically, but benign tumors are not.

The invasive capabilities of malignant tumors are associated with

enhanced tumor cell motility, increased production of proteases,
and altered tumor cell adhesion characteristics.
Although both benign and malignant tumors are composed of
proliferating cells, malignant tumors have essentially unlimited
replicative potential.

The tumors are relatively independent of exogenous growth

stimulatory molecules and are insensitive to growth inhibitory
signals from their environment.
Malignant cells are better able than benign cells to evade programmed
cell death (apoptosis) and to escape the host's cytotoxicimmune
response.

Compared with benign tumors, malignant tumors stimulate marked

angiogenesis thus assuring adequate tumor nutrition.

Some benign tumors evolve into malignant neoplasms and some

malignant tumors develop increasingly aggressive behavior over time
(malignant progression)

Tumors may be graded to indicate the risk the tumor poses to the host
and help determine therapeutic strategy.
 MORPHOLOGY DIFFERENTIATION
Neoplastic cells often show considerable morphologic variability
compared with the normal tissue from which they are derived.

Neoplastic tissues lose differentiation features of cellular morphology

and organization to a variable extent.

In general, malignant tumors appear less differentiated than benign

tumors. Loss of morphologic tissue maturity is often accompanied by
loss of functional capacity and development of aggressive behavior.

Tumor cells, especially malignant tumor cells, may exhibit anaplasia

(cellular atypia) that are poorly differentiated cells that exhibit notable
cellular and nuclear pleomorphism (variation in size and shape).

In some tumors giant cells are seen.

Mitotic figures in tumor cells may be numerous.

Pleomorphism
Nuclear pleomorphism are hyperchromatic (darkly staining) because of
increased DNA content and disproportionately large relative to cell size,
resulting in an increased of nuclearcytoplasmic ratio; and have prominent

nucleoli.
BEHAVIOR
Benign tumors are generally expansile and may compress adjacent
tissue, whereas malignant tumors have invasive and in many
instances metastatic capabilities.

Malignant cells completely independent of local growth regulatory

controls and acquire an independent blood supply. These features
allows tumors to spread well beyond their ordinary anatomic
niches.

Most tumors are composed of cells that lack fully differentiated

morphologic, functional, and behavioral characteristics.
CONTROL OF NORMAL CELL
PROLIFERATION AND
TISSUE GROWTH
 Cell Cycle
 Cell cycle consists of :

State Phase Abbreviation

Quiescent/senescent Gap 0 G0
Gap 1 G1
Interphase Synthesis S
Gap 2 G2
Cell Division Mitosis M

The cell cycle consists of G1 (pre synthetic) , S (DNA synthesis), G2

(premitotic), and M (mitotic) phases. Quiescent cells are in a
physiologic state called Go. In adult tissue, many cells reside in Go and
are unable to enter the cell cycle at all or do so only when stimulated by
extrinsic factors.
 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.)
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
 Cellproliferation 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
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
Mitotic index
 The number of cells in
microscopic field that
contain condensed
chromosome and
lack of nuclear membranes
Schematic of tumor growth as cell pop. expands, progressively higher
percentage of tumor cells leaves the replicative pool by reversion G0 , diff &
death 38
 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
apoptosis-inducing 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.
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)
papilloma
papilloma
squamous cell carcinoma
sqaumous cell carcinoma
papilloma
papilloma
squamous cell carcinoma
basal cell tumor
heavily pigmented multiplebasal cell tumor
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