Cell Injury, Cell

Death, and
Adaptations

Sisca Meida Wati, drg., M.Kes., PhD

Oral and Maxillofacial Pathology
Faculty of Dental Medicine
Universitas Airlangga
 Pathology
the study of disease

Pathology literally translates to the study of suffering

(pathos = suffering, logos = study)

Rudolf Carl Virchow (1821 – 1902)

 Pathology
identifying the underlying causes of disease as well as the
alterations in cells, tissues, and organs that are linked to disease
and result in the patient's outward signs and symptoms.

Etiology Pathogenesis
The normal cell is a highly complex unit in
which the various organelles and enzyme
systems continuously carry out the
Cells
metabolic activities that maintain cell
viability and support its normal functions.

Normal function is dependent on

1. the immediate environment of the cell
2. a continuous supply of nutrients such
as oxygen, glucose, and amino acids
3. constant removal of the products of
metabolism, including CO2.

The cell can be visualized

simplistically as a membrane-
enclosed compartment,
subdivided into numerous
smaller compartments
(organelles) by membranes
 Cell
Injury
 CELL INJURY
Cells constantly interact with their environment and try
to maintain homeostasis

cells respond to stress (e.g., physiologic and toxic) via

adaptation to maintain viability and function

cell injury results when the cell can no longer adapt

to the stress

REVERSIBLE IRREVERSIBLE
• once the stress is • when the stressful stimuli
removed the cell can is excessive or persistent
return to its original state the cellular damage
becomes irreversible and
cells undergo cell death
CAUSES OF CELL INJURY
Hypoxia and Ischemia Toxins Infectious Agents

Hypoxia à oxygen deficiency Daily exposure to potentially All types of disease-causing

harmful substances such as air pathogens, including
Ischemia à reduced blood pollutants, viruses, bacteria, fungi, and
supply pesticides/insecticides, CO, protozoans, injure cells
asbestos, cigarette smoke,
ethanol, and drug

deficiency of essential
nutrients and a build up
of toxic metabolites
CAUSES OF CELL INJURY
Genetics
Immunologic Reactions Nutritional Imbalance
Abnormalities
immune responses elicit Genetic defects may cause cell Protein–calorie insufficiency
inflammatory reactions, which injury as a consequence of lack of among impoverished populations
are often the cause of damage to functional proteins, such as remains a major cause of cell
cells and tissues enzymes in inborn metabolic injury, and specific vitamin
defects, or accumulation of deficiencies are not uncommon
• autoimmune reactions damaged DNA or misfolded even in developed countries with
against one’s own tissues proteins, both of which induce high standards of living
• allergic reactions against cell death when they are unable
environmental substances to be repaired Ironically, excessive dietary intake
• excessive or chronic immune may result in obesity and also is
responses to microbes an important underlying factor in
many diseases, such as type 2
diabetes mellitus and
atherosclerosis.
CAUSES OF CELL
INJURY
Physical Agents Aging

Trauma, extremes of temperature, Aging is characterized by

radiation, electric shock, and increased oxidative stress,
sudden changes in atmospheric heightened inflammatory
pressure all have wide-ranging response, accelerated cellular
effects on cells senescence and progressive
organ dysfunction.

The homeostatic imbalance with

aging significantly alters cellular
responses to injury à
diminished ability of cells to
respond to stress à the death of
cells and of the organism
 Reversible Injury
the stage of cell injury where the abnormal function and
morphology of the harmed cells can return to normal if the
detrimental stimulus is eliminated.

Intracellular changes associated with cell injury include:

a. plasma membrane alterations such as blebbing, blunting, or
distortion of microvilli, and loosening of intercellular
attachments;
b. mitochondrial changes such as swelling and the appearance
of phospholipid-rich amorphous densities;
c. Endoplasmic Reticulum à dilation of the ER with detachment
of ribosomes and dissociation of polysomes;
d. nuclear alterations, such as clumping of chromatin.
e. The cytoplasm may contain so-called “myelin figures,” which
are collections of phospholipids resembling myelin sheaths that
are derived from damaged cellular membranes.
The two main morphologic correlates of reversible cell injury
are cellular swelling and intracellular accumulation
cellular swelling / hydropic change / vacuolar degeneration
The initial response of the cell to perturbation of
homeostasis

commonly seen in cell injury associated with increased

permeability of the plasma membrane.

It may be difficult to appreciate with the light

microscope, but it is often apparent at the level of the (A) Normal kidney tubules with viable epithelial cells.
whole organ.

When it affects many cells in an organ, it causes pallor

(as a result of compression of capillaries), increased
turgor, and an increase in organ weight.

Microscopic examination à
small, clear vacuoles within the cytoplasm; these
represent distended and pinched-off segments of the (B) Early (reversible) ischemic injury showing surface
endoplasmic reticulum (ER) blebs, increased eosinophilia of cytoplasm, and
swelling of occasional cells
A, Hepatic swelling in a mouse exposed to chloroform 24
hours previously. The accentuated lobular pattern and
slight pallor in the liver on the left are the result of acute
cell swelling (hydropic degeneration) and necrosis of
centrilobular hepatocytes. The right liver is normal.

B, Liver from a mouse with chloroform toxicosis.

Although many hepatocytes in the centrilobular areas (at
right) are necrotic, several cells at the interface of normal
and necrotic (arrows) are still undergoing acute cell
swelling (hydropic degeneration). H&E stain.
Ballooning Degeneration, Papular
Stomatitis, Oral Mucosa, Ox.

Cells infected by certain poxviruses (e.g.,

papular stomatitis virus) cannot regulate
their volume and undergo hydropic
degeneration at certain stages of the
infection. These cells may become so
distended (ballooning degeneration) that
they eventually rupture. Note cytoplasmic
viral inclusion bodies (arrows). H&E stain.
intracellular accumulation
Intracellular accumulations – transient or permanent,
may acquire substances that arise either from cell itself
or from nearby cells

Intracellular accumulations may be categorized as:

• Excessive amounts of normal intracellular
substances from increased production, decreased
metabolism, etc (lipid accumulation in hepatocytes)
• Accumulaition of abnormal substances produced by
cell because of faulty metabolism or synthesis
(storage disease):
• Mutations causing alterations in protein
folding and transport so that defective
protein accumulate
• Deficiency of critical enzyme responsible for
lysosomal degradation
• Accumulation of pigments and particles that cell is
unable to degrade via decreased metabolism or
transport (carbon, silica)
 Cellular
Adaptations
 Adaptations are reversible changes in the number, size, phenotype, metabolic
activity, or functions of cells in response to changes in their environment

In the case of repetitive or continuous injury that is not inherently or

immediately lethal, cells of many different types can survive, even without
complete recovery, by adapting.

Adaptations

Physiologic Pathologic
represent responses to stress that
represent responses of cells to normal
allow cells to modulate their structure
stimulation by hormones or and function and thus escape injury,
endogenous chemical mediators
but at the expense of normal function
CELLULAR ADAPTATIONS TO STRESS

• Hypertrophy à increased cell and organ size,

often in response to increased workload; induced
by growth factors produced in response to
mechanical stress or other stimuli; occurs in
tissues incapable of cell division

• Hyperplasia à increased cell numbers in

response to hormones and other growth factors;
occurs in tissues whose cells are able to divide or
contain abundant tissue stem cells
• Atrophy à decreased cell and organ size, as a
result of decreased nutrient supply or disuse;
associated with decreased synthesis of cellular
building blocks and increased breakdown of cellular
organelles and autophagy

• Metaplasia à change in phenotype of

differentiated cells, often in response to chronic
irritation, that makes cells better able to withstand
the stress; usually induced by altered differentiation
pathway of tissue stem cells; may result in reduced
functions or increased propensity for malignant
transformation

• Dysplasia à abnormal differentiation with features

of cellular atypia. Dysplasia is an adaptation without
apparent advantages to the host. Indeed, dysplasia
can be a precursor to malignant neoplasia (cancer).
Physiologic hypertrophy of the uterus during pregnancy. (A) Gross appearance of a normal uterus (right) and a gravid uterus
(left) that was removed for postpartum bleeding. (B) Small spindle-shaped uterine smooth muscle cells from a normal uterus.
(C) Large, plump hypertrophied smooth muscle cells
from a gravid uterus; compare with B. (B and C, Same magnification.)
Atrophy as seen in the brain. (A) Normal brain of a young adult. (B)
Atrophy of the brain in an 82-year-old man with atherosclerotic
disease. Atrophy of the brain is caused by aging and reduced blood
supply. Note that loss of brain substance narrows the gyri and widens
the sulci. The meninges have been stripped from the bottom half of
each specimen to show the surface of the brain.

Metaplasia of normal columnar (left) to squamous

epithelium (right) in a bronchus, shown schematically
(A) and histologically (B).
Cell Death
 The cellular response to injury depends on:
(1) the type of cell injured and its susceptibility
and/or resistance to hypoxia and direct
membrane injury
(2) the nature, severity, and duration of the
injury.

The response to injury can be degenerative,

adaptive, or completely reversible with restoration
of normal structure and function for the affected
cell; however, with more severe or persistent
injury, acute cell swelling can progress to
irreversible cell injury and cell death.
 Note that cells may rapidly become non-functional after
the onset of injury, although they are still viable, with
potentially reversible damage; with a longer duration of
injury, irreversible injury and cell death may result. Note
also that cell death typically precedes ultrastructural, light
microscopic, and grossly visible morphologic changes.

“cellular function may be lost long before cell death

occurs, and that the morphologic changes of cell injury
(or death) lag far behind loss of function and viability”

The relationship among cellular function, cell death,

and the morphologic changes of cell injury
 Features of Necrosis and Apoptosis

Feature Necrosis Apoptosis

Cell size Enlarge (swelling) Reduced (shrinkage)

Nucleus Pyknosis à Karyorrhexis à Fragmentation into

Karyolysis nucleosome-sized fragments
Plasma membrane Disrupted Intact; altered structure,
especially orientation of lipids
Cellular contents Enzymatic digestion; may Intact; may be released in
leak out of cell apoptotic bodies
Adjacent inflammation Frequent No

Physiologic or pathologic role Invariably pathologic Other physiologic means of

(culmination of irreversible eliminating unwanted cells;
cell injury) may be pathologic after some
forms of cell injury; especially
DNA and protein damage
 NECROSIS
“Necrosis is a form of cell death in which cellular membranes fall apart,
and cellular enzymes leak out and ultimately digest the cell”

The enzymes responsible for digestion of the cell are Necrosis often is the culmination of reversible
derived from lysosomes and may come from the dying cell injury that cannot be corrected.
cells themselves or from leukocytes recruited as part of
the inflammatory reaction.
CYTOARCHITECTURE OF NECROTIC CELLS

Necrosis is characterized by changes in the

cytoplasm and nuclei of the injured cells

• Cytoplasmic changes • Nuclear changes

Necrotic cells show increased eosinophilia (i.e., they are Nuclear changes assume one of three patterns,
stained red by the dye eosin), attributable partly to all resulting from a breakdown of DNA and chromatin.
increased binding of eosin to denatured cytoplasmic proteins Pyknosis is characterized by nuclear shrinkage and increased
and partly to loss of basophilic ribonucleic acid (RNA) in the basophilia; the DNA condenses into a dark shrunken mass. The
cytoplasm (basophilia stems from binding of the blue dye pyknotic nucleus can undergo fragmentation; this change is
hematoxylin). called karyorrhexis. Ultimately, the nucleus may undergo
karyolysis, in which the basophilia fades because of digestion
Compared with viable cells, the cell may have a glassy, of DNA by deoxyribonuclease (DNase) activity. In 1 to 2 days,
homogeneous appearance, mostly because of the loss of the nucleus in a dead cell may completely disappear.
lighter staining glycogen particles.

Myelin figures are more prominent in necrotic cells than in • Fates of necrotic cells
cells with reversible injury. When enzymes have digested
cytoplasmic organelles, the cytoplasm becomes vacuolated Necrotic cells may persist for some time or may be digested by
and appears “moth-eaten.” By electron microscopy, necrotic enzymes and disappear. Dead cells may be replaced by myelin
cells are characterized by discontinuities in plasma and figures, which are either phagocytosed by other cells or further
organelle membranes, marked dilation of mitochondria degraded into fatty acids. These Fatty acids bind calcium salts,
associated with the appearance of large amorphous which may result in the dead cells ultimately becoming calcified.
intramitrochondrial densities, disruption of lysosomes, and
intracytoplasmic myelin figures.
A, Schematic representation of
nuclear and cytoplasmic
changes in the stages of
necrosis. rER, rough
endoplasmic reticulum.

B, Pyknosis and karyolysis,

renal cortex, chloroform
toxicosis, mouse. Some tubular
epithelial cells have undergone
hydropic degeneration; others
are necrotic with
pyknosis (arrow) or
karyolysis (arrowhead). H&E
stain.

C, Karyorrhexis, lymphocytes,
spleen, dog. Necrotic
lymphocytes have fragmented
nuclei (arrow) because of
parvovirus infection. H&E stain.
MORPHOLOGIC PATTERN OF TISSUE NECROSIS

COAGULATIVE
NECROSIS
is a form of necrosis in which the underlying tissue architecture
is preserved for at least several days after death of cells in the
tissue.

The affected tissues take on a firm texture. Presumably the injury

denatures not only structural proteins but also lysosomal
enzymes, thereby blocking the proteolysis of the dead cells; as a
result, eosinophilic, anucleate cells may persist for days or weeks.

Leukocytes are recruited to the site of necrosis, and the dead

cells are ultimately digested by the action of lysosomal enzymes
of the leukocytes.

The cellular debris is then removed by phagocytosis mediated

primarily by infiltrating neutrophils and macrophages.

Coagulative necrosis is characteristic of infarcts (areas of

necrosis caused by ischemia) in all solid organs except the brain.
MORPHOLOGIC PATTERN OF TISSUE NECROSIS

CASEOUS
NECROSIS
is most often encountered in foci of tuberculous infection.

Caseous means “cheeselike,” referring to the friable yellow-white

appearance of the area of necrosis on gross examination.

On microscopic examination, the necrotic focus appears as a

collection of fragmented or lysed cells with an amorphous
granular pink appearance in H&E stained tissue sections.

Unlike coagulative necrosis, the tissue architecture is completely

obliterated and cellular outlines cannot be discerned.

Caseous necrosis is often surrounded by a collection of

macrophages and other inflammatory cells; this appearance is
characteristic of a nodular inflammatory lesion called a
granuloma
MORPHOLOGIC PATTERN OF TISSUE NECROSIS

LIQUEFACTIVE
NECROSIS

is seen in focal bacterial and, occasionally, fungal infections

because microbes stimulate rapid accumulation of inflammatory
cells, and the enzymes of leukocytes digest (“liquefy”) the tissue.

hypoxic death of cells within the central nervous system often

evokes liquefactive necrosis.

Whatever the pathogenesis, the dead cells are completely

digested, transforming the tissue into a viscous liquid that is
eventually removed by phagocytes.

If the process is initiated by acute inflammation, as in a bacterial

infection, the material is frequently creamy yellow and is called
pus
 APOPTOSIS
Apoptosis extensively described as a significant mechanism of regulated death that
occurs not only as a result of cell damage or external stress but it also takes place during
normal development, and morphogenesis

The plasma membrane of the apoptotic cell remains intact,

The dead cell and its fragments are cleared with
but the membrane is altered in such a way that the
little leakage of cellular contents, so apoptotic cell
fragments, called apoptotic bodies, become highly “edible,”
death does not elicit an inflammatory reaction.
leading to their rapid consumption by phagocytes.
Physiologic and Pathologic Conditions
Associated With Apoptosis
Mechanism of Apoptosis

Apoptosis is regulated by
biochemical pathways that
control the balance of death-
and survival-inducing
signals and ultimately the
activation of enzymes called
caspases
 Morphology

the nuclei of apoptotic cells show various stages of

chromatin condensation and aggregation and,
ultimately, karyorrhexis at the molecular level, this is
reflected in the fragmentation of DNA into nucleosome-
sized pieces.

The cells rapidly shrink, form cytoplasmic buds, and

fragment into apoptotic bodies that are composed of
membrane bound pieces of cytosol and organelles

Because these fragments are quickly extruded and

phagocytosed without eliciting an inflammatory
response, even substantial apoptosis may be
histologically undetectable.
 Pathologic
Calcification
 Pathologic calcification, a common process in a wide variety of disease states, is the result of an
abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other
minerals

Dystrophic calcification
deposition of calcium at sites of cell
injury and necrosis

Pathologic
Calcification Metastatic Calcification
deposition of calcium in normal tissues,
caused by hypercalcemia (usually a
consequence of parathyroid hormone
excess)
Other
Extracellular
Accumulations
 Collagen (Fibrosis).

Fibrosis is an excess in fibrous collagen, predominantly

type I collagen fibers, in the interstitium of organs or
tissues.

Necrosis, especially necrosis that destroys epithelial

basement membranes, but also necrosis of mesenchymal
tissues, tends to induce proliferation of fibroblasts.

In many injured tissues, especially beneath ulcers or in

wound healing, fibroblastic proliferation is accompanied
by endothelial proliferation with formation of granulation
tissue (fibrosis plus neovascularization)

As granulation tissue matures, the neovascularization

subsides, fibroblasts become quiescent, collagen fibers
remain, and scar tissue is the end result.
Cholesterol.

The cell wall is made up of proteins, sugars, and fat.

One of these fats is called cholesterol. When cells

become damaged or break down, the cholesterol in
the cell wall is released into the tissue surrounding
the cell. Once in the tissue, cholesterol tends to clump
together to form little droplets that pathologists call
cholesterol clefts.

Cholesterol crystals are dissolved out of the tissue

specimen during histologic processing, leaving
characteristic acicular (needle-shaped) clefts in
histologic sections. In three dimensions the crystals
are thin rhomboidal plates with a notched corner. Cholesterol Granuloma, Mammary Gland, Dog.

Note the acicular cholesterol clefts (cholesterol is removed from

the histologic section in processing) with granulomatous
Cholesterol crystals often form in tissue at sites of inflammation. H&E stain.
hemorrhage or necrosis.
Oral Infections and Spread to systemic
Infections

Prof. Dr. Retno Pudji Rahayu,drg.,M.Kes

Departemen Patologi Mulut dan Maksilofasial
FKG Unair
Rongga Mulut
 Kondisi gigi dan mulut dapat mencerminkan
kondisi kesehatan tubuh manusia.
 Merupakan pintu masuk utama bagi 2 sistem
penting fungsi fisiologis (sistem pencernaan dan
pernapasan).
 Infeksi di rongga mulut dapat menjadi fokus
infeksi yang dapat mempengaruhi kesehatan
sistemik.
 Beberapa kasus yang sering
dijumpai, seperti gingiva berdarah
dan gigi yang tanggal dalam jumlah
banyak memiliki korelasi dengan
kesehatan tubuh dan penyakit
sistemik : diabetes melitus, penyakit
ginjal, penyakit jantung dan
pernafasan
Oral Manifestations and Systemic Diseases

 Beberapa faktor pada kondisi sistemik

berdampak bagi kesehatan rongga mulut :
malnutrisi, tobacco, stress, medications,
diabetes mellitus, HIV/ AIDS, dan
immunosuppression.
 Dampak infeksi di rongga mulut terhadap
penyakit sistemik : Cardiovascular diseases,
diabetes mellitus, kidney diseases, pulmonary
diseases, pregnancy-related complications
(Preterm birth dan low birth weight infants) ,
Bacteremia dan endocarditis
 Dampak penyakit sistemik terhadap
Kesehatan rongga mulut : HIV/AIDS , Mental
health diseases (stress, depression, eating
disorders), Osteoporosis, Diet dan nutrisi,
Obesitas, Alcohol use , Medications
 Manifestasi oral penyakit sistemik adalah
tanda dan gejala penyakit yang terjadi di
tempat lain di tubuh yang terdeteksi di rongga
mulut
Penyakit Cardiovascular
 Penyakit Cardiovaskular (CVD) adalah penyebab
utama kematian secara global
 Disebabkan oleh sumbatan pada pembuluh
darah jantung, peradangan, infeksi, atau kelainan
bawaan.
menghambat aliran darah menuju jantung,

suplai oksigen dan nutrisi di otot dan jaringan di

sekitar jantung berkurang.
 Etiologi
 Penyebab utama endokarditis adalah infeksi bakteri,
kuman, atau jamur masuk melalui aliran darah.
 Ketika aliran darah terkontaminasi oleh
mikroorganisme, terlebih pada seseorang yang
mengidap kelainan katup jantung akan rentan terjadi
infeksi endokarditis
 Kesehatan gigi dan mulut yang buruk meningkatkan
risiko terjadinya penyakit kardiovaskular, termasuk
serangan jantung dan stroke.
 Diabetes Melitus
 Diabetes Melitus (DM) terjadi ketika sistem kekebalan
tubuh menyerang dan menghancurkan sel-sel
pankreas yang memproduksi insulin.
 Peningkatan kadar gula darah yang tidak terkontrol
(hiperglikemia) menyebabkan respons sistem imun
melambat saat terpapar bakteri atau kuman penyebab
infeksi.
 Kadar glukosa tinggi meningkatkan kemampuan
kuman untuk tumbuh dan menyebar lebih cepat.
 Hyperglycemia menginduksi perubahan oral microbiome
karena poor glycemic control berhubungan dengan peningkatan
kadar dan frekuensi pathogen periodontal pada biofilm
subgingiva penderita
 Obesitasa berperan penting menginduksi dan progresivitas
DM
 Kondisi rongga mulut penderita DM cenderung mengalami
low salivary flow dan xerostomia yang tinggi
 Kadar mediator pro inflamasi sistemik ditemukan tinggi pada
penyakit periodontal yang dapat memperburuk resistensi
insulin
 DM type 1dan type 2

 Diabetes mellitus tipe 1 termasuk penyakit

autoimun yang cenderung merusak sel β
pankreas penghasil insulin.
 Pada DM tipe 1, pankreas tidak
menghasilkan insulin karena sistem imun
tubuh menyerang sel β pancreas.
 Penderita DM tipe 1 memerlukan
penggantian insulin seumur hidup melalui
penyuntikan insulin setiap hari
 DM tipe 2, pankreas menghasilkan lebih
sedikit insulin dibanding kondisi normal,
dan tubuh menjadi resisten terhadap
insulin
 DM tipe 2 biasanya menyerang lansia,
namun lebih sering terjadi pada anak-2.
 DM tipe 1 biasanya berkembang pada
anak-2 atau dewasa muda dan dewasa
 Hubungan DM - Penyakit Cardiovascular
 Didasarkan pada berbagai perubahan fisiopatologi pada
system cardiovascular.
 Disfungsi endotel dan gangguan hemostatik dapat
menyebabkan tingginya resiko coronary artery disease
(CAD) dan microangiopathy, myocardial fibrosis,
metabolism myocardial yang abnormal terlibat dalam
pathogenesis kardiomiopati DM
 Glukosa banyak menempel pada sel darah merah dan
terakumulasi di dalam darah bisa menyumbat dan
merusak pembuluh yang membawa darah ke dan dari
jantung.
 Hiperglikemia menyebabkan pembuluh darah menjadi
rusak dan terjadi komplikasi penyakit jantung
 Oral candidiasis
 Oral candidiasis adalah infeksi rongga mulut yang
disebabkan oleh spesies Candida khususnya
C.albicans
 Asymptomatic, berhubungan dengan ketidaknyamanan
kondisilokal, dysgeusia dan xerostomia
 Candida yang di temukan di rongga mulut, di vagina
dan di saluran pencernaan : C.albicans, C.tropicalis.
C.stellatoidea, C.pseudotropicalis, C.crusei,
C.parapsilosis, C. guilliermondii, C. galbrata, C. krusei
dan C. Dubliniensis
 Candida
 Candida adalah jamur yang tumbuh pada organ tubuh
manusia seperti di rongga mulut, tenggorokan, usus,
vagina (organ kewanitaan), atau pada kulit.
 Umumnya keberadaan jamur di rongga mulut tidak
berbahaya, apabila jamur atau fungi berkembang biak
secara tidak terkendali, dapat berubah menjadi infeksi
yang membahayakan

kandidiasis
Candida albicans (C.albicans)
 C.albicans merupakan flora normal di rongga mulut dan
organisme komensal, merupakan jamur dimorfik yaitu
patogen oportunistik
 Meningkatnya infeksi jamur dapat meningkatkan morbiditas
dan mortalitas penderita immunocompromised (HIV, Cancer)
 C. albicans merupakan jamur yang paling banyak diisolasi dan
di karakteriasi untuk keperluan penelitian.
 Candida albicans
Yeast with pseudohyphae (elongated budding)
Commensal organism

some “immunocompromise” usually accompanies

Disease Diabetes, HIV infection, newborns etc.
Gambaran Klinis
• Bercak putih atau kuning , berupa benjolan di
bagian dalam pipi, tongue, tonsils, gums dan
bibir
• Berdarah jika dikerok
• Rasa sakit atau burning in mouth
• a cotton-like sensation in mouth
• dry, kulit pecah-pecah di sudut mulut
• Kesulitan menelan
• Rasa tidak enak di mulut
• a loss of taste
Infeksi C.albicans pada manusia
dibutuhkan :
 kemampuan untuk menempel/menyerang
 kemampuan untuk memperbanyak diri
 kemampuan untuk menghindar dari
sistem imun inang
 kemampuan untuk merusak jaringan.
 Faktor virulensi

 Perlekatan pada sel inang

 kemampuan germinasi
 phenotypic switching
 sekresi enzim hidrolitik protease

Konsep penting dari patogenesis infeksi C.albicans adalah

multifaktorial
Risk Factor
• Wear dentures
• Diabetes Mellitus
• cancer
• HIV/AIDS
• Minum antibiotik atau kortiko steroid
termasuk kortikosteroid inhalasi
terutama untuk kondisi asma
• Minum obat yang menyebabkan
mulut kering atau memilik kondisi
medis yang berakibat mulut kering (dry
mouth).
• tobacco smoking
•salivary gland hypofunction.
•poor oral hygiene
HPA Candidiasis

 Spora jamur dan

pseuodohyphae
menyerang epitel
squamous rongga
mulut
 Candida Hyphae
 Candidial hyphae
dengan spora
tesebar di stratum
corneum
Gambar HPA Candidiasis
Pengecatan PAS
Candida Hyphae
Penyakit Ginjal
 Penyakit ginjal kronik (PGK) merupakan suatu sindrom klinis
disebabkan oleh kerusakan fungsi ginjal yang bersifat
menahun dan progresif
Kelainan gigi dan mulut pada penderita penyakit ginjal kronik

 Kelainan gigi dan mulut pada penderita penyakit

ginjal kronik meliputi hiperplasia gingiva,
karies gigi, kalkulus gigi, disgeusia, halitosis,
penurunan aliran saliva, uremik stomatitis,
serositis, hipoplasia email, infeksi dan keganasam
rongga mulut.
 Acquired Immunodeficiency Syndrome
(AIDS)
 Acquired immunodeficiency syndrome (AIDS) adalah kondisi
kronis yang berpotensi mengancam nyawa yang disebabkan
oleh infeksi kronis human immunodeficiency virus (HIV)

 Spreading HIV
HIV dan Lesi Oral

 Lesi Oral merupakan gambaran awal infeksi HIV

secara klinis.
 Lesi merupakan indikator adanya supresi system
imun dan sebagai test awal, diagnosis and
management pasien HIV/AIDS.
 Lesi oral berkontribusi terhadap morbiditas
pasien, berdampak secara psikologi dan fungsi
ekonomi secara individual maupun komunitas.
 Komponen Secretory rongga mulut meliputi IgA,
lysozymes, HDPs seperti cathelicidins, defensins
dan histatins merupakan system imun utama di
mucosal.
Pathophysiology
 Human Immunodeficiency Virus (HIV) terutama
mempengaruhi limfosit T melalui ikatan dengan protein
permukaan sel CD4 (Cluster of differentiation),
 CD4 juga diekspresikan pada permukan sel monosit,
makrofag dan dendritic
 HIV masuk kedalam tubuh melalui darah dan permukaan
mukosa
 Virus masuk ke jaringan lymphoid, replikasi dalam sel system
imun (Sel imfosit T, monosit dan makrofag)
 Progresifitas HIV ditandai dengan penurunan jumlah CD4+
secara signifikan.
 Penurunan berkisar 60-80 sel setiap tahunnya jika tanpa
intervensi.
 Kecepatan pengurangan jumlah CD4+ dipengaruih oleh
tingkat metabolisme dan aktivitas CD4 host.
 Pengurangan CD4 secara drastis menyebabkan pasien
mengalami imunosupresi, sehingga rentan terhadap infeksi
oportunistik.
 Diagnosis AIDS = jika jumlah CD4 < 200/ ml
Struktur Virus HIV
 Diameter HIV 100-150 nm,
spherical to oval : virion.
 Selubung lembaran virus sebagian
besar tersusun atas lipid dan
didalam selubung terdapat matrix
protein.
 Bagian internal HIV terdiri dari
komponen utama, yaitu genom dan
capsid
 Genome adalah materi dalam inti
sel virus yang berupa dua salinan
RNA untai tunggal.
 Protein capsid yang membungkus
dan melindungi genom.
 Symptomatic HIV infection

 Oral Ulcer
 Fever
 Fatigue
 Swollen Lymph
Nodes
 Diarrhea
 Weight loss
 Candidiasis
 Herpes Zoster
 Pneumonia
Ethiology : RNA Virus HIV
 Mekanisme Ikatan Virus - Host

 Proses entri virus HIV terbagi 3 tahap : ikatan virus ke sel,

aktivasi, dan fusi.
 Untuk mengenali target sel, diperantarai oleh protein envelop
kompleks gp120 dan gp41. Protein virus yang mengenali CD4
adalah gp120.
 Ikatan gp120 menempel ke CD4, terjadi perubahan konformasi
sehingga bagian protein gp120 akan terekspose dan dikenali oleh
reseptor kemokin lain di membran sel yang merupakan koreseptor
(CXCR4 dan CXCR5) untuk memfasilitasi entri dari HIV.
 Ligan CXCR4 adalah α-chemokine SDF-1 (stromal cell-
derived factor 1)
 Ligan CXCR5 family dari β-chemokine (RANTES,
macrophage inflammatory proteins [MIP]-1-α dan MIP-1-β.
 CXCR4 terdapat di permukaan sel limfosit T sedangkan
CXCR5 terdapat di monosit/makrofag, sel dendritik, dan
limfosit T teraktivasi.
Histopathological HIV

granulation tissue with acute

and chronic inflammation and
myositis
Thank You
HEMODYNAMIC
Theresia Indah Budhy
HYPEREMIA
HYPEREMIA (2)
HEMORRHAGE
EDEMA
COAGULATION
COAGULATION
NEUTROPENIA
CLINICALLY FEATURE
LEUKEMIA
CLINICALLY FEATURE
PLASMINOGEN DEFICIENCY
CLINICALLY FEATURE
Hypertension
HPA feature
Epidemiology of Hemodynamic dis
Patogenesis of Artherosclerotic Plaque
Nature History
Tumor of Bloods
Classification
Clinical and HPA feature
Sarcoma Kaposi
Angiosarcoma
 EPULIS
Sisca Meida Wati, drg., M.Kes., PhD
Department of Oral and Maxillofacial Pathology
Faculty of Dental Medicine, Universitas Airlangga
Epulis or epulides means “on the gums” are lesions Traumatic and inflammatory factors constitute
associated with the gingival tissues. favourable conditions for epulis development.
Their size varies from 2.5 to 3 cm, in most
The word epulis is a generic term that refers to a cases they are pedunculated, and their colour
growth on the gingiva or alveolar mucosa varies depending on the tissue structure.

Other literature states that when a reactive focal

connective tissue proliferation is confined to the It’s widely accepted that epulis is not the true
gingiva and its exact histologic nature is unknown, it is neoplasm but the hyperplastic lesion, which is
clinically designated as an epulis. the reason why epulis is not referred by the
World Health Organization Classification of
The most common lesions referred to as epulis are Tumors. Therefore, the classification and
peripheral fibroma, peripheral ossifying fibroma, terminology of epulis are conflicting in the
pyogenic granuloma, and peripheral giant cell literature.
granuloma.
 FIBROUS EPULIDES
(Irritation fibromas; fibroepithelial polyp, traumatic
fibroma, focal fibrous hyperplasia, fibrous nodule)

The most common epulis

they typically form narrow, firm, pale swellings of an anterior interdental

papilla and may ulcerate.

it is a reactive hyperplasia of fibrous connective tissue in response to local

irritation or trauma.

They are usually pink and firm but cannot be distinguished clinically with
certainty from neoplastic epulides or the usually softer and redder
pyogenic granulomas, or giant cell granulomas.
Histopathological findings à

• Collagen overproduction is the basic process that dominates the microscopy of this lesion.

• Fibroblasts are mature and widely scattered in a dense collagen matrix.

• Sparse chronic inflammatory cells may be seen, usually in a perivascular distribution.

• Overlying epithelium is often hyperkeratotic because of chronic low-grade friction.

 FIBROMYXOMATOUS EPULIDES
(Oral Focal Mucinosis)

rare mucosal disease of unknown etiology.

The overproduction of hyaluronic acid by fibroblasts

and consequent formation of myxoid lesion due to its
accumulation has been hypothesized as a mechanism
involved in this condition.

While the etiology is unknown, some papers have

proposed traumatic stimulation as an eliciting factor in
the disease mechanism.
Moreover, traumatic stimulation may be involved in
the increase in size of soft tissue lesions.

The clinical findings include a painless nodular mass of

elastic hardness with a similar colour as that of the
surrounding mucosa. However, there are no
characteristic clinical and radiological features;
Histopathological findings à

• Stratified squamous hyper-parakeratinized epithelium.

• Sub-epithelial stroma demonstrated loose, pale eosinophilic myxomatous connective tissue.
• Deeper stroma composed of stellate shaped fibroblasts interspersed between thin collagen fiber
bundles and numerous small capillaries
• Some chronic cell infiltration may exist
• The local deposition of mucin in connective tissue in which there has been mucoid degeneration à
Alcian blue at pH 2.5 showed strong blue staining due presence of abundant hyaluronic acid
 Granulomatous Epulides

Epulis granulomatosa is a term used to describe hyperplastic

growths of granulation tissue that sometimes arise in healing
extraction sockets.

These lesions resemble

pyogenic granulomas and usually represent a granulation
tissue reaction to bony sequestra in the socket.

Granulomatous epulis, a smooth or lobulated exophytic lesion with

a deep red or purplish colour easily haemorrhage and well-defined

Although the factors that influence the development, growth rate

and tendency of granulomatous epulis recurrence are still unknown
à local irritations (e.g. dental plaque, calculus, foreign material
within the gingival crevice or injury), pharmacotherapy (phenytoin,
cyclosporine or nifedipine) and hormonal status (estrogen or
pregnancy)
Histopathological findings à

• Encapsulated with acanthotic stratified squamous epithelium

• the chronic inflammatory granulation tissue with increased vascularity
• numerous inflammatory cells
 Giant Cell EPULIDES
(Pheripheral giant cell granuloma)

the most common oral giant cell lesion appearing as a soft tissue
extra-osseous purplish-red nodule

It probably does not represent a true neoplasm but rather is a

reactive lesion caused by local irritation or trauma

The peripheral giant cell granuloma occurs exclusively on the

gingiva or edentulous alveolar ridge, presenting as a red or red-blue
nodular mass

They presumably arise from periodontal ligament or periosteum,

and occasionally cause resorption of alveolar bone. When this
process occurs on the edentulous ridge, a superficial, cup-shaped
radiolucency may be seen.

can develop at almost any age, especially during the first through
sixth decades of life. The mean age in several large series ranges
from 31 to 46 years. Approximately 52% to 60% of cases occur in
females.
Histopathological findings à

a proliferation of multinucleated giant cells within a background of plump ovoid and spindle-shaped
mesenchymal cells/fibroblast

The giant cells may contain only a few nuclei or up to several dozen. Some
of these cells may have large, vesicular nuclei; others demonstrate
small, pyknotic nuclei à believed to be related to osteoclasts. The giant cells appear to be
nonfunctional in the usual sense of phagocytosis and bone resorption.

Abundant hemorrhage is characteristically found throughout the mass,

which often results in deposits of hemosiderin pigment,
especially at the periphery of the lesion.

The overlying mucosal surface is ulcerated in about 50%

of cases. A zone of dense fibrous connective tissue usually
separates the giant cell proliferation from the mucosal
surface.

Adjacent acute and chronic inflammatory cells are

frequently present.
 Pyogenic Granuloma
(Lobular capillary hemangioma)

This presents as a focal mass of benign reactive granulation tissue in

response to local injury or irritation, such as from dental calculus or
bite trauma.

These lesions are seen most commonly on the gingiva near the
interdental papilla and occur more frequently in women, often
during pregnancy.

Although it was originally thought to be caused by pyogenic

organisms, it is now believed to be unrelated to infection. Instead,
the pyogenic granuloma is thought to represent an exuberant tissue
response to local irritation or trauma.

The term pyogenic granuloma is a misnomer because it does not

produce pus, nor does it represent granulomatous inflammation
Pyogenic granulomas occur mostly in the second decade of life
and are most commonly seen on the attached gingiva (75%),
where they presumably are caused by the presence of calculus or
foreign material within the gingival crevice.

The tongue, lower lip, and buccal mucosa are the next most
common sites.

typically red and smooth or lobulated with hemorrhagic

features.

Young pyogenic granulomas are highly

vascular in appearance; older lesions tend to become
more collagenized and pink.

They characteristically become ulcerated because of secondary

trauma.

A yellow, fibrinous membrane may then cover the ulcerated

lesions.

They may be pedunculated or broad based and may range in size

from a few millimeters to several centimeters.
Histopathological findings à

• Lobular masses of highly vascular hyperplastic

granulation tissue
• The surface is usually ulcerated and replaced by a
thick fibrinopurulent membrane
• Some scarring may be noted in some of these
lesions, suggesting that occasionally maturation of
the connective tissue repair process may occur à
fibrosis.
• Variable numbers of chronic inflammatory cells
may be seen.
• Neutrophils are present in the superficial zone of
ulcerated pyogenic granulomas.
Dental Granuloma
Periapical inflammation is due to spread of
infection, bacterial products or other irritants
through the apex into the periodontal ligament
following death of the pulp

The most frequent outcome is for a necrotic pulp to

form a chronic periapical granuloma, a focus of
chronic inflammation at the root apex.

Clinical features

The tooth is non-vital and may be slightly tender to percussion,

but otherwise, symptoms may be minimal.

The granuloma forms a ‘periapical area’ of radiolucency a few

millimetres in diameter with loss of continuity of the lamina dura
around the apex.

The margins of the radiolucency may appear fuzzy when

inflammation or infection are active, but are usually well defined and
appear sharp in larger lesions.
A periapical granuloma is a typical focus of chronic
inflammation characterised by lymphocytes, macrophages and
plasma cells in granulation tissue.

Inflammation is densest in the centre close to the root apex,

and an uninflamed layer of fibrous tissue Around the
periphery separates the inflamed tissue from the bone.

Osteoclasts resorb the bone to make space for the granuloma.

There may be a central cavity with a few neutrophils, but no
pus and no infection

Inflammation may trigger epithelial rests of Malassez in the

adjacent periodontal ligament to proliferate, and this is the
mechanism by which radicular cysts develop
 Oral Potentially Malignant
Disorders
Various oral mucosal lesions indicate that a patient is at risk of developing an oral squamous cell carcinoma

v This is meant to emphasize that the risk is only potential and may never materialize

v ”premalignancy” and ”precancer” à cancer will definitely develop, and these terms
are best avoided, although they are widely used

In general, the oral white lesions have lowest risk of malignant transformation
and red and speckled lesions the highest risk
The risk of OPMDs in India reported that 80% of oral
cancers were preceded by OPMDs
 FIELD CHANGE

v Potentially malignant disorders are thought to result from field change

v This is process whereby a wide area of tissue becomes genetically altered à prone to
develop cancer anywhere within the field

v The genetic changes in the altered field are not in themselves sufficient to cause
cancer, but they increase the likelihood of cancer developing

v Dysplasia à the best predictor of risk

 Oral Epithelial Dysplasia (OED)

v OPMD is a clinical diagnosis for which the histological diagnosis may be

hyperplasia, hyperkeratosis, oral epithelial dysplasia (OED) or oral squamous cell
carcinoma (OSCC).

v OED is characterized by cytological and architectural alterations reflecting the loss

of normal maturation and stratification pattern of surface epithelium.
Epithelial dysplasia Grading
Mild Dysplasia

Ø Mild dysplasia is confined to the lower

one-third of the epithelium (basal and
parabasal layers) exhibiting cytologic
and/or architectural alterations.

Ø Disorganisation of basal cell

Ø Increased proliferation with several

layers of basaloid cells with large
nuclei

Ø Scattered cells with very abnormal

shape and/ size
Moderate Dysplasia

Ø Moderate dysplasia exhibits

disordered maturation from the basal
layer extending to the midportion of
the spinous layer (middle third).

Ø Has more layers of basaloid cells

Ø Usually increased intercellular spaces

as a result of loss of cohesion

Ø There is a disorganized higgledy-

piggledy appearance in basal layers

Ø Mitotic figures and abnormal cells

may be seen not only in the basal
cells but also in the middle of the
epithelium
Severe Dysplasia

Ø Severe dysplasia/carcinoma in situ reveals

abnormal maturation extending from the basal
cells to a level above the midpoint of the
epithelium (upper third) to the entire thickness of
the epithelium.

Ø Most marked abnormalities

Ø Loss of normal layered structure of the

epithelium

Ø Most of the thickness is occupied by basal type

cells

Ø There are few or no prickle cells or organised

keratin layer

Ø Dyskeratosis

Ø Loss of cell cohesion

 Leukoplakia
A descriptive clinical term indicating a white patch or plaque of oral mucosa that
cannot be rubbed off and cannot be characterized clinically as any other disease

Leukoplakia may range microscopically from

benign hyperkeratosis to invasive squamous
carcinoma à a biopsy is mandatory to establish a
definitive diagnosis

Leukoplakia is common à ¾ of all potentially

malignant condition and being present 1%-5% of the
population

The malignant transformation rate à relatively low

Homogenous, flat leukoplakias have a lower risk than

those with a nodular or verrucous surface clinically
 Etiology
• Tobacco use --> smoke or smokeless form
• Alcohol abuse
• Trauma
• C. albicans infection
• Nutritional factors à iron deficiency anemia
Clinical Features

• Leukoplakia is a condition associated with middle-

aged and older populations à >40y

• Visual examination à vague whiteness on a base of

uninflamed, normal appearing tissue to a definitive
white, thickened, leathery, fissured, verrucous
(wartlike) lesion

• Red zones may also be seen à speckled

leukoplakia (erythroleukoplakia)

• On palpation à
• soft, smooth, or finely granular
• Roughened, nodular, and indurated
Histopathology

• Histologic changes range from hyperkeratosis,

dysplasia, and carcinoma in situ to invasive
squamous cell carcinoma

• Its generally accepted that the more severe the

epithelial changes à more likely lesion is to evolve
into cancer
Hyperkeratosis:
a thickened stratum korneum (keratin layer of the
surface epithelium)

Hyperparakeratosis:
Imperfect keratinization, there is no granular cell layer
and the epithelial nuclei are retained in the keratin
layer.

Acanthosis:
a thickened spinous layer (hypeprplasia of stratum
Spinosum

Dyskeratosis:
abnormal, premature keratinization within cells below
the stratum granulosum
Nevus pigmentosus / Melanocytic
nevus
Collection of nevus cells that are round or polygonal and are typically seen in a nested
pattern

Nevus is a general term that may refer to any

congenital lesion of various cell types or tissue
types

MN may be found in epithelium or supporting

connective tissue or both
 Clinical Features

• Papular lesions that usually appear shortly after birth

and through out childhood

• Intraoral MN à rare

• Most oral lesions present as small (<0.5cm) elevated

papules or nodules
 Histopathology

- Characterized by a benign, unencapsulated proliferation of nevus cells

- Nevus cells appear to be brown-colored as its abundant cytoplasm has intracellular melanin

- Melanocytic nevi are classified histopathologically according to the location of nevus cells:
a. Junctional nevus: in which nevus cells are confined to the junction of the epithelium and
connective tissue, especially at the tips of the rete ridges.
b. Intradermal nevus: in which the nevus cell located in the underlying dermis or lamina propria
c. Compound nevus: nevus cells are present along the junctional area and within the connective
tissue
d. Blue nevus: cells are spindle shaped and are found deep in the connective tissue
 Erythroplakia
A predominantly red lesion of the oral mucosa that cannot be characterized clinically
or pathologically as any other definable lesion

It does not indicate a particular microscopic

diagnosis, although after biopsy most cases are
found to be severe dysplasia or carcinoma

Erythroplasia --> sometime used to indicate that

these lesions are often not raised plaques like
leukoplakias, but flat or slightly depressed
Etiology
The causes of this lesion are believed to be
similar to those responsible for oral cancer:
• Tobacco use à smoke or smokeless
• Alcohol consumption
• Nutritional deficits à iron deficiency of
Plummer-Vinson syndrome
• Candida albicans
• Human Papilomavirus (HPV)
Clinical Features
v Much less commonly than its white lesion
counterpart, leukoplakia

v The lesions of erythroplakia are usually

irregular in outline, although well defined,
and have a bright red velvety surface.

v A more serious lesion than leukoplakia,

because of the significantly higher
percentage of malignancies associated with
it:
v SCC à 50% Biopsy must be performed
v Severe dysplasia or in situ carcinoma à
40%
v Mild to moderate dysplasia à 10%

v Common sites:
v Floor of the mouth
v Tongue
v Retromolar mucosa
v Soft palate

v Focal white areas representing keratosis

may be seen in some lesion à
 Histopathology
v SCC à 50%
v Severe dysplasia or in situ carcinoma à 40%
v Mild to moderate dysplasia à 10%

v A relative reduction in keratin production and

relative increase in vascularity account for the
clinical color of these lesion

Nonkeratinizing Carcinoma In Situ

Carcinoma In Situ
Invasion of OSCC Well differentiated OSCC

poorly differentiated OSCC

THANKS!!
 THANKS!
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Please keep this slide for attribution
 Benign Tumors of
Mesenchymal Tissue Origin
Sisca Meida Wati, drg., M.Kes., PhD
Department of Oral and Maxillofacial Pathology
Faculty of Dental Medicine
Universitas Airlangga
 Mesenchymal Tissues

• The three major embryologic categories of

cells, called the germ cell layers, are:
• Ectoderm: forms the epithelium that
covers the body, and gives rise to cells
in the nervous system
• Endoderm: forms the gastrointestinal
tract and associated structures
involved in digestion
• Mesoderm: forms the connective
tissues and "soft" tissues such as bone,
muscle, and fat
• Soft tissue or connective tissue à The greatest amount forming
tissue of the body

• These are embryologically derived from the mesoderm. Hence, they

are often called "mesenchymal" tissues.

• The major cell types derived from mesoderm are:

• Fibroblasts
• Mesothelium
• Endothelium
• Adipocytes
• Myoblasts
• Chondroblasts
• Osteoblasts
 FIBROMA
Arising from fibrous connective tissue

The fibroma, also referred to as irritation fibroma, is by far

the most common of the oral fibrous tumorlike growths

Majority of the fibromas occurring in the oral cavity are

reactive in nature and represent a reactive hyperplasia of
fibrous connective tissue in response to local irritation or
trauma rather than being a true neoplasm

Fibroma is the result of a chronic repair process that

involves the formation of granulation tissue and scars
resulting in a fibrous sub-mucosal mass
doi: 10.19044/esj.2017.v13n6p267
Clinical Features
• Painless slow growing
• Sessile or pedunculated lesion
with smooth surface
• Firm consistency
• Ranging in size
Histopathology Features
• Radiating, circular or harphazardly
arranged interlacing bundles of
collagen fibres with variable
number of fibroblast or fibrocytes
• The overlaying stratified
squamous epithelium is atrophic
• There maybe hyperkeratosis of
the surface epithelium
• Chronic inflammatory cell
infiltration may be seen
• Scanty blood vessels
x200

x400
 LIPOMA
Benign neoplasm of fat à uncommon neoplasm that may
occur in any region of oral cavity

About 15%-20% of soft tissue lipomas occur in the head

and neck area, of which only 1%-4% are observed
intraorally.

Occur in the middle aged and eaderly

DOI: 10.1002/ccr3.2099
 Clinical Features
• Asymptomatic
• Slow growing nodular mass
• Soft in consistency with smooth https://doi.org/10.1155/2014/480130
surface
• Varying in size usually up to 2-
3cm
• Yellowish color submucosal
masses

doi: 10.19044/esj.2016.v12n12p211
Histopathology Features
• Composed of mature fat cells
• Cells are round or ovoid, with
empty looking cytoplasm and
eccentrically placed nucleus that
is pressed against the cell
membrane
• The lesion is well circumscribed
à may have connective tissue
capsule
doi: 10.19044/esj.2016.v12n12p211
• Connective tissue septa is often
seen
 OSTEOMA
Benign tumors consist of mature, compact or cancellous
bone

Relatively rare in the jaws

The cause à unknown

Osteoma:
• Periosteal osteoma à osteomas that arise on the
surface of bone
• Endosteal or solitary central osteomas à osteomas
that develop centrally within the bone

http://dx.doi.org/10.1016/j.jds.2012.10.002
 Clinical Features
• Commonly indentified during the second to fifth
decades of life
• Male>F
• Usually solitary except in patients with
gardner’s syndrome
DOI 10.1007/s12663-011-0223-z
• Periosteal osteoma à Clinically
asymptomatic, slow growing, bony sharp
masses, assymetri may be noted

• Endosteal osteoma àDiscovered during

routine radiographic exam as dense, well-
circumscribed radiopacities
• Symptoms occasionally accompany these
tumors: headaches, reccurent sinusitis,
ophthalmologic complaints

doi:10.1155/2010/834761
 Histopathology Features
• Compact osteoma

• Composed of Well-
circumscribed mass of dense
lamellar bone arranged like
layers of an onion with only
minimal marrow elements

• Cancellous osteoma

• Composed of trabeculae of
cancellous bone with fibrofatty
marrow spaces. Osteoblastic
activity may be seen http://dx.doi.org/10.4317/jced.52792
doi:10.1155/2010/834761

Journal of Dental Sciences (2017) 12, 185e189

 CHONDROMA

Benign intraosseous tumor composed of mature hyaline

cartilage

Relatively uncommon in the jaws, in comparison with

their occurence in other skeletal parts

Rev Esp Cir Oral y Maxilofac 2006;28,5 (septiembre-octubre):295-300

 Clinical Features
http://dx.doi.org/10.1016/j.pdj.2014.12.001

• Commonly appears as painless, slowly

progressive swelling

• Gradually expansion à rarely result in mucosal

ulceration

• Most lesion in craniofacial region à nasal

septum and ethmoid sinuses

• Ro à variable but often occurred as an irregular

radioluscent area. Foci of calcification might be
present within.
 http://dx.doi.org/10.1016/j.pdj.2014.12.001

Histopathology Features
• The lesions consist of well
circumscribed lobules of mature
hyaline cartilage

• The chondrocytes are small and

contain single regular nuclei

Rev Esp Cir Oral y Maxilofac 2006;28,5 (septiembre-octubre):295-300

 HAEMANGIOMA
Benign proliferation of blood vessels and is considerd as
a hamartoma (tumor-like malformation native to the site)

Imbalance in the angiogenesis, à uncontrolled

proliferation of vascular elements, associated with
substances such as vascular endothelial growth factor
(VEGF), basic fibroblast growth factor(BFGF) and
indole-amine 2,3-dioxygenase (IDO), which are found in
large amount during proliferative stages
doi: 10.5005/jp-journals-10005-1253
 Clinical Features
• painless

• described clinically as a soft tissue mass,

smooth or lobulated sessile or
pedunculated with variable size.

• They may be smooth or irregular bulbous in

outline

Contemporary Clinical Dentistry | Jan-Mar 2014 | Vol 5 | Issue 1

 Histopathology Features
• Capillary haemangioma

Composed of abundant small capillaries

which are lined by a single layer of
endothelial cells

• Cavernous haemangioma

Composed of large, dilated, thin walled,

blood filled vascular spaces with an
endothelial lining

doi: 10.5005/jp-journals-10005-1253
Contemporary Clinical Dentistry | Jan-Mar 2014 | Vol 5 | Issue 1
 LYMPHANGIOMA
Uncommon vascular malformations arising before birth or
in infancy

In the oral cavity, it is located just below the overlying

epithelium replacing the connective tissue papillae and
consist of multiple dilated lymphatic vessels

Lymphangiomas have marked predilection for the head

and neck region [50-70%]. About half of the lesions are
noted at birth and around 90% develop by 2 years of age.

Lymphangiomas may be present anywhere on the skin Contemporary Clinical Dentistry | Oct-Dec 2015 | Vol 6 | Issue 4

and mucosa, commonly seen in head and neck region,

followed by the proximal extremities, buttocks, and
trunk.
 Clinical Features
Oral cavity à tongue, palate, gingival and oral
mucosa, lips, and alveolar ridge of the mandible.

oral lymphangiomas manifest as a plaque

Cons tituted from small vesicles with thin
walls, translucent like frog eggs. Part of the
vesicles are full with clear content (lymph), part
has a blood content suggesting co-existence of
the involvement of the lymphatic anomalies
with abnormalities of the blood vessels

The commonest site is tongue à large and

diffuse à macroglossia

Normally asymptomatic but may be present due

to bleeding in to the lymphatic spaces
Contemporary Clinical Dentistry | Jan-Mar 2012 | Vol 3| Issue 1
 Histopathology Features
• Consist of thin-walled lymphatics
containing lymph, seen as pinkish
amorphous material in sections

• The adjacent connective tissue stroma

is loose and fibrovascular à with
lymphocytes deposition forms limfolikel
or germinal centre

Contemporary Clinical Dentistry | Jan-Mar 2012 | Vol 3| Issue 1

 Schwannoma/Neurilemmoma
Benign neoplasm that is derived from a proliferation of
Schwan cells of the neurilemma, or nerve sheath

Clinical Features https://doi.org/10.1155/2017/7401631 DOI: 10.1159/000513568

• Encapsulated submucosal mass

• Asymptomatic
• The tongue is the common location, although lesions
have been described throughout the mouth
• Slowly development, but it may suddenly undergo a
sudden increase in size
• 25–40% are found in the soft tissues of the head and http://dx.doi.org/10.1155/2014/780762

neck region, but they are uncommonly located in the

oral cavity,
 Histopathology Features
• Antony tipe A à predominates and
forms streaming fascicles of elongated-
shaped cells (Schwann cells), nuclei of
which are aligned in parallel rows
https://doi.org/10.1155/2017/7401631
forming a typical palisading pattern.

Verocay bodies are found à acellular,

eosinophilic masses

• Antony tipe B à less cellular and

consist of disorderly arrangement of
elongated cells (spindle shaped) and
fibres with a loose myxomatous stroma
thanks
MALIGNANT TUMOURS
THEORY
PROF. DR. THERESIA INDAH BUDHY. S
EPITHELIAL
CHARACTERISTIC
TYPES OF CARCINOMA
GLANDULAR CARCINOMA
HITOLOGICALLY FORMS
MESENCHYMAL MALIGNANT
CONTINUED OF SARCOMA
TYPES OF SARCOMA
OTHER TYPE OF MALIGNANT
OTHER TYPE
OTHER TYPE OF SARCOMA
OTHER TYPE OF MALIGNANT
CONTINUED OF MM
MALIGNANT SPREAD
CONTINUED OF SPREAD
CONTINUED OF SPREAD
CONTINUED OF SPREAD
CONTINUED OF SPREAD
CONTINUED OF SPREAD
CONTINUED OF SPREAD
Odontogenic and Non Odontogenic
Cyst

Prof. Dr. Retno Pudji Rahayu,drg.,M.Kes

Departemen Patologi Mulut dan Maksilofasial
FKG Unair
DEFINISI KISTA :
Rongga patologis berisi bahan cair/ setengah cair, dibatasi
dinding kista yang dilapisi epitel menghadap lumen dan
bagian luarnya dilapisi oleh jaringan ikat dan pembuluh
darah.

▪ Cairan bukan dari akumulasi pus

atau darah
▪ Lapisan epitel dikelilingi jaringan ikat fibrokolagen
▪ Klasifikasi menurut WHO 2017 : penyebabnya terdiri
dari : inflamasi dan gangguan pertumbuhan dan
masuk dalam klasifikasi Tumor Odontogen
▪ Urutan terbanyak :
1. Kista Radikuler 53,5 %
2.Kista dentigerous 22,3 %
3, kista odontogenik 19,1 %
4. Kista residual cyst 4.6 %
5. Kista lateral periodontal 0,3 %
 KISTA ODONTOGEN

1. Kista Primordial (kerato cyst)

2. Gingival cyst of infants
3. Gingival cyst of adults
4. Kista lateral Periodontal
5. Kista Dentigerous/ Folikuler
6. Calcyfying Odontogenic Cyst (COC)
8. Kista Radikuler
Kista Radikuler
- kista odontogen
- kista karena keradangan
- merupakan kista rahang
yang terbanyak
 KISTA RADIKULER = Kista Periapikal
✓ ETIOLOGI : keradangan pulpa
✓ KLINIS :
- usia 30-59 tahun → terbanyak 40-49
tahun
- laki – laki > perempuan
- asimptomatik → sekunder infeksi :
sakit
- RA > RB regio insisivus
- tumbuh lambat dan fluktuasi
- gigi non vital → karies atau
tumpatan besar, sisa akar
✓ Rö foto: radiolusen periapikal berbatas
jelas dengan tepi radiopak tipis
✓ HPA: - lumen kista
- epitel bertatah tebal akantonik
- dinding kista : jar. granulasi
✓ TERAPI :
▪ 1. apeks reseksi → perawatan saluran
akar ✓ DD (Rö) :
▪ 2. marsupialisasi - Dental granuloma
- Traumatic bone cyst
Gambaran HPA

- Lumen Kista
- Epitel pelapis
- Dinding kista
dari jaringan
granulasi
KISTA DENTIGEROUS = KISTA FOLIKULER
✓ Patogenesa :
1. Terjadinya penumpukan cairan intra folikuler
di dalam enamel organ (diantara sisa epitel
pembenuk enamel dan mahkota gigi).
2. Hancurnya sel epitel pada folikel (yg
berproliferasi) gigi yang impaksi dan
terjadinya peningkatan tekanan osmotik →
cairan masuk → kista.
▪ Semuanya terjadi pada awal odontogenesis.
▪ Berkembang dalam folikel dental yang
normal dan mengelilingi gigi yang tidak
erupsi
▪ Selama proses odontogenesis terjadi
degenerasi stellate reticulum pada
komponen enamel organ
RŐ :
- Folikuler radiolusen berbatas jelas
dengan tepi radiopak pada mahkota
gigi yang impaksi.
▪ Gambaran radiolusen dapat central,
lateral, circumferential
KLINIS :
- Berkaitan dengan gigi yg tidak erupsi terutama
M3, C & P
- Prefalensi : Kista odontogen terbanyak
sesudah kista radikuler.
- Tumbuh sentral, lambat → Mencapai ukuran
besar
- asimtomatik
- usia : pada semua dekade → puncaknya dekade
III& IV
- tidak sakit kecuali bila ada sekunder infeksi
HPA:
- Epitel pelapis dpt pipih/ kubis/kolumnar
bersilia → 1-2 lapis → non keratinisasi.
- sel goblet
- Dinding kista jar. ikat fibrous → fibroblas
- epitel permukaan secara morfologi mirip epitel
pelapis ameloblastoma.
✓ TERAPI:
- Penderita dewasa M3 → enucleation +
pengambilan M3
- Anak2 : dianjurkan marsupialisasi→
diharapkan tumbuh normal.
✓DD (Rö):
- Unilokuler ameloblastoma
- Adenomatoid odontogenik tumor
- Ameloblastik Fibroma
- Odontogenic keratocyst
▪ Penegakkan diagnosa dengan cara aspirasi
Bila tidak ada cairan lesi padat

biopsi insisional
▪ KISTA PRIMORDIAL = KERATOCYST
= ODONTOGENIC KERATOCYST

Yaitu: suatu kista rahang yang membentuk keratin

K. Folikuler Beberapa dari kista dari kista tsb. juga

K. Radikuler membentuk keratin → termasuk
dalam kategori odontogenic
keratocyst
▪ Kista Primordial adalah lesi kistik mandibula yang jarang
terjadi, diduga akibat degenerasi folikel gigi.
▪ Kista odontogenik yang berkembang dari stelate reticulum yang
terbentuk menggantikan gigi.
▪ Kista Primordial sering dihibungkan dengan gigi unerupted
✓ETIOLOGI:
Berasal dari : - epitel odontogen saat
pertumbuhan gigi
- sisa-sisa dental lamina
✓ KLINIS :
- Terbanyak usia : 20–29 tahun (dekade III)
10-19 tahun (dekade II)
- Lokasi : - mandibula > maksila
- dpt terjadi pada semua tempat RA/RB
- terutama sudut mandibula, ramus ascenden
- Assymtomatis
- Rekuren : (+)

✓ Rö FOTO :
- Radiolusen bulat kecil atau oval :
unilokuler ++
multilokuler +

✓ DD (Rö foto) : - Kista dentigerous

- Ameloblastoma
- Calcyfying odontogenic cyst
- Adenomatoid odontogenic cyst
- ameloblastik fibroma
✓ HPA:
- Kista sangat kecil
- epitel berlapis pipih ± 5-8
lapis dengan keratin
- Epitel tanpa retepek
- Sel Palisade
- Terdapat mikro satelit cyst
- Dinding kista : jaringan ikat
fibrous.
▪ KISTA ERUPSI :

Yaitu: - suatu kista dentigerous pada jar.

Lunak
- terjadi pada anak-anak
- kista meliputi gigi yg akan erupsi
- gigi dalam keadaan impaksi

- Kista erupsi dari akumulasi cairan di

dalam area folikel gigi yang sedang
erupsi
- Dilapisi epitel dari epitel email yang
tereduksi
✓KLINIS
- Berupa pembesaran yang halus pada
mukosa sesaat sebelum erupsi
- Tumbuh pada gigi yang akan erupsi
- Warna normal/ biru
- tidak sakit, fluktuasi +
- ukuran 1-1,5 cm

✓ PATOGENESA :
- Mirip dengan kista dentigerous
- tetapi terjadi pada jar. Lunak
✓
✓HPA:
- Epitel pelapis : epitel berlapis pipih
dengan keratin
- Dinding : Jar. ikat kendor, disertai
infiltrasi sel radang.
✓ TERAPI :
- marsupialisasi : bila tidak dapat
hilang sendiri
- tanpa terapi → akan pecah spontan
pada waktu gigi erupsi

▪
GINGIVAL CYST OF INFANT
- Gingival Cyst of the new born
- Dental Lamina Cyst of the new born
- Bohn’s Nodules
- Epstein’s Pearls

- Gingival cyst of newborn adalah lesi mukosa mulut yang

bersifat sementara
- Ditemukan setelah 15 hari kelahiran
- Berasal dari sisa dental lamina yang mengalami degenerasi
- Sisa dental lamina menimbulkan kista gingiva atau kista
alveolar
dilapisi oleh epitel yang mampu menghasilkan keratin.
- Epstein pearls terlihat seperti
bintil kuning keputihan, ukuran
1- 3 mm.
- Nodul berisi keratin yang
ditemukan di sepanjang raphe
midpalatal
- Bohns nodul adalah kista berisi
keratin

✓PATOGENESA:
Berasal dari dental lamina (sisa-sisa
epitel)
HPA:
- Kista bulat atau oval
- epitel pelapis tipis → 2-3 lapis →
epitel berlapis pipih dengan keratin.

TERAPI :
Tidak perlu

usia 3 bln akan hilang

GINGIVAL CYST OF ADULTS
✓ PATOGENESA:
Berasal dari: - sisa2 epitel odontogen (dental lamina)
- krn traumatic implantation epitel
permukaan
- degenerasi kistik epitel permukaan
KLINIS:
- Pembesaran lambat, berbatas jelas ø ± 1 cm
- Tidak sakit
- kista terletak pada : ▪ free gingiva
▪ attached gingiva
▪ gingival papila
-
- Lesi halus, fluktuasi (+), warna kebiruan
- gigi regio bersangkutan vital
- usia dekade II-VIII → puncak dekade V & VI
- laki2 > perempuan

✓HPA:
- umumnya kecil
- epitel bertatah yang tipis → 1-2 lapis
- dinding jar. ikat dg infiltrasi sel radang
khronis yg bervariasi
✓ TERAPI:
- lokal surgical excision
- rekuren : (-)
▪ KISTA LATERAL PERIODONTAL

✓ PATOGENESA:
Ada 2 kemungkinan:
1. Berasal dari sisa-sisa enamel epithelium → pada
fase awal pertumbuhannya seperti kista
dentigerous → folikel berekspansi sepanjang
permukaan lateral mahkota → bila mahkota
tumbuh normal → kista terletak pada bagian
lateral akar.
2. Berasal dari sisa2 epitel malassez → berproliferasi
→ degenerasi kistik → kista.
 KLINIS:
- lokasi : terutama RB regio C & P
- usia > 20 th
- asimtomatis
- pembesaran gingiva mirip dg gingival cyst
- gigi regio bersangkutan vital
✓ HPA:
- Kista dilapisi epitel bertatah atau kubis yg tipis →
2-5 lapis
- tanpa keratin
- dinding jar. ikat fibrous → inflamasi (+)/(-)
✓ Rö FOTO:
- radiolusen bulat atau oval berbatas jelas
- lokasi antara apex dan cervical margin
- ukuran ± 1 mm
- unilokuler atau multilokuler

✓ TERAPI:
- surgical enucleation
- rekuren –
▪ CALCIFYING ODONTOGENIC CYST (COC)
= Odontogenic cell tumor = Keratinizing and Calcifying
epithelial Odontogenic Cyst = Gorlin Cyst = Cystic
Keratinizing Tumor.

Merupakan suatu neoplasma yang unik karena sebagian

berbentuk solid → pd neoplasma yg solid mengandung
bentukan kistik.

✓ PATOGENESA
Masih menjadi perdebatan
✓ KLINIS & HPA:
Terbagi dalam 3 variasi berdasar gambaran kistik.
• Tipe IA : tipe unikistik simpel
• Tipe IB : tipe seperti odontoma
• Tipe IC : tipe yang mirip prolifersi ameloblastoma

✓ Tipe IA.
- pada semua usia
- extra dan intra osseus
- epitel pelapis kista (1-3 lapis) : ▪Kubis
▪skuamus
- stelate retikulum +
- ghost cell +
✓ Tipe IB.
- usia : 10-29 th
- extra dan intra osseus
▪ secara HPA → unilokuler kistik seperti
tipe IA tetapi pada dinding kista
mengandung bentukan jaringan
berkapur seperti pada dinding kista dari
compound & Complex odontoma,
tampak proliferasi jaringan mirip
ameloblastik fibroma.
✓ Tipe IC.
- Terutama pada dekade akhir
- lesi intra & ekstra osseus
- gambaran HPA mirip ameloblastoma bentuk
pita-pita/ pulau2 epitel odontogen.
- ghost cell + dalam ukuran bervariasi
- dentinoid + pada epitel odontogen disebut
dentinogenic ghost cell tumor.
▪ Rö FOTO :
▪ sentral : radiolusen, berbatas jelas + fokus radiopak
▪ ukuran mm - cm

▪ TERAPI & PROGNOSA

▪ - sugical excisi
▪ - recurent ±
▪ - perubahan → karsinoma
Potensi keganasan
▪ Setiap folikel pada gigi impaksi atau tidak erupsi berpotensi
menjadi kista dentigerus
▪ Kista dentigerus berpotensi menjadi amaloblastoma (33%)
yang berasal dari dinding kista dari lapisan epitel atau sisa
epitel
▪ Transformasi malignant menjadi SCC, yang berasal dari
lapisan epitelium
▪ Mucoepirdemoid carcinoma yaitu bentuk dari kelenjar saliva
malignan dari lapisan epitel kista dentigerus yang
mengandung sel sekresi mukus
▪ KISTA DERMOID
▪Dermal Cyst
▪Epidermal Cyst

- kista non odontogen

- kista jar. lunak (perferi)
- kista karena gangguan pertumbuhan

✓ PATOGENESA :
- Pada masa embrional terjadi penyatuan beberapa
tulang/processus → diikuti penyatuan epitel
permukaan/kulit.
- Seringkali epitel tertinggal → degenerasi kistik →
kista Dermoid.
✓ KLINIS:
- Lokasi : leher tengah/samping/dasar mulut/sub
maksilaris/sub lingualis/sub mentalis.
- Batas jelas → dapat digerakkan
- Fluktuasi + kasar
- ø beberapa cm
- bila terjadi pada dasar mulut → mengganggu
fungsi bicara/ menelan.
- laki2 dan perempuan sama dengan usia 12-15
tahun
✓HPA:
- Lumen : mengandung bahan
lemak
- Epitel : epitel bertatah + keratin
- Dinding : ▪ jar. ikat kendor
▪ adneksa kulit: folikel
rambut, kelenjar lemak, kelenjar
keringat.
- Epidermoid cyst → adneksa kulit
- Complex teratoma → pada jar.
ikat terdapat jar. organoid :
mirip tulang/ rambut, otot,
gastro intestinal
TERAPI: Eksisi → prognosa baik
▪ KISTA BRANCHIOGENIK
▪Branchial Cleft cyst
▪Benign Cervical Lymphe Epithelial Cyst
▪Benign Cyst Lymphenode

✓ PATOGENESA:
- Berasal dari epitel cervical lymphenode (dulu diduga dari
sisa epitel cabang branchial atau pharyngeal

✓ KLINIS:
- Pembesaran berbatas jelas, ø 2 - 10 cm, rata2 3 - 4 cm.
- tumbuh lambat
- dapat digerakkan dari dasar
✓ DD (klinis):
- hygromacoli
- lymphadenitis
- lymphoma

✓ TERAPI :
Eksisi → prognosa baik
✓ HPA:
Lumen : mengandung bahan
gelatin/ mukoid Epitel : epitel
bertatah/silindris bulu getar/
kombinasi
Dinding : jar. ikat yang banyak
mengandung sel limfosit
bahkan dapat membentuk
limfolikel atau germinal senter.
▪ KISTA DUCTUS THYROGLOSSUS

✓ PATOGENESA:
Berasal dr sisa epitel saluran embrional mulai dr foramen
caecum lidah s/d os. Hyoid. Saluran bercabang dua
membentuk kelenjar thyroid seharusnya kelenjar hilang
→ tdk hilang → degenerasi kistik → kista.
- lokasi : leher bag samping, angulus mandibula, dasar
mulut
- asimtomatik
✓ KLINIS:
- Lokasi yang umum :
dibawah foramen caecum, dasar mulut,
supra hyoid /sub hyoid, cartilago thyroid,
setinggi supra sternal notch
- dungkul lunak, ø 1-10 cm, ± 3 cm
- dapat digerakkan
- tumbuh lambat
- asimtomatik → kadang membentuk fistel
- semua usia → >> 30 th
- pada dasar mulut → disphagia.
✓HPA:
- Epitel pelapis :
epitel bertatah, epitel silindris + bulu
getar
- Dinding : jar. Ikat kendor, jar. Limfoid ±
kelenjar mucous ± epitel asini kelenjar
Thyroid embrional membentuk asini,
kumpulan epitel embrional berbentuk
kumpulan/pita-pita.
✓ TERAPI:
complete surgical excise → prognosa

papillary carsinoma
▪ HYGROMA COLI = Cervical Cystic Hygroma

✓ Patogenesa:
Gangguan pertumbuhan dari lymphatic cyst pada saat
embrional → pembesaran daerah leher
lateral/bilateral

✓ Klinis:
- Leher membesar lateral/bilateral
- Usia: kurang dari 2 th
- Perluasan & pembesaran pada dasar mulut serta
pertumbuhan progresif → kesukaran bernafas.
- Rasa sakit pada saluran pernafasan bag atas disertai
demam & toxemia → † (sebelum antibiotik
ditemukan).
- Sering disertai lymphangioma lidah.
✓HPA :
Proliferasi pembuluh lymphe lebar, dilapisi
endotel
- Stroma : jar. ikat kendor, dgn Lumen: berisi
cairan/kosong
- sabut2 kolagen, banyak mengandung sel
limfosit bahkan dapat membentuk
limfolikel atau germinal senter.
- Kapsul : (-)

✓ TERAPI:
Surgical eksisi → prognosa baik.
GAMBARAN UMUM IMUNOLOGI KARIES GIGI