Chapter

Chapter 55

Neoplasms
(1
(1ststLecture)
Lecture)

S. Sunardhi Widyaputra, DDS, MS, PhD

Department of Anatomical Pathology
Faculty of Dentistry
Universitas Padjadjaran

?
Neoplasm
Neoplasia
Tumour
Cancer

1. Definition, Classification, Nomenclature,

and Epidemiology of Neoplasms

Neoplasm
is an abnormality of:
Cellular differentiation
Maturation
Control of growth

Definition of Neoplasms
NEOPLASMS is an abnormal mass of tissue, the growth of
which exceeds and is uncoordinated with that of the
surrounding normal tissues and persists in the same
excessive manner after cessation of the stimuli that
evoked the change
(Ruppert
(Ruppert Willis,
Willis, 1950)
1950)

Classification of Neoplasms
Classification of neoplasms has major implication for
prognosis and therapy
Two major approaches are employed:
Biologic behavior benign vs malignant
Cell or tissue of origin (histogenesis)
Other features:
Site
Embryologic derivation
Gross features

Biologic behavior of Neoplasms

Types of biologic behavior:

Benign
Malignant
Intermediate

Classification of biologic behavior by

pathologic examination

Rate of growth
Size
Degree of differentiation
Changes in DNA
Infiltration and invasion
Metastasis

Cell or Tissue of origin

(Histogenesis)
Based upon differing potentials for further development:
Totipotent
Pluripotent
Unipotent (differentiated)
Based upon cell type

Neoplasms of Totipotent cells

Totipotent cells: cells that are capable of differentiating
(maturing) into any cell type
In postnatal life the only totipotent cells are only the germ cells
Germ cell neoplasms may:
Show minimal differentiation (seminoma and embryonal
carcinoma)
Develop into a variety of tissues, including:

trophoblast
trophoblast (choriocarcinoma),
(choriocarcinoma),
yolk
yolk sac
sac (yolk
(yolk sac
sac carcinoma),
carcinoma),
somatic
somatic structures
structures (teratoma)
(teratoma)

Teratomas
Show somatic differentiation and contain elements
elements of
of all
all three
three
germ layers:
entoderm
ectoderm
Mesoderm
Mesoderm
Are further classified as:
mature (well-differentiated, usually benign) or
immature (made up of fetal-type tissues, malignant)

Neoplasms of Embryonic Pluripotent Cells

The corresponding neoplasms have the potential

for formation of diverse structural elements
Generally called embryomas or blastomas
Usually occur in early childhood

Neoplasms of Differentiated
(Unipotent) Cells
Most neoplasms of adults are derived from differentiated
cells
Classification is based upon a combination of several
criteria:
Epithelial vs mesenchymal
Benign vs malignant
Tissue of origin

A. Nomenclature of neoplasms of
differentiated cells
1.

Epithelial neoplasms

Benign
Benign epithelial
epithelial neoplasms
neoplasms are
are called:
called:

Adenomas
Adenomas arising
arising from
from epithelium
epithelium within
within aa gland
gland

Papillomas
Papillomas arising
arising from
from the
the surface
surface of
of squamous,
squamous, galndular,
galndular,
or
transitional
epithelium,
and
growing
upward
in
a
papillary
or transitional epithelium, and growing upward in a papillary
structure
structure

Malignant
Malignant epithelial
epithelial neoplasms
neoplasms are
are called
called carcinomas,
carcinomas, which
which
include:
include:

Adenocarcinomas
Adenocarcinomas from
from glandular
glandular epithelia
epithelia

Squamous
Squamous carcinomas
carcinomas from
from squamous
squamous epithelia
epithelia

Transitional
Transitional cell
cell carcinomas
carcinomas from
from transitional
transitional epithelia
epithelia

A. Nomenclature of neoplasms of
differentiated cells
2. Mesenchymal neoplasms

Benign mesenchymal neoplasms are named after the cells of origin

followed by the suffix oma

Malignant mesenchymal neoplasms are named after the cell of

origin followed by suffix sarcoma

B. Exceptions to these rules

Neoplams
Neoplams that
that sound
sound benign
benign but
but are
are really
really malignant:
malignant:

Neoplasms
Neoplasms that
that sound
sound malignant
malignant but
but are
are really
really benign:
benign:

Lymphoma
Lymphoma
Plasmacytoma
Plasmacytoma
Melanoma
Melanoma
Glioma
Glioma
Astrocytoma
Astrocytoma
Osteoblastoma
Osteoblastoma
Chondroblastoma
Chondroblastoma
Ameloblastoma
Ameloblastoma

Leukemias
Leukemias
Mixed
Mixed tumors
tumors
Neoplasms
Neoplasms whose
whose cell
cell of
of origin
origin is
is unknown:
unknown:

Hodgkins
Hodgkins disease
disease
Kaposis
Kaposis sarcoma
sarcoma
Ewings
Ewings sarcoma
sarcoma

Hamartomas & Choristomas

These tumorlike growths are thought to be the results of

developmental anomalies
They are not true neoplasms
A
A hamartomas
hamartomas is
is composed
composed of
of tissues
tissues that
that are
are normally
normally
present
present in
in the
the organ
organ in
in which
which tumor
tumor arises
arises
A
A choristomas
choristomas contains
contains tissues
tissues that
that are
are not
not normally
normally present
present
in
in its
its site
site of
of origin
origin

Incidence & Distribution of Cancer in

Humans (1)

Incidence & Distribution of Cancer in

Humans (2)

Major factors affecting incidence

1.
2.
3.
4.
5.

Sex
Age
Occupational, social, and geographic factors
Family history
History of associated diseases

1.

Sex

Man:
Man:
Prostate
Prostate cancer
cancer
Women:
Women:
Uterine
Uterine cancer
cancer
Breast
Breast cancer
cancer

2. Age
In children:
Carcinoma is rare
Leukemias, malignant lymphomas, and various blastomas are
relatively common
In adults:
Carcinomas make up by far largest group of malignant tumors

3. Occupational, social, and geographic

factors (1)

The social habit of cigarette smoking

Sexual and childbearing histories
Herpesvirus and papovavirus infections
Geographic variations
Differences in occupations
Shipyard workers asbestosis and mesothelioma
Diet aflatoxin and liver cancer
Endemic viruses Epstein-Barr virus and Burkitts
lymphoma

3. Occupational, social, and geographic

factors (2)

4. Family history
A few cancer have a simple pattern of genetic inheritance:
Retinoblastoma
Polyposis coli and carcinoma of the colon
Medullary carcinoma of the thyroid
Other cancer, the genetic link is not as strong:
Breast carcinoma
Lung cancer (almost nonexistent)

5. History of associated diseases

A history of previous cancer greatly increases the chances that the
current illness represent either a metastasis or a second primary
tumor
Certain nonneoplastic diseases carry an associated higher risk of
development of cancer

Table 5.1.1. Diseases associated with

increased risk of neoplasm
Nonneoplastic or Preneoplastic
Condition

Neoplasm

Mongolism (trisomy 21)

Acute myeloid leukemia

Xeroderma pigmentosum (+ sun exposure)

Squamous cell carcinoma of skin

Gastric atrophy (pernicious anemia)

Gastric carcinoma

Tuberous sclerosis

Cerebral gliomas

Caf au lait skin patches

Neurofibromatosis (dominant inheritance); accoustic

neuroma; pheochromocytoma

Actinic dermatitis

Squamous carcinoma of skin; malignant melanoma

Glandular metaplasia of esophagus (Barretts

esophagus)

Adenocarcinoma of esophagus

Dysphagia + anemia (Plummer-Vinson syndrome)

Esophageal carcinoma

Cirrhosis (alcoholic, hepatitis B)

Hepatocellular carcinoma

Ulcerative colitis

Colon carcinoma

Pagets diseases of bone

Osteosacroma

Immunodeficiency states

Lymphomas

AIDS

Lymphoma; Kaposis sarcoma

Autoimmune diseases (eg. Hashimotos thyroiditis)

Lymphoma (rg. Thyroid lymphoma)

Dysplasia (eg. Cervical dysplasia)

Cancer

End of first lecture

Chapter
Chapter 5.
5.

Neoplasms
nd Lecture)
(2
(2nd
Lecture)

S.
S. Sunardhi
Sunardhi Widyaputra,
Widyaputra, DDS,
DDS, MS,
MS, PhD
PhD
Department
Department of
of Anatomical
Anatomical Pathology
Pathology
Faculty
Faculty of
of Dentistry
Dentistry
Universitas
Universitas Padjadjaran
Padjadjaran

2. Mechanisms and Causes of Neoplasm

Theories of Origin of Neoplasm

Viral theory:
Rous sarcoma, 1908
Shope papilloma, 1933
Bittner milk factor, 1935

Immunologic theory:
Tumor transplantation in animal,: Ehrlich, 1908
Immune surveilance: Burnet, 1950s

DNA mutation theory:

Watson and Crick, 1950s

Multifactorial Origin of Neoplasms

An initiator produces the first in a series of change leading to

neoplasm (initiation)

This is followed by prolonged action on one or more promoters

that eventually lead to neoplasm (promotion)

The requirement of successive insults (multiple hit theory)

account fo the long latent period

Genetic Mutation Theory

Neoplasm may follow changes in growth-regulating genes due

to spontaneous mutation or the action of external mutagens

Abnormal production of regulatory proteins alters the pattern

of cell growth or differentiation

Many different oncogenic agents, including chemical

carcinogen and viruses, may exert their effects through this
mechanism

A. Neoplasm associated with constant

genetic abnormalities:

Retinoblastoma:
Families with a high incidence show partial deletion of the
long arm of chromosome 13
The missing genetic material (the Rb gene) controls the
growth of retinal cells
Retinoblastoma develops when the second Rb gene is also
lost due to mutation or abnormal mitosisof the residual
normal chromosome 13
The Rb gene is thus a recessive tumor suppressor gene

B. Neoplasm associated with chromosomal

instability:

Certain rare syndromes associated with chromosomal

instability and abnormal DNA repair mechanisms have a high
risk of cancer

These conditions include Blooms syndrome, Fanconis

syndrome, ataxia telangiectasia, and xeroderma pigmentosum

In xeroderma pigmentosum the action of UV light (the

promoter) produces multiple skin cancers, due to inherited
failure of DNA repair mechanisms (the initiator)

C. Neoplasm associated with aging:

The increased incidence of cancer in the aged may be due to

faulty DNA repair

Virogene Oncogene Theory (1)

Specific DNA sequences (cellular oncogenes [C-ONC]) are

present in normal cells and produce growth factors that
regulate normal growth

These oncogenes may be abnormally activated (or de-represed)

by various carcinogens, including viruses, radiation, and
chemicals, producing cancer

Certain RNA oncogenic viruses contain viral onvogenes (VONC) that are essentially identical to cellular oncogenes

Cellular oncogenes are inherited as part of the cell genome

Table 5.2.1. Representative Oncogenes

Viral oncogene

Species Origin

Tumor type

Virally
Determined DNA
in Host Cell

Tyrosine
Phosphorylase
Product

V-src

Chicken

Sarcoma

Yes

Yes

V-yes

Chicken

Sarcoma

Yes

Yes

V-myc

Chicken

Carcinoma,
sarcoma,
leukemia

Yes
?

V-myb

Chicken

Leukemia

Yes

V-abl

Mouse

Leukemia

Yes

yes

V-mos

Mouse

Sarcoma

Yes

V-ras

Rat

Sarcoma,
leukemia

Yes

V-fes

Cat

Sarcoma

Yes

Yes

V-sis

Monkey

Sarcoma

Yes

Table 5.2.2. Oncogenic Viruses

Group

Virus

Host

Tumor

RNA viruses
(retrovirus)
Type C

Avian leukemia-sarcoma complex

Murine leukemia-sarcoma compl.
Feline leukemia-sarcoma complex

Chicken
Mouse, rat, hamster
Cat, dog

Leukosis, Rous sacrcoma

Leukemia, sarcoma
Leukemia, sarcoma

Type B

Murine mammary tumor virus

(Bittner milk factor)

Mouse

Breast cancer

Type C-like

HLTV-I
HIV

Human
Human

T cell leukemia
AIDS-related lymphomas

DNA viruses
Papovavirus

Papilloma virus
Polyoma virus
SV-40

Human, rabbit, cow, dog

Mouse
Monkey

Papilloma, conylomata accuminata

Many tumors in newborn hamster
Tumors in hamster only

Herpesvirus

Herpes simplex type 2

Epstein-Barr virus
Avian
Rabbit

Human
Human
Chicken
Rabbit

?Carcinoma of cervix
Ca nasopharynx, Burkitts lymphoma
Mareks diseases
Lymphoma

Poxvirus

Fibroma-myxoma
Molluscum contagiosum

Rabbit
Human

Fibromyxoma
Molluscum contagiosum

Parapoxvirus

Hepatitis B

Human, rodent, duck

Hepatocellular carcinoma

Virogene Oncogene Theory (2)

Many oncogenes tested to date code for either

A protein kinase (tyrosine phosphorylase) with growthregulating properties, or
A cell surface receptor for known growth factors 9 eg. erbB
and EGF)

DNA oncogenic viruses also appear to contain oncogene

segments

Theory of Failure of Immune Surveillance

Immune surveillance encompasses several concepts:

Neoplastic changes frequently occur in the body
Neoplastic cells produce new molecules (neoantigens,
tumor-associated antigens)
The immune system reacts again these new antigens
Clinically detectable neoplasms appear only if they escape
recognition and destruction by the immune system
Failure of immune surveillance has been invoked to explain
the higher incidence of neoplasm in immunodefficiency
states, in transplant recipients, and in the elderly

Agents causing Neoplasms

Known as Oncogenic agents or Carcinogens

Carcinogens are substances that are known to cause cancer

or at least produce an increased incidence of cancer in an
animal or human population

Except for cigarette smoking, the agents usually have been

implicated in only a small percentage of cases

The marked geographic variation in the incidence of different

cancer is thought to result more from the action of different
carcinogens than from variations in genetic makeup

Chemical Oncogenesis

One of the major problems associated with the identification of

chemical carcinogenesis is the long lag phase, sometimes 20
years or more between exposure and the development of
cancer

Most chemical carcinogens act by producing changes in DNA

A small number act by epigenetic mechanisms, ie, they
cause changes in growth-regulating proteins without
producing changes in DNA
Others may serve as promoters for viruses or other
carcinogens

A.

Polycyclic hydrocarbons

The first recognized carcinogen in humans was soot, which

caused scrotal cancer in chimney sweeps (Sir Percivall Pott,
1775)

Later it was shown that the active carcinogens in soot were

polycyclic hydrocarbons benzo()pyrene and
dibenzanthracene

B. Cigarette smoking

Cigarette smoking, including cigar and pie smoking, is

associated with an increased risk of cancer of the lung,
bladder, oropharynx, and esophagus

Smoking accounts for more cancer deaths than all other known
carcinogens combined

Cigarette smoke contains numerous carcinogens, the most

important of which are polycyclic hydrocarbons (tars)

The risk of developing cancer is about 10 times higher in

someone who smokes a pack of cigarette a day for 10 years (10
pack years) than in a nonsmoker

If a smoker stop smoking, the risk drops almost to that of a

nonsmoker after 10 years

C. Aromatic amines

Exposure to benzidene and naphthylamine is associated with

bladder cancer (first recognized in workers in the leather and
dye industries)

Aromatic amines are procarcinogens that enter the body

through the skin, lung, or intestine and are converted to
carcinogenic metabolites that are excreted in the urine

D. Cyclamates and Saccharin

These artificial sweeteners cause bladder cancer in

experimental animals

No carcinogenic effect has been demonstrated in humans

E. Azo dyes

These dyes were used as food coloring agents (scarlet red and
butter yellow)

They cause liver tumors in rats, and have been withdrawn from
commercial use

F. Aflatoxin

Aflatoxin is produced by the fungus Aspergillus flavus, which

grows on improperly stored food, particularly grain,
groundnuts, and peanuts

Can causes liver necrosis and, in the long-term, liver cancer

G. Nitrosamines

Small amounts of these compounds are carcinogenic in

animals

Nitrosamines are produced in the stomach from nitrites, which

are commonly used as food preservatives

The high incidence of gastric cancer in Japanese thought to be

related more to high intake of smoked fish (containing
polycyclic hydrocarbons) than to high nitrosamine levels

H. Betel leaf

The chewing of betel leaf in Sri Lanka and parts of India is

responsible for an extremely high incidence of cancer of the
oral cavity

I. Anticancer drugs

Alkylating agents interfere with nucleic-acid synthesis and may

cause oncogenic mutations (leukemia is a common
complication of cancer chemotherapy)

J. Asbestos

Has been widely used as an insulating material and fire

retardant

Is inhaled into the lung, where it produces chronic pulmonary

fibrosis and fibrous proliferation of the pleura

It also associated with two types of cancer:

Malignant mesothelioma
Brochogenic carcinoma

Patients with asbestos exposure also have a risk of lung cancer

about twice that of the general population

This risk is greatly magnified by smoking

Family members of shipyard workers also are at risk

K. Other industrial carcinogens

Include in these carcinogens are:

Heavy metals (nickel, chromium, cadmium) lung cancer
Arsenic skin cancer
Vinyl chloride angiosarcoma of the liver

Radiation Oncogenesis

A. Ultraviolet radiation

Sunlight is associated with various kinds of skin cancer,

including squamous cell carcinoma, basal cell carcinoma, and
malignant melanoma

Skin cancer is seen more often in the elderly

UV radiation is especially a problem for fair-skinned individuals

in sunny climates who are continually exposed to the sun

B. X-ray radiation

Early radiologist developed radiation dematitis, with a high

incidence of skin cancer

With the use of penetrating X-rays, radiologists suffered an

increased incidence of leulemia

Today the risk is minimized by effective protective measures

against X-rays: diagnostic X-rays deliver very small doses

Radiation-induced malignant neoplasms, commonly sarcomas,

occur 10-30 years after radiation therapy

C. Radioisotopes

Osteosarcoma once occurred among factory workers who used

radium-containing paints to produce luminous watch faces;
trace amounts of radium were ingested and deposited in bone

Exposure of miners to radioactive minerals is associated with

an increased incidence of lung cancer

Thorotrast, a dye formerly used in diagnostic radiology, is

deposited in the liver, leading to an increased risk of
angiosarcoma, liver-cell carcinoma, and cholangiocarcinoma

Radioactive iodine is associated with an increased risk of

thyroid cancer developing 15-25 years later

Genetic Oncogenesis (3)

(The role of Inheritance in Oncogenesis)
Retinoblastoma (2)
Actual omcogenesis requires a second event, namely,
deletion of the corresponding part of the long arm of the
ramaining chromosome 13, producing a homozygous state
and development of retinoblastoma
In sporadic cases, two mutational deletions, involving both
chromosomes 13, must occur
The result is an apparent dominant pattern of inheritance
due to the high rate of conversion of the heterozygous state
(lacks on Rb gene) to homozygous (lacks both Rb genes), in
which the recessive change is expressed
A similar abnormality of chromosome 13 occurs in smallcell undifferentiated carcinoma of the lung

Genetic Oncogenesis (4)

(The role of Inheritance in Oncogenesis)

Wilms tumor (nephroblastoma)

Many cases are associated with deletion of part of
chromosome 11
Both sporadic and familial cases occur, by mechanisms
thought to resemble those described for retinoblastoma

Genetic Oncogenesis (5)

(The role of Inheritance in Oncogenesis)

Other inherited neoplasms with an apparent autosomal dominat

inheritance pattern:
Neurofibromatosis (von Recklinghausens disease)
Multiple endocrine adenomatosis, manifested by benign
neoplasms in the thyroid, parathyroid, pituitary, and adrenal
medulla
Familial polyposis coli, characterized by innumerable
adenomatous polyps in the colon; cancer eventually
develops in all patients unless they undergo colectomy
Gardners syndrome is a variant, associated with benign
neoplasms in bone, soft tissue, and skin

Nevoid basal-cell carcinoma syndrome is characterized by

dysplatic melanocytic nevi and basal cel carcinoma in the
skin

Genetic Oncogenesis (6)

(The role of Inheritance in Oncogenesis)
2. Neoplasms with polygenic inheritance:

Many common human neoplasms are familial, without a clear

pattern of inheritance

Breast cancer:

First-degree female relatives of premenopausal woman with

breast cancer have a fivefold risk of developing breast
cancer

Colon cancer:

Occurs both as a complication of inherited familial polyposis

coli and independently
Some cancer families exist, with abnormally high
incidences of multiple cancers, including colon,
endometrium and breast
This the result of inheritance of multiple genes, some of
which may be oncogenes

Genetic Oncogenesis (7)

(The role of Inheritance in Oncogenesis)
3. Neoplasms occuring more frequently in inherited diseases
Inherited diseases with a high risk of neoplasm include:
Syndromes characterized by increased chromosomal
fragility, ie.:

Xeroderma pigmentosum
Blooms syndrome
Fancinis syndrome
Ataxia telangiectasia

Syndromes of immunodefficiency

End of second lecture

Chapter
Chapter 5.
5.

Neoplasms
(3r
(3rdd Lecture)
Lecture)

S. Sunardhi Widyaputra, DDS, MS, PhD

Department of Anatomical Pathology
Faculty of Dentistry
Universitas Padjadjaran

3. Biologic and Clinical Effects of Neoplasms

Origin of Neoplasm
Monoclonal origin
The neoplastic change occurs in single cell, which then multiples
and give rise to a clone (the neoplasm)
A monoclonal origin has been clearly shown in neoplasms of
B lymphocytes (lymphomas and plasma cell myelomas) that
produce immunoglobulin
Field origin
The action of a carcinogen produces a field of potentially
neoplastic cells, several of which progress to overt neoplasm
Multifocal (field) neoplasma occur in skin, urothelium, liver,
breast, and colon
These theories are not mutually exclusive

Characteristics of neoplasm (1)

The lag period
Is the interval between exposure (to the carcinogen) and the
development of the neoplasm
In most instances, no abnormality is apparent during the lag
period
Precancerous (premalignant) changes
Sometimes neoplasm is preceded by an intermediate abnormal,
non-neoplastic growth pattern a precancerous lesion
It is important to recognize precancerous lesions, because
surgical excision is curative

Characteristics of neoplasm (2)

Occult cancer
So named because they remain undiscovered during life
Eg. Up to 80% of males dying of other causes at age 80
show occult carcinoma of the prostate)

Changes in structure & Function (1)

A. Surface membrane alterations

Changes include alterations in the activity level of membrane
enzymes, loss of contact inhibition, wherein cancer cells in
culture grow over the top of one another (normal cells do not)

Changes in structure & Function (2)

B. Immunologic alterations
1. Appearance of tumor-associated antigens:
Most neoplastic cells express new antigens (neoantigens,
tumor-associated antigens)
A. Common viral antigens:
In viral-induced neoplasms, new antigens are frequently coded by
the virus
All neoplasms caused by particular virus will show the same new
antigen

B. Unique antigens:
Neoplasms induced by chemicals or radiation manifest new
antigens that are distinctive for each different neoplasm induced

C. Oncofetal antigens:
Are expressed both in cancer (onco) and fetal tissues
Include carcinoembryogenic antigen (CEA) and a-fetoptotein
(AFP)

Changes in structure & Function (3)

2. Loss of antigens normally present

neoplastic cells also frequently lack antigens that are present

in normal cells (eg. Loss of blood-group antigens in invasive
bladder cancer)

Changes in structure & Function (3)

C. Karyotypic abnormalities
Many malignant cells show major chromosomal abnormalities
such as aneuploidy and polyploidy.
Some neoplasms show distinctive changes of diagnostic value
The first to be identified was Philadelphia chromosomes (Ph1),
an abnormally small chromosome 22 resulting from reciprocal
translocation of genetic material between chromosome 22 and
chromosome 9
90% of patients with chronic granulocytic leukemia have Ph1; the
10% who do not have a worse prognosis

Changes in structure & Function (4)

D. Tumor cell products

The secretion of various tumor cell products is important for two
reasons;
They act as tumor markers
They may produce clinical effects (paraneoplastic
syndromes) unrelated to direct involvement of tissue by the
tumor

Changes in structure & Function (5)

1. Oncofetal antigens:
Carcinoembryonic antigen (CEA)
Found in most malignant neoplasms arising from tissues that
develop from the embryonic ectoderm (eg. Colon and
pancreatic cancer and some cases of gastric and lung
cancer)
It is not specific for cancer, since slight increases in serum
levels also occur in several non-neoplastic diseases (eg.
Ulcerative colitis and cirrhosis of the liver)
Alpha-fetoprotein (AFP)
Is synthesized by primitive gonadal germ-cell neoplasms
(embryonal or yolk sac carcinoma) and liver cell carcinoma
Mildly elevated levels may be seen in cirrhosis

Changes in structure & Function (6)

2. Enzymes
Elevated serum levels of prostate-specific acid phosphatase
(PSAP) occur in invasive prostate cancer
3. Immunoglobulins
Neoplasms of B lymphocytes (some B cell lymphomas,
myeloma) frequently synthesize immunoglobulins that may be
detected as a monoclonal band on serum protein electrophoresis
4. Excessive hormone secretion
Well-differentiated neoplasms of endocrine cells may produce
excess hormones, eg.:

Parathyroid tumors parathormone

Medullary carcinoma of the thyroid calcitonin
Pituitary adenoma prolactin, growth hormone, etc.
Pheochromocytoma catecholamines
Islet cell adenomas insulin, glucagon, gastrin

Changes in structure & Function (7)

5. Ectopic hormone production

Malignant neoplasms derived from cells that normally do not
secrete hormones may sometimes do so (ectopic hormone
production), eg.:
Small cell carcinoma of the lung ACTH, antidiuretic
hormone
Squamous carcinoma of the lung parathormone
Renal cell carcinoma - erythropoietin

Changes in growth pattern of neoplastic

cells (1)

A. Excessive cell proliferation

Neoplastic cells usually multiply more rapidly than their normal
counterparts
They usually accumulate to form a tumor (except for leukemia,
which are spread throughout the bone marrow and blood)
Rate of growth and malignancy:
As a general rule, the degreee of maligancy of a neoplasm
correlates with its rate of growth: the more rapid, the more
malignant
Assesment of growth rate:
Clinically, the doubling time is a crude neasure: for Burkitts
lymphoma, it is a few days; for some slow-growing cancers, a
few years

Changes in growth pattern of neoplastic

cells (2)

B. Anbormal differentiation and anaplasia

Benign and slow-growing malignant neoplastic cells tend to
differentiate normally and resemble their normal counterparts (ie,
they are well-differentiated)
As the degree of malignancy increases, the degree of
differentiation decreases, and they show less resemblance to
normal cells (poor differentiated)
When the differentiation is not so slight that there is no
resemblance to normal, a neoplasm is said to be undifferentiated
or anaplastic

Changes in growth pattern of neoplastic

cells (3)

Cytologic abnormalities that increase in degree in proportion to

malignancy include:
Pleomorphism (in appearance of cells)
Increased nuclear size
Increased nuclear:cytoplasmic ratio
Hyperchromatism
Prominent large nucleoli
Abnormal chromatin distribution
Nuclear membrane abnormalities
Failure of cytoplasmic differentiation

Changes in growth pattern of neoplastic

cells (4)

C. Invasion (infiltration)
Benign neoplasms do not invade they compress the
surrounding normal tissue forming a fibrous capsule
Malignant neoplasma invede of infiltrate normal tissues
Invasion of the basement membrane distinguishes invasive
cancer from intraepithelial (or in situ) cancer
Having penetrated the basement membrane, malignant cells
gain access to the lymphatics and blood vessels
This lead to distant metastasis (secondary growth)
Microscopic examination during surgery of rapidly frozen tissue
sections is helpful in determining the extent of spread and the
margins of excision

Changes in growth pattern of neoplastic

cells (4)

D. Metastasis
Secondary neoplasms (metastases) arising by dissemination of
malignant cells from the primary tumor to distant sites occurs
only in malignant neoplasms
1. Lymphatogenous metastasis:
Occurs early in carcinomas and melanomas
Sarcomas tend to spread mainly via bloodstream
Lymphatic spread is first to regional nodes, which thus
present an important site for clinical or surgical examination

Changes in growth pattern of neoplastic

cells (5)

2. Hematogenous metastasis:
Entry of cancerous cells into bloodstream is a common event
with many malignant neoplasms
Most of these malignant cells do not survive to grow into
metastases
The most common site of metastasis is the first capillary bed
encountered by blood draining from the primary site, eg.
Liver, for intestinal cancers draining via portal vein
Lung, for cancers draining into systemic veins
Skeletal metastases are common in cancer of the prostate,
thyroid, lung, breast, and kidney

Changes in growth pattern of neoplastic

cells (6)

3. Metastasis in body cavities (seeding) :

Less often, malignant cells may spread via the body cavities
(eg, pleura, peritonium, or pericardium) or the subarachnoid space.

Changes in growth pattern of neoplastic

cells (7)

4. Dormancy of metastases
Cancerous cells that spread to distant siter nay remain dormant
there (or at least undetected) for many years.
This makes it difficult to to pronounce a patient cured after many
years.

Effects of Neoplasia on The Host

Neoplasia may be the underlaying cause of almost any sign or
symptom anywhere in the body.

Direct Effects of Local Growth of Primary Tumors

The signs and symptoms arising from local growth of a benign
neoplasm or a primary malignant neoplasm vary with the site of the
lesion. The growing tumor may compress or destroy adjacent
structures, and cause inflammation, pain, vascular changes, and
varying degrees of functional deficits.

Effects of Neoplasia on The Host

Direct Effects of Growth of Metastases

Metastases may compress and destroy adjacent tissues in the same
way that a primary lesion does, but effects may become manifest at
multiple sites.

Paraneoplastic (nonmetastic) Syndromes

Cancer may also cause various signs and symptoms, distant from
the primary lesion that are unassociated with metastases.
These effects are termed paraneoplastic (or nonmetastatic) syndroms.
The mechanisms are largely unknown.

End of third lecture

Chapter
Chapter 5.
5.

Neoplasms
(4
(4thth Lecture)
Lecture)

S. Sunardhi Widyaputra, DDS, MS, PhD

Department of Anatomical Pathology
Faculty of Dentistry
Universitas Padjadjaran

4. Approach to Cancer Diagnosis

Approach to Cancer Diagnosis

Clinical Suspicion
The diagnosis of cancer is particularly difficult because of its protean
manifestations
A throrough clinical history is essential, this includes:

Family history
Social history
Occupational history
Diet and geographic origin
Sexual and childbearing history

Early diagnosis
Cytologic diagnosis
Histologic diagnosis:

Frozen section method

Paraffin section method
Immunohistochemistry
Electron microscopy

sectioning with microtome.mpeg

Information provided by pathologic diagnosis:

Type of neoplasm
Biologic behavior
Histologic grade
Degree of invasion and spread
Pathologic stage

Serologic diagnosis
Radiologic diagnosis

End of all lectures