L12 Advanced Cellular pathology abcd.pdf
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About This Presentation
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Slide Content
MED 4005 Clinical Laboratory Cellular Pathology
Lecture 12 –Advanced Cellular pathology
Albert LI
Lecture 12 –Advanced Cellular pathology
Albert LI
1. Cellular Adaptations
➢Adaptations are reversible changes in the size, number,
phenotype, metabolic activity or functions of cells in
response to changes in their environment
➢Cells must constantly adapt, even under normal conditions
➢These physiological adaptations usually represent responses
of cells to normal stimulation by hormones or endogenous
chemical substances
2
➢Adaptations are reversible changes in the size, number,
phenotype, metabolic activity or functions of cells in
response to changes in their environment
➢Cells must constantly adapt, even under normal conditions
➢These physiological adaptations usually represent responses
of cells to normal stimulation by hormones or endogenous
chemical substances
2
Cell can adapt themselves by undergoing
5 different conditions:
1.Hyperplasia
2.Hypertrophy
3.Atrophy
4.Metaplasia
5.Dysplasia
3
5 different conditions:
1.Hyperplasia
2.Hypertrophy
3.Atrophy
4.Metaplasia
5.Dysplasia
3
Two types of Hyperplasia:
(A) Physiological
1.Hormonal : influence of hormonal stimulation
•Hyperplasia of the female breast epithelium at puberty or
in pregnancy
•Pregnant uterus
•Normal endometrium after a normal menstrual cycle
•Prostatic hyperplasia in old age
4
(A) Physiological
1.Hormonal : influence of hormonal stimulation
•Hyperplasia of the female breast epithelium at puberty or
in pregnancy
•Pregnant uterus
•Normal endometrium after a normal menstrual cycle
•Prostatic hyperplasia in old age
4
BPH is characterized by a varying combination of epithelial and
stromal hyperplasia in the prostate
5
Benign Prostatic Hyperplasia
stromal hyperplasia in the prostate
5
Benign Prostatic Hyperplasia
Physiological adaptations
Enlargement of the breast and induction of
lactation by pregnancy
6
Normal Breast
Enlargement of the breast and induction of
lactation by pregnancy
6
Normal Breast
2. Compensatory: hyperplasia occurring following
removal of part of an organ or a contralateral organ in
paired organ
• Regeneration of the liver following partial hepatectomy
• Regeneration of epidermis after skin abrasion
• Following nephrectomy on one side, there is hyperplasia
of nephrons of the other kidney
7
removal of part of an organ or a contralateral organ in
paired organ
• Regeneration of the liver following partial hepatectomy
• Regeneration of epidermis after skin abrasion
• Following nephrectomy on one side, there is hyperplasia
of nephrons of the other kidney
7
(B) Pathological
• Excessive stimulation of hormones or growth factors
– Endometrial hyperplasia
– Wound healing of granulation tissue due to proliferation
of fibroblasts and endothelial cells
– Skin warts from hyperplasia of epidermis due to human
papilloma virus
– Pseudocarcinomatous hyperplasia of the skin
8
• Excessive stimulation of hormones or growth factors
– Endometrial hyperplasia
– Wound healing of granulation tissue due to proliferation
of fibroblasts and endothelial cells
– Skin warts from hyperplasia of epidermis due to human
papilloma virus
– Pseudocarcinomatous hyperplasia of the skin
8
Granulation tissue in an infected woundHyperplasia of the Endometrium
9
9
Pseudoepitheliomatous hyperplasia
Histological section under low power showing
condyloma acuminata changes with prominent
rete ridges and hyperkeratosis
Human papillomavirus infection
10
Histological section under low power showing
condyloma acuminata changes with prominent
rete ridges and hyperkeratosis
Human papillomavirus infection
10
Hypertrophy
Definition:
An increase in the size of cells and with such change, an
increase in the size of the organ
Two types:
• Physiologic: Occurs due to a normal stressor. For example,
enlargement of skeletal muscle with exercise
• Pathologic: increased workload, hormonal stimulation
and growth factors stimulation
11
Definition:
An increase in the size of cells and with such change, an
increase in the size of the organ
Two types:
• Physiologic: Occurs due to a normal stressor. For example,
enlargement of skeletal muscle with exercise
• Pathologic: increased workload, hormonal stimulation
and growth factors stimulation
11
❖The patient had high
blood pressure, which
increased the workload of
the left ventricle and
resulted in concentric
hypertrophy of the left
ventricular myocardium
❖In response to the
increasing pressure load,
the cardiac myocytes
increased their content of
contractile proteins,
resulting in enlargement
of individual myocytes
12
Cross-section of the heart of a patient
with systemic hypertension
blood pressure, which
increased the workload of
the left ventricle and
resulted in concentric
hypertrophy of the left
ventricular myocardium
❖In response to the
increasing pressure load,
the cardiac myocytes
increased their content of
contractile proteins,
resulting in enlargement
of individual myocytes
12
Cross-section of the heart of a patient
with systemic hypertension
Hyperplasia vs Hypertrophy
Hyperplasia Hypertrophy
Increase in the amount of a tissue due
to cell proliferation
Increase in the volume of an organ or a tissue
due to the enlargement of cells
Provoked due to excessive cell
stimulation
Provoked due to increased demand
Increases the size of the tissue by cell
division
Stromal and cellular components are enlarged
by increasing their size without multiplying
Morphology of hyperplasia and hypertrophy:
Both hyperplasia and hypertrophy result in
an increase in organ size; therefore, both
cannot always be distinguished grossly and
microscopic examination is required to
distinguish the two
13
Hyperplasia Hypertrophy
Increase in the amount of a tissue due
to cell proliferation
Increase in the volume of an organ or a tissue
due to the enlargement of cells
Provoked due to excessive cell
stimulation
Provoked due to increased demand
Increases the size of the tissue by cell
division
Stromal and cellular components are enlarged
by increasing their size without multiplying
Morphology of hyperplasia and hypertrophy:
Both hyperplasia and hypertrophy result in
an increase in organ size; therefore, both
cannot always be distinguished grossly and
microscopic examination is required to
distinguish the two
13
Atrophy
Definition:
Acquired loss of size due to reduction of cell size or number
of parenchyma cells in an organ
Two types:
• Physiologic: A normal process of aging in some tissues,
which could be due to loss of endocrine stimulation or
arteriosclerosis (poor circulation, poor nourishment)
– Atrophy of lymphoid tissue in lymph nodes, appendix
and thymus
– Atrophy of gonads after menopause
– Atrophy of brain with aging
14
Definition:
Acquired loss of size due to reduction of cell size or number
of parenchyma cells in an organ
Two types:
• Physiologic: A normal process of aging in some tissues,
which could be due to loss of endocrine stimulation or
arteriosclerosis (poor circulation, poor nourishment)
– Atrophy of lymphoid tissue in lymph nodes, appendix
and thymus
– Atrophy of gonads after menopause
– Atrophy of brain with aging
14
• Pathologic: occurs as a result of disease or loss
of trophic support because of other diseases
– Starvation atrophy
– Ischaemic atrophy
– Disuse atrophy
– Neuropathic atrophy
– Endocrine atrophy
– Pressure atrophy
– Idiopathic atrophy
15
of trophic support because of other diseases
– Starvation atrophy
– Ischaemic atrophy
– Disuse atrophy
– Neuropathic atrophy
– Endocrine atrophy
– Pressure atrophy
– Idiopathic atrophy
15
Metaplasia
Definition:
Metaplasia is a reversible substitution of one type of fully
differentiated cell for another within a given tissue; it is seen
most commonly in epithelial tissues
Causes:
•Changes in environment
•Chronic physical or chemical irritation
•Nutritional
•Inflammation 16
Definition:
Metaplasia is a reversible substitution of one type of fully
differentiated cell for another within a given tissue; it is seen
most commonly in epithelial tissues
Causes:
•Changes in environment
•Chronic physical or chemical irritation
•Nutritional
•Inflammation 16
17
The following table lists some common tissues susceptible to
metaplasia, and the stimuli that can cause the change:
Tissue Normal Metaplasia Stimulus
Airways
Pseudostratified columnar
epithelium
Squamous epithelium Cigarette smoke
Urinary bladder Transitional epithelium Squamous epithelium Bladder stone
Esophagus Squamous epithelium Columnar epithelium (Barrett's Esophagus) Gastro-esophageal reflux
Cervix Glandular epithelium Squamous epithelium Low pH of vagina
The following table lists some common tissues susceptible to
metaplasia, and the stimuli that can cause the change:
Tissue Normal Metaplasia Stimulus
Airways
Pseudostratified columnar
epithelium
Squamous epithelium Cigarette smoke
Urinary bladder Transitional epithelium Squamous epithelium Bladder stone
Esophagus Squamous epithelium Columnar epithelium (Barrett's Esophagus) Gastro-esophageal reflux
Cervix Glandular epithelium Squamous epithelium Low pH of vagina
Two basic types of Metaplasia
1. Epithelial Metaplasia
– Squamous metaplasia: changes in bronchus, endocervix,
gallbladder, prostate, renal pelvis and urinary bladder
– Columnar metaplasia: Intestinal metaplasia in healed
chronic gastric ulcer and Barrett’s oesophagus
2. Mesenchymal Metaplasia
– Osseous metaplasia
– Cartilaginous metaplasia
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/metaplasia
18
1. Epithelial Metaplasia
– Squamous metaplasia: changes in bronchus, endocervix,
gallbladder, prostate, renal pelvis and urinary bladder
– Columnar metaplasia: Intestinal metaplasia in healed
chronic gastric ulcer and Barrett’s oesophagus
2. Mesenchymal Metaplasia
– Osseous metaplasia
– Cartilaginous metaplasia
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/metaplasia
18
19
Keratinizing squamous metaplasia of the urinary bladder
Keratinizing squamous metaplasia of the urinary bladder
Squamous metaplasia in endocervical gland
https://commons.wikimedia.org/wiki/File:Squamous_metaplasia_in_endocervical_gland.jpg
20
https://commons.wikimedia.org/wiki/File:Squamous_metaplasia_in_endocervical_gland.jpg
20
Intestinal (Barrett's) metaplasia of the esophagus
21
21
22
Osseous metaplasia
Osseous metaplasia
Cartilaginous metaplasia in placenta
23
23
Dysplasia
➢Abnormal changes in cellular shape, size, and/or organization
➢Dysplasia is not considered a true adaptation
➢Disordered cellular development
➢Referred to as an atypical hyperplasia
➢Although dysplasia is reversible, if stress persists, then
dysplasia progresses to irreversible carcinoma
24
➢Abnormal changes in cellular shape, size, and/or organization
➢Dysplasia is not considered a true adaptation
➢Disordered cellular development
➢Referred to as an atypical hyperplasia
➢Although dysplasia is reversible, if stress persists, then
dysplasia progresses to irreversible carcinoma
24
• Epithelial dysplasia is characterized by cellular proliferation
and cytological changes
–Increased number of layers of epithelial cells
– Disorderly arrangement of cells
– Loss of basal polarity
i.e. nuclei lying away from basement membrane
– Cellular and nuclear pleomorphism
– Increased nucleocytoplasmic ratio (NC ratio)
– Nuclear hyperchromatism
– Increased mitotic activity
• The two most common examples of dysplastic changes are
the uterine cervix and respiratory tract
25
and cytological changes
–Increased number of layers of epithelial cells
– Disorderly arrangement of cells
– Loss of basal polarity
i.e. nuclei lying away from basement membrane
– Cellular and nuclear pleomorphism
– Increased nucleocytoplasmic ratio (NC ratio)
– Nuclear hyperchromatism
– Increased mitotic activity
• The two most common examples of dysplastic changes are
the uterine cervix and respiratory tract
25
Dysplasia of Uterine Cervix Normal Uterine Cervix
26
26
Dysplasia of bronchial epitheliumNormal bronchial epithelium
27
27
2. Inflammation
• Inflammation is defined as the local response
of living mammalian tissues to injury
• Body defense reaction – eliminate or limit the
spread of injurious agent
28
• Inflammation is defined as the local response
of living mammalian tissues to injury
• Body defense reaction – eliminate or limit the
spread of injurious agent
28
Causes of Inflammation
1.Infective agents like bacteria, viruses and their
toxins, fungi, parasites
2.Immunological agents like cell-mediated and antigen
antibody reactions
3.Physical agents like heat, cold, radiation, mechanical
trauma
4.Chemical agents like organic and inorganic poisons
5.Inert materials such as foreign bodies
29
1.Infective agents like bacteria, viruses and their
toxins, fungi, parasites
2.Immunological agents like cell-mediated and antigen
antibody reactions
3.Physical agents like heat, cold, radiation, mechanical
trauma
4.Chemical agents like organic and inorganic poisons
5.Inert materials such as foreign bodies
29
Histologic analysis of amebic colitis
A) Trophozoites of Entamoeba histolytica ingesting erythrocytes (arrows) (H&E stain)
B) Numerous amebic trophozoites on the mucosal surface (periodic acid–Schiff stain)
Amoebic colitis
30
A) Trophozoites of Entamoeba histolytica ingesting erythrocytes (arrows) (H&E stain)
B) Numerous amebic trophozoites on the mucosal surface (periodic acid–Schiff stain)
Amoebic colitis
30
Two types of inflammation
• Acute Inflammation
– sudden onset and short duration (hours - days)
– represents the early body reaction
- followed by healing
• Chronic inflammation
– gradual onset and long duration (days -years)
– causative agent of acute inflammation persists
for a long time
31
• Acute Inflammation
– sudden onset and short duration (hours - days)
– represents the early body reaction
- followed by healing
• Chronic inflammation
– gradual onset and long duration (days -years)
– causative agent of acute inflammation persists
for a long time
31
Acute Inflammation
The main features of acute inflammation are:
– accumulation of fluid and plasma at the affected site
– intravascular activation of platelets
– polymorphonuclear neutrophils as inflammatory cells
32
The main features of acute inflammation are:
– accumulation of fluid and plasma at the affected site
– intravascular activation of platelets
– polymorphonuclear neutrophils as inflammatory cells
32
Cardinal Signs and Symptoms of Acute Inflammation
1.Redness: Caused by vasodilatation of the capillaries
2.Hotness: Caused by arteriolar dilatation and increased blood
flow
3.Swelling: Caused by the vascular dilatation and the
accumulation of the inflammatory fluid and cellular exudate
4.Pain: Caused by irritation of the nerve endings by toxins and
pressure of the inflammatory exudate on the sensory nerves
5.Loss of function: due to destruction of tissues or to avoid pain
33
1.Redness: Caused by vasodilatation of the capillaries
2.Hotness: Caused by arteriolar dilatation and increased blood
flow
3.Swelling: Caused by the vascular dilatation and the
accumulation of the inflammatory fluid and cellular exudate
4.Pain: Caused by irritation of the nerve endings by toxins and
pressure of the inflammatory exudate on the sensory nerves
5.Loss of function: due to destruction of tissues or to avoid pain
33
Acute Inflammation
• Divided into following two events
– Vascular events
– Cellular events
• This 2 events are followed intermittently by
release of mediators of acute inflammation
34
• Divided into following two events
– Vascular events
– Cellular events
• This 2 events are followed intermittently by
release of mediators of acute inflammation
34
Vascular Events
• Alteration in the microvasculature
• This is again divided in 2 phases
– Hemodynamic changes
– Changes in the vascular permeability
35
• Alteration in the microvasculature
• This is again divided in 2 phases
– Hemodynamic changes
– Changes in the vascular permeability
35
Hemodynamic changes
1.Transient vasoconstriction : immediate vascular response
irrespective of the type of injury, mainly arterioles
– Mild injury - 3-5 seconds
– Severe injury - 5 minutes
2.Persistent progressive vasodilatation : mainly arterioles,
others to a lesser extent
– obvious within half an hour of injury
– increased blood volume in microvascular bed of the area
– redness and warmth
3.Slowing or stasis increased concentration of red cells and
thus raised blood viscosity 36
1.Transient vasoconstriction : immediate vascular response
irrespective of the type of injury, mainly arterioles
– Mild injury - 3-5 seconds
– Severe injury - 5 minutes
2.Persistent progressive vasodilatation : mainly arterioles,
others to a lesser extent
– obvious within half an hour of injury
– increased blood volume in microvascular bed of the area
– redness and warmth
3.Slowing or stasis increased concentration of red cells and
thus raised blood viscosity 36
Hemodynamic changes
4. Progressive vasodilatation elevate the local hydrostatic
pressure
– transudation of fluid into the extracellular space
– swelling
5. Leucocytic margination of leucocytes (mainly neutrophils)
along the vascular endothelium
– stick to the vascular endothelium
– move and migrate through the gaps between the
endothelial cells - extravascular space
– This is known as emigration
37
4. Progressive vasodilatation elevate the local hydrostatic
pressure
– transudation of fluid into the extracellular space
– swelling
5. Leucocytic margination of leucocytes (mainly neutrophils)
along the vascular endothelium
– stick to the vascular endothelium
– move and migrate through the gaps between the
endothelial cells - extravascular space
– This is known as emigration
37
Altered Vascular Permeability
• Accumulation of oedema fluid - interstitial compartment
which comes from blood plasma by its escape through the
endothelial wall of peripheral vascular bed
• Escape of fluid is due to vasodilatation and consequent
elevation in hydrostatic pressure - transudate
• Subsequently, the characteristic inflammatory oedema,
appears by increased vascular permeability of microcirculation
– exudate
38
• Accumulation of oedema fluid - interstitial compartment
which comes from blood plasma by its escape through the
endothelial wall of peripheral vascular bed
• Escape of fluid is due to vasodilatation and consequent
elevation in hydrostatic pressure - transudate
• Subsequently, the characteristic inflammatory oedema,
appears by increased vascular permeability of microcirculation
– exudate
38
Functions of Exudate
1.It dilutes bacterial toxins and chemical irritants
2.It brings antibodies to the area of inflammation
3.It brings the chemical mediators derived from plasma to
the area
4.It contains fibrinogen which changes to fibrin by activation
of clotting system - fibrin helps in localization of
inflammation by surrounding the area
39
1.It dilutes bacterial toxins and chemical irritants
2.It brings antibodies to the area of inflammation
3.It brings the chemical mediators derived from plasma to
the area
4.It contains fibrinogen which changes to fibrin by activation
of clotting system - fibrin helps in localization of
inflammation by surrounding the area
39
Fate of Acute inflammation
1.Complete resolution
2.Healing by scarring
3.Progression and spread: direct, lymphatic
& blood spread
4.Chronicity
40
1.Complete resolution
2.Healing by scarring
3.Progression and spread: direct, lymphatic
& blood spread
4.Chronicity
40
Two types of Acute Inflammation
1. Suppurative Inflammation
a)Diffuse: Cellulitis, Suppurative appendicitis,
Suppurative cholecystitis, Suppurative
peritonitis, Suppurative meningitis
b) Localized: Abscess, furuncle, carbuncle
2.Non-Suppurative Inflammation
41
1. Suppurative Inflammation
a)Diffuse: Cellulitis, Suppurative appendicitis,
Suppurative cholecystitis, Suppurative
peritonitis, Suppurative meningitis
b) Localized: Abscess, furuncle, carbuncle
2.Non-Suppurative Inflammation
41
Image source: https://twitter.com/JRamirezMD/status/808763472985001984/photo/3
Cellulitis Histology
42
Cellulitis Histology
42
Acute Appendicitis
Section shows appendix which is permeated with numerous
polymorphonuclear leukocytes 43
Section shows appendix which is permeated with numerous
polymorphonuclear leukocytes 43
The inflammatory exudate in the subarachnoid space
is layered-neutrophils on top, fibrin in the deeper layer
Meningitis Histology
44
is layered-neutrophils on top, fibrin in the deeper layer
Meningitis Histology
44
Non-Suppurative inflammations are divided as:
1.Catarrhal Inflammation: Mild acute inflammation of the mucous
membranes of the respiratory and GIT characterized by excess mucus
secretion e.g. catarrhal rhinitis (common cold), bronchitis... etc
2.Membranous Inflammation (Pseudomembranous):
Severe acute inflammation characterized by the formation of a
pseudomembrane on the affected surface formed of necrotic cells,
fibrin threads, leucocytes and the causative organism e.g. diphtheria
and bacillary dysentery
3. Sero-fibrinous Inflammation: It involves serous sacs as pleura,
peritoneum and pericardium. Characterized by excess serous exudates
in the sac and deposition of fibrin on the surface
45
1.Catarrhal Inflammation: Mild acute inflammation of the mucous
membranes of the respiratory and GIT characterized by excess mucus
secretion e.g. catarrhal rhinitis (common cold), bronchitis... etc
2.Membranous Inflammation (Pseudomembranous):
Severe acute inflammation characterized by the formation of a
pseudomembrane on the affected surface formed of necrotic cells,
fibrin threads, leucocytes and the causative organism e.g. diphtheria
and bacillary dysentery
3. Sero-fibrinous Inflammation: It involves serous sacs as pleura,
peritoneum and pericardium. Characterized by excess serous exudates
in the sac and deposition of fibrin on the surface
45
4. Fibrinous Inflammation: Characterized by an exudate rich in
fibrinogen e.g. lobar pneumonia, fibrinous pericarditis, fibrinous
peritonitis... etc
5. Haemorrahgic Inflammation: Characterized by cellular exudate
rich in the red blood cells due to vascular damage e.g. smallpox and
haemolytic streptococcal infection
6. Necrotizing Inflammation: Acute inflammation characterized by
marked tissue necrosis
7. Allergic Inflammation: It is an antigen antibody reaction
characterized by abundant fluid exudates and eosinophils
46
fibrinogen e.g. lobar pneumonia, fibrinous pericarditis, fibrinous
peritonitis... etc
5. Haemorrahgic Inflammation: Characterized by cellular exudate
rich in the red blood cells due to vascular damage e.g. smallpox and
haemolytic streptococcal infection
6. Necrotizing Inflammation: Acute inflammation characterized by
marked tissue necrosis
7. Allergic Inflammation: It is an antigen antibody reaction
characterized by abundant fluid exudates and eosinophils
46
Lobar Pneumonia Histology
47
47
Chronic inflammation
Chronic inflammation is characterized by the following:
1.The irritant is mild and has a prolonged action
2.Chronic inflammation may follow acute inflammation
or starts as slowly progressing chronic disease as in
tuberculosis and syphilis
3.The tissue response is gradual and prolonged
4.The small arteries and arterioles show thickening and
narrowing called endarteritis obliterans
5.The inflammatory fluid exudates is scanty
6.The inflammatory cellular exudates consists of
lymphocytes, plasma cells, macrophages and foreign
-body giant cells
48
Chronic inflammation is characterized by the following:
1.The irritant is mild and has a prolonged action
2.Chronic inflammation may follow acute inflammation
or starts as slowly progressing chronic disease as in
tuberculosis and syphilis
3.The tissue response is gradual and prolonged
4.The small arteries and arterioles show thickening and
narrowing called endarteritis obliterans
5.The inflammatory fluid exudates is scanty
6.The inflammatory cellular exudates consists of
lymphocytes, plasma cells, macrophages and foreign
-body giant cells
48
Differences between acute and chronic inflammation
49
49
Types of Chronic inflammation:
(1)Chronic non-specific inflammation: Different irritants
produce inflammatory reactions of the same microscopic
picture e.g. chronic abscess and chronic tonsillitis
(2)Chronic specific inflammation : Each irritant or organism
produces a characteristic microscopic picture called
granuloma e.g. tuberculosis, bilharziasis and leprosy
50
(1)Chronic non-specific inflammation: Different irritants
produce inflammatory reactions of the same microscopic
picture e.g. chronic abscess and chronic tonsillitis
(2)Chronic specific inflammation : Each irritant or organism
produces a characteristic microscopic picture called
granuloma e.g. tuberculosis, bilharziasis and leprosy
50
Tuberculosis lung histology
Under the microscope multinucleate giant cells are seen Caseous necrosis
51
Under the microscope multinucleate giant cells are seen Caseous necrosis
51
Leprosy
Tuberculoid leprosy – There is a tuberculoid or
sarcoidal granulomatous reaction throughout the
dermis consisting of some Langhans giant cells,
macrophages in tight clusters, and few
accompanying lymphocytes
Lepromatous leprosy – Underneath a normal
epidermis and Grenz zone, there are sheets or
clusters of macrophages
Image source: https://dermnetnz.org/topics/leprosy-pathology/52
Tuberculoid leprosy – There is a tuberculoid or
sarcoidal granulomatous reaction throughout the
dermis consisting of some Langhans giant cells,
macrophages in tight clusters, and few
accompanying lymphocytes
Lepromatous leprosy – Underneath a normal
epidermis and Grenz zone, there are sheets or
clusters of macrophages
Image source: https://dermnetnz.org/topics/leprosy-pathology/52
Granuloma
Definition:
Chronic specific inflammation characterized by focal
accumulation of large number of chronic inflammatory
cells to form tumour like mass
53
Definition:
Chronic specific inflammation characterized by focal
accumulation of large number of chronic inflammatory
cells to form tumour like mass
53
Two/ three types of granuloma
1. Infective granuloma
– Bacterial as TB, leprosy and syphilis
– Parasitic as bilharziasis and leishmaniasis
– Mycotic as madura foot and actinomycosis
– Viral as granuloma inguinale
2. Non-infective granuloma
– silicosis, asbestosis and foreign-body granuloma
3.Unknown
– sarcoidosis and crohns disease
54
1. Infective granuloma
– Bacterial as TB, leprosy and syphilis
– Parasitic as bilharziasis and leishmaniasis
– Mycotic as madura foot and actinomycosis
– Viral as granuloma inguinale
2. Non-infective granuloma
– silicosis, asbestosis and foreign-body granuloma
3.Unknown
– sarcoidosis and crohns disease
54
The epidermis shows a psoriasiform
hyperplasia with superficial neutrophils
The epidermis also shows a lichenoid tissue
reaction, epidermal apoptosis and exocytosis
of neutrophils
Histology of syphilis
55
hyperplasia with superficial neutrophils
The epidermis also shows a lichenoid tissue
reaction, epidermal apoptosis and exocytosis
of neutrophils
Histology of syphilis
55
The epidermis is thinned and exhibits hyperkeratosis. In mid dermis there is a
dense inflammatory infiltrate composed of lymphocytes and histiocytes with
perivascular distribution and well-defined granulomas without necrosis
Image source: Dermatology Online Journal, Volume 18, Issue 9, 2012
Leishmaniasis histology
56
dense inflammatory infiltrate composed of lymphocytes and histiocytes with
perivascular distribution and well-defined granulomas without necrosis
Image source: Dermatology Online Journal, Volume 18, Issue 9, 2012
Leishmaniasis histology
56
Abdominal actinomycosis presenting as appendicitis:
two case reports and review - Scientific Figure on
ResearchGate
The image shows an actinomycotic (sulfur) granule
enveloped by an infiltrate composed of neutrophils,
foamy histiocytes, lymphocytes and plasma cells
Actinomycosis histology
57
two case reports and review - Scientific Figure on
ResearchGate
The image shows an actinomycotic (sulfur) granule
enveloped by an infiltrate composed of neutrophils,
foamy histiocytes, lymphocytes and plasma cells
Actinomycosis histology
57
Section shows granulation tissue with numerous large histiocytes
containing the dark particulate inclusions (Donovan bodies)
Granuloma inguinale histology
58
containing the dark particulate inclusions (Donovan bodies)
Granuloma inguinale histology
58
Silicosis histology
A silicotic nodule within lung parenchyma is seen here. It is
composed mainly of bundles of interlacing pink collagen 59
A silicotic nodule within lung parenchyma is seen here. It is
composed mainly of bundles of interlacing pink collagen 59
Micrograph of asbestosis (with ferruginous bodies), a type of
pneumoconiosis H&E stain
Ferruginous bodies
60
Asbestosis histology
pneumoconiosis H&E stain
Ferruginous bodies
60
Asbestosis histology
Histopathologic features of sarcoidosis showing the hallmark
noncaseating granulomas 61
Sarcoidosis histology
noncaseating granulomas 61
Sarcoidosis histology
Granulomatous colitis in Crohn’s disease
Crohn's disease of colon resembles ulcerative colitis but Crohn's colitis
also has fistulas / sinus tracts, skip lesions, deep ulcerations, marked
lymphocytic infiltration, serositis, granulomas, fewer plasma cells
granuloma
62
Crohn's disease of colon resembles ulcerative colitis but Crohn's colitis
also has fistulas / sinus tracts, skip lesions, deep ulcerations, marked
lymphocytic infiltration, serositis, granulomas, fewer plasma cells
granuloma
62
63
NEOPLASM
NEOPLASM
Terminology
Neoplasia
- New growth
-The autonomous growth of tissue which have escaped
normal constraints on cell proliferation
-Uncoordinated with that of the surrounding normal tissues
-Persists in the same manner even after cessation of the
stimulus which produced the change
Tumour-synonymous with neoplasm
Cancer-common term for malignant tumour of whatever type
Oncology-study of tumour
64
Neoplasia
- New growth
-The autonomous growth of tissue which have escaped
normal constraints on cell proliferation
-Uncoordinated with that of the surrounding normal tissues
-Persists in the same manner even after cessation of the
stimulus which produced the change
Tumour-synonymous with neoplasm
Cancer-common term for malignant tumour of whatever type
Oncology-study of tumour
64
HK Registry: Top 10 Cancers –Incidence
Source from: http://www3.ha.org.hk/cancereg/default.asp
65
Source from: http://www3.ha.org.hk/cancereg/default.asp
65
HK Registry: Top 10 Cancers –Incidence
Source from: http://www3.ha.org.hk/cancereg/default.asp
Source from: http://www3.ha.org.hk/cancereg/default.asp
HK Registry: Top 10 Cancers –Incidence
Source from: http://www3.ha.org.hk/cancereg/default.asp
Source from: http://www3.ha.org.hk/cancereg/default.asp
HK Registry: Top 10 Cancers –Incidence
Source from: http://www3.ha.org.hk/cancereg/default.asp
Source from: http://www3.ha.org.hk/cancereg/default.asp
Source from: http://www3.ha.org.hk/cancereg/topten.html
69
69
Source from: http://www3.ha.org.hk/cancereg/topten.html
70
70
Source from: http://www3.ha.org.hk/cancereg/topten.html
71
71
Tumour Growth
Rates of tumor cell growth (Gompertzian model)
Pre-clinical phase
• From 1 transformed cell to smallest clinically detectable mass
(1 gm) of 10
9
cells = 30 doublings
Clinical phase
• To reach 10
12
cells (1 kg) requires only 10 additional
doublings–Doubling time of tumour cells 72
Rates of tumor cell growth (Gompertzian model)
Pre-clinical phase
• From 1 transformed cell to smallest clinically detectable mass
(1 gm) of 10
9
cells = 30 doublings
Clinical phase
• To reach 10
12
cells (1 kg) requires only 10 additional
doublings–Doubling time of tumour cells 72
Classification of Tumours:
•Typeof the tumour: Solid / Haematologiccancers
•Behavior of tumour: Benign or malignant
•Cell of origin
•Degree of differentiation
73
•Typeof the tumour: Solid / Haematologiccancers
•Behavior of tumour: Benign or malignant
•Cell of origin
•Degree of differentiation
73
Solid tumours
•Initially confined to a specific tissue or organs
•Metastasize through detaching cells from original
tumourmass invade the surrounding tissue
•Enter blood and lymph system to spread to distant
sites
Haematologic cancers
•Involve with blood and lymph
•They are referred to as leukaemia, lymphoma and
myeloma depending on the type of cell affected
74
•Initially confined to a specific tissue or organs
•Metastasize through detaching cells from original
tumourmass invade the surrounding tissue
•Enter blood and lymph system to spread to distant
sites
Haematologic cancers
•Involve with blood and lymph
•They are referred to as leukaemia, lymphoma and
myeloma depending on the type of cell affected
74
Two types of neoplasm: Benign and Malignant
Benign neoplasm: – grow slowly
– low mitotic rate
– well differentiated
– not invasive
– well-defined borders
– remain localized
– do not metastasize
– surrounded by a fibrous capsule
75
Benign neoplasm: – grow slowly
– low mitotic rate
– well differentiated
– not invasive
– well-defined borders
– remain localized
– do not metastasize
– surrounded by a fibrous capsule
75
Malignant neoplasm:
– cancer from Latin word meaning ‘crab-like’
– grow rapidly
– high mitotic rate
– poorly differentiated
–invadesurrounding tissues
–metastasizefrom the primary to a secondary site
–do not have a capsule
76
– cancer from Latin word meaning ‘crab-like’
– grow rapidly
– high mitotic rate
– poorly differentiated
–invadesurrounding tissues
–metastasizefrom the primary to a secondary site
–do not have a capsule
76
BENIGN MALIGNANT
Nuclear variation in size and shape
minimal
Nuclear variation in size and shape minimal to marked,
often variable
Diploid Range of ploidy
Low mitotic count, normal mitosisLow to high mitotic count, abnormal mitosis
Retention of specialization Loss of specialization
Structural differentiation retainedStructural differentiation shows wide range of changes
Organized Not organized
Functional differentiation usually Functional differentiation often lost
Differences between Benign and Malignant Neoplasms
77
Nuclear variation in size and shape
minimal
Nuclear variation in size and shape minimal to marked,
often variable
Diploid Range of ploidy
Low mitotic count, normal mitosisLow to high mitotic count, abnormal mitosis
Retention of specialization Loss of specialization
Structural differentiation retainedStructural differentiation shows wide range of changes
Organized Not organized
Functional differentiation usually Functional differentiation often lost
Differences between Benign and Malignant Neoplasms
77
Nomenclature – Benign Tumours
-oma= benign neoplasm
Mesenchymal tumours
➢Chrondroma: cartilaginous tumour
➢Fibroma: fibrous tumour
➢Osteoma: bone tumour
Epithelial tumour
➢Adenoma: tumour forming glands
➢Papilloma: tumour with finger like projections
➢Papillary cystadenoma: papillary and cystic tumour
➢Polyp: a tumour that projects above a mucosal surface
78
-oma= benign neoplasm
Mesenchymal tumours
➢Chrondroma: cartilaginous tumour
➢Fibroma: fibrous tumour
➢Osteoma: bone tumour
Epithelial tumour
➢Adenoma: tumour forming glands
➢Papilloma: tumour with finger like projections
➢Papillary cystadenoma: papillary and cystic tumour
➢Polyp: a tumour that projects above a mucosal surface
78
Mesoderm originated benign neoplasms
Smooth muscle: Leiomyoma
Striated muscle:Rhabdomyoma
Fibrous tissue:Fibroma
Bone: Osteoma
Cartilage: Chondroma
Adipocyte: Lipoma
Nerve: Neurofibroma
Nerve sheath: Neurilemmoma
Glial cells: Glioma
79
Prefix (origin)+ suffix (oma)
Smooth muscle: Leiomyoma
Striated muscle:Rhabdomyoma
Fibrous tissue:Fibroma
Bone: Osteoma
Cartilage: Chondroma
Adipocyte: Lipoma
Nerve: Neurofibroma
Nerve sheath: Neurilemmoma
Glial cells: Glioma
79
Prefix (origin)+ suffix (oma)
Malignant tumours
– classified by embryonic origin of tissue
Carcinomas come from ectoderm and Endoderm
- epithelial and glandular tissue
Sarcomas arise from mesoderm
- connective tissue, muscle, nerve and endothelial
tissues
80
– classified by embryonic origin of tissue
Carcinomas come from ectoderm and Endoderm
- epithelial and glandular tissue
Sarcomas arise from mesoderm
- connective tissue, muscle, nerve and endothelial
tissues
80
Mesoderm originated malignant neoplasms
Prefix (origin)+ suffix (sarcoma)
81
Smooth muscle: Leiomyosarcoma
Striated muscle:Rhabdomyosarcoma
Fibrous tissue:Fibrosarcoma
Bone: Osteosarcoma
Cartilage: Chondrosarcoma
Adipocyte: Liposarcoma
Nerve: Neurofibrosarcoma
Nerve sheath: Neurilemmosarcoma
Glial cells: Malignant glioma
Prefix (origin)+ suffix (sarcoma)
81
Smooth muscle: Leiomyosarcoma
Striated muscle:Rhabdomyosarcoma
Fibrous tissue:Fibrosarcoma
Bone: Osteosarcoma
Cartilage: Chondrosarcoma
Adipocyte: Liposarcoma
Nerve: Neurofibrosarcoma
Nerve sheath: Neurilemmosarcoma
Glial cells: Malignant glioma
Some tumours have names that do not
conform with general rules:
Hepatoma: malignant liver tumour
Melanoma: malignant skin tumour
Seminoma: malignant testicular tumour
Lymphoma: malignant tumour of lymphocytes
Some tumours are named eponymously e.g. Hodgkins
lymphoma, Wilm’s tumour….etc
82
conform with general rules:
Hepatoma: malignant liver tumour
Melanoma: malignant skin tumour
Seminoma: malignant testicular tumour
Lymphoma: malignant tumour of lymphocytes
Some tumours are named eponymously e.g. Hodgkins
lymphoma, Wilm’s tumour….etc
82
Tumoursof mixed origin :
Teratoma–made of a variety of parenchymal cell
types that derive from more than one germ cell layer
formed by totipotent cells that are able to form
ectoderm, endoderm & mesoderm
•May be benign or malignant depending on structure,
site, age, sex ….
•Contain skin, sebaceous & mucus glands, hair,
cartilage, bone, respiratory epithelium, glial
tissue…..etc.
83
Teratoma–made of a variety of parenchymal cell
types that derive from more than one germ cell layer
formed by totipotent cells that are able to form
ectoderm, endoderm & mesoderm
•May be benign or malignant depending on structure,
site, age, sex ….
•Contain skin, sebaceous & mucus glands, hair,
cartilage, bone, respiratory epithelium, glial
tissue…..etc.
83
Tumoursof primitive fetal origin :
Blastoma :from immature tissue
•May arise in kidney, liver, retina…etc
e.g. Retinoblastoma
•The great majority of these tumoursare
malignant & occur in infants & children
84
Blastoma :from immature tissue
•May arise in kidney, liver, retina…etc
e.g. Retinoblastoma
•The great majority of these tumoursare
malignant & occur in infants & children
84
Differentiation
➢Well differentiated neoplasm - resembles mature
cells of tissue of origin
➢Poorly differentiated neoplasm - composed of
primitive cells with little differentiation
➢Undifferentiated or “anaplastic” tumour
➢Correlation with biologic behaviour
-Benign tumours are well differentiated
-Poorly differentiated malignant tumours usually
have worse prognosis
85
➢Well differentiated neoplasm - resembles mature
cells of tissue of origin
➢Poorly differentiated neoplasm - composed of
primitive cells with little differentiation
➢Undifferentiated or “anaplastic” tumour
➢Correlation with biologic behaviour
-Benign tumours are well differentiated
-Poorly differentiated malignant tumours usually
have worse prognosis
85
Invasion
➢Direct invasion into surrounding tissues, seeding of
cancer cells in body cavities and metastatic spread
➢Tumour synthesize and secrete enzymes that break
down proteins, contribute to infiltration, invasion and
penetration of surrounding tissues
Metastasis
➢Cells in a primary tumour develop the ability to escape,
travel, survive and develop a secondary tumour
➢Liver and bone are the most frequent metastatic site
86
➢Direct invasion into surrounding tissues, seeding of
cancer cells in body cavities and metastatic spread
➢Tumour synthesize and secrete enzymes that break
down proteins, contribute to infiltration, invasion and
penetration of surrounding tissues
Metastasis
➢Cells in a primary tumour develop the ability to escape,
travel, survive and develop a secondary tumour
➢Liver and bone are the most frequent metastatic site
86
87
Preferential metastatic sites
Cancer TypeMost Common Site of Metastasis
Bladder Bone, liver, lung
Breast Bone, brain, liver, lung
Colon Liver, lung, peritoneum(abdominal cavity)
Kidney Adrenal gland, bone, brain, liver, lung
Lung Adrenal gland, bone, brain, liver, other lung
Melanoma Bone, brain, liver, lung, skin, muscle
Ovary Liver, lung, peritoneum
Pancreas Liver, lung, peritoneum
Prostate Adrenal gland, bone, liver, lung
Rectal Liver, lung, peritoneum
Stomach Liver, lung, peritoneum
Thyroid Bone, liver, lung
Uterus Bone, liver, lung, peritoneum, vagina
https://www.cancer.gov/types/metastatic-cancer
Preferential metastatic sites
Cancer TypeMost Common Site of Metastasis
Bladder Bone, liver, lung
Breast Bone, brain, liver, lung
Colon Liver, lung, peritoneum(abdominal cavity)
Kidney Adrenal gland, bone, brain, liver, lung
Lung Adrenal gland, bone, brain, liver, other lung
Melanoma Bone, brain, liver, lung, skin, muscle
Ovary Liver, lung, peritoneum
Pancreas Liver, lung, peritoneum
Prostate Adrenal gland, bone, liver, lung
Rectal Liver, lung, peritoneum
Stomach Liver, lung, peritoneum
Thyroid Bone, liver, lung
Uterus Bone, liver, lung, peritoneum, vagina
https://www.cancer.gov/types/metastatic-cancer
The routes of tumoursspread
1.Direct extension - This includes fibroblastic proliferation (“ a desmoplastic
response”), vascular proliferation (angiogenesis) and an immune response
2.Haematogenous (via blood vessels) - The blood vessels usually invaded are
the venules and capillaries because they have thinner walls. Most sarcomas
metastasize first via the blood vessels
3.Lymphatic (via lymphatics to lymph nodes and beyond) - The pattern of
spread is dictated by the normal lymphatic drainage of the organ in question.
Most epithelial cancers metastasize first via the lymphatics
4.Transcoelomic (seeding of body cavities) - The commonest examples are
the pleural cavities (for intrathoracic cancers) and the peritoneal cavities
(for intra-abdominal cancers)
5.Perineural (via nerves) - This is an uncommon route of cancer spread
88
1.Direct extension - This includes fibroblastic proliferation (“ a desmoplastic
response”), vascular proliferation (angiogenesis) and an immune response
2.Haematogenous (via blood vessels) - The blood vessels usually invaded are
the venules and capillaries because they have thinner walls. Most sarcomas
metastasize first via the blood vessels
3.Lymphatic (via lymphatics to lymph nodes and beyond) - The pattern of
spread is dictated by the normal lymphatic drainage of the organ in question.
Most epithelial cancers metastasize first via the lymphatics
4.Transcoelomic (seeding of body cavities) - The commonest examples are
the pleural cavities (for intrathoracic cancers) and the peritoneal cavities
(for intra-abdominal cancers)
5.Perineural (via nerves) - This is an uncommon route of cancer spread
88
CA Colon metastasize to lymph node
89
89
Etiology of cancer
➢Cancer is caused by accumulated damage to genes
➢Such changes may be due to the error during DNA
replication, mitosis and meiosis or the exposure to
a cancer causing substance called carcinogen
➢A carcinogen may be a chemical substances,
bacterial, viral, occupational risk factors, genetic
factors, environmental agents or lifestyle-related
factors
90
➢Cancer is caused by accumulated damage to genes
➢Such changes may be due to the error during DNA
replication, mitosis and meiosis or the exposure to
a cancer causing substance called carcinogen
➢A carcinogen may be a chemical substances,
bacterial, viral, occupational risk factors, genetic
factors, environmental agents or lifestyle-related
factors
90
Bacteria and viruses can cause cancer:
•Helicobacter pylori (H. pylori, which causes
gastritis)
•HBV, HCV (hepatitis viruses that cause hepatitis)
•HPV (human papilloma virus, papilloma virus,
which causes changes eg. cervical cells)
•EBV (Epstein-Barr virus, the herpes virus that
causes inflammation of the throat lymphoid)
91
•Helicobacter pylori (H. pylori, which causes
gastritis)
•HBV, HCV (hepatitis viruses that cause hepatitis)
•HPV (human papilloma virus, papilloma virus,
which causes changes eg. cervical cells)
•EBV (Epstein-Barr virus, the herpes virus that
causes inflammation of the throat lymphoid)
91
Radiation can cause cancer:
•Ionizing radiation (e.g. X-ray radiation, soil
radon)
•Non-ionized radiation (the sun’s ultraviolet
radiation)
92
•Ionizing radiation (e.g. X-ray radiation, soil
radon)
•Non-ionized radiation (the sun’s ultraviolet
radiation)
92
Environmental agents:
•Asbestos fibres
•Tar
•Polynuclear hydrocarbons (e.g. benzopyrene)
•Some metal compounds
•Some plastic chemicals (e.g. Vinyl chloride)
93
•Asbestos fibres
•Tar
•Polynuclear hydrocarbons (e.g. benzopyrene)
•Some metal compounds
•Some plastic chemicals (e.g. Vinyl chloride)
93
Lifestyle-related factors:
•Tobacco
•Alcohol
•UV radiation in sunlight
•Some food-related factors, such as nitrites and
polyaromatic hydrocarbons generated by
barbecuing food)
94
•Tobacco
•Alcohol
•UV radiation in sunlight
•Some food-related factors, such as nitrites and
polyaromatic hydrocarbons generated by
barbecuing food)
94
Some drugs may increase the risk of cancer:
•Certain antineoplastic agents
•Certain hormones
•Medicines that cause immune deficiency
95
•Certain antineoplastic agents
•Certain hormones
•Medicines that cause immune deficiency
95
Molecular basis of cancer
➢ Carcinogenesis is a multistep process
➢ Clonal expansion of a precursor cell
➢ Main classes of genes involved
1)Oncogenes
2)Tumour suppressor genes
3)Genes regulating apoptosis
4)DNA repair genes
96
➢ Carcinogenesis is a multistep process
➢ Clonal expansion of a precursor cell
➢ Main classes of genes involved
1)Oncogenes
2)Tumour suppressor genes
3)Genes regulating apoptosis
4)DNA repair genes
96
Cancer Progression is Multi-stepped
97
97
Oncogenes
•Function as growth factors, receptors, signal
transducers, transcription factors and cell-cycle
components
•Have similar functions as protooncogenes but lack
regulation
•Oncogenes are activated by gene amplification,
activating mutations and chromosomal
rearrangements
98
•Function as growth factors, receptors, signal
transducers, transcription factors and cell-cycle
components
•Have similar functions as protooncogenes but lack
regulation
•Oncogenes are activated by gene amplification,
activating mutations and chromosomal
rearrangements
98
Activation of proto-oncogenes
• Mutation
–H-ras, K-ras, N-ras
–EGFR
• Gene amplification
–Myc
–ErbB2/HER2
• Chromosomal translocations
–Myc
–Bcr/Abl
99
• Mutation
–H-ras, K-ras, N-ras
–EGFR
• Gene amplification
–Myc
–ErbB2/HER2
• Chromosomal translocations
–Myc
–Bcr/Abl
99
Activation of Ras by mutation
Oncogenic H‐Ras mutation in bladder ca:
Glycine Valine
https://media.springernature.com/full/springer-
static/image/art%3A10.1038%2Fs41598-018-30205-
2/MediaObjects/41598_2018_30205_Fig1_HTML.png
100
Oncogenic H‐Ras mutation in bladder ca:
Glycine Valine
https://media.springernature.com/full/springer-
static/image/art%3A10.1038%2Fs41598-018-30205-
2/MediaObjects/41598_2018_30205_Fig1_HTML.png
100
Oncogene activation by gene amplification
•Multiple copies of Myc greater expression
FISH results using a MYC break-apart probe. Representative tumour cell
(indicated by arrow) is showing an increased number of fusion signals
(more than 20), indicative of high-level amplification of the MYC locus.
Source from:
https://www.researchgate.net/publication/284
434185/figure/fig1/AS:614264805015567@
1523463550459/FISH-results-using-a-MYC-
break-apart-probe-Representative-tumor-
cell-indicated-by.png
101
•Multiple copies of Myc greater expression
FISH results using a MYC break-apart probe. Representative tumour cell
(indicated by arrow) is showing an increased number of fusion signals
(more than 20), indicative of high-level amplification of the MYC locus.
Source from:
https://www.researchgate.net/publication/284
434185/figure/fig1/AS:614264805015567@
1523463550459/FISH-results-using-a-MYC-
break-apart-probe-Representative-tumor-
cell-indicated-by.png
101
Chromosomal rearrangement
Genetic instability
➢Place strong promoter in front of an oncogene
➢Formation of novel hybrid proteins
102
Genetic instability
➢Place strong promoter in front of an oncogene
➢Formation of novel hybrid proteins
102
t(8;14)
•Burkitt’s Lymphoma
•Fusion of chromosomes 2,14 or 22 to chromosome 8
•Place Myc under the Ig promote
https://www.researchgate.net/profile/Gustav_Nossal/publication/10
939086/figure/fig1/AS:280315697352724@1443843878327/Recipr
ocal-chromosomal-translocations-in-Burkitts-lymphoma-a-solid-
tumour-of-B.png
103
•Burkitt’s Lymphoma
•Fusion of chromosomes 2,14 or 22 to chromosome 8
•Place Myc under the Ig promote
https://www.researchgate.net/profile/Gustav_Nossal/publication/10
939086/figure/fig1/AS:280315697352724@1443843878327/Recipr
ocal-chromosomal-translocations-in-Burkitts-lymphoma-a-solid-
tumour-of-B.png
103
Bcr-Abl
•Chronic myelogenous leukemia (CML)
•Abl – oncogene located on chromosome 9
•Breakpoint cluster region – chromosome 22
•Translocation t(9;22)
•Result: CA version of Abl
Source from:
https://www.hybrigenics.com/contents/inecalcitol-
2/chronic-myeloid-leukemia
104
•Chronic myelogenous leukemia (CML)
•Abl – oncogene located on chromosome 9
•Breakpoint cluster region – chromosome 22
•Translocation t(9;22)
•Result: CA version of Abl
Source from:
https://www.hybrigenics.com/contents/inecalcitol-
2/chronic-myeloid-leukemia
104
Tumour suppressor gene
•Tumour suppressor genes are genes that regulate the
growth of cells
•When these genes are functioning properly, they can
prevent and inhibit the growth of tumours
•When tumour suppressor genes are altered or
inactivated (due to a mutation), they lose the ability
to make a protein that controls cell growth
105
•Tumour suppressor genes are genes that regulate the
growth of cells
•When these genes are functioning properly, they can
prevent and inhibit the growth of tumours
•When tumour suppressor genes are altered or
inactivated (due to a mutation), they lose the ability
to make a protein that controls cell growth
105
Categories of tumour suppressor genes
Caretaker genes
– Maintain the stability of the genome by repairing DNA
damage
Gatekeeper genes
– Inhibit the proliferation or inducing apoptosis of cell with
damaged DNA
Landscaper genes
– encode products that help create environments that control
unregulated proliferation
106
Caretaker genes
– Maintain the stability of the genome by repairing DNA
damage
Gatekeeper genes
– Inhibit the proliferation or inducing apoptosis of cell with
damaged DNA
Landscaper genes
– encode products that help create environments that control
unregulated proliferation
106
Tumor Suppressor Gene Category Function
Rb Gatekeeper/ LandscaperInhibition of cell cycle
p53 Gatekeeper/ Caretaker
DNA repair; cell cycle and apoptosis
regulator
BRCA1 Caretaker DNA repair
PTEN Landscaper
Regulation of extracellular matrix proteins,
cellular surface markers, cellular adhesion
molecules and growth factors
Various Tumour Suppressor Genes and their roles
107
Rb Gatekeeper/ LandscaperInhibition of cell cycle
p53 Gatekeeper/ Caretaker
DNA repair; cell cycle and apoptosis
regulator
BRCA1 Caretaker DNA repair
PTEN Landscaper
Regulation of extracellular matrix proteins,
cellular surface markers, cellular adhesion
molecules and growth factors
Various Tumour Suppressor Genes and their roles
107
Retinoblastoma (Rb) gene
▪First phenotypic cancer suppressor gene to be
discovered
▪Responsible for retinoblastoma, a malignant tumour
of retina, a rare childhood tumour
▪60% are sporadic, remaining ones are familial
▪The Rb protein prevents cells from entering S phase
of the cell cycle by binding to a transcription factor
called E2F
108
▪First phenotypic cancer suppressor gene to be
discovered
▪Responsible for retinoblastoma, a malignant tumour
of retina, a rare childhood tumour
▪60% are sporadic, remaining ones are familial
▪The Rb protein prevents cells from entering S phase
of the cell cycle by binding to a transcription factor
called E2F
108
p53 Gene
•Situated at the short arm of the chromosome 17
•More than half of all human cancers do harbour p53
mutations and have no functioning p53 protein
•It can activate DNA repair proteins when DNA has sustained
damage
•It can arrest growth by holding the cell cycle at the G1/S
regulation point on DNA damage recognition
•It can initiate apoptosis, the programmed cell death, if DNA
damage proves to be irreparable
109
•Situated at the short arm of the chromosome 17
•More than half of all human cancers do harbour p53
mutations and have no functioning p53 protein
•It can activate DNA repair proteins when DNA has sustained
damage
•It can arrest growth by holding the cell cycle at the G1/S
regulation point on DNA damage recognition
•It can initiate apoptosis, the programmed cell death, if DNA
damage proves to be irreparable
109
BRCA1 gene
Breast (BR) cancer(CA) susceptibility genes, also
incriminated in some ovarian cancers
Involved in G1 check point
Block entry of cell into S phase, particularly by
inducing cyclin-dependent kinase inhibitor p21 which is
a regulator of cell cycle progression at G1 and S phase
Promote DNA repair by binding to RAD51
110
Breast (BR) cancer(CA) susceptibility genes, also
incriminated in some ovarian cancers
Involved in G1 check point
Block entry of cell into S phase, particularly by
inducing cyclin-dependent kinase inhibitor p21 which is
a regulator of cell cycle progression at G1 and S phase
Promote DNA repair by binding to RAD51
110
PTEN Gene
•Mutations of PTEN are found in the development of many cancers
•PTEN gene encodes Phosphatase and Tensin homolog protein
•This phosphatase is involved in the regulation of the cell cycle,
preventing cells from growing and dividing too rapidly
•PTEN specifically catalyzes the dephosphorylation of the 3`
phosphate of the inositol ring in PIP3, resulting in the biphosphate
product PIP2
•This dephosphorylation is important because it results in inhibition
of the Akt signaling pathway, which plays an important role in
regulating cellular behaviours such as cell growth, survival and
migration 111
•Mutations of PTEN are found in the development of many cancers
•PTEN gene encodes Phosphatase and Tensin homolog protein
•This phosphatase is involved in the regulation of the cell cycle,
preventing cells from growing and dividing too rapidly
•PTEN specifically catalyzes the dephosphorylation of the 3`
phosphate of the inositol ring in PIP3, resulting in the biphosphate
product PIP2
•This dephosphorylation is important because it results in inhibition
of the Akt signaling pathway, which plays an important role in
regulating cellular behaviours such as cell growth, survival and
migration 111
Cancer Diagnosis
➢History & clinical examination
➢Radiographic techniques
i-X ray
ii-CT scan
iii-MRI
iv-Ultrasound
➢Laboratory tests : general & specialized
112
➢History & clinical examination
➢Radiographic techniques
i-X ray
ii-CT scan
iii-MRI
iv-Ultrasound
➢Laboratory tests : general & specialized
112
Laboratory tests
A. Morphological Methods
1.Cytological methods : Study of individual cells
-Smear
-FNA, Brush, Fluid tapping…etc
-False(+ve), False (-ve)
-A negative report does not exclude malignancy
-Suggest Repeat
-Advise biopsy, even if (+ve)
113
A. Morphological Methods
1.Cytological methods : Study of individual cells
-Smear
-FNA, Brush, Fluid tapping…etc
-False(+ve), False (-ve)
-A negative report does not exclude malignancy
-Suggest Repeat
-Advise biopsy, even if (+ve)
113
2. Histological methods : Study of architecture of cells
-Biopsy of tissue: Needle & core biopsy,
Endoscopic Biopsy or open surgical biopsy
-Frozen Section
-Paraffin Section
-H&E, Special stains
114
-Biopsy of tissue: Needle & core biopsy,
Endoscopic Biopsy or open surgical biopsy
-Frozen Section
-Paraffin Section
-H&E, Special stains
114
3. Immunohistochemical methods :
-Staining by use of monoclonal antibody directed
against various components in cell may help in
diagnosis of undifferentiated cancers or help in
identifying source of a metastatic tumour
Examples
Cytokeratin Carcinoma
Leukocyte common antigen Lymphoma
S100 Neural tissue, melanocytic lesions
Desmin, Vimentin Sarcoma
115
-Staining by use of monoclonal antibody directed
against various components in cell may help in
diagnosis of undifferentiated cancers or help in
identifying source of a metastatic tumour
Examples
Cytokeratin Carcinoma
Leukocyte common antigen Lymphoma
S100 Neural tissue, melanocytic lesions
Desmin, Vimentin Sarcoma
115
4. Electron Microscopy:
Electron Microscopy (EM) is a powerful diagnostic
tool used to assist in the diagnosis of Kidney Disease,
Muscle Disorders, Neurological Disorders, Ciliary
Dysfunction, Viral Gastroenteritis, Viral Infections or
any disorder that may benefit from the analysis of the
fine structures of a biopsy
116
Electron Microscopy (EM) is a powerful diagnostic
tool used to assist in the diagnosis of Kidney Disease,
Muscle Disorders, Neurological Disorders, Ciliary
Dysfunction, Viral Gastroenteritis, Viral Infections or
any disorder that may benefit from the analysis of the
fine structures of a biopsy
116
5. Biochemical Assays :
-Used to identify tumourassociated enzymes,
hormones, antigens … etc
-These are useful as markers for diagnosis of a
tumouror for assessing the progress of a known
tumour
117
-Used to identify tumourassociated enzymes,
hormones, antigens … etc
-These are useful as markers for diagnosis of a
tumouror for assessing the progress of a known
tumour
117
Tumour markers represent biochemical indicators
of the presence of a tumour
•Their uses are to :
➢Confirm diagnosis
➢Determine the response to treatment
➢Detect early relapse
•Present in serum or urine
•Many are present in normal & tumourtissue so they
are not very specific but their level is important
118
of the presence of a tumour
•Their uses are to :
➢Confirm diagnosis
➢Determine the response to treatment
➢Detect early relapse
•Present in serum or urine
•Many are present in normal & tumourtissue so they
are not very specific but their level is important
118
Types of Tumour Markers
1)Hormones
•Human Chorionic Gonadotrophic Hormone (HCG)
Elevated levels are seen in Pregnancy
&Gestational Trophoblastic Disease
•Calcitoninuseful in diagnosis of some thyroid
carcinomas
119
1)Hormones
•Human Chorionic Gonadotrophic Hormone (HCG)
Elevated levels are seen in Pregnancy
&Gestational Trophoblastic Disease
•Calcitoninuseful in diagnosis of some thyroid
carcinomas
119
2) OncofetalAntigens
•Carcinoembryonic Antigen (CEA):
in fetal tissue & some malignancies
–Colorectal CA & pancreatic CA
•Alpha Fetoprotein (AFP):
Cirrhosis : Elevated
Hepatocellular carcinoma : Extremely high
120
•Carcinoembryonic Antigen (CEA):
in fetal tissue & some malignancies
–Colorectal CA & pancreatic CA
•Alpha Fetoprotein (AFP):
Cirrhosis : Elevated
Hepatocellular carcinoma : Extremely high
120
3) Isoenzymes
•Prostatic Acid Phosphatase (PAP)
levels seen in metastatic prostatic CA
Useful in : * Staging prostatic CA
* Assessment of prognosis
* Response to therapy
121
•Prostatic Acid Phosphatase (PAP)
levels seen in metastatic prostatic CA
Useful in : * Staging prostatic CA
* Assessment of prognosis
* Response to therapy
121
4) Specific Proteins
•Immunoglobulins secreted in Multiple Myeloma
•Prostate -specific antigen (PSA):
Present in epithelium of prostatic ducts
* prostatic hyperplasia &
* in prostatic CA
* Level correlates with stage of CA
122
•Immunoglobulins secreted in Multiple Myeloma
•Prostate -specific antigen (PSA):
Present in epithelium of prostatic ducts
* prostatic hyperplasia &
* in prostatic CA
* Level correlates with stage of CA
122
5) Oncoprotein
Mucin 1 (MUC1) is a glycoprotein that has been
demonstrated to be involved in the metastasis and
invasion of multiple tumor types in breast CA
•CA-125 is a protein that is elevated in blood of
50% of ovarian cancer patients
•CA 19-9 (cancer antigen 19-9) in pancreatic &
hepatobiliary CA
123
Mucin 1 (MUC1) is a glycoprotein that has been
demonstrated to be involved in the metastasis and
invasion of multiple tumor types in breast CA
•CA-125 is a protein that is elevated in blood of
50% of ovarian cancer patients
•CA 19-9 (cancer antigen 19-9) in pancreatic &
hepatobiliary CA
123
C. Molecular Diagnosis :
Methods used:
-PCR (Polymerase Chain Reaction)
-FISH (Fluorescent In Situ Hybridization)
To detect gene rearrangement, translocations, amplifications etc
Examples
-BCR-ABL1 confirms the diagnosis of CML
-HER-2 in breast carcinoma
-N-MYC in neuroblastoma
-Detection of genes of hereditary cancer
e.gBRCA-1 in CA breast
124
Methods used:
-PCR (Polymerase Chain Reaction)
-FISH (Fluorescent In Situ Hybridization)
To detect gene rearrangement, translocations, amplifications etc
Examples
-BCR-ABL1 confirms the diagnosis of CML
-HER-2 in breast carcinoma
-N-MYC in neuroblastoma
-Detection of genes of hereditary cancer
e.gBRCA-1 in CA breast
124
Grading
•Histological indication of the degree of malignancy
•Based on morphology, differentiation
•Degree of histological invasion and vascularization of tumour,
structural features
•I– IV
•Degree of malignancy often given as description
Staging
•Estimate the degree of spread of tumour, based on size
and metastatic spread
•Dukes’ for colorectal tumours
•FIGO for ovarian malignancy
•TNM (Tumour-Node-Metastases) system
•AJCC Cancer Staging
125
Grading and staging of malignancy
•Histological indication of the degree of malignancy
•Based on morphology, differentiation
•Degree of histological invasion and vascularization of tumour,
structural features
•I– IV
•Degree of malignancy often given as description
Staging
•Estimate the degree of spread of tumour, based on size
and metastatic spread
•Dukes’ for colorectal tumours
•FIGO for ovarian malignancy
•TNM (Tumour-Node-Metastases) system
•AJCC Cancer Staging
125
Grading and staging of malignancy
Staging, clinical, radiographic, surgical examination of extent
and spread treatment, prognosis
The TNM Classification of Malignant Tumours (TNM)
TNM was developed and is maintained by the Union for
International Cancer Control (UICC)
T-primary Tumour, N-regional Lymph Node involvement, M- Metastasis
T1-4 = Tumour size and the degree of spread into nearby tissues
N0-3 = Lymph Node involvement
M0-1 = Metastasis
126
and spread treatment, prognosis
The TNM Classification of Malignant Tumours (TNM)
TNM was developed and is maintained by the Union for
International Cancer Control (UICC)
T-primary Tumour, N-regional Lymph Node involvement, M- Metastasis
T1-4 = Tumour size and the degree of spread into nearby tissues
N0-3 = Lymph Node involvement
M0-1 = Metastasis
126
American Joint Committee on Cancer (AJCC):
There are five stages of cancer:
Stage 0 (carcinoma in situ), Stage 1, Stage 2, Stage 3 and Stage 4
Lower stages indicate that the disease is more localized, or
contained, whereas higher stages refer to cancers that have spread
into other areas of the body
Stages 0 - 4 = size of primary lesion and presence of nodal spread
and metastasis
127
There are five stages of cancer:
Stage 0 (carcinoma in situ), Stage 1, Stage 2, Stage 3 and Stage 4
Lower stages indicate that the disease is more localized, or
contained, whereas higher stages refer to cancers that have spread
into other areas of the body
Stages 0 - 4 = size of primary lesion and presence of nodal spread
and metastasis
127
Types of cancer treatments
• Surgery
• Radiation therapy
• Chemotherapy
• Hormone therapy
• Immunotherapy
• Targeted therapy
128
• Surgery
• Radiation therapy
• Chemotherapy
• Hormone therapy
• Immunotherapy
• Targeted therapy
128
Surgery is common treatment option for many types of
cancers
A surgeon will use it to treat solid tumour cancers, by
removing the cancer and surrounding tissue from the body
It is not used for leukaemia (a type of blood cancer) or for
cancers that have spread
Surgery
129
cancers
A surgeon will use it to treat solid tumour cancers, by
removing the cancer and surrounding tissue from the body
It is not used for leukaemia (a type of blood cancer) or for
cancers that have spread
Surgery
129
Radiation therapy uses radiation to safely treat and manage
cancer by destroying cancer cells, reducing the growth and
spread of cancer or relieving cancer symptoms
Radiation therapy attacks cancer cells and limits damage to
healthy cells, as cancer cells are more sensitive to radiation
When small doses of radiation are provided over a period of days
and weeks, normal cells can recover from the radiation, but
cancer cells cannot
Radiation is similar to having an x-ray and is targeted to the part
of the body being treated
Radiation therapy
130
cancer by destroying cancer cells, reducing the growth and
spread of cancer or relieving cancer symptoms
Radiation therapy attacks cancer cells and limits damage to
healthy cells, as cancer cells are more sensitive to radiation
When small doses of radiation are provided over a period of days
and weeks, normal cells can recover from the radiation, but
cancer cells cannot
Radiation is similar to having an x-ray and is targeted to the part
of the body being treated
Radiation therapy
130
Chemotherapy is the use of drugs that destroy cancer cells. Chemotherapy
kills all rapidly-diving cancer cells but also attacks the body’s fast-
growing healthy cells (such as hair follicles or cells in the mouth). There
are many different kinds of chemotherapy medicines that may be used in
different ways
They include:
• Oral chemotherapy – which can be taken as pills or liquid
•Intravenous (IV) chemotherapy – where chemotherapy is slowly
inserted through a needle into a vein
• Topical chemotherapy – applied as a cream to the cancerous area
•Chemotherapy through injection – which is injected directly into the
area affected by cancer
Chemotherapy
131
kills all rapidly-diving cancer cells but also attacks the body’s fast-
growing healthy cells (such as hair follicles or cells in the mouth). There
are many different kinds of chemotherapy medicines that may be used in
different ways
They include:
• Oral chemotherapy – which can be taken as pills or liquid
•Intravenous (IV) chemotherapy – where chemotherapy is slowly
inserted through a needle into a vein
• Topical chemotherapy – applied as a cream to the cancerous area
•Chemotherapy through injection – which is injected directly into the
area affected by cancer
Chemotherapy
131
Some cancers ‘feed’ on male or female hormones to grow
Examples would be some types of breast cancer (hormone
receptor-positive breast cancers) and the majority of prostate
cancers
Hormone therapy (Endocrine therapy) describes the use of
drugs (given in the form of oral tablets, subcutaneous
injections or intramuscular injections) to deprive the cancer
cells of the specific hormones that feed them
The cancerous tumour should gradually shrink over time
Hormone therapy
132
Examples would be some types of breast cancer (hormone
receptor-positive breast cancers) and the majority of prostate
cancers
Hormone therapy (Endocrine therapy) describes the use of
drugs (given in the form of oral tablets, subcutaneous
injections or intramuscular injections) to deprive the cancer
cells of the specific hormones that feed them
The cancerous tumour should gradually shrink over time
Hormone therapy
132
Immunotherapy
Immunotherapy uses your immune system to
slow the growth of cancer cells and destroy
existing cancer cells
133
Immunotherapy uses your immune system to
slow the growth of cancer cells and destroy
existing cancer cells
133
Targeted therapy only targets and attacks cancer cells and
block the abnormal growth of those cells which cause the
cancer
Herceptin® may block the action of an abnormal protein,
HER2 that stimulates the growth of breast cancer cells
Gefitinib has become standard therapy for patients with non-
small cell lung cancer (NSCLC) with an activating epidermal
growth factor receptor (EGFR) mutation
Targeted therapy
134
block the abnormal growth of those cells which cause the
cancer
Herceptin® may block the action of an abnormal protein,
HER2 that stimulates the growth of breast cancer cells
Gefitinib has become standard therapy for patients with non-
small cell lung cancer (NSCLC) with an activating epidermal
growth factor receptor (EGFR) mutation
Targeted therapy
134
Histology of Tumours
135
135
136
Malignant
Criteria
Cytologic Features
General Variation in nuclear or cell size (pleomorphism)
Lack of differentiation
Nuclear Abnormal mitoses
Variable nuclear size and shape
Increased nuclear/cytoplasmic ratio--N/C ratio
Prominent nucleoli
Large irregularly shaped nucleoli
Increased nuclear DNA content with subsequent dark staining on H&E
slides (hyperchromatism)
Coarse and irregular chromatin pattern
Irregular prominence of nuclear margin
StructuralCarcinoma--round to oval cells arranged in sheets of acinar patterns
Sarcoma--spindle shaped cells
Cytologic criteria of malignancy
Malignant
Criteria
Cytologic Features
General Variation in nuclear or cell size (pleomorphism)
Lack of differentiation
Nuclear Abnormal mitoses
Variable nuclear size and shape
Increased nuclear/cytoplasmic ratio--N/C ratio
Prominent nucleoli
Large irregularly shaped nucleoli
Increased nuclear DNA content with subsequent dark staining on H&E
slides (hyperchromatism)
Coarse and irregular chromatin pattern
Irregular prominence of nuclear margin
StructuralCarcinoma--round to oval cells arranged in sheets of acinar patterns
Sarcoma--spindle shaped cells
Cytologic criteria of malignancy
Colorectal Carcinoma
137
137
Colorectal Carcinoma
138
138
Ca Colon histology
139
139
Breast Fibroadenoma histology
140
140
Ductal Carcinoma In Situ (DCIS)
141
141
Invasive lobular Carcinoma
142
142
Invasive Ductal Carcinoma
143
143
Lung Adenocarcinoma - Papillary subtype
144
144
Lung Adenocarcinoma
145
145
Lung small cell carcinoma
146
146
Adenosquamous Carcinoma of Lung
147
147
Adenosquamous Carcinoma of Lung (High magnification)
148
148
Normal Cervix histology
149
149
Ca Cervix histology
150
150
Oesophagus squamous cell CA histology
151
151
Astrocytoma histology
152
152
Ca Prostate histology
153
153
Ca Stomach histology
154
154
Ca Endometrium histology
155
155
Germ Cell tumour histology
156
156
Fibrosarcoma histology
157
157
Nodular hyperplasia histology
158
158
Thyroid Papillary Ca histology
159
159
Thyroid Papillary Ca histology
160
160
Osteosarcoma histology
161
161
Thyroid Papillary Ca metastasized lymph node
162
162
Transitional Cell Carcinoma
163
163
Adrenal cell tumour histology
164
164
Hepatocellular Carcinoma histology
165
165
Metastatic Carcinoma of Liver histology
166
166
Metastatic Adenocacinoma of Liver histology
167
167
Fibroma histology
168
168
Fibrosarcoma histology
169
169
Leiomyoma histology
170
170
Leiomyosarcoma histology
171
171
Lipoma histology
172
172
Liposarcoma histology
173
173
Melanoma histology
174
174
Skin Papilloma Histology
175
175
Squamous cell CA histology
176
176
Reference websites:
1.Proto-oncogenes to Oncogenes to Cancer
2.Mechanisms of Oncogene Activation
3.Oncoviruses: An overview of oncogenic and oncolytic viruses
177
1.Proto-oncogenes to Oncogenes to Cancer
2.Mechanisms of Oncogene Activation
3.Oncoviruses: An overview of oncogenic and oncolytic viruses
177
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