MHAM

COLLEGE OF MEDICINE CLASS 2024

NEOPLASIA (part 1)
Dr. Annette L. Salillas | September 23, 2021
GENERAL PATHOLOGY LEC

Outline → behave as parasites and compete with

I. Neoplasia normal cells and tissues for their metabolic
A. Growth of tumor cells needs
II. Tumor Nomenclature
A. Carcinoma GROWTH OF TUMOR CELLS
B. sarcoma • Autonomous
III. Characteristics of a tumor → independent of growth factors and regulatory
A. Cell organelles in malignant vs. normal cells mechanism operating inside the normal
B. Biochemical changes in malignant cells tissue
C. Growth rates between benign and
malignant tumors • Disorganized
D. Monoclonality in benign and malignant → The structure formed by tumor cells differ
tumors from normal tissue and do not fit into the
E. Telomerase activity in benign and malignant general organization scheme of the normal
tumors body
F. Upregulation of decay accelerating factor
(DAF) by malignant cells • Excessive
IV. Local invasion and metastasis → this excess may be evident in the size of the
A. Invasion and metastasis outgrowth and the duration of the
B. Grading proliferation.
C. Staging
V. Epidemiology
A. Cancer incidence
B. Geographic and environmental factors
C. Racial and ethnic differences affect cancer
incidence
D. Possible environmental influences are
E. Age
F. Heredity
G. Autosomal recessive syndromes of
defective DNA repairs
VI. Acquired preneoplastic disorder
A. Modify Lifestyle
ONCOLOGY
B. Immunization
→ the study of tumor
→ comes from the Greek word “oncos” which
means tumor and “logos” which means study
LEGENDS
Presentations remember lecturer previous
of
exams
Tumors may be classified into two ways:
• Clinical
I. NEOPLASIA → It can be benign/ malignant
→ (new growth/tumor) • Histological origin
→ abnormal mass tissue growth of which → based on the character of the
exceeds and uncoordinated with that of the parenchyma
normal tissues. → may arise from any tissue of the
→ persist in the same excessive manner after body
the cessation of the stimuli which evoke the → Tumors often take origin from tissues which normally
change. (Sir Rupert Willis) have rapid turnover of cells and are active in repair
→ tumor cells are transformed cells because e.g. (epithelia of the skin and mucous membranes,
they continue to replicate and are non- breast and female reproductive organs, connective
responsive to normal cell growth control tissue, bone & hematopoietic cells.

GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
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LEUKEMIA → Cystadenoma- adenomas produce large
cystic masses ex: Ovary

Two Basic Components of a Tumor:

• Transformed neoplastic cells
→ determines the tumors biologic
behavior.

• Supporting stroma
→ composed of non-transformed
elements such as connective tissue &
blood vessels.
→ This tumor cells need a connective
tissue that could adhere to its cells and
blood vessels.

II. TUMOR NOMENCLATURE

→ based on their appearance and presumed
histogenetic origin
This why histology is very important. For knowing
the normal tissue, you will be able to name the
tumor
→ Tumors of connective tissue origins arise from
mesoderm (leiomyoma- smooth muscle)
→ Picture below (ex. of Leiomyoma in the Uterus)
since it is more common in the uterine wall

BENIGN TUMOR
→ characterized by an unregulated proliferation
of cells epithelial or connective tissue origin
that do not invade or spread to other sites.

MALIGNANT TUMOR
→ characterized by unregulated proliferation of
cells that invade and tissue are
→ capable of spreading to other sites that are
remote from the primary site of origin • PAPILLOMAS
→ epithelial tumors which form microscopic or
• Benign macroscopic finger-like projections
→ add -”oma”
→ tumors of epithelial origin arise from either
ectoderm or endoderm (adenomas arise
from glands)
→ Ectoderm- SKIN
→ Endoderm- GLANDS

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 are lined by cuboidal to columnar cells and it has
myeo-epithelial layer and this myeo- epithelial
cells are the ones that produces connective
tissue stroma.
So, in one tumor which is called pleomorphic
adenoma or mixed tumor/benign mixed tumor you
will see both the epithelial components and the
connective tissues but they arise by one germ cell
layer differentiating into one cell type.

• POLYP
→ tumor projecting from mucosa into the lumen
of a hollow viscous
→ anything that protrudes or projects into a
hollow viscous

• TERATOMAS
→ parenchymal cell types representative of
(refer to the picture above) >1 germ cell layer usually 3.
→ arise from totipotential cells that retain
→ First picture- This intestine has multiple the ability to form:
polyps
→ Endoderm
→ Second picture- this is the photomicrograph, - (GI, Bronchial like structures)
histologic septa of the intestine\ → Ectoderm
→ Fifth picture- one polyp which histologically - (skin, neural tissue)
would show this mass → Mesoderm
→ Fourth picture- this tumor projects into the - (fat, bone & cartilage)
lumen of the hollow viscous
(refer to the picture below) you see this Cyst with
Tumor with >1 Parenchymal Cell Type: keratin and you see them as sebum so they are
derived from the skin and you see hairs and they are
• MIXED TUMOR ectoderm in origin, you see glands and is derived
→ composed of both epithelial and connective from endoderm, you also see cartilage which is
tissue tumor cells, derived from one germinal derived from \the mesoderm
layer that differentiates into more than one So, in teratoma, you see structures that are derived
parenchymal cell type from the three germ cell layers.
→ e.g. Pleomorphic Adenoma of the salivary
gland

(refer to picture below) You see these epithelial

cells is ductal cells and connective tissue in a
background of a myxoid stroma. So, this myxoid
stroma are actually produced by your myeo
epithelial cells. The tumor cells arise from one
germ cell layer – endoderm but differentiates into
a connective tissue which is a mesoderm. We
have a tumor wherein we see connective tissue
cells and epithelial cells, the ducts. These ducts
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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
• MALIGNANT If this is the normal stratified squamous epithelium:
→ Malignant tumors are called cancer
Cancer can be a:
→ Carcinoma – arising from epithelial
cells.
→ Sarcoma – arising from mesenchymal
tissues.

• Carcinoma
When is a tumor referred to as a carcinoma?
→ When a tumor arises from epithelial
cells, such as those found in the skin This is how a malignant tumor arising from the
(stratified squamous epithelium), it is stratified squamous look like:
referred to as carcinoma.

They closely resemble the parent tissue or the tissue

→ Malignant tumors arising from epithelial
of origin.
cells are called carcinoma.
→ Add the suffix “carcinoma”.
• Adenocarcinoma
Sites of adenocarcinoma (glandular epithelium):
• Sarcoma
→ Malignant tumors arising from → Lung
mesenchymal tissues. → Distal esophagus to rectum
→ Add the suffix “sarcoma”. → Pancreas
→ Example: Leiomyosarcoma: A → Liver
malignant tumor arising from a smooth → Breast
muscle. → Endometrium
→ Ovaries
→ Kidney
A. CARCINOMA → Prostate
→ Carcinomas derived from epithelial tissue
(squamous, glandular, and transitional)
→ Know the lining epithelium of each organ, so
that you can differentiate carcinomas from
sarcomas.

• Squamous Cell Carcinoma

Sites of SCCA:
→ Oropharynx
→ Larynx
→ Upper to middle esophagus
→ Lung
→ Cervix → Adenocarcinoma tumor resembles glands.
→ Skin → Hyperdramatic or darkly staining nuclei.
→ This malignant tumor resembles a normal → This gland contains several layers, as
stratified squamous epithelium. compared to the normal, which is lined by a
single cell.
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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 Again, adenocarcinoma is a malignant epithelial
tumor with glandular growth patterns such as this
one:

→ A normal urothelium is lined by five cell

layers thick.
→ A malignant urothelial carcinoma is lined by
more than 10. You can see that the thickness
Leiomyosarcoma is a sarcoma or malignant tumor is wider and it's more cellular compared to
which resembles a smooth muscle cell the normal urothelial epithelium. They form
finger-like projections called papilloma or
papillary like structures.

B. SARCOMA
→ Sarcomas derived from connective tissues.
o Osteogenic sarcoma in bone
o Chondrosarcoma
o Leiomyosarcoma
→ A malignant tumor arising from the bone is
• UROTHELIAL CELL CARCINOMA called osteogenic sarcoma.
Sites: → A malignant tumor arising from the cartilage
is called chondrosarcoma.
→ Bladder → A malignant tumor arising from a smooth
→ Ureter muscle is called leiomyosarcoma.
→ Renal pelvis
This is how a chondrosarcoma looks like:
This is the normal urothelium or transitional cell
epithelium:

Leiomyosarcoma: A sarcoma arising from smooth

muscle cells.
This is how a malignant carcinoma arising from the
urothelium looks like, and it's called urothelial cell
carcinoma:

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 → This resembles a smooth muscle but notice
the nuclei, they are more darkly stained,
which is called hyperchromatic.
→ Also, they are more pleomorphic.

Two Non-Neoplastic Lesions Simulating Tumors

→ They form a nodule but are not considered a
neoplasm, so they are referred to as non- For example, a pulmonary hemorrhoma. A lung
neoplastic lesions. mass is present, but in that nodule, it is composed of
blood vessels bronchi and cartilage which are native
• CHORISTOMA to that organ. These are normal tissue which forms
→ Either heterotrophic rest or ectopic, a nodule in that particular organ where they are
sometimes nodular, rest of non-transformed normally found.
tissues (pancreatic cells under small bowel).
→ Remember choristoma as “c” ectopic. On the basis of their histologic features on
→ Ectopic means abnormal location. What presume cells or tissue of origin.
does this mean? You have a normal tissue,
which is the pancreas, in an abnormal • Neoplasm can be classified into:
location, the duodenum. → Epithelia
o majority of human tumors –
80% of all human tumors
o Can be benign or malignant
→ Connective tissue tumors
o Leiomyosarcoma
o Chondrosarcoma
o Osteosarcomas
→ Tumors of blood cells and
lymphocytes
o lymphomas
In the image below, the normal pancreatic acini are o leukemias
covered by a normal duodenal mucosa. So, you o multiple myeloma
have a normal tissue in an abnormal location – o polycythemia vera
ectopic. For example, ectopic pregnancy in the o Hodgkin's disease
fallopian tube rather than the uterus.
→ Tumors of neural and glial cells
and neural support structures
o neuroblastomas
o gliomas
o meningiomas
→ Germ cell tumors
o Seminoma
o teratoma
o teratocarcinoma
o choriocarcinoma
• HAMARTOMA
→ A malformation that presents a mass of
• BLASTOMAS
disorganized tissue indigenous to the → these are tumors of immature cells
testicular side (hamartomatous nodules in resembling those that form the fetal
the lung may contain blood vessels, bronchi, anlage or primordial of other organs.
cartilage).
• RETINOBLASTOMA
→ tumor of the eye

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 • NEUROBLASTOMA
→ tumor composed of nerve cell Chondrocytes Chondroma Chondrosarcoma
precursors (neuroblasts).

• HEPATOBLASTOMA
→ tumor composed of fetal hepatocytes Osteocytes Osteoma Osteogenic sarcoma

There are malignant tumors that do not follow the

ENDOTHELIAL & RELATED DERIVATIVES
word “sarcoma” or “carcinoma”, but they end in
“oma”.

• SEMINOMA Blood vessels Hemangioma Angiosarcoma

→ malignant tumor of the seminal
epithelium in the testis
• Dysgerminoma
Lymph vessels Lymphangioma Lymphangiosarcoma
→ female germ cells in the ovary

• Glioma
→ (astrocytoma, oligodendroglioma, Mesothelium Benign Fibrous Mesothelioma
and ependymoma) – derived from Tumor
glial cells.

• Lymphoma Brain Meningioma Invasive Meningioma

→ lymphoid tissue Coverings

• Insulinoma, gastrinoma, somatostatinoma,

glucagonoma-endocrine pancreatic tumors
originating from the islets of Langerhans. BLOOD CELLS AND RELATED CELLS

BENIGN MALIGNANT Hematopoietic Leukemias

cells

Composed of One Parenchymal Cell Type

Lymphoid Lymphomas
tissue

A-Tumors of mesenchymal origin

MUSCLE

CONNECTIVE TISSUE & DERIVATIVES

Smooth Leiomyoma Leiomyosarcoma

Fibrous tissues Fibroma Fibrosarcoma

Striated Rhabdomyoma Rhabdomyosarcoma

Fatty tissues Lipoma Liposarcoma Epithelial Tumors

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 Stratified Squamous cell Squamous cell Totipotential Mature Immature teratoma,
Squamous papilloma carcinoma cells in teratoma, teratocarcinoma
dermoid cyst
Gonads or in
embryonic
Glandular Adenoma Adenocarcinoma rests
lining or ducts
Papilloma Papillary carcinomas

Cystademona Cystadenocarcinoma

Renal Renal tubular Renal cell carcinoma

Epithelium adenoma

Liver cells Hepatic Hepatocellular

adenoma carcinoma

Transitional Transitional cell Transitional cell

papilloma carcinoma

Placental Hydatidiform Choriocarcinoma

epithelium mole

Testicular Seminoma
epithelium
(germ cells) Embryonal carcinoma

II - MIXED TUMOR

Salivary gland Pleomorphic Malignant mixed

adenoma tumor of salivary origin

Renal anlage Wilmus tumor

III - >1 GERM LAYER

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 III. CHARACTERISTICS OF A TUMOR can go anywhere and invade other
→ A tumor is a proliferation of cells which is: tissues.
1. Progressive
2. Nuclear features when compared to a
2. Purposeless normal cell
→ like a tumor of fibrous tissue in origin, with a. Nucleus is larger, has irregular
no regular arrangement, has no purpose, borders, and has more chromatin
just there to compress the surrounding (hyperchromatic)
parenchyma b. Nucleolus is larger and has irregular
borders
3. Regardless of the surrounding tissue. c. Mitoses have normal and atypical
→ e.g. smooth muscle of the uterus mitotic spindles
compresses normal tissues and distorts
uterine cavity. It can even go bigger as a
basketball size. BIOCHEMICAL CHANGES IN MALIGNANT
→ Causes the compression of the endometrial CELLS
cavity, causing severe bleeding in the 1. Malignant cells rely on anaerobic
patient. glycolysis for energy
→ This explains why more lactic acid
4. Not related to the needs of the body. is produced under hypoxic
→ Like in Leukemia, it can have a WBC count conditions than one would see in a
of hundreds of thousands. normal cells.
→ Leukocytic cells enter the bloodstream, and 2. Malignant cells also have an increased
don’t function. The antibodies produced by uptake of a glucose analog.
the lymphocytes are useless, they will kill the a. PET scan is a special test has
patient by using up energy and nutrition. been developed in which cancer
→ e.g. certain tumors of the bone marrow cells cells take up glucose analog with
produce enormous numbers of leukocytes positron emission tomography
which enter the blood stream (PET)
b. PET scan is widely used in
5. Parasitic. the diagnosis, staging, and
→ The tumor draws nourishment from the body monitoring of therapy of various
whilst contributing nothing to its function. So, kinds of cancer because of its
these tumors are parasites, they cannot grow principle that cancer cells would
in size without the blood supply take up glucose

3.Cancer cells do not process glucose as well

CELL ORGANELLES IN MALIGNANT VS.
as normal cells, and store glucose in the form
NORMAL CELLS
of glycogen within the cytosol.
1. Organelles in the cytoplasm when
compared to a normal cell
4.Some cancers, like prostate cancer, derive
In malignant:
energy from beta oxidation of fatty acids
a. less mitochondria
rather than anaerobic glycolysis.
b. Rough endoplasmic reticulum (RER) is
less prominent
c. Loss of cell-to-cell adhesion molecules
(Cadherins) GROWTH RATES BETWEEN BENIGN AND
MALIGNANT TUMORS
→ Cadherins are the cell to cell
1. Benign tumors usually have a slow growth
adhesion molecules. Calcium
rate.
dependent.
→ So, you ask a patient, the history of the mass.
→ Loss of adhesion, means the
Five or ten years-- good indication that the
malignant cells can extend into
mass is benign,
surrounding tissue. That is why they
can infiltrate the surrounding
2. Malignant have a variable growth rate.
parenchyma. They are loose, and they

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 a. Growth rate correlates with degree of
differentiation of the malignant tumor.
→ For e.g: anaplastic (high grade) cancers
have an increased growth rate, whereas low
grade cancers tend to grow more slowly
→ For example, when the patient says they
have a huge mass, and they said they
noticed it a month ago, and it’s ten cm. This
is a good indication that it is malignant.
3. Clinically detectable tumor mass must have 30
population doublings to produce 10 cells,
which equals a gram of tissue.
→ A palpable mass would be at least 1cm or
10mm in size. If it is superficial.
Malignant cells with an increased growth rate
(myelogenous leukemia) are treated with cell
specific chemotherapy agents
a. Methotrexate (MTX), which inhibits the
synthesis or the S phase of the cell cycle
(duplication of DNA), whereas vincristine
inhibits the mitotic or the M phase of the cell
cycle.
Malignant cells with an increase in growth rate (e,g,
acute myelogenous leukemia) are treated with cell
cycle-specific chemotherapy agents
b. When malignant cells are killed, other
malignant cells quickly enter the cycle,
and the cycle repeats itself so that the size
of the tumor begin to shrink
So, this is the principle and the basis of
chemotherapeutic tracts. So, these drugs kills the
malignant cells and it enters the cycle then the cycle
would repeat itself. You have another group of
malignant cells getting killed. So, that would
decrease or shrink the size of the mass. So, when
the patient, by 3rd or 4th cycle you can see the
response of the drugs because of the decrease in its
size because these malignant cells are being killed
by the chemotherapeutic tracts.
MONOCLONALITY IN BENIGN AND
MALIGNANT TUMORS
1. Non neoplastic tumors derive from multiple
cells (polyclonal)
2. Benign and most malignant tumors derive
from a single precursor cell.
→ This is the basis of the tumor
nomenclature.
GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
→ For e.g. a squamous cell carcinoma arises
from a single cell, a squamous cell. A
leiomyeoma arises from smooth muscle.
→ This is derived from one single parent/one
single cell precursor
The monoclonal origin of neoplasms has been
shown by studying glucose-6-phosphate
dehydrogenase (G6PD) isoenzymes A and B in
selected neoplasms
All the neoplastic smooth muscle cells in uterine
leiomyomas have either the A or the B G6PD
isoenzyme.
Nonneoplastic smooth muscle proliferations in the
uterus (pregnant uterus) have some cells with the A
isoenzyme and others with the B isoenzyme,
indicating their polyclonal origin.
Monoclonal
→ one cell origin.
Polyclonal
→ can have either both A or B isoenzymes
In a pregnant uterus, you have an enlarged uterus
because of hypertrophy and hyperplasia of individual
cells. Hypertrophy of the smooth muscle, but this
enlargement of the uterine muscle is non neoplastic.
When you study this nonneoplastic smooth muscle
you will see that the cells of A and B isoenzymes.
Meaning they both have two origins. Whereas a
neoplastic smooth muscle only has A or B origin
(monoclonal).
TELOMERASE ACTIVITY IN BENIGN AND
MALIGNANT TUMORS
1. Telomere complexes
a. Definition: are repetitive sequences of
non-transcribed DNA located at the ends of
chromosomes.
b. They prevent end-to-end fusion of
chromosomes during normal mitosis and,
along with other factors, are important in
determining the longevity of a cell
c. Shorten with each round of replication
and eventually, when only a few
nucleotide bases remain, genome
becomes unstable with produces a signal
for apoptosis
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2. Benign tumors have normal telomerase
activity.
3. Malignant cells have upregulation of
telomerase activity, which prevents naturally
programmed shortening of telomere complexes with
cell replication, hence the cell no longer undergoes
apoptosis.
In malignant tumors, there is an upregulation the
telomerase activity such that it prevents the naturally
programmed shortening of complexes with cell
replication so the cells don't die, so, this is the basis
on immortality of the cells more cell production over
cell death.
UPREGULATION OF DECAY ACCELERATING
FACTOR (DAF) BY MALIGNANT CELLS
1. DAF normally degrades C3 convertase and C5
convertase in the classical and alternative
complement pathways
2. Upregulation of DAF ensures that degradation
of the convertases just mentioned prevents
formation of the membrane attack complex
(MAC; C5b-9); therefore, cancer cells cannot
be killed by the MAC. Remember the attack
complex.
So again, the decay accelerating factor. So, this
factor degrades C3 convertase and C5 convertase
in the classical and alternative pathways. So, when
this factor, the DAF is abrifiliated by malignant cells,
it ensures degradation of these convertases
preventing formation of the membrane attack
complex. Therefore, the cancer cells cannot be killed
by the map.
IV. LOCAL INVASION AND METASTASIS
1. Benign tumors do not invade
→ Benign tumors are usually enclosed by a
fibrous tissue capsule. Exception is a
uterine leiomyoma (benign tumor of
smooth muscle), which does not have a
fibrous
But this leiomyoma in the uterus appears well
circumscribed even if they are not enclosed by a
capsule, they are well demarcated so that you can
identify the tumor from the adjacent myometrium.
2. Malignant tumors
→ Malignant tumors on the other hand, they
invade.
a. Invade tissue
GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
→ Invasion is an important criterion for
malignancy.
b. Bone tissues resist invasion.
→ Examples include mature cartilage and
the elastic tissue of arteries.
This cartilage and elastic tissue of arteries are the
tissues that resist invasion. That’s why in metastasis,
what is affected are the veins and not the arteries in
hematogenous descrimination of tumor cells.
c. All malignant tumors require oxygen and
nutrients to survive and do so by stimulating
angiogenesis within the tumor and its metastatic
sites
(1) Angiogenesis, or new blood vessel formation,
occurs by forming capillary sprouts from
preexisting capillaries (parent capillaries)
and/or by stimulating the synthesis of
endothelial precursor cells (EPCs) from the
bone marrow that migrate to the tumor site.
(2) Vascular endothelial growth factor (VEGF)
and other growth factors produced by the
tumor directly act on endothelial cells in the
parent capillaries to develop new capillary
sprouts.
→ They are the ones that fed the tumor,
parent, or even the metastatic subcons.
So, there’s a factor, a substance called
tumor necrosis factor which is released
by macrophages.
→ Tumor necrosis factor (TNF) released by
macrophages is important in stimulating
tumor cells to produce these
angiogenesis factors.
(3) Chemotactic factors produced by the tumor
cells and inflammatory cells (particularly
macrophages) assist in attracting endothelial
cells from the present capillaries to form the
new capillary sprouts.
(4) Enzymes (e.g., proteases) regulate the
balance between angiogenesis and the
many factors that can inhibit angiogenesis
(e.g., angiostatin, endostatin).
(5) Enzymes also degrade basement
membranes in parent vessels to allow
endothelial cells to migrate and form new
capillary sprouts.
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 (6) EPCs from the bone marrow are also used in
new vessel formation.
So that’s how this tumor, malignant tumor can get
enough blood supply
(7) Monoclonal antibodies have been developed
to inhibit tumor angiogenesis.
→ So, when there’s angiogenic factors,
there are also anti-angiogenic factors like
the monoclonal antibodies. In this anti-
angiogenic factors can be acted upon by
drugs like:
→ For example, bevacizumab is a
recombinant humanized antibody that
inhibits the binding of VEGF to
endothelial cells in new capillary sprouts.
Monoclonal antibodies are indicated for
the treatment of metastatic colon cancer
and non-small cell carcinoma of the
lung.
These monoclonal antibodies are now used to inhibit
tumor angiogenesis or anti-angiogenesis. And these
are the drugs that inhibit the binding.
This is a diagram to compare a benign and
malignant tumor using a thyroid neoplasm as an
example.
In a benign tumor, it is well circumscribed and
encapsulated. So, you have a smooth border while
a malignant tumor has an irregular border and is
infiltrative. You have an invasive growth, the
presence of necrosis and invasion of the nearby
structures. So, this is how to differentiate a benign
from a malignant tumor
.
The growth or benign is slow, malignant is fast. And
of course, malignant tumors they metastasize. So,
appearance, when you have a smooth surface, it’s
GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
more benign and irregular, it is malignant. If it’s
encapsulated, more often, it is benign.
Presence of necrosis and hemorrhoids would
indicate malignancy. And microscopically, when the
malignant tumor or the cells are prolly differentiated
and they have a pleomorphic and hyperchromatic
nuclei, that’s malignant. But for benign tumors, they
resemble normal tissue with fewer mitosis.
Malignant tumors
→ rapid growth
Rapidly growing malignant tumors often contain
central areas of ischemic necrosis because of tumor,
blood supply fails to keep pace with the oxygen
needs of the expanding mass of cells.
Such that in a 20 cm mass, you would expect that
the center of that mass appears soft because of
necrosis. While the ones at the periphery wherein
they receive direct blood supply then they are the
ones that are more viable. So, for biopsy, we usually
take the mass that is on the peripheral side because
these are the ones that are viable. We don’t sample
areas that are necrotic because it’s not diagnostic.
What is the difference between tumor invasion
and metastasis?
• Invasion
→ tumors invade locally and extend into the
surrounding normal tissues
• Metastasis
→ spread of tumors to sites that are
anatomically separate from their site of
origin
ALL CANCERS CAN METASTASIZE EXCEPT
GLIOMAS AND BASAL CELL CARCINOMA.
So, if we have the choice to ask what kind of cancer
you like to have? What do you like?
→ Doc: Well, for me, I would prefer a basal cell.
Why? Because basal carcinoma is just like
a mole. You excise it with an adequate
margin. That’s all. You’re safe.
→ But for gliomas, they don’t metastasize but
it’s in the brain. No matter how small the size
is. It can compress adjacent neural tissues.
And can cause symptoms.
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 INVASION AND METASTASIS
→ is the major cause of cancer related
morbidity and mortality.
→ Direct invasion of arteries is rare because of
the physical barrier provided by the thick
muscular and elastic walls of the arteries.

• Local Invasion
→ Nearly all benign tumors grow as cohesive
expansile masses that remain localized to
their site of origin and do not have the
capacity to infiltrate or metastasize.
→ Growth of cancer is accompanied by This is a 10 year history of thyroid mass (goiter) It's
progressive infiltration, invasion and movable.
destruction of surrounding tissues.
→ Invasiveness is the most reliable feature that
differentiates malignant from benign tumors.
→ Once a tumor has invaded, invade is local
extension or infiltration of the mass or
adjacent tissue. so, when a tumor infiltrates r
invades a local tissue that is INVASION but
in METASTASIS is when the tumor goes to
another organ distant from its site. e.g Breast
Cancer.

• Metastasis
→ Tumor implants discontinuous with the
primary tumor
This is a 1 year history of an anterior neck mass. The
Pathways of Spread: mass has already extended to the lateral neck and it
→ Seeding of body cavities and surface. E.g has already involved the nodes.
→ Lymphatic spread
- Route of spread of Carcinomas.
→ Hematogenous spread Radiological Findings
- Route of spread of Sarcomas • Benign Tumors
→ are Circumscribed
→ There are carcinomas that spread via the → It can have a smooth surface.
blood vessels like Hepatocellular • Malignant Tumors
Carcinoma, Follicular Carcinoma of the → have irregular outlines and invade the
Thyroid and Renal Cell Carcinoma. surrounding tissues.

Clinical Findings between Benign and Malignant Gross Features:

Tumors: → During surgery, one may assess tumors by
• Benign tumors direct inspection or palpation.
→ tend to grow slowly and remain → When you can easily palpate the mass then
localized. that is Benign, but if the mass is adherent to
• Malignant tumors adjacent structures because of invasion,
→ tend to develop fast. infiltration, then that is Malignant.

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 → Loss of Polarity.
→ Atypical Mitoses.

Histological Examination

• Benign
→ Smooth Surface Encapsulated. (Top
Picture)

→ (Refer to the picture above) On the left is a

benign tumor of the tissue, Lipoma and in
the middle and left are malignant tumors
arising from fat called Liposarcoma. In the
Malignant tumor, you can see more of the
hyperchromatic Nuclei and bizarre/ugly
looking cells.

GRADING
→ based on the microscopic examination of
• Malignant tumor tissues obtained at the time of
→ Irregular, no borders and non-capsulated. operation or by biopsy.
→ Also based on the degree of differentiation of
tumor cells and the number of mitoses within
the tumor.
→ I - IV with increasing anaplasia or well,
moderately or poorly differentiated.

STAGING
→ It is based on the size of the primary lesion,
extent of spread to regional lymph nodes and
+/- blood borne metastasis.
→ UICC-TNM system. (T=Tumor N=Nodal
Metastasis and M=Distant Metastasis).
→ AJC-O TO IV
→ More predictive of tumor behavior
and is more valuable for prognosis.
→ Staging would depend on the presence or
Cytopathologic Features absence of metastasis, you need a work-up
Common features of Anaplasia: first, like CT scan to check if you have nodal
→ Pleomorphism. metastasis or metastasis to the lungs or to
→ Hyperchromatic Nuclei. other organs, because staging is dependent
→ High Nucleocytoplasmic Ratio. For normal on the nodes apart from the size of the tumor
cells the ratio is 1:3 or 1:4 but for malignant and the presence of metastasis.
cells the ratio is 1:1 or 1:2.
→ Bizarre Cells.

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 EPIDEMIOLOGY → skin cancer is more common in fair-skinned
CANCER INCIDENCE people than dark-skinned people because of
→ 2014 estimated cancer incidence by site and the protective effect of melanin ultraviolet
sex light. Such that, melanomas are not common
among Filipinos but for white-skinned like the
• MALE Caucasian they are more prone to develop
→ Prostate 30% Squamous Cell Carcinomas and Melanomas
→ Lung and Bronchus 14% → Breast cancer has low incidence in Japanese
→ Colon and Rectum 11% and Asian women, whereas the incidence is
• FEMALES highest in north American and European
women.
→ breast 31%
→ Lung and bronchus 12% → liver cancer is lethal among native Africans.
But, it is still high in Filipinos because of
→ colon and rectum 12% alcoholism and more incidence of hepatitis
viral infections.
• Cancer Death (male)
→ Lung and bronchus 31% POSSIBLE ENVIRONMENTAL INFLUENCES
→ Prostate 11% ARE
→ Colon and rectum 10% → workplace
→ diet
• Cancer Death (female) → personal practices like cigarette smoking and
→ Lung and bronchus 25% chronic alcohol consumption, sexual habits.
→ -Breast 15% (risk of cervical cancer is linked to age at first
→ -Colon and rectum 11% intercourse and the number of sex partners –
oncogenic virus)
GEOGRAPHIC AND ENVIRONMENTAL
FACTORS AGE
→ Environmental cause 60% → frequency of cancer increases with age the
majority are in persons 55 years or older
→ Heritable Cause 26-42%
o The rising incidence with age is due
to accumulation of somatic mutations
associated with the emergence of
• External factors malignant neoplasms and decline in
→ Tobacco (#1) immune competence that
→ alcohol accompanies aging
→ chemical o Such that in Carcinogens, you don’t
→ radiation develop cancer right away it takes
→ microbial pathogens years.
→ Colorectal, lung, and prostate cancer
• Internal factors: progressively increase in incidence with age.
→ Hormones o Whereas others reach a peak and
→ Immune conditions begin to decline (e.g. malignant
→ Inherited Mutations. melanoma)
→ Most cancer occurs between 55-75
RACIAL AND ETHNIC DIFFERENCES AFFECT → Cancer causes slightly more than 10% of all
CANCER INCIDENCE deaths among children younger than 15
→ Blacks have greater risk for developing years.
prostate cancer than white Americans → Major lethal; cancers in children, leukemia,
→ Japanese men have a low incidence of tumor of the CNS, lymphomas, soft tissue
prostate cancer, but they have high and bone sarcomas.
incidence of gastric cancer because of the
smoked foods HEREDITY

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 → Mortality from lung cancer is 4x greater → So, you decrease eating fatty food but you
among non-smoking relatives of lung cancer increase eating fruits or vegetables and
patients (parents and siblings) that reduce alcohol intake
nonsmoking relatives of controls • Reducing Alcohol Intake
• Reducing Weight
Heredity Forms of Cancer: (1) more adipose tissue increases
• INHERITED CANCER SYNDROMES aromatase conversion of androgens to
→ single mutant gene greatly increases the risk estrogen
of a person developing a tumor. (2) increased levels of estrogen increase
→ autosomal dominant pattern of inheritance the risk for developing endometrial and
childhood retinoblastoma breast cancer.
→ familial adenomatous polyposis
→ associated with specific marker type → sunscreen protection decreases the risk for
developing BCC, SCC, and malignant melanoma
• FAMILIAL CANCERS of skin
→ all common types of sporadic cancers are
carcinomas of colons, breast, ovary and IMMUNZATION
brain. • HBV immunization
Features that characterize familial cancers → decreases the risk for developing HCC, due
are: to HBV-induced cirrhosis
→ early age onset • HPV immunization
→ tumors arising in two or more close relatives → against HPV decreases the risk for
of the index case. developing SCC of the cervix and penis
→ multiple or bilateral
Because cell replications are involved in cancerous
Certain Familial cancer can be linked to the transformation, regenerative, hyperplastic and
dysplastic proliferations
inheritance of mutant genes
→ are fertile soil for the origin of a malignant
→ linkage of BRCA 1 and BRCA 2 genes to
neoplasm
familial breast and ovarian cancers
→ you have to prevent this to happen
AUTOSOMAL RECESSIVE SYNDROMES OF
There is well defines association between:
DEFECTIVE DNA REPAIRS
• Endometrial Hyperplasia and Endometrium
→ characterized by chromosomal or DNA
Carcinoma
instability ex. Xeroderma Pigmentosum
→ because of excessive estrogen
• Cervical Dysplasia and Cervical Carcinoma
→ because of HPV infection
• Bronchial Dysplasia and Cervical Carcinoma
→ because of smoking
• Liver Cirrhosis Hepatocellular CA
→ because of alcoholism and hepatitis
infection
• Villous Adenoma of Colon and Colorectal
CHECK THE BOOK FOR CLEAR PHOTO Carcinoma
→ because of high saturated fat diet
ACQUIRED PRENEOPLASTIC DISORDER
MODIFY LIFESTYLE Precancerous conditions (non-neoplastic
• Cessation of smoking cigarettes disorders)
→ most important lifestyle modification to • Chronic Atrophic Gastritis of Pernicious
prevent cancer Anemia
• Increasing dietary fiber and decreasing dietary → can be pre-dispose to develop gastric
saturated animal fat carcinoma
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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez
 • Solar Keratosis of Skin
→ can develop squamous carcinoma of
the skin
• Chronic Ulcerative Colitis
→ patient will develop colorectal cancer
• Leukoplakia of Oral Cavity, Penis, Vulva
→ patients with leukoplakia they can
develop Squamous cell carcinoma

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GENPATH TRANS 1.01 Trans Team:| Alinoor, Banuag, Haghiri, Macaayan, Nadera, Pantao, H. Rasul, Yap | Editor: Alcuitas, Alvarez, Bernadez