HISTOPATHOLOGY

Pathology 1. Decreased workload

 From the Greek words pathos (suffering) & logos
(study) meaning the study of disease and involves the
investigation of causes at cellular, tissue, and organ
level
 Scientific foundation of practice of medicine
 Bridge between medicine and science
Study of:
Etiology
 Cause or origin of disease
Pathogenesis
 Mechanisms of its development. Describe how
etiologic factors trigger cellular & molecular changes
that give rise to abnormalities and dse
Molecular & Morphologic Changes
 Biochemical alterations induced in the cells and
organs of the body
Clinical Manifestations
 Functional consequences of these changes
2. Loss of innervation (denervation)
Examples:
 ALS
Amyotrophic Lateral Sclerosis
 Death of nerves from down to up
 Dangerous if reach diaphragm
 ICU patients
3. Diminished blood supply/pressure
4. Inadequate nutrition
5. Loss of endocrine stimulation
6. Aging
↓ metabolic activity = ↓ CHON synthesis
↓ nutrients, disuse = ↑ CHON degradation
*Atrophic organs do not contain dead cells
*They only shrink
Ubiquitin Proteasome Pathway
 Nutrient deficiency  Ubiquitin ligase will be activated
 target cell protein with the help of proteasome

Divisions of Pathology Autophagy

1. Gross Pathology  “Self-eating”
 Macroscopic examination of different tissues and  Starved cells will eat its own components inorder to
organs survive
2. Microscopic Pathology
o Anatomic Pathology
 Surgical
 Autopsy (dead) / Biopsy (living)
o Clinical Pathology
 Hematology  Immuno/Sero
 Microbiology  Clinical Microscopy
 Clinical Chem  Parasitology

Gross Exam ------- HP Techniques -------> Microscopic

TAHBSO
 Total Abdominal Hysterectomy with Bilateral Salpingo-
Oophorectomy
 Remove uterus, fallopian tube, and ovary
2. Hypertrophy
 Physiologic or Pathologic
 No or limited ability to undergo mitosis
 Increase in cell size
 Occurs concurrently with hyperplasia
 Caused either by:
 Increased functional demand
Ex. Cardiomyopathy
Pregnancy
 Specific hormonal stimulation

↑ metabolic activity = ↑ CHON synthesis

*Hypertropic Cardiomyopathy
 -adrenergic receptors = make more protein

Pathologic Physiologic

Cellular Adaptation
 Changes made by a cell in response to adverse
environmental changes
 May be:
 Physiologic
 Pathologic
Adaptive Responses:
o Atrophy o Hyperplasia
o Hypertrophy o Metaplasia

Major Forms of Adaptation

1. Atrophy
 Physiologic Causes
 Pathologic Causes

DDD | MLS - 4B
3. Hyperplasia
o Physiologic
1. Hormonal hyperplasia
Ex. In Breasts during mens / preg
2. Compensatory hyperplasia
Ex. Partial Resection of Liver

o Pathologic
 Mostly caused by excessive hormonal or
growth factor stimulation
 Ex. Endometrial Hyperplasia, Papilloma

*Fertile soil for cancer

4. Metaplasia
 “Change in form”
 One adult cell type is replaced by another adult cell
type
 Occurs as a response to chronic physical or chemical
irritation

o 2 Types:
1. Epithelial metaplasia
2. Mesenchymal metaplasia

Tissue Normal Metaplasia Stimulus

Airways Pseudo- Squamous Cigarette

stratified epithelium smoke
columnar
epithelium

Urinary Transitional Squamous Bladder

Bladder epithelium epithelium stone

Oeso- Squamous Columnar Gastro

phagus epithelium epithelium esopha
-geal reflux

DDD | MLS - 4B
General Pathology

Nuclear Changes
The Cell and The Environment

Cell Injury
 An alteration in cell structure or functioning that occurs
when cells are
 Severely stressed, they are no longer able to adapt
 Exposed to inherently damaging agents
 Suffer from intrinsic abnormalities

General Principles
 The cellular response to injurious stimuli depends on:
 The type of injury, its duration, and its severity Pyknosis - clumping or condensation of nucleus
 The consequences of cell injury depend on: Karyorrhexis - fragmentation
 The type, state, & adaptability of the injured cell Karyolysis - not seen

Causes Kinds of Cell Injury

 Hypoxia  Immunologic Agents
 Physical Agents  Genetic Defects Apoptosis
 Chemicals & Drugs  Nutritional Imbalances  Limits neoplastic growth
 Microbiologic Agents  Aging  Does not stimulate
inflammatory response
Predisposing Factors
 Age  Environment Stimuli That Activates Apoptosis
 Gender  Pre-existing Conditions  Cell membrane damage
 Nutritional Status  Immune-compromised  Mitochondrial damage
 Genes  DNA damage
 Viral Infection
 Immune-mediated attack

Necrosis
Causes of Necrosis
1. Ischemia or Anoxia
 Loss of blood supply to an area that leads to death of
cells due to deprivation of their oxygen and nutrients
2. Physical Agents
 May act directly upon the cells
 May also produce indirect effects by rendering the
blood supply inadequate, like:
 Damage to the blood vessels
 Increase in cellular metabolism
 Examples:
 Trauma  Radiant Energy
 Extreme Heat or Cold  Electrical Energy
3. Chemical Agents
 Any chemical in sufficient concentration may exert toxic
effects; May even cause death of cells
 Concentrated solutions of substances like salt &
glucose may cause local destruction of tissues by
derangement of cell’s osmotic equilibrium
 Examples: Strong acids, alkalis, Bacterial Toxin

Basic Morphologic Changes

1. Microscopic Changes
o Cytoplasmic Changes
 Cell may appear larger and granular
 Becomes more acidophilic
 Dense and opaque
 Boundary is lost with consequent granular
coagulation and fragmentation

Reversible Cell Injury Irreversible Cell Injury

 Generalized swelling of the
cell and its organelles
 Blebbing of the plasma
membrane
 Detachment of ribosomes
from ER
 Clumping of nuclear
chromatin
 Increased Swelling of the
cell
 Swelling and disruption of
lysosomes
 Presence of large
2. Macroscopic Changes
amorphous densities
a. Coagulation Necrosis
 Profound nuclear changes:
b. Liquefaction Necrosis
 Pyknosis c. Fat Necrosis
 Karyorrhexis d. Caseous Necrosis
 Karyolysis e. Gangrenous Necrosis

DDD | MLS - 4B
Types of Necrosis
1. According to Location or Extent
o Focal - isolated in particular location
o Massive - spread

2. According to Basic Morphologic Changes

o Coagulation Necrosis
 Denaturation and precipitation of cellular proteins
 Occurs when arterial supply is cut off, producing
anemic or ischemic infarction
 May be caused by
 Local bacterial action  Wet Gangrene
 Digestive ferments  Venous occlusion
 Intracellular enzymes from disintegrated cells  Bacterial infection + ischemic injury =
 Chemical and physical agents putrefaction
 Architecture or form of tissue is the same or  Offensive, foul-odored fluid
preserved but the protein and enzyme is  Liquefaction necrosis & toxemia
denatured. Thus without enzymes  protein  No sharp line of demarcation
structure is not denatured

o Liquefaction Necrosis
 Enzymatic digestion of cells by its own hydrolytic
lysosomal enzymes
 Ischemic brain injury. Bacterial infections
 Lead to pus formation
 Necrosis of tissues rich in liquid usually induces
them to absorb fluid, leading to softening and
liquefaction

o Fat Necrosis
 Destruction of adipose tissue Feature Necrosis Apoptosis
 Pancreatic lipase splits adipose / neutral fats into Cell Size Enlarged Reduced (shrinkage)
FA & glycerol (swelling)
 FA combine w/ Ca to form soaps forming white
Nucleus Pyknosis  Fragmentation into
precipitates of CaPO4 & CaCo3
Karyorrhexis  nucleosome size
Karyolysis fragments
Plasma Disrupted Intact; altered
Membrane structure, especially
orientation of lipids
Cellular Enzymatic Intact; may be
Contents digestion; may released in apoptotic
leak out of cell bodies
Adjacent Frequent No
Inflammation
Physiologic or Invariably Often physiologic;
Pathologic pathologic means of eliminating
Role (culmination of unwanted cells; may
o Caseous Necrosis irreversible cell be physiologic after
 Resemble soft, friable cheese injury) some forms of cell
 Cells are converted into a granular, friable mass of injury, especially
coagulated CHON & fat, with total loss of cell detail DNA and protein
 Syphilis, Tularemia, Lymphogranuloma vereum damage
(LGV), Tuberculosis (TB)

o Gangrenous Necrosis
 Tissue death due to ischemia & superimposed
bacterial infection
 Combination of coagulation and liquefaction
necrosis
 2 Types (only based on appearance. Reasons may
vary depending on cause)
 Dry Gangrene
 Sterile Necrosis
 Arterial Occlusion  Ischemic necrosis 
desiccation / mummification
 Sharp demarcation line
 Less foul odor (less bacterial infection)
 (-) pyknosis or karyorrhexis

DDD | MLS - 4B
Other Forms of Cellular Responses

1. Autophagy
2. Intracellular Accumulations
3. Pathologic Calcification
4. Cellular Aging

1. Autophagy
 “Self-eating”
 lysosomal digestion of the cell’s own components 3. Lack of enzyme (e.g. Gaucher’s cell)
 Several mechanism in times of nutrient deprivation  Failure to degrade a metabolite due to
 Starved cell cannibalizes itself and recycles digested inherited enzyme def. The resulting
contents; may also signal apoptosis later on disorders are called storage diseases 

 Regulated by a defined set of Autophagy genes
(Atgs)
 Also involved in the clearance of misfolded proteins
(e.g. neurons and hepatocytes)
 Defective autophagy may be a cause of neuronal
death induced by accumulation of these proteins and
subsequent, neurodegenerative disease

4. Ingestion of indigestible materials (exogenous)

 Cell has no enzymatic machinery to digest
and transport
 Ex. Dust & Accumulation of carbon in lungs
 Deposition & accumulation of an abnormal
Intracell Sequestered w/in an Vacuole fuses w/ exogenous substances when the cell has
organelles autophagic vacuole lysosome, forming
& portions (formed from autophagoolysosome &
neither the enzymatic machinery to
of cytosol ribosome-free lysosomal enzymes degrade the subs nor the ability to transport
regions of ER) digest cell components it to other sites. Accumulation of carbon or
silica particles is an example of this type of
alteration. 

2. Intracellular Accumulations
 Cells may accumulate abnormal amounts of various
substances:
 Cytoplasm
 Within organelles (typically lysosomes)
 Nucleus
a. Normal cellular constituent
 Lipids
 Proteins
 Carbohydrates
b. Abnormal substances (Not normally found in cells)
 Exogenous
o Lipids
 Minerals
 Steatosis / Fatty Change
 Toxic waste / product
 Accumulation of fats
 Infectious Agents
 Can be in heart, kidney, and commonly
 Endogenous in liver (fatty liver) because it is the
 Waste products produced by our own cells primary storage of fats
c. Time  Caused by: Toxins, Obesity, Anoxia,
 Transient Malnutrition, Diabetes Milletus
 Permanent  Alcohol abuse and diabetes associated
with obesity are the most common
 4 Main Pathways of Abnormal Intracell accumulations causes of fatty change in the liver (fatty
1. Abnormal Metabolism (e.g. Fatty Liver) liver) in indus- trialized nations
 Inadequate removal of a normal substance  Atherosclerosis / Cholesterol deposition
secondary to defects in mechanisms of  Most important disease caused by
packaging and transport, as in fatty change accumulation of triglycerides,
in the liver cholesterol, and cholesteryl esters
 Due to excessive intake or defective
catabolism

o Proteins
 Less common than lipid
 When excess protein are presented in cell
or excess synthesis
 Associated with certain disorders
 Reabsorption in tubules
 Defective intracellular transport
2. Defect in protein folding & transport  Reversible
 Accumulation of an abnormal endogenous  Russel bodies
substance as a result of genetic or acquired  Found in plasma cell
defects in its folding, packaging, transport,  Accumulation of immunoglobulin
or secretion, as with certain mutated forms
of α1-antitrypsin 
 o Hyaline
 Alteration within cells or extracellular space
 Homogenous, glassy pink appearance of
tissues

DDD | MLS - 4B
 o Glycogen
 Energy source
 Deposits are seen in abnormalities in
glucose / glycogen metabolism
 Glycogen storage disease / glycogenoses
 Poorly controlled diabetes milletus

o Pigments
 Endogenous
 Lipofucsin
 Insoluble abnormal pigment
 Brownish-yellow
Injurious Stimuli Cellular Response
 Also known as “Lipochrome” or
the “Wear-and-Tear Pigment” Altered Physiological Stimuli; Cellular Adaptations
caused of lipid peroxidation and Nonlethal Injurious Stimuli
is a sign of free radical injury  Increased demand,  Hyperplasia
 Not injurious to cell but a tell tale Increased stimulation Hypertrophy
sign of free radical injury and  Decreased nutrients,  Atrophy
usually seen in aging patients Decreased stimulation
(liver / heart / brain) or patients  Chronic Irritation  Metaplasia
with severe malnutrition & cancer
 Brown atrophy: if in large amount Injurious Agent Cellular Response
 Melanin Reduced Oxygen Supply; Cell Injury
 Example of normal body pigment Chemical Injury;
 Brown-black Microbial Infection
 Synthesized by melanocytes  Acute and transient  Acute reversible injury
against UV radiation
 Progressive and severe  Irreversible injury  cell
 Keratinocytes (freckles) (Including DNA damage) death
 Hemosiderin
(Necrosis / Apoptosis)
 Hemoglobin derived
 Golden yellow to brown
Injurious Agent Cellular Adaptations
 Seen if there is excess iron
Metabolic Alterations, Intracellular Accumulations;
 Pathologic but if in small
Genetic or Acquired; Calcification
amounts, normal
Chronic Injury
 Exogenous Cumulative Sub-lethal Injury Cellular Aging
 Carbon / Coal dust Over Long Life Span
 Accumulation of coal in alveolar
macrophage
 Most common exogenous
pigment
 Tattooing
 Pigments are inoculated and
phagocytized by dermal
macrophage

3. Pathologic Calcification
 Abnormal tissue deposition of calcium salts
 Smaller amounts of Fe, Mg & other mineral salts
 Dystrophic or Metastatic

2 Forms:
 Dystrophic Calcification
 Local accumulation in dying tissue
 Not associated with high calcium levels in
our serum  loss of ATP, influx of Ca
 Metastatic Calcification
 Deposition of calcium in normal tissue due
to hypercalcemia
 Almost always secondary to some
derangement in calcium metabolism
 Common causes:
 Parathyroid hormone
 Destruction of bone (Paget’s dse)
 Vit D related disorders
 Renal failure

4. Cellular Aging
 Result of a progressive decline in the life span and
functional capacity of cells
 Ex. Age: Alzheimer’s, Parkinsons, Other neuro dse
 Mechanisms
o DNA Damage
o Decreased cellular replication
 Replicative senescence
 Time when cell is no longer able to
divide
 Ex. Halting of spermatogenesis and
oogenesis
o Defective protein homeostasis
 Chaperone molecules
 Help in folding proteins
 Werner syndrome (premature aging)

DDD | MLS - 4B
Inflammation

 Cytopathologic Changes in Disease

 A universal response to tissue damage by a wide range of
harmful stimuli including:
 Mechanical trauma
 Tissue necrosis
 Infection
 A protective response involving host cells, blood vessels,
protein, and other mediators that is intended to”
 Eliminate the initial cause of cell injury
 As well as the necrotic cells & tissues resulting from
the original insult
 And to initiate the process of repair
 Can be acute / chronic & beneficial / harmful

2 Stages of Inflammation
1. Vascular stage
2 Cellular stage

Functions
o Contain and isolate the injury
o Destroy microbe or toxin
o Prepare tissue for healing and repair
Mediators of Inflammation
Cardinal Signs 1. Plasma Derived
 Already known 2000 years ago written in “De Medicina” o Bradykinin
 Functio Laesa was introduced in 1800 by Rudolf Virchow  Vascular permeability and causes pain
 Rudolf Virchow is the father of Pathology  Derived from plasma protein
 Rubor - redness (ruby)
 Tumor - swelling o Complement System
 Calor - heating  Causes cell lysis and is plasma derived
 Dolor - pain
 Functio Laesa - loss of function o Arachidonic Acid (AA) Derivative
 Forms in phospholipid of cell wall of epithelial cells
Causes of Inflammation
 Metabolized to form:
 Infection - most common
 Leukotrienes
 Tissue necrosis
 Foreign bodies  Prostaglandin
 Immune response  Prostacyclin - pain
 Sensors of cell damage  Thromboxane - clotting
 Circulating proteins
2. Cell Derived
Events in Inflammation o Histamine
1. Vasoconstriction  Vascular permeability
 Vascular stage  Cell derived
 Happens first and only last for seconds  Released from:
 Blood - basophil
2. Vasodilation  Tissue - mast cells
 Vascular stage
 Change in size of caliber of blood vessels (expand)
 Increases blood flow for neutrophil activation
 Leads to erythema (heat & redness on site of infxn)

3. Endothelial activation
 Vascular stage
 Increase vascular permeation
 Edema formation (extravasation) liquid portion of blood,
plasma

4. Neutrophil activation
 Cellular stage
 WBC enter site of injury, kill organisms and mop debris
 Release chemokines

In the lumen: Cellular Components of Acute Inflammation

 Margination a. Neutrophil
 Rolling - P-selectin & E-selectin  Acute inflammation
 Adhesion to the endothelium (integrin)  Phagocyte; first to enter site of injury & is short lived
 diapedesis / extravasation (PECAM)
 chemotaxis  Phagocyte killing b. Eosinophil
 Phagocyte; longer lived
 Margination across the endothelium & vessel wall  Allergic rxns, parasitic infection, chronic inflammation
(diapedesis)
 Margination in the tissues toward a chemotactic c. Basophil
stimulus (chemotaxis / chemokines)  Release histamine = vascular permeability
 Macrophage
 first to release chemokines d. Macrophage
 Major phagocyte
 Exudation  Enter site 3-4 days after injury; Chronic inflammation
 movement of cells & proteins from intravascular
to extravascular system e. Lymphocyte / Plasma Cells
 extravasation of CHON  Immune function to chronic inflammation

DDD | MLS - 4B
Exudate VS Transudate 3. According to Location
 Exudate o Localized
 Protein rich fluid  One site / not wide spread
 Contains WBC and protein fluid due to inflammation
o Generalized / Systemic
 Transudate  Whole organ / area of tissue / region
 Protein poor fluid
 Few cells formed because of disturbances in force Effects of Inflammation
across the vessel Beneficial
 Dilution of toxins
 Pus / Purulent  Entry of antibodies
 Inflammatory exudate  Drug transport
 Contains many neutrophil due to bacterial infection  Delivery of nutrients and oxygen
 Fibrin formation
Classification of Inflammation  Stimulation of immune response
According to:
1. Duration Harmful
o Acute / Excudative  Digestion of normal tissues
 Sudden onset  Swelling
 With vascular & exudative changes; PMNs  Inappropriate inflammatory response

o Chronic The Typical Inflammatory Reaction Develops Through a

 Involves persistence of injurious agent Series of Sequential Steps
1. The offending agent, which is located in extravascular
 Proliferative response
tissues, is recognized by host cells and molecules
 Mononuclear cells (3-4 days)
2. Leukocytes and plasma proteins are recruited from the
 Monocyte - blood circulation where the offending agent is locted
 Macrophage - tissues 3. The leukocytes and proteins are activated and work
together to destroy and eliminate the offending substance
4. The reaction is controlled and terminated
5. Damaged tissue is repaired

Feature Acute Chronic

Onset Fast: mins / hrs Slow: days

Cellular Infiltrate Mainly neutrophils Monocytes

Macrophage
Lymphocytes

Tissue Injury, Usually mild and Often severe and

Fibrosis self-limited progressive

Local & Systemic Prominent Less

Signs

2. Character of Exudate
o Serous
 Out-pouring of water relatively protein poor fluid
depends on the site of injury (Effusion)
 Common in cavities (peritoneal/cardial, & pleural)

o Fibrinous
 More severe than serous
 Consequence of more severe injury = more
vascular permeability = more protein leaking
 Extravasation of large molecules like fibrinogen
which is the precursor of fibrin
 Accumulation of extravascular fibrin
 Meninges, pericardium, pleura
 Can result to resolution or resolution

o Catarrhal
 Increased blood flow to mucosal vessels
 Edema of interstitial fluid
 Enlargement of secretory cells
 Discharge of mucus & epithelial debris
 Ex. Enteritis (small intestine) / rhinitis

o Hemorrhagic
 Disruption of vessel wall  leakage of large
number of RBCs

o Suppurative / Purulent
 There is a collection of large amount of pus
 Composed of:
 Neutrophils
 Necrotic cells
 Edema fluid
 Mainly caused by bacterial infection especially by
pyogenic bacteria or by a secondary condition
 Abscess = collection of pus

DDD | MLS - 4B
Sequelae of Acute Inflammation

Possible Outcomes of Acute Inflammation 4. Chronic Inflammation

1. Resolution  May result following acute inflammation
2. Organization & Repair / Healing by Fibrosis  Presence of injurious agent
3. Suppuration (Abscess formation)
4. Chronic Inflammation

Possible Outcomes Depend On:

 Type of tissue involved
 Amount of tissue destruction
 Nature of injurious agent

1. Resolution
 Occurs when connective tissue is intact
 Involved tissue has the capacity to replace any
specialized cells that may have been lost

2. Organization & Repair

 Occurs when there is substantial damage to the
connective tissue framework; and or
 Tissue lacks the ability to regenerate specialized cells

Removal of dead tissues & acute inflammatory

exudate from damaged area (macrophage)

Filling of defect by in growth of a specialized

vascular connective tissue called granulation tissue

Gradual production of collagen by granulation

tissue to form a fibrous (collagenous) scar
constituting the repair process

Re-establishment of structural integrity

3. Suppuration / Abscess formation

 The acute inflammatory reaction fails to destroy /
remove the cause of tissue damage

Progression of acute inflammation

Liquefaction of tissue to form pus

At the periphery of this area, a chronic

inflammatory component surrounds the area

Fibrous tissue is laid down

Walling off the suppuration

DDD | MLS - 4B
Abnormalities in Cell Growth and Somatic Death

1. Primary Changes g. Autolysis

o Circulatory failure  Self digestion of cells
 Cardiac function ceases  Eventually undergone by all tissues
 Absence of pulse & heart beat  Putrefactive bacteria
 Progressive dessication
o Respiratory failure  Last organ not digested: bone
 Following cardiac failure (bc made of inorganic phosphate & calcium)
 Leads to death (absence of O2 & CO2)
 Loss of oxidative process

o Nervous failure
 Loss of reflexes

2. Secondary Changes
a. Algor Mortis
 Cooling of body
 Body temperature decreases @ 7oF/hr
 No metabolism = no heat production
 Accelerated by:
 Cold weather
 Severe hemorrhage
 After long wasting diseases
 In lean, malnourished, dehydrated individual
 Slowed by:
 Consumption of drugs
 Extreme physical activity
 Fever

 Glaister Equation
 Estimates the hours elapsed since death as a
linear function of rectal temperature

b. Rigor Mortis
 Rigidity or stiffening of muscle
 6-12hrs after death & persists for 3-4 days
 Head & neck first then towards the lower
extremities (rigid due to chemical changes in
muscle)
 Muscular activity at time of death affects body
position

c. Liver Mortis
 Purplish discoloration of skin due to stasis
 Discoloration in contrast to ecchymosis
 Absent when blood clots are found in the
interstitial tissues

d. Post-Mortem Clotting
 Occurs slowly, immediately after death
 Should be first but not apparent / seen after
death. Only seen in autopsy
 Settling & separation of RBCs from fluid phase of
blood (rubbery)
 With RBCs: “Currant Jelly” Clots

 Ante-Mortem Clotting
 Happens when the person is still alive
 Friable, entangled, & irregular
 (+) Fibrin precipitin

e. Dessication
 Drying & wrinkling of fluid-filled organs
 Cornea & anterior chamber of eye
(most apparent)

f. Putrefaction
 Loss of rigor mortis due to autolysis of cells
 Foul selling odor due to bacterial invasion
(normal flora, especially the gut)
 Associated with the following changes:
 Greenish blue discoloration
(Iron sulfide formation)
 Refraction of cornea
 Loss of rigor mortis
 Peeling of skin & swelling of face

DDD | MLS - 4B
Abnormalities in Cell Growth

1. Retrogressive Changes  Proto-oncogenes

 Developmental defect (from birth)  Prototype / precursor
 Congenital Disorders  Regulation of cell growth, differentiation, & apoptosis
 Problem arise if it becomes activated
o Aplasia  Oncogene  uncontrolled cell growth
 The organ is represented only by a mass of fatty
fibrous tissue  Tumor Suppressor Gene
 The failure of organ / tissue to function normally or  Anti oncogenic gene
to develop normally  If suppressed  cancer
 Aplasia Cutis Congenita
 No epidermis  Tumor
 “Congenital absence of skin / scar”  Mass of neoplasia / neoplastic cells
 Aplastic Anemia

o Hypoplasia General Characteristic of Tumor Cell

 Failure of an organ to reach mature size
 Under development of tissue / organ
 Inadequate / below normal cells
 Congenital tibial hypoplasia
 Lung hypoplasia
 Finger hypoplasia
o Atresia
 Failure of an organ to form an opening
 Absence or abnormal narrowing of opening or
passage in the body
 Congenital microtia with external canal atresia
 Congenital atresia of the fallopian tube
 Intestinal Atresia
 Atresia of the valves / Atretic pulmonary valve
1. Usually resemble & imitate normal cell well enough
2. Capable of secreting substances
3. Parasitic nature; competes w/ cell for metabolic needs
4. Autonomy; non-responsive to normal growth factors
5. Steadily size regardless of environment & host’s health
2 Parts of Tumor / Neoplastic Issue
1. Parenchyma
 Active element of tumor
 Made of cells that are actively dividing
2. Stroma
 Connective tissue framework w/ lymphatic and
vascular channels

o Agenesia Classification of Tumor

 Complete non-appearance of an organ 1. Based on Capacity to Produce Death
 Penile agenesis o Benign Tumor
 Testicular agenesis  Do not usually produce death
 MRKH (Mayer-Rokitansky-Kuster-Hauser)  More common in younger age
 Group, grows slowly by expansion
2. Degenerative Changes  Not fix
 Change of normal healthy cell into:  Metastasis (-)
 No cachexia
o Dysplasia
 Malformation o Malignant Tumor / Cancer
 Immature cells; mature cells  Cause death
 Delayed maturation & differentiation  Found on the older age group
 Often indicative of an early neoplastic process  Grows rapidly by infiltration / expansion
 Change in size, shape, orientation  Fixed to tissues
 Often leads to cancer but not necessarily progress  Ultimate death by cachexia
 Reversible

 Characterized by 4 major patho micro changes: Benign Tumor Malignant Tumor

 Anisocytosis
Normal cells (differentiated) Undifferentiated
 Variation in cell size
 Poikilocytosis Less mitotic figures More mitotic figures
 Variation in cell shape Not hyperchromic Hyperchromic
 Hyperchromatism Less tendency to More tendency to
 Excessive nuclear staining because of too hemorrhage and necrosis hemorrhage and necrosis
much DNA (active mitosis)
 Presence of mitotic figures 2. Based on Histologic Characteristic
o Carcinoma
*dysplasia = reversible  Malignant tumor of epithelial origin
*neoplasia = irreversible  Less tendency to produce supporting tissue or
stroma
o Anaplasia
 Dev’t of cell towards more primitive cell types o Sarcoma
 Adult cell  embryonic cell typee  Malignant tumors of connective tissue origin
 Poor cellular differentiation  (+) Intracellular tissue framework
 Loss of morphology& characteristic of immature cell
 Loss of orientation
Grading of Tumors
Normal: undifferentiated  differentiated  Attempts to establish an estimate of the level of
Dedifferentiation: differentiated  undifferentiated malignancy
Metaplasia: differentiation  differentiation  Based on cytologic differentiation of tumor cells & number
of mitoses within the tumor
o Neoplasia  Guide for treatment and diagnosis
 Transformation of proto-oncogenes into oncogenes
/ loss of tumor suppressor gene function Well-differentiated tumors, as a rule, are less malignant
 Uncontrolled growth than undifferentiated cells
 Causes:
 Carcinogens
 DNA alteration

DDD | MLS - 4B
Grading of tumors is based on:
1. Degree of differentiation of tumor cell
2. Degree of pleomorphism
3. Mitotic index
4. Degree of anaplasia or undifferentiation
5. An estimate of the rate of growth
6. Degree of invasion

Border’s Classification of Tumor

Grade Differentiated Cells Undifferentiated Cells
I 100% - 75% 0% - 25%
II 75% - 50% 25% - 50%
III 50% - 25% 50% - 75%
IV 25% - 0% 75% - 100%

Limitations of Grading
1. Tumors present a homogenous appearance throughout
but grading may vary from section to section
2. Higher grades of tumors generally have more tendency to
metastasize
3. Usually the metastasis is of the same grade as the
primary tumor
4. Some tumors cannot be graded as most of the sarcomas

DDD | MLS - 4B