Pathology slides on overview of pathology and cell injury

This is a pathology slide that covers cell injury, and the overview of pathology

1. General
Pathology
Samuel Essien-Baidoo, PhD.

2. Course Objectives
By the end of the course, students should be able to:
1.explain the concept of pathology, the history and role of the discipline
2.describe the cellular basis of disease, cell adaptation, injury, and death
3.describe acute and chronic inflammatory processes
4.describe healing of wounds, fractures, and special tissues
5.explain the basic concept of immunology
6.state pathological processes in shock, embolism, infarction, and neoplasm
7.describe pathological processes in cardiac, renal, and liver failure

3. Unit 1:
Introduction to
Pathology

4. What is Pathology?
•Pathology is the scientific study
(logos) of disease (pathos).
•It mainly focuses on the study
of the structural, biochemical
and functional changes in cells,
tissues and organs in disease.
4

5. FIELDS OF
PATHOLOGY
•General Pathology:
•This deals with all changes that occur in tissue. It deals with the study of mechanism, basic reactions of cells and tissues to abnormal stimuli and to inherited defects.
•Systemic pathology:
•Deals with the pathologic manifestations in various organs. This deals with the changes in specific diseases/responses of specialized organs and tissues.
5

6. Branches of
pathology
•Forensic Pathology: This deals with medical-legal
autopsies and determine cause and manner of death
when an obvious medical cause is not evident, particularly for deaths outside the hospital.
•Cellular pathology, includes histopathology (the study
of tissues) and cytopathology (study of separated cells).
•Chemical pathology or clinical biochemistry is the study
of body chemistry, usually by assaying the level of
substances –electrolytes, enzymes, lipids, trace
elements –in the blood or urine.
•Anatomic Pathology: This deals with evaluation of
tissue, either as specimen taken at surgery or biopsy, or
autopsy due to medical deaths usually in a hospital and
with cytology specimens (PAP smears, or smears from
other procedures.
6

7. DISEASE
•An abnormal alteration in
structure or function of any
part of the body
•A state in which an individual
exhibits an anatomical
physiological or biochemical
deviation from the normal
7

8. Disease process can bestudied under following
aspects:
•Etiology
•The etiology of a disease is its cause. The causative factors ofa disease can be
divided into two major categories: Geneticand acquired (e.g. infectious,
chemical, hypoxia, nutritional,physical). Most common diseases are
multifactorial due tocombination of causes.
•Pathogenesis
•It refers to the sequence by which the causative factor(s)produces cellular,
biochemical and molecular abnormalities following the exposure of cells or
tissues to an injurious agent. Pathogenesis deals with sequence of events that
occur in the cells or tissues from the beginning of any disease process.
8

9. Disease study includes
9
MOLECULAR
LEVEL
CELLULAR LEVELTISSUE LEVELORGAN AND
SYSTEM LEVEL

10. Methods of
studying
pathology
10
Gross examination
Light microscopy
Immunohistochemistry
Electron microscopy
Molecular biology

11. MANIFESTATION OF
DISEASE
•Signs: These are objective as perceived by the examiner.
•Symptoms: These are functional manifestations or evidences of disease processes
•Lesions: These are visible changes produced by a disease in tissues or organs.
•Exacerbation: Increase in the severity of signs or symptoms of a disease
•Remission: Decrease in intensity of the disease
•Complications: Unfavorable outcomes of a disease.
•Sequelae: These are remote consequences of a disease.
11

12. Causes and
classification of
Disease
12

13. Cell
Injury
•These are the sequence of events when the limits of adaptive capability are exceeded, or no adaptive response is possible.
•Depending on the nature of stimulus/injury, the cellularresponses can be mainly divided into four types:
1. Cellular adaptations
2. Cell injury
•Reversible cell injury
•Irreversible cell injury.
3. Intracellular accumulations
4. Pathologic calcification.
13

14. 14

15. Causes of
Cell Injury
•Oxygen deprivation (hypoxia or ischemia)
•Physical Agents (trauma)
•Chemical agents and Drugs
•Infectious Agents
•Immunologic Reactions
•Genetic Derangements
•Nutritional Imbalances

16. 16

17. Mechanisms
of Cell Injury
Cellular response to injury depends on
•Nature of the injury
•Duration of the injury
•Severity of the injury.
17

18. Mechanisms
of Cell
Injury
The outcome of injury depend on
•Type of cell
•State of the cell
•Adaptability of the injured cell.
•Cell injury results from different
biochemical mechanisms acting on
essential cellular components.
18

19. CELLULAR
ADAPTATION
•Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
•Under normal conditions, cells must constantly adapt to changes in their environment (physiological, pathological).
1.Increase in the number of cells (Hyperplasia).
2.Alterations in the size of cells (Hypertrophy and atrophy).
3.Alteration in cellular differentiation (metaplasia).

20. Hyperplasia
•Increase in the number of cells in an organ or tissue. (increase
rate of cellular division/ DNA synthesis)
•Hypertrophy and hyperplasia are closely related (exp : gravid
uterus)
•Physiologic or pathologic
•Physiologic –Two types
•Compensatory hyperplasia (exp: liver),
•Hormonal hyperplasia (exp: uterus, breast)
•Pathological –excessive and persistent hormonal or growth
factor stimulation
(exp: endometrial hyperplasia/BPH)
•Hyperplasia is important in wound healing (fibroblast and
blood vessels)
•Benign may lead to malignancy when it persist
20

21. Hypertrophy
•Increase the size of the cells and
consequently the size of the organs
•Increased the synthesis of structural
protein and organelles
•Can be physiologic (ex; increase workload
during exercise, uterine myometrium
during pregnancy)
•Pathologic (hypertrophy of myocardium –
hypertension/aortic valve disease)
21

22. Uterine
hypertrophy

23. Muscular
hypertrophy

24. Atrophy
•Shrinkage of the size of the cells by the lost
of the cell's substance.
•Decrease proteins synthesis and increase
degradation
1.Decrease metabolic activity
2.Ubiquitin-proteasome pathway
•The entire tissue or organs diminishes in size
and function
•Atrophy also may be physiologic or
pathologic.
•Physiologic-Regression of embryonic
structures -notochord, loss of hormone
stimulation in menopause.
•Pathologic-denervation 24

25. Causes
of
atrophy
•Decreased workload e.g., atrophy of skeletal muscle after immobilisation in POP
•Loss of innervation e.g., flaccid paralysis.
•Diminished blood supply e.g., cerebral atrophy in the elderly as a result of atherosclerotic narrowing of cerebral vessels. (senile atrophy)
•Inadequate nutrition e.g., chronic malnutrition (marasmus).
•Loss of endocrine stimulation e.g., atrophy of the breast and endometrium after menopause.
•Pressure atrophy. Compression of an organ by a mass can leadto atrophy of that organ, probably due to ischemia.

26. Metaplasia
•Is a reversible change in which one adult cell
type is replaced by another cell type.
•Adaptation of cells that sensitive to particular
stressto cell types better able to withstand
the adverse of environment
•Columnar to squamous metaplasia is
commonly seen and itsas a result of chronic
irritation (e.g., pseudo stratified ciliated
columnar to squamous in chronic smoker)
•Persistent metaplasia may lead to malignancy
26

27. 27

28. The relationship
among normal,
adapted,
reversibly injured,
and dead
myocardial cells

29. Cell Injury.
•If the cells fail to adapt under
stress, they undergo certain
changes called cell injury.
•Injury may progress through a
reversible stage and culminate
in cell death

30. Reversible and
irreversible cell injury
•The affected cells may recover
from the injury (reversible) or may
die (irreversible).
•Reversibility depends on the type,
severity and duration of injury.
•Cell death is the result of
irreversible injury

31. Reversible cell
injury
The hallmarks of reversible injury are:
1.Reduced oxidative phosphorylation
2.Adenosine triphosphate (ATP) depletion
3.Cellular swelling (hydropic degeneration) caused by changes in ion concentrations and water influx.
4.Fatty change (Steatosis)-Excess fat in a form of small or large droplet

32. Reversible Injury --Morphology
Light microscopic changes
•Cell swelling (aka hydropic
change)
•Increase in weight of the
organ
•Pale appearance
Ultrastructural changes
•Alterations of cell membrane
•Swelling of and small
amorphous deposits in
mitochondria
•Swelling of RER and
detachment of ribosomes
•Nuclear change

33. Irreversible cell injury
•“point of no return”
•Irreversible responses of cell injury refer tochanges that lead to a new equilibrium in the cellular environment.
•Types of irreversible responses include interruption of membrane integrity; hydrolysis of phospholipids, proteins and nucleic acids; and necrosis, where organelles undergo a sequence of changes.
•Persistent or excessive injury
•Characterized by:
§Severe mitochondrial damage and nuclear dissolution
§Loss of membrane permeability

34. Irreversible
Injury --
Morphology
•Light microscopic changes
•Increased cytoplasmic eosinophilia (loss of RNA, which is more basophilic)
•Cytoplasmic vacuolization
•Nuclear chromatin clumping
•Ultrastructural changes
•Breaks in cellular and organellar membranes
•Larger amorphous densities in mitochondria
•Nuclear changes
•Pyknosis
•Nuclear shrinkage and increased basophilia
•Karyorrhexis
•Fragmentation of the pyknotic nucleus
•Karyolysis
•Fading of basophilia of chromatin

35. CAUSES OF
CELL
INJURY
(O2 Deprivation)
•Hypoxia is an extremely important and
common cause of cell injury and cell
death.
•Hypoxia is a deficiency of oxygen, which
causes cell injury by reducing aerobic
oxidative respiration.
Causes of hypoxia
1.Reduced blood flow (called ischemia)
2.Hypoxemia (pneumonia)
3.Carbon monoxide poisoning
4.Decreased oxygen-carrying capacity of
the blood (blood loss anemia)

36. Physical
Agents
Physical agents capable of
causing cell injury include:
1.mechanical trauma
2.extremes of
temperature
3.radiation

37. Chemical Agents and Drugs
•Poisons, such as arsenic, cyanide, or mercuric salts,
may destroy enough cells within minutes or hours to cause death.
•Other potentially injurious substances such as air
pollutants, insecticides, and herbicides; industrial and
occupational hazards, such as carbon monoxide and
asbestos.
•Drugs, alcohol and the ever-increasing variety of
therapeutic drugs.

38. Infectious
Agents
•The viral,
protozoa,
bacteria,
fungi, and
parasites.

39. Immunologic Reactions
1.Autoimmunity
2.Hypersensitivity

40. Genetic
Derangements
Disease may result
from:
•abnormal
mutated genes or
•chromosomal
abnormalities.

41. Nutritional
Imbalances
•Nutritional Deficiencies
•Nutritional excesses

42. AGING
•Aged cells become larger, less able
to divide and multiply
•Alterations in repair mechanism
•Less ability to respond to damage
or injury and may lead to death
•Lose their ability to functions, or
function abnormally

43. Cell Injury –
General
Mechanisms
•The cellular response to injurious stimuli depends on the type of injury, its duration, and its severity
•The consequences of cell injury depend on the type, state, and adaptability of the injured cell.
•Four very interrelated cell systems and biochemical mechanism are particularly vulnerable to injury:
•Aerobic respiration involving mitochondrial oxidative phosphorylation and production of ATP and ROS
•The integrity of cell membranes, on which the ionic and osmotic homeostasis of the cell and its organelles depends
•Calcium homeostasis
•The integrity of the genetic apparatus of the cell and protein synthesis.

44. Cell Injury –
General
Mechanisms
•ATP depletion
•Loss of calcium homeostasis
•Defects in membrane permeability
•Oxygen and oxygen-derived free
radicals
•Mitochondrial damage
•Misfolded protein and DNA damage

45. ATP DEPLETION
•Mitochondrial oxidative phosphorylation is disrupted first àDecreased ATP à
•Decreased Na/K ATPase àgain of intracellular Na àcell swelling
•Decreased ATP-dependent Ca pumps àincreased cytoplasmic Ca concentration
•Altered metabolism àdepletion of glycogen
•Lactic acid accumulation àdecreased pH, chromatin clumping
•Detachment of ribosomes from RER àdecreased protein synthesis
•End result is cytoskeletal disruption with loss of microvilli, bleb formation, etc

46. Mitochondrial
damage
•Mitochondria can be damaged by
increases of cytosolic Ca2+, oxidative stress, breakdown of phospholipids
through phospholipase A2 and
sphingomyelin pathways, and by lipid
breakdown products such as free fatty
acids and ceramide.
•There is formation of a high-
conductance channel, the so-called
mitochondrial permeability transition,
in the inner mitochondrial membrane
This is initially reversible but may progress to irreversibility if injury
persist

47. CALCIUM
HOMEOSTASIS
•Membrane damage and loss of calcium homeostasis are most crucial
•Gradients are modulated by membrane-associated, energy-dependent Ca2+,Mg2+ -ATPases
•Ca accumulation trigger many enzymatic reaction i.eATPase, Phospholipase, endonucleases and proteases,
•Too much cytoplasmic calcium:
•Denatures proteins
•Poisons mitochondria
•Inhibits cellular enzymes
•Apoptosis is also activated

48. DEFECTS IN MEMBRANE PERMEABILITY
•Early loss of selective membrane permeability leading ultimately to overt membrane damage is a consistent feature of most forms of cell injury
•Ischaemia, ATP depletion, Bacteria toxin, lytic complement pathways, viral proteins and numerous chemical and physical agent could cause this defect
•Biochemical Pathways that contributes to this damage include:
•Hypoxia -decrease phospholipids synthesis and increase phospholipid breakdown
•Increased Ca level (activates enzymes, mitochondrial permeability)
•Cytoskeletal abnormalities
•Reactive oxygen species
•Three main site:
•Mitochondria membrane damage
•Plasma membrane damage
•Lysosomal membrane damage

49. Clinical
Correlation
•Injured membranes are
leaky
•Enzymes and other
proteins that escape
through the leaky
membranes make their
way to the bloodstream,
where they can be
measured in the serum

50. ACCUMULATION OF OXYGEN-DERIVED
FREE RADICALS (REACTIVE OXYGEN SPECIES)
•Reduced reactive oxygen products are generated unavoidably in the process of energy generation when oxygen is reduced to water
•Free radicals have an unpaired electron in their outer orbit
•Free radicals cause chain reactions
•An imbalance between free radical-generating and radicals scavenging systems results in cell injury seen in many pathologic conditions.
•Five main causes:
•Absorption of radiant energy (e.g., ultraviolet light, xrays).
•Enzymatic metabolism of exogenous chemicals or drugs
•The reduction-oxidation reactions that occur during normal metabolic processes
•Transition metals such as iron and copper donate or accept free electrons during intracellular reactions and catalyze free radical formation
•Nitric oxide (NO), an important chemical mediator generated by endothelial cells, macrophages, neurons and other cell types can act as a free radical
•Inflammation

51. Cellular mechanism of
dealing with free radicals
•Antioxidants either block the initiation of free radical formation or inactivate (e.g., scavenge) free radicals and terminate radical damage e.g., vit A,C, E and Glutathione
•Binding of Fe and Cu by transferrin, ferritin, lactoferrin, and ceruloplasmin
•Enzymes which acts as free radical–scavenging systems and break down hydrogen peroxide and superoxide anion e.g., Catalase, superoxide dismutase, Glutathione Peroxidase

52. Mechanism of
Free Radical
Injury
•Lipid peroxidation à
damage to cellular and
organellar membranes
•Protein cross-linking and
fragmentation due to
oxidative modification of
amino acids and proteins
•DNA damage

53. MISFOLDED
PROTEIN AND
DNA DAMAGE
•Normal proteinsfoldinto3
dimensional architecture
•Misfoldedproteinsget
injuredanddie
•DNA mutationdueto
exogenousreasons
•Cellsdie byapoptosis

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55. Types of Cell Death
•There are two types of cell death, necrosis and apoptosis, which differ in their morphology, mechanisms, and roles in disease and physiology
•Apoptosis
•Usually a regulated, controlled process
•Plays a role in embryogenesis
•Necrosis
•Always pathologic –the result of irreversible injury
•Numerous causes

56. Necrosis
Necrosis = Death / premature death of cells in
living tissue.
It occurs when there is severe damage to the cell
resulting in loss of membrane permeability
Lysosomal enzyme enter the cytoplasm and digest
the cells
There is leakage of cellular content to the
surrounding which result in inflammation

57. Morphology
of Necrosis
•Early changes : morphologically normal
•Nuclear changes :
•Pyknosis
•Nuclear shrinkage and increased basophilia
•Karyorrhexis
•Fragmentation of the pyknotic nucleus
•Karyolysis
•Fading of basophilia of chromatin
•Cytoplasmic changes :
•Necrotic cells show increased eosinophilia and decrease basophilia
•Have a glassier homogeneous appearance than do normal cells, mainly as a result of the loss of glycogen particles.
•The cytoplasm becomes vacuolated and appears moth-eaten.
•Dead cells may be replaced by large, myelin figures.
•The dead cells may ultimately become calcified.
57

58. Types of Necrosis
•There are four of five major types:
1.Coagulative (most common)
2.Liquefactive
3.Caseous
4.Fat necrosis
5.Gangrenous necrosis

59. Coagulative Necrosis
•Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction.
•A localized area of coagulative necrosis is called an infarct.
•E.g. Ischemic injury in any organ ( heart, kidney, adrenal glands), except the brain
•Denaturation of protein albumin causes coagulation
•In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days.

60. Liquefactive
necrosis

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62. Caseous
Necrosis
•Gross: Resembles cheese
•Micro: Amorphous, granular eosinophilic material surrounded by a rim of inflammatory cells withacharacteristicof a focus of inflammation known as a granuloma
•No visible cell outlines –tissue architecture is obliterated
•Usually seen in infections (esp. mycobacterial and fungal infections)

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64. Fat
Necrosis
•Results from hydrolytic action of lipases on fat
•Most often seen in and around the pancreas (enzymatic
fat necrosis); can also be seen in other fatty areas of the
body (breast and other abdominal structures), usually due
to trauma(traumatic fat necrosis)
•Lipases enzymes which break down triglycerides (lipid)
into fatty acids
•Fatty acids then combine with Ca to form Calcium Soaps
(Saponification-soapy deposits in tissues)
•The necrotic tissue appears opaque and chalk white
•Histologically, one sees shadowy outlines of fat cells (like
coagulative necrosis), but with Ca++ deposits, foam cells,
and a surrounding inflammatory reaction

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66. Fibrinoid
Necrosis
•Usually seen in the walls of blood
vessels (e.g., in vasculitis)
•Complexes of antigens and antibodies
are deposited in thewallsofarteries
•Glassy, eosinophilic fibrin-like material
is deposited within the vascular walls
•Complexes togetherwiththefibrin
producesbrightpinkandamorphous
appearance

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68. Gangrenous Necrosis
(gangrene)
•Extensive tissue necrosis. Most often seen on
extremities, usually due to trauma or physical injury
•Divide into two; dry and wet
•Dry –occurs in extremities as a results of ischemic
coagulative necrosis due to arterial obstruction
•Wet –occurs in extremities and internal organ as a
results of liquefactive necrosis due to bacterial infection.
•Gas –necrotic tissue infected by clostridium perfringes
68

69. AUTOLYSIS
•Lysis of tissues by their own enzymes, following the death of the organism.
•Therefore, the key difference is that there is no vital reaction (i.e., no inflammation).
•Autolysis is essentially rotting of the tissue.
•Early autolysis is indistinguishable from early coagulative necrosis due to ischemia, unless the latter is focal.

70. Apoptosis
•Four main points
•Cells commit suicide
•Program cell death
•Activates certain enzymes
•Intact membrane
•A pathway of cell death that is induced by a tightly
regulated intracellular program in which cells destined to
die activate enzymes that degrade the cells’ own nuclear
DNA and nuclear and cytoplasmic proteins
•Apoptotic cells break up into fragments, called apoptotic
bodies, which contain portions of the cytoplasm and
nucleus

71. •The plasma membrane of the apoptotic cell and bodies remains
intact, but its structure is altered in such a way that these become
“tasty” targets for phagocytes.
•The dead cell is rapidly cleared, before its contents have leaked
out, and therefore cell death by this pathway does not elicit an
inflammatory reaction in the host nor followed by calcification

72. CAUSES OF
APOPTOSIS
•Apoptosis occurs normally both during development and throughout adulthood, and serves to eliminate unwanted, aged or potentially harmful cells.
•It is also a pathologic event when diseased cells become damaged beyond repair and are eliminated.
•DNA damage
•Lack of hormones, cytokines, growth factors
•Death receptors like FAS, TNFR1

73. Apoptosis in Physiologic Situations
•During development for removal of excess cells during embryogenesis
•To maintain cell population in tissues with high turnover of cells, such as skin.
•Hormone-dependent involution -Endometrium, prostate, breasts etc.
•Elimination of potentially harmful self-reactive lymphocytes, Cytotoxic T lymphocytes
•Elimination of cells that have served their useful purpose, suchas neutrophils

74. Apoptosis in Pathologic Situations
•To eliminate cells with DNA damage by radiation, cytotoxic agents,
hypoxia etc.
•To remove damaged cells by virus or immune response
•Cell death in tumours
•Accumulation of misfolded proteins

75. Apoptosis –Morphologic Features
•Cell shrinkage with increased cytoplasmic density
•Chromatin condensation
•Formation of cytoplasmic blebs and apoptotic bodies
•Content will contain cytoplasm, densely packed organelles and with or
without nuclear material
•Phagocytosis of apoptotic cells by adjacent healthy cells (microphages)

77. BIOCHEMICAL
FEATURES OF
APOPTOSIS
•Threemainfeatures
•Proteincleavage
•DNA breakdown
•Phagocytoserecognition

78. MECHANISM
OF
APOPTOSIS
•When a cell is compelled to commit
suicide , proteins called caspases go into action. They break down the
cellular components needed for survival
•Two phases:
•Initiation
•Intrinsic (Mitochondrial)
Pathway
•Extrinsic ( Death Receptor)
Pathway
•Execution

79. INTRINSIC (MITOCHONDRIAL) PATHWAY

80. INTRINSIC
(MITOCHONDRIAL)
PATHWAY

81. EXTRINSIC (DEATH RECEPTOR) PATHWAY

83. Autophagy
•Autophagy is a process in which a cell
eats its own contents.
•It is a survival mechanism in times of
nutrient deprivation.
•In this process intracellular
organelles and portions of cytosol are
first sequestered from the cytoplasm
in an autophagic vacuole, which
subsequently fuses with lysosomes to
form an autophagolysosome, and the
cellular components are digested by
lysosomal enzymes

84. Intracellular
Accumulations
Accumulation of abnormal
amounts of various substances
due to manifestations of
metabolic derangements in the
cell.

85. FOUR MAJOR PATHWAYS
•Inadequate removal of a normal
substance
•Accumulation of an abnormal
endogenous substance
•Failure to degrade a metabolite due
to inherited enzyme deficiencies.
•Deposition and accumulation of an
abnormal exogenous substance

86. PATHOLOGIC
CALCIFICATION
•Abnormal tissuedepositionofcalciumsalttogetherwithsmallamountofiron, magnesium, mineral salts
•Depositionofcalciumsaltsin tissuesotherthanosteoidandenamels
•Twotypes(Typeoftissueandserumcalciumlevel)•Dystrophic
•Metastatic(Involvein intestitialcellofgastricmucosa, kidney, systemicarteries, pilmonaryveins, lungs)

87. Dystrophic Calcification
Dead and degenerative tissues
•Past Injury or organ dysfunction
Typical example: Atheromas (fatty materials forms in
arteries)
•Intimal injury in the aorta and large arteries and characterized by
lipid accumulation

88. PATHOGENESIS
OF
PATHOLOGICAL
CALCIFICATION
•Bindingofcalciumto phospholipidson
vesiclemembrane
•Phosphatasein phospholipidproduce
phophate
•Calcium-phospatebindingleads to increase
concentrationofitsdepositiononthe
vesiclemembrane
•Crystalline calcium phosphate
•Structuralchangesin calciumandphospate
givesmicrocrystal–Calcification.

89. METASTATIC CALCIFICATION
Excessive mobilation of calcium from bone
•yper-parathyroidism (Parathyroid adenoma, chronic renal failure,
parathyroid hyperplasia)
•Bony lesion (multiple myeoloma, Leukemia)
•Prolonged bed rest (disuse atrophy of the bone)
Excess absorption of Ca from the Intestine (Gut)
•Excess Vitamin D (Hypervitaminosis D)
•Milk Alkali Syndrome
•ypercalcemia of infancy

90. MORPHOLOGY OF CALCIFICATION
•WithH&E stains, calcificationappearsbasophilic, amorphousor
granular orsometimesclumpsy
•Eitherintracellarorextracellularorboth
•PsammomaBodies –Grainofseed(Dystrophic, in certaintumors)
•E.g.
•Papillarycarcinoma ofthethyroid, papillaryserouscyst
adenocarcinoma
•Somatostatinoma
•Meningioma(tumor ofthemeninges)