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Neoplasia
References:
Pathologic Basis of Disease by Robbins and Cotran, 8th Ed. (2010)
Neoplasia (TUMOR)
Definitions
- “New growth” = Neoplasm
- Tumor
Oncology
- Greek “oncos” = tumor
- Study of tumors or neoplasms
- Cancer = Malignant tumors
Neoplasia (TUMOR)
Tumor
- An abnormal mass of tissue
- Growth exceeds that of normal tissues
- Growth persists after cessation of
the stimuli that initiated change
- Classified: Benign vs. Malignant
What is the relationship
of neoplasia to
metaplasia and
dysplasia?
Metaplasia -replacement of one type
of cell with another type.
• found in association with tissue
damage, repair, and regeneration.
• the replacing cell type is more suited
to a change in environment
Dysplasia –means disordered growth.
often occurs in metaplastic epithelium,
but not all metaplastic epithelium is
also dysplastic
- characterized by changes that
include a loss in the uniformity of the
individual cells as well as a loss in
their architectural orientation.
When dysplastic changes are marked
and involve the entire thickness of
the epithelium but the lesion remains
confined by the basement
membrane, it is considered a
preinvasive neoplasm and is referred
to as carcinoma in situ
Once the tumor cells breach the
basement membrane, the tumor is
said to be invasive.
However, dysplasia does not
necessarily progress to cancer. Mild
to moderate changes that do not
involve the entire thickness of
epithelium may be reversible, and
with removal of the inciting causes
the epithelium may revert to normal.
Even carcinoma in situ may take years
to become invasive.
The growth of cancers is accompanied
by progressive infiltration, invasion,
and destruction of the surrounding
tissue.
Malignant tumors are poorly
demarcated from the surrounding
normal tissue.
Metaplasia and dysplasia are still
forms of cellular adaptation in
response to stress/injury.
Neoplasia is not.
However, metaplasia and
dysplasia may lead to neoplasia.
NEOPLASIA
Nomenclature
Table on Nomenclature of Tumors
a. Origin
b. Cell type
c. Benign and Malignant types
2 Basic Components of Tumor
The “transformed” neoplastic cells
 Parenchyma
The nontransformed elements such as
connective tissues & blood vessels
 Supporting stroma
Characteristics of Benign vs.
Malignant Neoplasms
• Differentiation and Anaplasia
• Rate of Growth
• Local Invasion
• Metastasis
Differentiation & Anaplasia
Parenchymal cells of neoplasms
Differentiation
- the extent to which parenchymal cells
resemble comparable normal cells
- morphologically & functionally
Differentiation
Well-differentiated
- resemble mature normal cells
of the tissue origin
Poorly differentiated (anaplastic)
- Undifferentiated
- primitive, unspecialized cells
Differentiation
All benign tumors
- well-differentiated
Malignant neoplasms
- range from well-differentiated
to undifferentiated
Anaplasia
Definition
- lack of differentiation
- hallmark of malignant transformation
- “ to form backward”
Lack of differentiation, or
anaplasia, is often associated
with many other morphologic
changes.
Pleomorphism. Both the cells and
the nuclei characteristically display
pleomorphism—variation in size and
shape. Cells within the same tumor are
not uniform- some are large, some are
small.
Abnormal nuclear morphology.
• nuclei contain abundant chromatin and
are dark staining (hyperchromatic)
• nuclei are disproportionately large for
the cell, and the nuclear-to-cytoplasm
ratio may approach 1 : 1 instead of the
normal 1 : 4 or 1 : 6.
• nuclear shape -variable and irregular
Mitoses
• undifferentiated tumors possess large
numbers of mitoses, reflecting the
higher proliferative activity of the
parenchymal cells.
The presence of mitoses, however,
does not necessarily indicate that a
tumor is malignant or that the tissue
is neoplastic.
Loss of polarity
• anaplastic cells is markedly disturbed
(i.e., they lose normal polarity). Sheets
or large masses of tumor cells grow in
an anarchic, disorganized fashion.
Other changes
• formation of tumor giant cells, some
possessing only a single huge
polymorphic nucleus and others having
two or more large, hyperchromatic
nuclei
• vascular stroma is scant, and in many
anaplastic tumors, large central areas
undergo ischemic necrosis.
Rate of Growth
Most malignant tumors grow more
rapidly than benign tumors
Cancers from hormone sensitive
tissues affected by hormone levels
 E.g.
uterus
Hormone dependence & adequacy
of blood supply
Local Invasion
Benign tumors
- cohesive expansile masses with
capsule
- do not penetrate capsule &
normal tissues
- Discrete, readily palpable and
easily movable mass
- Surgically enucleated
Local Invasion
Malignant tumors
- Invasive, infiltrating and
destroying normal tissues
- Lack encapsulation
- Enucleation is difficult
- Surgery requires removal of some
healthy, uninvolved tissues
Local Invasion
Carcinoma in situ
- Preinvasive stage
- Cytologic features of malignancy
without invasion of the basement
membrane
- e.g. carcinoma of uterine cervix
Metastasis
Definition
- This process involves invasion of
the lymphatics, blood veseels and
body cavities by the tumor
- Tumor implants discontinuous
with the primary tumor
- Single most important feature that
differentiates from benign tumors
Metastasis
All cancers can metastasize
Few and major exceptions:
- Gliomas
- Basal cell carcinomas of the skin
The more aggressive, the more
rapidly growing, the larger the
primary neoplasm, the greater
likelihood of metastasis
Pathways of Spread
1. Spread into body cavities
2. Invasion of lymphatics
3. Hematogenous spread
Seeding of body cavities and
surfaces
Occurs by seeding of surfaces in
peritoneal, pleural, pericardial,
subarachnoid and joint spaces
Example: Carcinoma of the ovary
Lymphatic Spread
Most common pathway for the initial
dissemination of carcinoma
Pattern of lymph node involvement
follows the natural routed of
drainage
Lymph nodes are frequently
enlarged
Hematogenous spread
Typical of all sarcomas
Favored route for some carcinoma
e.g. Kidney (renal cell carcinoma)
Veins are more frequently invaded
than arteries
Lung and liver are common sites
Other sites: Brain and bones
Comparisons between benign
and malignant tumors
Differentiation/anaplasia
Benign
Malignant
-well
-lack of
differentiated
differentiation with
-structure typical anaplasia
of tissue of origin - structure often
atypical
Comparisons between benign
and malignant tumors
Rate of growth
Benign
-usually progressive
and slow
-mitotic figures are
rare and normal
Malignant
-erratic and maybe
slow to rapid
-mitotic figures
maybe numerous
and abnormal
Comparisons between benign
and malignant tumors
Local Invasion
Benign
-cohesive and
espansile well
demarcated masses
-do not invade or
infiltrate normal
tissues
Malignant
-locally invasive,
infiltrating
surrounding normal
tissues
Comparisons between benign
and malignant tumors
Metastasis
Benign
-absent
Malignant
-frequently present
-More likely for
larger and more
undifferentiated
masses
Grading and Staging of Cancer
Grading
- classified as grades I to IV with
increasing anaplasia
- higher grades tumors are more
aggressive than lower grade tumors
Grade refers to the degree of differentiation of
a neoplasm.
Grade I (or well differentiated) neoplasms
closely resemble the normal tissues from
which they are derived.
Grade IV(or poorly differentiated) only slightly
resemble the tissues they are derived from.
Patients with Grade IV tumors have a poorer
prognosis than those with Grade I tumors.
Grading and Staging of Cancer
Staging
- (T) based on the size of the primary tumor
- (N) extent of spread to regional lymph nodes
- (M) presence and absence of blood-borne
metastases
- TNM system (tumor,node,metastases)
- Higher stages -larger, locally invasive,
metastatic tumors
Staging (TNM system)
- T1 to T4 (increasing size)
- N0 ( no nodal involvement)
N1 to N3 (involvement of increasing
number and range of nodes)
- M0 (no distant metastases)
M1 to M2 (presence of metastases)
Stage of a tumor refers to the extent of
spread.
system used is the TNM (tumor, node,
metastasis)
There are different TNMs developed for
various cancers
STAGING (TNM)
TNM for breast cancer (different for other
cancers):
Tis - Carcinoma-in-situ
T1 - Gross size of tumor is less than 2.0
cm diameter
T2 - Gross size of tumor is between 2-5
cm diameter
T3 - Gross size of tumor is above 5 cm
diameter
T4 - Tumor of any size involving chest wall
or skin
N0 - No axillary node involved
N1 - Metastases to axillary nodes that
are freely mobile
N2 - Metastases to fixed (immobile)
axillary nodes
N3 - Metastases to internal mammary
nodes
M0 – No metastases outside of local
nodes
M1 - Metastases present
Use of these grading and staging can
predict prognosis for an individual
patient and also allows comparison of
treatment results from one centre to
another.
Predisposition to cancer
• Geographic and Racial factors
• Environmental and cultural influences
• Age and childhood cancer
• Heredity
• Acquired preneoplastic disorders
Race and Geographic locale
Leading cause of death in males
- cancers of the lung, colon & prostate
Leading cause of death in females
- cancers of the lung, breast & colon
Environmental factors influence
occurrence of specific forms of cancer
in different parts of the world
Environmental influences
examples of environmental factors
* increased risk with occupational
exposure to asbestos, vinyl chloride
and naphthylamine
* association of CA of the oropharynx,
larynx and lung with cigarette smoking
* alcohol abuse – risk of CA in
esophagus and liver carcinoma
Age
Most common = > 55 years of age
Common in children < 15 years
e.g. leukemias and lymphomas
neuroblastomas, Wilm’s tumor,
retinoblastomas and sarcomas of
bone and skeletal muscle
Heredity
Close relatives of cancer patients
have a higher than normal
incidence of the same neoplasm
Approximately 40% of
retinoblastomas are familial
Some defect in DNA repair
e.g. xeroderma pigmentosum
Acquired Preneoplastic Disorders
Clinical conditions associated with
increased risk of cancers
of liver – hepatocellular CA
 Atrophic gastritis – stomach CA
 Chronic ulcerative colitis – colon CA
 Leukoplakia of the oral and genital
mucosa – squamous cell CA
 Cirrhosis
Acquired Preneoplastic Disorders
Association between
- Endometrial hyperplasia and
endometrial carcinoma
- Cervical dysplasia and cervical
carcinoma
- Bronchial mucosal metaplasia and
dysplasia and bronchogenic CA
Clinical Manifestations
Varied and inconstant
Asymptomatic lesions or nonspecific
symptoms
2 categories for advancing
neoplasms:
 Abnormalities
from the tumor mass
 Physiologic derangements produced
indirectly
Cancer’s 7 Warning Signals
1. Change in bowel or bladder habits
2. A sore that does not heal
3. Unusual bleeding or discharge
4. Thickening or lump in breast or elsewhere
5. Indigestion or difficulty in swallowing
6. Obvious change in wart or mole
7. Nagging cough or hoarseness
Signs of expansile growth
Near or on the surface of the body
- visible or palpable mass
GIT,GUT, Respiratory
-obstruction, vomiting, jaundice,
cough, urinary retention
CNS
- pain, paralysis or sensory loss
Signs of infiltrative growth
Pain
Numbness
Paralysis
Signs of nerve invasion are also
signs of incurability
Signs of tumor necrosis
Tumor  necrosis, ulceration,
bleeding
Fatigue and weakness (signs of
anemia)
Edema, pain, tenderness and fever
Fever, leukocytosis, elevation of
ESR, anorexia and malaise
Cachexia
Loss of body fat , wasting, and profound
weakness  Cancer cachexia
Multifactorial
1. Loss of appetite
2. Infections due to immunosuppression
3. Bleeding from ulcerative lesions
4. Production of cachectin
PAP SMEAR
• A cytologic screening (cells are
collected and examined) which aims
for cervical cancer prevention and
control
• Short for Papanicolaou test to detect
potentially pre-cancerous and
cancerous processes of the cervix
• recommended for females 21 yrs old
and above to be done every 3 years
THE END