TISSUES

Four types of Tissues:

1. Epithelial Tissues
2. Connective Tissues
3. Nervous Tissues
4. Muscle Tissues

Epithelial Tissues – covering, lining or glandular tissue of the body

1. Protection – Ex. skin, against bacterial, chemical change
- Epith lining resp tract – cilia , sweep dust and debris away from the lungs
2. Absorption – digestive organs; stomach and small intestine, large intestine –
food nutrients into the body
3. Filtration – kidneys, absorb and filter
4. Secretion – glandular , produce substances as sweat, oil, digestive enzymes
and mucus
EPITHELIAL TISSUES FUNCTIONS ORGANS

One layer - Simple Flattened like fish scales,
Squamous for filtration, Diffusion,
Secretion in serous
membrane (body cavity)
Alveoli, Air sacs of the
lungs; respiration
Walls of the capillaries, for
nutrients and gases pass
between; blood and
interstitial fluid

Serous membrane
(serosae)

Lines ventral cavity ,

covers the organ in that
cavity

Simple cuboidal Cube-shaped, Secretion In ducts (salivary glands

and absorption, ciliated and pancreas; wall of
types propel mucus and kidney tubules and
reproductive cells surface of the ovaries

Resting on a basement
membrane

Simple columnar Like columns; Secretion Has goblet cells, produce

and absorption; ciliated
types propel mucus and
reproductive cells
lubricating mucus;
Columnar Epith lines
entire digestive tract (from
stomach to anus); line
body cavities called
mucosae or mucus
membrane

Stratified epithelia At free surface of the epith Urinary bladder

membrane, NOT resting
 on the basement
membrane;

for protection, Stretching

to accommodate
distention

Stratified squamous Encounter friction Surface of the skin,

mouth, esophagus

Stratified Ducts of large glands

columnar/cuboidal (liver)

Transitional Epith stretching Urinary bladder

(squamous)

Glandular epith Secretion, protein in Endocrine (ductless)

aqueous glands diffuse into blood
vessels – hormones as
thyroid, adrenal, pituitary

Exocrine glands – sweat,

oil

MOST Connective Tissue – well vascularized (good blood supply)

Tendons and ligaments – poor blood supply
Cartilage – avascular
Heal very slowly
Connective tissue – made up of many different types of cells with non-living
substances outside the cells called extracellular matrix made up of ground
substance – adhesion protein and polysaccharide

Types of CT:
1. Bone – hard matrix, few cells; osseous tissue; osteocyte in the cavities called
lacunae, with Calcium salts with collagen fibers, protecting body organs;
framework
2. cartilage – less hard matrix, more flexible, few cells
a. Hyaline cartilage –with abundant collagen fibers hidden by rubbery matrix,
glassy blue-white – attaches ribs to breast bone, trachea (wind pipe),
cover bone ends at joints
- Bones of fetus largely hyaline cartilage, became bones at birth except
epiphyseal or growth plates of long bone
b. Fibrocartilage – highly compressible, forms cushionlike disk between
vertebrae of the spinal column
c. Elastic cartilage – external ear
3. Dense CT or dense fibrous tissue – main matrix elements are collagen fibers;
make the lower layers of the skin (dermis)
a. Tendons – attach skeletal muscles to bones
b. Ligaments – connects bone to bone at joints; more stretchy and has more
elastic fibers
4. Loose CT – softer and have more cells, fewer fibers
a. Areolar CT – soft, pliable, “cobwebby” tissue that cushions and protects
the body organs; universal packing tissue and connective tissue glue,
holding internal organs together
 - Lamina propria – underlies the mucous membrane, with small spaces like
sponge
- Edema – when body regionis inflamed, local areolar tissue soaks up the
excess fluid like sponge, swells and become puffy. Phagocytes wander
through the tissue, scavenging for bacteria, dead cells and other debris
b. Adipose CT – fat, an areolar tissue with plenty of adipose cells; at the
subcutaneous tissue (beneath the skin); protects some organs – kidney,
adipose tissue cushions the eyeballs in their sockets; at hips, belly,
breasts
- Fat stored and available as fuel
c. Reticular CT – at limited sites; forms stroma (bed or mattress) or internal
framework of the organ; support free blood cells ( large lymphos) in
lymphoid organs as lymph nodes, spleen, and bone marrow
- Cellular bleachers – other cells can observe their surroundings
5. Blood – vascular tissue; considered connective, surrounded by non-living fluid
matrix called blood plasma
- Fibers of blood, soluble proteins visible during clotting
- Transport vehicle for the cardiovascular system, carrying nutrients,
wastes, respiratory gases, WBC

NERVOUS Tissue –
1. Neuroglia – “nerve glue”; glial cells; has many types of cells that support,
insulate and protect the delicate neurons; supporting cells in the CNS
“lumped together” called neuroglia
a. Astrocytes – star-shaped,nearly half of neural tissue,
- most abundant and versatile neuroglia;
- with swollen ends that cling to neuron to brace and anchor to their nutrient
supply lines, the blood capillaries;
- serve as living barrier between capillaries and neurons that determine
capillary permeability

https://jonlieffmd.com/blog/astrocytes-control-synapse-function
THE ASTROCYTES

- Einstein’s cortex has astrocytes unusually large and more complex than
others
- In humans, astrocytes have tentacles that travel through multiple layers
of the cortex 6-layered structure
- Glial cells are considered filler, of secondary importance in brain function,
as immune-brain interaction
 b. Microglia – spider-like phagocytes that monitor the health of nearby
neurons and dispose debris such as dead brain cells and bacteria
c. Ependymal cells – neuroglia that line the central cavities of the brain
and spinal cord
- The beating of their cilia helps to circulate the CSF that fill those cavities
and forms protective watery cushion around CSF
d. Oligodendrocytes – neuroglia that wrap their flat extension
(processes) tightly around the nerve fibers, producing fatty insulating
coverings called myelin sheaths

Neuroglia resembles neuron (both have cell extensions), not able to

transmit nerve impulses unlike neurons
- Neuroglia never lose their ability to divide, neurons never divide or
regenerate
- (renew themselves)
- Most brain tumors are gliomas (tumor formed by neuroglia)

Schwann cells – form the myelin sheaths around the nerve fibers in the PNS
- Guillain-Barre Syndrome –demyelination due to respiratory or
gastrointestinal infection , muscle weaknes, poor vision . . .
- Satellite Cells - act as protective , cushioning cells for peripheral neuron
cells

2. Neuron – nerve cells; transmit messages (nerve impulses),from one part

of the body to another, has cell body and one or more slender processes
(dendrites, axons)

MUSCLE tissues – Skeletal, Cardiac, smooth (Discussed)

Inflammation - a local response (reaction) of living vascularized tissues to

endogenous and exogenous stimuli
• a physiologic (protective) response to injury
Causes of inflammation:
1. physical agents - mechanical injuries, alteration in temperatures and
pressure, radiation injuries
2. chemical agents- increasing lists of drugs and toxins
3. biologic agents (infectious) - bacteria, viruses, fungi, parasites
4. immunologic disorders- hypersensitivity reactions, autoimmunity,
immunodeficiency states,etc
5. genetic/metabolic disorders- Ex. gout, diabetes mellitus, etc…
Nomenclature - of inflammatory lesion are usually indicated by the suffix 'itis'.
Ex. inflammation of the appendix - appendicitis meningitis - for meninges, etc.
…
- has exceptions, Ex. pneumonia
Classification of Inflammation based on duration of the lesion and histologic
appearances :
1. acute inflammation
2. chronic inflammation

ACUTE INFLAMMATION
1. Acute inflammation - immediate and early response to an injurious agent;
- relatively of short duration, lasting for minutes, several hours or few days
- characterized by exudation of fluids and plasma proteins
- emigration of predominantly neutrophils to the site of injury
 Figure. Inflammation and diapedesis
Five cardinal signs of acute inflammation
1. Redness (rubor) - due to dilation of small blood vessels within damaged tissue
as it occurs in cellulitis
2. Heat (calor) - results from increased blood flow (hyperemia) due to regional
vascular dilation
3. Swelling (tumor) - due to accumulation of fluid in the extravascular space which,
in turn, is due to increased vascular permeability
4. Pain (dolor) - partly results from the stretching & destruction of tissues due to
inflammatory edema and in part from pus under pressure in as abscess cavity
Some chemicals of acute inflammation, including bradykinins, prostaglandins and
serotonin are also known to induce pain.
5. Loss of function: The inflamed area is inhibited by pain while severe swelling
may also physically immobilize the tissue

Foot Inflammation

Categories of Acute inflammation :

1. early, vascular response 2. Late, cellular responses
1. Steps in Vascular response :
a. Immediate (momentary) vasoconstriction in seconds due to neurogenic or
chemical stimuli
b. Vasodilatation of arterioles and venules resulting in increased blood flow
c. After the phase of increased blood flow, blood flow slows down and stasis
(equilibrium) due to increased vascular permeability that is most remarkably seen in
the post-capillary venules.
- increased vascular permeability oozes protein-rich fluid into extravascular
tissues
- the already dilated blood vessels will be packed with RBC resulting in stasis
- EXUDATE the protein-rich fluid in the extravascular space will occur
- presence of exudates clinically appears as swelling
2) Stages of Cellular response:
A. Migration, rolling, pavementing, & adhesion of leukocytes
B. Transmigration of leukocytes
C. Chemotaxis
D. Phagocytosis
- Normally blood cells particularly erythrocytes in venules are confined to
the central (axial) zone and plasma assumes the peripheral zone
- As a result of increased vascular permeability (refer to vascular events
above), more and more neutrophils accumulate along the endothelial surfaces
(peripheral zone).

A. Migration, rolling, pavementing, and adhesion of leukocytes

1. Margination - a peripheral positioning of WBC along the endothelial cells
2. Rolling - rows of leukocytes tumble slowly along the endothelium
3. Pavementing - the endothelium can be virtually lined by white blood cells
4. Adhesion of WBC - the binding of leukocytes with endothelial cells facilitated
by cell adhesion molecules such as selectins, immunoglobulins, integrins, etc

B. Transmigration of leukocytes
1. WBC escape from venules and small veins but only occasionally from capillaries
- diapedesis - movement of leukocytes by extending pseudopodia through the
vascular wall
- widening of inter endothelial junctions after endothelial cells contractions (the
most important mechanism of leukocyte emigration)
- basement membrane is disrupted and resealed thereafter immediately.

Diapedesis and chemotaxis

C). Chemotaxis: - unidirectional attraction of leukocytes from vascular channels

towards the site of inflammation within the tissue space guided by chemical gradients
(including bacteria and cellular debris)
- All granulocytes, monocytes and to lesser extent lymphocytes respond to
chemotactic stimuli
D) Phagocytosis - process of engulfment and internalization by specialized cells of
particulate material, w/c includes invading microorganisms, damaged cells, and
tissue debris.
- The phagocytic cells are polymorphonuclear leukocytes (particularly
neutrophils), monocytes and tissue macrophages.
 . Neutrophils, the quick and first responders leukocytes

Monocytes, respond slower but strong

Healing - in a pathological context, it refers to the body’s replacement of destroyed

tissue by living tissue; a closure of a skin wound
.
Tissue Damage Inflammation

Removal of dead tissue & injurious agent

Replacement by

Fibrous tissue Specialized tissue

(scarring) (Regeneration)

Healing

Factors that Determine Healing:

1. the type of cells in the damaged organ
 2. the destruction or the intactness of the stromal frame work of the organ.

Types of cells acc. to proliferative capacity:

1. Labile cells
2. Stable cells
3. Permanent cells

1. Labile cells - cells which have a continuous turn over by programmed division of
stem cells
- are found in the surface epithelium of the gastrointestinal tract, urinary tract or the
skin
- cells of lymphoid and haemopoietic systems are further examples
- chances of regeneration are excellent
2. Stable cells - cells have normally a much lower level of replication and there are
few stem cells
- the cells of such tissues can undergo rapid division in response to injury.
- Ex. mesenchymal cells such as smooth muscle cells, fibroblasts, osteoblasts
and endothelial cells are stable cells which can proliferate.
- Liver, endocrine glands and renal tubular epithelium has also such type of cells
which can regenerate.
- their chances of regeneration are good
3. Permanent cells - non-dividing cells.
- if lost, permanent cells cannot be replaced, because they do not have the
capacity to proliferate
- Ex. adult neurons, striated muscle cells, and cells of the lens

two types of healing processes :

1. Regeneration - the replacement of lost tissue by the similar type of tissues; Ex.
superficial epidermis
2. Repair (healing by scarring) - the replacement of lost tissue by granulation
tissue which matures to form scar tissue
- Healing by fibrosis is inevitable when the surrounding specialized cells do not
possess the capacity to proliferate.
Fibrosis – thickening and scarring of connective tissue due to injury

Healing by regeneration - (generare=bring to life) renewal of a lost tissue in which

the lost cells are replaced by identical one
- wound in which only the lining epithelium is affected heals exclusively by
regeneration

Two Processes Regeneration:

1. Proliferation of surviving cells to replace lost tissue
2. Migration of surviving cells into the vacant space.

Repair (Healing by connective tissue) - the orderly process by which lost tissue is
eventually replaced by a scar.
- wounds that extend through the basement membrane to the connective tissue,
Ex. the dermis in the skin or the sub-mucosa in the gastrointestinal tract, lead to the
formation of granulation tissue and eventually scarring.
- Tissues containing terminally differentiated (permanent) cells such as neurons
and skeletal muscle cells can not heal by regeneration.
- lost permanent cells are replaced by formation of granulation tissue

Three phases of granulation-tissue formation

 1. Phase of inflammation - inflammatory exudate containing polymorphs is
seen in the area of tissue injury.
- there is platelet aggregation and fibrin deposition
2. Phase of demolition - dead cells liberate their autolytic enzymes, and other
enzymes (proteolytic) come from disintegrating polymorphs.
- There is an associated macrophage infiltration.
- These cells ingest particulate matter, either digesting or removing it.
3. Ingrowth of granulation tissue -
a. characterized by proliferation of fibroblasts and an ingrowth of new blood
vessels into the area of injury, with a variable number of inflammatory cells.
b. Fibroblasts actively synthesize and secrete extra-cellular matrix
components, including fibronectin, proteoglycans, and collagen types I and III.
c. fibronectin and proteoglycans form the ‘scaffolding’ for rebuilding of the
matrix
d. Fibronectin binds to fibrin and acts as a chemotactic factor for the recruitment
of more fibroblasts and macrophages.
e. The synthesis of collagen by fibroblasts begins within 24 hours of the injury
although its deposition in the tissue is not apparent until 4 days.
f. By day 5, collagen type III is the predominant matrix protein being produced;
g. but by day 7 to 8, type I is prominent, and it eventually becomes the major
collagen of mature scar tissue. This type I collagen is responsible for providing
the tensile strength of the matrix in a scar.
h. Coincident with fibroblast proliferation is angiogenesis (neovascularization) -
proliferation and formation of new small blood vessels.
i. Vascular proliferation starts 48 to 72 hours after injury and lasts for several days.
j. Further healing will have an increase in extracellular constituents, mostly
collagen, with a decrease in the number of active fibroblasts and new vessels.
k. despite an increased collagenase activity in the wound (responsible for
removal of built collagen), collagen accumulates at a steady rate, usually reaching
a maximum 2 to 3 months after the injury.
l. The tensile strength of the wound continues to increase many months after
the collagen content has reached a maximum.
m. As the collagen content of the wound increases, many of the newly formed
vessels disappear.
n. vascular involution which takes place in a few weeks, dramatically transforms
a richly vascularized tissue into a pale, avascular scar tissue.
WOUND CONTRACTION
- a mechanical reduction in the size of the defect
- wound is reduced approximately by 70-80% of its original size
- Contraction results in much faster healing, since only one-quarter to one-
third of the amount of destroyed tissue has to be replaced.
- If contraction is prevented, healing is slow and a large ugly scar is formed.

Causes of contraction - due to myofibroblasts

- Myofibroblasts have the features intermediate between those of fibroblasts and
smooth muscle cells.
- Two to three days after the injury they migrate into the wound and their active
contraction decrease the size of the defect.

Healing is determined by:

a. the degree of tissue destruction,
b. the capacity of the parenchymal cells to proliferate,
c. the degree of destruction of stromal framework

Sequence of events in Healing :

1. Regeneration and migration of specialized cells,
2. angiogenesis,
3. proliferation of fibroblasts and related cells,
4. matrix protein synthesis
5. cessation of these processes

Skin wound Healing - demonstrates :

1. epithelial regeneration (healing of the epidermis)
2. repair by scarring (healing of the dermis).
 Two patterns of wound healing depending on the amount of tissue damage:
1. Healing by first intention (Primary union)
2. Healing by second intention (secondary union

Healing by first intention (primary union) - the least complicated: Ex. healing
of a clean surgical incision
a. The wound edges are approximated by surgical sutures, and healing occurs
with a minimal loss of tissue
b. incision causes the death of a limited number of epithelial cells as well as
of dermal adnexa and connective tissue cells;
c. incisional space is narrow and immediately fills with clotted blood,
containing fibrin and blood cells;
d. dehydration of the surface clot forms the well-known scab that covers the
wound and seals it from the environment almost at once.
e. Within 24 hours, neutrophils appear at the margins of the incision, moving
toward the fibrin clot.
f. epidermis at its cut edges thickens as a result of mitotic activity of basal
cells and,
g. within 24 to 48 hours, spurs of epithelial cells from the edges both migrate
and grow along the cut margins of the dermis and beneath the surface scab to
fuse in the midline, thus producing a continuous but thin epithelial layer.
h. By day 3, the neutrophils have been largely replaced by macrophages.
i. Granulation tissue progressively invades the incisional space.
j. Collagen fibers are now present in the margins of the incision, but at first these
are vertically oriented and do not bridge the incision.
k. Epithelial cell proliferation continues, thickening the epidermal covering layer.
l. By day 5, the incisional space is filled with granulation tissue.
Neovascularization is maximal.
m. Collagen fibrils become more abundant and begin to bridge the incision.
n. The epidermis recovers its normal thickness and differentiation of surface
cells yields a mature epidermal architecture with surface keratinization.
o. During the second week, there is continued accumulation of collagen and
proliferation of fibroblasts.
p. Leukocytic infiltrate, edema, and increased vascularity have largely
disappeared.
q. At this time, the long process of branching begins, accomplished by the increased
accumulation of collagen within the incisional scar, accompanied by regression of
vascular channels.
r. By the end of the first month, the scar comprises a cellular connective tissue
devoid of inflammatory infiltrate, covered now by an intact epidermis
s. The dermal appendages that have been destroyed in the line of the incision are
permanently lost.
t. Tensile strength of the wound increases thereafter, but it may take months for
the wounded area to obtain its maximal strength

2. Healing by second intention (secondary union

- more extensive loss of cells and tissue, as in infarction, inflammatory ulceration,
abscess formation, and surface wounds that create large defects, the reparative
process is more complicated.
- The common denominator in all these situations is a large tissue defect that
must be filled.
- Regeneration of parenchymal cells cannot completely reconstitute the original
architecture.
- Abundant granulation tissue grows in from the margin to complete the repair.
COMPLICATIONS OF WOUND HEALING:
1. Infection – delay healing, and if severe stop it completely
- A wound may provide the portal of entry for many organisms.
2. Deficient Scar Formation – due inadequate formation of granulation tissue or an
inability to form a suitable extracellular matrix

Complications of deficient scar formation :

a. Wound dehiscence & incisional hernias
b. Ulceration

a. Wound Dehiscence and Incisional Hernias:

Dehiscence (bursting of a wound) - after abdominal surgery.
- insufficient extracellular matrix is deposited or there is inadequate cross-linking of
the matrix, weak scars result.
- Dehiscence occurs in 0.5% to 5% of abdominal operations
- Inappropriate suture material and poor surgical techniques are important
factors.
- Wound infection, increased mechanical stress on the wound from vomiting,
coughing, or ileus is a factor in most cases of abdominal dehiscence.
Systemic factors that cause dehiscence:
a. Poor metabolic status,
b. vitamin C deficiency,
c. hypoproteinemia,
d. inanition that often accompanies metastatic cancer
Inanition – exhaustion caused by lack of nourishment
- Dehiscence of an abdominal wound can be a life threatening complication,
mortality as high as 30%.

Incisional hernia – caused by incompletely-healed surgical wound

- classified as ventral hernia (abdominal exploratory surgery) following surgery into
which the intestines protrude

woundsource.com teachmesurgery.com

Figure: Dehiscence
 www1.racgp.org.au mskcc.org
Figure . Abdominal or ventral incisional hernia

3. Excessive Scar Formation - excessive deposition of extracellular matrix at the

wound site results in a hypertrophic scar or a keloid
“maturation arrest”, or block, in the healing process are due to high rate of collagen
synthesis,
3.b. Hypertrophic Scar - similar to keloid
- hypertrophic scar never gets worse after 6 months unlike keloid,
- keloid gets worse even after a year and some may even progress for 5 to
10 years
- Following excision keloid recurs, whereas a hypertrophic scar does not
4. Excessive contraction - decrease in the size of a wound depends on the
presence of myofibroblasts, development of cell-cell contacts and sustained cell
contraction.
- contracture (cicatrisation) - exaggeration of the processes results in severe
deformity of the wound surrounding tissues
- Contracture (cicatrisation) - arise as a result of late reduction in the size of the
wound.
- the regions that normally show minimal wound contraction (such as the
palms, the soles, and the anterior aspect of the thorax) are prone to contractures.
- Contractures are conspicuous in the healing of serious burns.
- Contractures of the skin and underlying connective tissue can be severe
enough to compromise the movement of joints.
Neoplasia - new growth as 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 stimulus, evoking the transformation
or change (Willis).
 Figure 5-1. Neoplasia vs. dysplasia

Dysplasia – tissues becomes disordered in appearance with an increase in numbers

of immature cells and greater variability between cells; NOT a cancer but may
become a cancer.

Nomenclature: Neoplasms - named based on two factors

1. on the histologic types : mesenchymal and epithelial
2. on behavioral patterns : benign and malignant neoplasms
suffix –”oma “ - benign neoplasm.
Nomenclature has some exceptions:
1. Nonneoplastic misnomers hematoma, granuloma, hamartoma
Granuloma – a structure formed during inflammation that is found in many
diseases (macrophage - a collection of immune cells)
- when immune system attempts to wall off substances it perceives as foreign but
is unable to eliminate
hamartoma – mostly benign, local malformation of cell that resembles neoplasm
of local tissue but usually due to overgrowth of multiple aberrant cells, with a basis in
a systemic genetic condition, rather than a growth descended from a single mutated
cell (monoclonality)
2. Malignant misnomers melanoma, lymphoma, seminoma, glioma, hepatoma
melanoma – tumor of melanin-forming cells associated with skin cancer
seminoma – germ cell tumor of the testicle ; a malignant neoplasm
glioma – type of tumor that starts in the glial cells of the brain or spine
hepatoma – cancer of the cells of the liver
- Malignant neoplasm nomenclature essentially follows the same scheme used for
benign neoplasm with certain additions.
1. sarcomas (Greek sar =fleshy) - Malignant neoplasms arising from mesenchymal
tissues ; a fleshy tumor.
Ex. fibrosarcoma, liposarcoma,osteosarcoma, hemangiosarcoma
2. carcinomas - Malignant neoplasms of epithelial cell origin derived from any of
the three germ layers
Metaplasia – reversible replacement of one differentiated cell type with another
mature differentiated cell type which may be part of normal maturation process or
caused by some sort of abnormal stimulus. Ex. chronic smoking
 ar.utmb.com.
Figure 5-2. Metaplasia vs. dysplasia

Cervical dysplasia

Characteristics of Benign and Malignant Neoplasms can be based on:

1. Differentiation & anaplasia
2. Rate of growth
3. Local invasion
4. Metastasis
1. Differentiation and anaplasia
a. Differentiation - the extent to which parenchymal cells resemble comparable
normal cells both morphologically and functionally.
- well-differentiated tumors cells resemble mature normal cells of tissue of origin
- Poorly differentiated or undifferentiated tumors have primitive appearing,
unspecialized cells.
- Benign neoplasms are well differentiated
- Malignant neoplasms range from well differentiated, moderately differentiated
to poorly differentiated types.
b. anaplastic, - Malignant neoplasm composed of undifferentiated cells
- anaplasia means to form backward.
- Morphology of anaplastic cell includes large Pleomorphic; hyperchromatic
nucleus with high nuclear cytoplasmic ratio 1:1(normally 1:4 to 1:6). The cell
usually reveals large nucleoli with high and often abnormal mitoses. Tumor giant
cells and frequent loss of polarity of epithelial arrangements are encountered.
pleomorphic – varies in size, shape and staining of cells and/or their nuclei
c. On functional differentiation, the well differentiated the neoplasm, the more
completely it retains the functional capabilities found in its normal counterparts t
-thus, endocrine tumors produce hormone (ex. Thyroid, adrenal)
 - well differentiated squamous cell carcinoma produce keratin
- well differentiated hepatocellular carcinomas produce bile
d. chemical convergence - highly anaplastic or undifferentiated cells of what cell
tissue of origin come to resemble each other functionally and morphologically more
than the normal cells

2. Rate of growth
a. Most benign tumors grow slowly
b. Most malignant tumors grow rapidly
- sometimes, at erratic pace.
- In general, the growth rate of neoplasms correlate with their level of
differentiation
- Some benign tumors Ex. uterine leiomyoma increase in size during pregnancy
due to probably steroidal effects (estrogen) and regress in menopause.
leiomyoma – known as fibroids, a benign smooth muscle tumor
Occasionally, cancers have been observed to decrease in size and even
spontaneously disappear.
Ex. renal cell carcinoma, malignant melanoma, choriocarcinoma (germ cell tumor,
Hydatidiform mole)

3. Local invasion
a. Nearly all benign neoplasms grow as cohesive expansile masses that
remains localized to their site of origin and do not have the capacity to invade or
metastasize to distant sites, as do malignant neoplasms
b. Rims of fibrous capsules, encapsulated mostly benign neoplasms
- but hemangiomas and neurofibromas are exceptions.
- encapsulations tend to contain the benign neoplasms as a discrete, rapidly
palpable and easily movable mass that can easily surgically enucleated (remove
the tumor from the surrounding capsule)
c. growth of malignant neoplasms is accompanied by progressive infiltration,
invasion and destruction of the surrounding tissue.
- Generally, poorly demarcated from the surrounding normal tissue (and a well-
defined cleavage plane is lacking).
d. invasiveness - is next to the development of metastasis, differentiates malignant
from benign neoplasms.
- connective tissues are the favored invasive path for most malignant
neoplasms due to the elaboration of some enzymes such as type IV collagenases &
plasmin, which is specific to collagen of basement membrane.
- Several matrix-degrading enzymes including glycosidase may be associated
with tumor invasion.
e. Arteries - much more resistant to invasion than are veins and lymphatic
channels due to its increased elastic fibers contents and its thickened wall.
- Densely compact collagens such as membranous tendons, and joint
capsules.
- Cartilage is probably the most resistant of all tissues to invasions ,may be
due to the biologic stability and slow turnover of cartilage.
 Tumor Invasion

Metastasis

4. Metastasis - a transfer of malignant cells from one site to another not directly
connected with it
- Metastasis - most reliable sign of malignancy.
- invasiveness of cancers permits them to penetrate in to the blood vessel,
lymphatic and body cavities providing the opportunity to spread.
- Most malignant neoplasm metastasize except few such as gliomas in the
central nervous system, basal cell carcinoma (Rodent ulcer) in the skin and
dermatofibrosarcoma in soft tissues.
- Organs least favored for metastatic spread include striated muscles and
spleen.

Hyperplasia – tissues or organs enlarged due to some irritants or conditions that

stimulate the cell.
Ex. Women’s breast – enlarged during pregnancy due to increased hormone
Anaplasia – malignant neoplasm composed of undifferentiated cell (young)
Atrophy - decreased in size of organ or tissue due to loss or decreased stimulation.
Ex. legs that lack exercise
Hypertophy – increased in size of organs ex. Muscles of body builders, strenuous
exercise