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Neoplasia
.
Neoplasia
Upon completion of these lectures, the student should:
 Define a neoplasm. Contrast neoplastic growth with
hyperplasia, metaplasia, and dysplasia.
 Know the basic principles of the nomenclature of benign and
malignant processes.
 Define and use in the proper context:
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Adenoma.
Papilloma.
Polyp.
Cystadenoma.
Carcinoma.
Adenocarcinoma.
Sarcoma.
Teratoma.
Blastoma.
Hamartoma.
Neoplasia
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Cancer is one of the leading causes of death
worldwide.
Emotional and physical suffering by the
patient.
Different mortality rate …..
Some are curable
 Others are fatal

Neoplasia
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Neoplasia = new growth
Neoplasm = tumor
Tumor = swelling
The study of tumors = Oncology

Oncos = tumor + ology = study of
Neoplasia
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Definition:
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is an abnormal mass of tissue,
the growth of which is uncoordinated with that of
normal tissues,
and that persists in the same excessive manner after the
cessation of the stimulus which evoked the change“
With the loss of responsiveness to normal growth
controls
Different from hyperplasia, metaplasia and dysplasia.
Neoplasia

Classification
Benign
 malignant

Neoplasia
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Benign tumors :
Will remain localized
 Cannot spread to distant sites
 Generally can be locally excised
 Patient generally survives

Neoplasia
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Malignant neoplasms:
Can invade and destroy adjacent structure
 Can spread to distant sites
 Cause death (if not treated )

Neoplasia
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All tumors have two basic components:
 Parechyma: made up of neoplastic cells
 Stroma: made up of non-neoplastic, hostderived connective tissue and blood vessels
The parenchyma:
Determines the biological
behavior of the tumor
From which the tumor
derives its name
The stroma:
Carries the blood supply
Provides support for the
growth of the
parenchyma
Neoplasia

Nomenclature

Benign tumors:
prefix + suffix
 Type of cell + (-oma)

Neoplasia
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Examples:
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Benign tumor arising in fibrous tissue:
Fibro + oma = Fibroma
Benign tumor arising in fatty tissue:
Lipo + oma = lipoma
Neoplasia
Benign tumor arising in cartilage
chondro + oma = chondroma
 Benign tumor arising in smooth muscle
Leiomyo + oma = leiomyoma
 Benign tumor arising in skeletal muscle
Rhabdomyo + oma = rhabdomyoma

Neoplasia
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epithelial benign tumors are classified on the
basis of :
The cell of origin
 Microscopic pattern
 Macroscopic pattern

Neoplasia

Adenoma : benign epithelial neoplasms producing
gland pattern….OR … derived from glands but not
necessarily exhibiting gland pattern
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Papilloma : benign epithelial neoplasms growing
on any surface that produce microscopic or
macroscopic finger-like pattern
Adenoma
Papilloma
Neoplasia

Polyp : a mass that projects above a mucosal
surface to form a macroscopically visible
structure.
e.g. - colonic polyp
- nasal polyp
Polyp
Neoplasia

Examples :
Respiratory airways: Bronchial adenoma
 Renal epithelium: Renal tubular adenoma
 Liver cell : Liver cell adenoma
 Squamous epithelium: squamous papilloma

Neoplasia
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Malignant tumors arising from epithelial origin :
CARCINOMA
Squamous cell carcinoma
 Renal cell adenocarcinoma
 cholangiocarcinoma

Carcinomas arising from any epithelium of the body that exhibit
squamous differentiation are termed squamous cell carcinoma.
Neoplasia
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Malignant tumors:
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Malignant tumor arising in mesenchymal tissue :
SARCOMA
From fibrous tissue: Fibrosarcoma
 From bone : Osteosarcoma
 From cartilage : chondrosarcoma
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Osteosarcoma
Nomenclature
other descriptive terms may be added such as:
Papillary Cystadenocarcinoma of the Ovary
Neoplasia
Exceptions
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Melanoma ( skin )
Mesothelioma (mesothelium )
Seminoma ( testis )
Lymphoma ( lymphoid tissue )
See table 6 – 1 ( Robbin’s )
Nomenclature of tumors
Tissue of Origin
Benign
Malignant
Composed of One parenchymal
cell Type
Connective tissue and derivatives
Endothelial and related tissues
Blood vessels
Lymph vessels
Synovium
Mesothelium
Brain coverings
Fibroma
Lipoma
Chondroma
Osteoma
Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteogenic sarcoma
Hemangioma
Lymphangioma
Angiosarcoma
Lymphangiosarcoma
Synovial sarcoma
Mesothelioma
Invasive meningioma
Meningioma
Nomenclature of tumors
Tissue of Origin
Blood cells and related cells
Hematopoietic cells
Lymphoid tissue
Muscle
Smooth
Striated
Benign
Malignant
Leukemias
Lymphomas
Leiomyoma
Rhabdomyoma
Leiomyosarcoma
Rhabdomyosarcoma
Epihelial tumors
Stratified squamous
Basal cells of skin or adnexa
Epithelial lining
Glands or ducts
Squamous cell papilloma
Adenoma
Papilloma
Cystadenoma
Squamous cell carcinoma
Nomenclature of tumors
Tissue of Origin
Epihelial tumors
Stratified squamous
Basal cells of skin or adnexa
Epithelial lining
Glands or ducts
Benign
Squamous cell papilloma
Adenoma
Papilloma
Cystadenoma
Malignant
Squamous cell or epidermoid
carcinoma Basal cell carcinoma
Adenocarcinoma
Papillary carcinoma
Cystadenocarcinoma
Nomenclature of tumors
Tissue of Origin
Respiratory passages
Neuroectoderm
Renal epithelium
Liver cells
Urinary tract epithelium (transitional)
Placental epithelium (trophoblast)
Testicular epithelium (germ cells)
Tumours of melanocytes
Benign
Bronchial adenoma
Nevus
Renal tubular adenoma
Liver cell adenoma
Transitional cell papilloma
Hydatidiform mole
Nevus
Malignant
Bronchogenic carcinoma
Bronchial adenoma (carcinoid)
Malignant melanoma
Renal cell carcinoma
Hepatocellular carcinoma
Transitional cell carcinoma
Choriocarcinoma
Seminoma
Embryonal carcinoma
Malignant melanoma
Nomenclature of tumors
Tissue of Origin
Benign
Malignant
More Than One Neoplastic Cell
Type- Mixed Tumors, Usually
Derived From One Germ Layer
Salivary glands
Pleomorphic adenoma (mixed Malignant mixed tumor
tumor of salivary origin)
salivary gland origin
Breast
Fibroadenoma
Malignant cystosarcoma phyllodes
of
Nomenclature of tumors
Tissue of Origin
Benign
Malignant
More Than One Neoplastic
Cell Type Derived From
More Than One Germ
Layer- Teratogenous
Totipotential cells in gonads Mature
or in embryonic rests
cyst
teratoma,
dermoid Immature
teratocarcinoma
teratoma,
Neoplasia
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Based on the biological behavior :
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Benign and malignant
Based on the cell of origin :
One neoplastic cell type : lipoma, adenocarcinoma
 More than one neoplastic cell type : fibroadenoma
 More than one neoplastic cell type derived from
more than one germ-cell layer: teratoma
 Derived from embryonic tissue: blastoma
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(could be benign e.g. osteoblastoma, or malignant e.g.
neuroblastoma)
Lipoma
Fibroadenoma
Teratoma
Neoplasia
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Teratoma:
Teratoma contains recognizable mature or
immature cells or tissues representative of more
than one germ-cell layer and some times all
three.
 Teratomas originate from totipotential cells
such as those normally present in the ovary and
testis.
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Neoplasia
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Such cells have the capacity to differentiate into
any of the cell types found in the adult body. So
they may give rise to neoplasms that mimic bone,
epithelium, muscle, fat, nerve and other tissues.
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Most common sites are: ovary & testis
Neoplasia
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If all the components parts are well differentiated,
it is a benign (mature) teratoma.
If less well differentiated, it is an immature
(malignant) teratoma.
Neoplasia nomenclature
- historic eponyms – “first described by…”
Hodgkin’s
disease
Malignant lymphoma (HL) of B Ly cell origin
Burkitt tumor
NHL – B Ly cell in children (jaw and GIT)
Ewing tumor
Bone tumor
Grawitz tumor
Kidney tumor - clear cell adenocarcinoma
Kaposi sarcoma
Malignant tumor derived from vascular epithelium
(AIDS)
Brenner tumor
Ovarian tumor derived from Brenner cells
Askin tumor
Malignant chest wall tumor
Merkel tumor
Skin tumor derived from Merkel cell
Hamartoma: a mass composed of cells native
.
to the organ
e.g. pulmonary hamartoma.
Choristoma: a mass composed of normal cells
in a wrong location
e.g. pancreatic choristoma in liver or stomach.
 Malformation and not neoplasm.
Pulmonary Hamartoma
Pancreatic choristoma in gall bladder
Neoplasia
Hamartoma and Choristoma
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They are distinguished from neoplasms by the fact
that they do not exhibit continued growth. they
are group of tumor-like tissue masses which may
be confused with neoplasms
Classification according to biological behavior
benign
borderline
malignant
Neoplasia
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Dysplasia :
Definiton: a loss in the uniformity of the individual
cells and a loss in their architectural orientation.
 Non-neoplastic
 Occurs mainly in the epithelia
 Dysplastic cells shows a degree of : pleomorphism,
hyperchromasia,increased mitosis and loss of
polarity.
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Neoplasia
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Dysplasia does not mean cancer
Dyplasia does not necessarily progress to cancer
Dysplasia may be reversible
If dysplastic changes involve the entire thickness
of the epithelium it is called :
CARCINOMA IN-SITU
Neoplasia
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Carcinoma in-situ
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Definition: an intraepithelial malignancy in which
malignant cells involve the entire thickness of the
epithelium without penetration of the basement
membrane.
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Applicable only to epithelial neoplasms.
Dysplasia Features:
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Increased rate of
multiplication.
Disordered
maturation.
• Nuclear abnormality
– Increased N/C ratio
– Irregular nuclear membrane
– Increased chromatin content
• Cytoplasmic abnormalities
Dysplasia
Uterine cervix
Sever Dysplasia
Mild Dysplasia
Dysplasia (Papanicolaou test (pap
smear)
Dysplasia
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Clinical significance:
It is a premalignant condition.
 The risk of invasive cancer varies with:
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grade of dysplasia (mild, moderate, sever)
duration of dysplasia
site of dysplasia
Dysplasia
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Differences between dysplasia and cancer.
lack of invasiveness.
Reversibility
Carcinoma in situ
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A true neoplasm with all of the features of
malignant neoplasm except invasiveness
Displays the cytological features of malignancy
without invasion of the basement membrane.
CHANGES IN UTERINE
CERVIX
Squamous cell Carcinoma
Uterine Cervix
Dysplasia
Rate of neoplastic growth
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How long does it take to produce a clinically
overt tumor mass?
original transformed cell ~1ng mass
 30 doublings (2^30) yields 10^9 cells, 1 g
 10 more doublings yields 10^12 cells, 1kg
 For more than ¾ total life span, tumor is not palpable
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How long does 30 to 40 doublings take?
doubling time of tumor cells
 growth fraction of tumor cells
 rate at which tumor cells are shed or die
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Tumor proliferation
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Proportion of cells in growth fraction declines as tumor
grows
High growth fraction tumors progress rapidly
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Low growth fraction tumors progress slowly
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Leukemias, lymphomas, small-cell carcinoma
cell production 10% greater than loss
Colon, breast adenocarcinoma
Doubling time of clinically detectable colon or lung
tumors averages about 2 to 3 months
Causes infiltration, invasion, and destruction of the
surrounding tissue
Metastasis
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Benign neoplasms do not metastasize
All malignant tumors can metastasize
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Except gliomas and basal cell carcinomas of the skin
Metastatic spread strongly reduces the possibility
of cure
Overt metastases upon diagnosis in 30% cases,
with occult metastases in 20% more
Pathways for metastases
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Direct seeding of body cavities or surfaces
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Lymphatic spread
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Most frequently peritoneal cavity by ovarian cancer
common for dissemination of carcinomas
sarcomas may also use this route
pattern of lymph node involvement follows the natural routes
of lymphatic drainage
biopsy of sentinel nodes is often used to assess metastasis
Hematogenous spread
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typical of sarcomas but is also seen with carcinomas
blood-borne cells follow the venous flow draining the site of
the neoplasm
liver and lungs are most frequently involved
Location preference
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Despite pathway of venous or lymphatic flow,
some metastatic sites are frequently associated
with some primary tumors:
breast carcinoma spreads to bone
 bronchogenic carcinomas tend to involve the
adrenals and the brain
 neuroblastomas spread to the liver and bones
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Despite the large percentage of blood flow,
skeletal muscles and spleen are rarely the site of
secondary deposits
Cancer incidence, risk
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US risk of cancer death 1 in 5
1.5 m new cancer cases and 0.5 m deaths from
cancer in 2008
Cancers of the lung, female breast, prostate, and
colon/rectum constitute more than 50% of
cancer diagnoses and deaths
2008 statistics
Pakistan
 In Pakistan data from various cancer registries during
1995-1997 showed that the most common types of
cancer in males were lung, oral cavity, urinary bladder
and larynx; while in female’s, breast, oral cavity and
ovary cancers were the most common malignancies.
 Data from 1998-2002 showed an increased incidence
for lung, larynx and urinary bladder in males; and
breast, oesophagus and cervix in females.
 Data from 2004 - 2008 showed that breast and
oropharyngeal cancers were the most common cancers
(16.1% and 9.9% respectively) which have significantly
higher incidence as compared to all other types of
cancers
Epidemiology of cancer
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Incidence varies with age, race, geographic factors, and genetic
backgrounds
Cancers are most common at the two extremes of age
Geographic variation results mostly from different
environmental exposures
Most cancers are sporadic, but some are familial
Hereditary predisposition may be autosomal dominant or
autosomal recessive
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Dominant are usually linked to inheritance of a germ-line mutation of
cancer suppressor genes
Recessive are typically associated with inherited defects in DNA repair
Familial cancers tend to be bilateral and arise earlier in life than
sporadic cancers
.
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The mean age of the patients was 51 years in
males and 50 years in females in 1995-1997 data,
which changed to 49 and 53 years respectively in
1998-2002 data. The data from 2004-2008
showed an overall drop in the mean age to 45
years for all patients.
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Tobacco related cancers
Tobacco is the main independent risk factor for
the development of cancer, especially those of
the head and neck area and upper aero digestive
tract.
In Pakistan, about 50% tumors in males and
25% those of in females are associated with
consumption of tobacco products.
These include seven of the top ten cancers in
males (lung, oral cavity, larynx, urinary bladder,
pharynx, esophagus and prostate) and two of the
top ten cancers in females (oral cavity and
esophagus).
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. about 37.4% were
Of all the cancer patients
users of Smokeless Tobacco (ST) while 23.6%
were tobacco smokers.
Over all oropharyngeal cancers have been
shown to be the second most common
malignancies throughout Pakistan and have
significantly higher incidence as compared to
other countries from WHO’s Eastern
Mediterranean Region
.
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Majority of the patients (65%) at the time of
diagnosis were in stage III or IV while about
40% were at stage I or II, with a small
percentage with no histological confirmation.
Data from 2004-2008 showed that 53% were
male patients.
Pashtun represention was more (56%) followed
by Baluchis and Punjabis
Molecular basis of cancer
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Nonlethal genetic damage
Tumors are monoclonal
Four classes of normal regulatory genes are principal
targets of genetic damage
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growth-promoting proto-oncogenes
growth-inhibiting tumor suppressor genes
genes that regulate programmed cell death (apoptosis)
genes involved in DNA repair
Carcinogenesis is a multistep process
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accumulation of multiple mutations required
monoclonally initiated tumors evolve
Tumor progression
Steps of normal proliferation
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Growth factor binds to its specific receptor
Transient, limited activation of the growth factor
receptor with signal transduction
Transmission of signal across the cytosol to
nucleus via second messengers or signal
transduction cascade
Initiation of DNA transcription
Entry and progression into the cell cycle
Proto-oncogenes, oncogenes
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Proto-oncogenes: normal cellular genes whose
products promote cell proliferation
Oncogenes: mutant versions of proto-oncogenes
that function autonomously without a
requirement for normal growth-promoting
signals
Oncoproteins: proteins encoded by oncogenes
Cancer growth self sufficiency
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Growth factors
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Growth factor receptors
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Over-expression or always “on”
Signal transduction proteins
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Autocrine loops
Intermediates in cascade, especially Gproteins,
phosphorylases, kinases
Transcription factors
Cyclins and CDKs

Uncontrolled cell cycle progression
• Cyclin D–CDK4, cyclin D–
CDK6, and cyclin E–CDK2
regulate the G1-to-S transition
by phosphorylation of the RB
protein (pRB).
• Cyclin A–CDK2 and cyclin A–
CDK1 are active in the S
phase.
• Cyclin B–CDK1 is essential for
the G2-to-M transition.
• Two families of CDKIs can
block activity of CDKs and
progression through the cell
cycle. The INK4 inhibitors
(p16, p15, p18, and p19) act
on cyclin D–CDK4 and cyclin
D–CDK6. The others (p21,
p27, and p57) can inhibit all
CDKs.
Insensitivity to supressor signals

Classic example retinoblastoma gene
Both copies of gene must be inactivated to block
hold
 Familial predisposition due to one bad copy
 Sporadic cases arise from somatic mutations of both
copies
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RB Gene and Cell Cycle
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RB controlls G1-to-S transition of the cell cycle
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active RB (hypophosphorylated) binds to E2F preventing transcription of
genes like cyclin E that are needed for DNA replication, resulting in G1
arrest
Growth factor signaling leads to cyclin D expression, activation of the
cyclin D-CDK4/6 complexes, inactivation of RB by phosphorylation, and
thus release of E2F
Loss of cell cycle control is fundamental to malignant
transformation
Almost all cancers will have disabled the G1 checkpoint, by
mutation of either RB or genes that affect RB function, like
cyclin D, CDK4, and CDKIs

Many oncogenic DNA viruses, like HPV, encode proteins (e.g., E7) that
bind to RB and render it nonfunctional.
Activation of normal p53 by
DNA-damaging agents or by
hypoxia leads to cell cycle
arrest in G1 and induction of
DNA repair, by transcriptional
up-regulation of the cyclindependent kinase inhibitor
CDKN1A (p21) and the
GADD45 genes. Successful
repair of DNA allows cells to
proceed with the cell cycle; if
DNA repair fails, p53 triggers
either apoptosis or senescence.
In cells with loss or mutations of
p53, DNA damage does not
induce cell cycle arrest or DNA
repair, and genetically damaged
cells proliferate, giving rise
eventually to malignant
neoplasms.
Tumor Host Interactions Clinical aspects of
neoplasia
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Local Effects
Cancer Cachexia
Paraneoplastic Syndromes
Endocrinopathies
 Neuromyopathies
 Osteochondral Disorders
 Vascular Phenomena
 Fever
 Nephrotic Syndrome

Local Effects


Tumor Impingement on nearby
structures
 Pituitary adenoma on normal gland,
Pancreatic carcinoma on bile duct,
Esophageal carcinoma on lumen
Ulceration/bleeding
 Colon, Gastric, and Renal cell
carcinomas
Local Effects


Infection (often due to obstruction)
 Pulmonary infections due to blocked
bronchi (lung carcinoma), Urinary
infections due to blocked ureters
(cervical carcinoma)
Rupture or Infarction
 Ovarian, Hepatocellular, and Adrenal
cortical carcinomas; Melano-carcinoma
metastases
Cancer Cachexia
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Progressive weakness, loss of appetite,
anemia and profound weight loss (>20
lbs.)
Often correlates with tumor size and
extent of metastases
Etiology includes a generalized increase
in metabolism and central effects of
tumor on hypothalamus
Probably related to macrophage
production of TNF-a and IL-1
Paraneoplastic Syndromes
Endocrinopathies


Cushing’s Syndrome
 Adrenal carcinoma (cortisol) more common
with benign adrenal processes.
 Small cell undifferentiated lung cancer
(ACTH) released
Inappropriate ADH syndrome
(Hyponatremia)
 Small cell undifferentiated lung cancer
(vassopressin-like hormone.
 Hypothalamic tumors (vasopressin)
Paraneoplastic Syndromes
Endocrinopathies

Hypercalcemia (Cancer is the most
common cause of hypercalcemia by either
humoral or metastatic mechanisms)
 Squamous cell lung cancer (PTH-like
peptide)
 Renal cell carcinoma (prostaglandins)
 Parathyroid carcinoma (PTH)
 Multiple myeloma and T-cell lymphoma (IL1 and perhaps TGF-a)
 Breast carcinoma, usually by bone
metastasis
Paraneoplastic Syndromes
Endocrinopathies
 Hypoglycemia - caused by tumor
over-production of insulin or insulin like
activities
 Fibrosarcoma, Cerebellar
hemangioma, Hepatocarcinoma

Carcinoid syndrome - Caused by
serotonin, bradykinin or histamine
produced by the tumor
 Bronchial carcinoids, Pancreatic
carcinoma, Carcinoid tumors of the
Paraneoplastic Syndromes
Endocrinopathies

Polycythemia - caused by tumor production
of erythropoietins
 Renal cell carcinoma, Cerebellar
hemangioma, Hepatocarcinoma

WDHA syndrome (watery diarrhea,
hypokalemia, and achlorhydria) - caused by
tumor production of vasoactive intestinal
polypeptide (VIP).
 Islet cell tumors, Intestinal carcinoid tumors
Paraneoplastic Syndromes
Neuromyopathies

Myasthenia - A block in neuromuscular
transmission possibly caused by host
antibodies against the tumor cells that cross
react with neuronal cells or perhaps caused
by toxins.
 Bronchogenic carcinoma, Breast cancer

Carcinomatous Myopathy - probably
immune-mediated
Paraneoplastic Syndromes
Osteochondral Disorders

Hypertrophic Osteoarthropy clubbing, periosteal new bone, and
arthritis
 Isolated clubbing occurs in chronic
obstructive pulmonary disease and in
cyanotic congenital heart disease, but
the full-blown syndrome is limited to
lung cancer.
Paraneoplastic Syndromes
Vascular Phenomena

Altered Coagulability - caused by the
release of tumor products
 Migratory
Venous Thromboses
(Trousseau’s sign) Pancreatic, gastric,
colon, and bronchogenic carcinomas;
particularly adenocarcinoma of the lung.
 Marantic
endocarditis - Small thrombotic
vegetations on mitral or aortic valves that
occur with advanced carcinomas.
Paraneoplastic Syndromes

Fever
Associated with bacterial infections
Common where blockage of drainage
occurs
 Decreased immunity may play a role


Not associated with infection
Episodic as in Pel-Ebstein fever with
Hodgkin’s lymphoma; poor prognostic sign
in sarcomas, indicates dissemination
 Likely caused by response to necrotic
tumor cells and/or immune response to
necrotic tumor proteins.

Paraneoplastic Syndromes
Nephrotic Syndrome

Excessive loss of protein in the urine

probably caused by damage to renal
glomeruli by tumor antigen-antibody
complexes.
GRADING AND STAGING OF
TUMORS
.
GRADING
•
Degree of maturity or differentiation under the microscope
1.Histologic
grade – resemblance between tumor and normal cells
2.Nuclear grade – size and shape of nucleus, dividing cells
How is tumor grade determined?

Biopsy – benign or malignant - pathologist
– level of differentiation
TUMOR GRADES



Microscopic apperance of cancer cells
4 degrees of severity
Grade:
GX
G1
G2
G3
G4
Grade cannot be assessed (Undetermined grade)
Well-differentiated (Low grade)
Moderately differentiated (Intermediate grade)
Poorly differentiated (High grade)
Undifferentiated (High grade)
GRADING SYSTEMS
•
Different for different types of cancers
Gleason – prostate cancer
Bloom-Richardson – breast cancer
Fuhrman – kidney cancer
GRADING – TREATMENT

For treatment and prognosis

Lower grade  better prognosis (outcome of diease)
Higher grade  worse prognosis


Important in treatment of  prim. brain tumors (astrocytomas)
lymphomas
breast cancer
prostate
STAGING

Extent of the prim. tumor and extent of spread in the body

Important - helps planning treatment
- helps estimating prognosis
- helps identifying clinical trials
STAGING SYSTEMS

No unique staging system

Common elements :
- Location of the primary tumor
- Tumor size and number of tumors
- Lymph node involvement (spread of cancer
into lymph
nodes)
- Cell type and tumor grade (how closely the cancer cells
resemble normal tissue)
- Presence or absence of metastasis
TNM - system



Most common
Based on : T  extent of the tumor
N  extent of spread to the lymph nodes
M  presence of metastasis
Number  indicates size or extent of the prim. tumor and the extent
of spread of metastasis
Primary Tumor (T)
TX
Primary tumor cannot be evaluated
T0
No evidence of primary tumor
Tis
Carcinoma in situ (has not spread)
T1, T2, T3, T4
Size and/or extent of the primary tumor
Regional Lymph Nodes (N)
NX
Regional lymph nodes cannot be evaluated
N0
No regional lymph node involvement
N1, N2, N3
Involvement of regional lymph nodes (number and/or extent of
spread)
Distant Metastasis (M)
MX
M0
M1
Distant metastasis cannot be evaluated
No distant metastasis
Distant metastasis (cancer has spread to distant parts of the body)