DGP_3101.

GENERAL PATHOLOGY
MIDTERM
MODULE 5. NEOPLASIA mutations (genetics) affecting a
single cell and its clonal progeny.
Organ Parenchyma • Two Components of Tumors:
Bone Osteon 1. Parenchyma – neoplastic cells
Liver Hepatocyte 2. Reactive stroma
Nervous system Neurons - Connective tissue, blood vessels,
Cartilage Chondrocytes and cells of the adaptive and
innate immune system
Fat/Adipose tissue Adipocytes
- Supports parenchyma
Striated muscle Rhabdocyte - The more reaction happen, the
Smooth muscle Leiomyocyte more damage the tissue will be
Germ Cell Layers:

1. Ectoderm
• Epidermis
• Nervous system
2. Mesoderm
• Adipose
• Dermis layer
• Bone
• Cartilage
3. Endoderm
• Glands
• Liver

Mesenchymal

- Arise from mesoderm

- Connective tissue
- Bone, muscle, blood cells, cartilage, and
fats

Epithelial

- Squamous cells
- Epithelial layers
- Liver
- Neurons

INTRODUCTION TO NEOPLASIA
Tissue components:
Nomenclature P – parenchyma
S – stroma
• Neoplasia
- “Neo” = new Classification of Tumor
- “Plasia” = growth
- New growth • Tumors classification and their behavior
- The collection of cells and the are primarily based on the parenchymal
stroma composing new growths component.
are referred to as neoplasms • Tumor growth and spread are critically
• Tumor dependent on their stroma.
- now equated with neoplasm Scant Stroma
• Oncology
- Greek “oncos” = tumor” - less fibrous
- The study of neoplasms - smooth tumor
• Modern Era - soft and fleshy
- A neoplasm is defined as a genetic
Desmoplasia
disorder of cell growth
- Triggered by acquired (health - When parenchymal cells stimulate the
habits) or less commonly inherited formation of abundant collagenous
stroma

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Scirrhous tumors

- Stony hard tumors because of the

desmoplastic stroma
- Example: some cancers of the breast
Normal Benign
Digestive Parenchyma
Tract -
NORMAL

Stroma
Invasive Ductal Carcinoma - MALIGNANT
Tumor or neoplasia of the breast

Normal Pathological

Benign Malignant

Digestive Tract -
ABNORMAL

Invasive Ductal Carcinoma (highly desmoplastic) –

Scirrhous (stony-hard tumor)
Normal Pathological

Pathological Normal
1. Identify the tissue (both images came from
the same). HYALINE CARTILAGE
2. Which is normal, which is pathological.
3. Is the pathological one benign or
malignant? MALIGNANT
4. Give your histopathologic diagnosis for
your answer in number.
Breast - Normal
CHONDROSARCOMA

BENIGN VS. MALIGNANT

BENIGN

• Remain localized at their site of origin and

are generally amenable to surgical
removal
Fibroadenoma – benign (not cancerous) • Not cancerous
Tumor or neoplasia of the breast • Easily removed

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• When benign tumors occur in vulnerable
locations such as the brain may cause
significant morbidity and are sometimes
even fatal
• Benign mesenchymal tumors
- in general, the suffix “oma” is
attached from which the tumor Leiomyosarcoma
Leiomyoma (Benign)
arise: (Malignant)
1. Fibroma – Fibrocytes
(fibroblast-like cells)
2. Lipoma – Lipocyte
3. Chondroma – Adipose Tissue -
Chondrocytes (benign Normal
cartilaginous tumor)
4. Osteoma – Osteocytes
5. Myoma – Myocyte
- Neoplastic form of
muscle
▪ Striated –
Rhabdomyoma Lipoma
▪ Smooth – Leiomyoma

Collagen
fibers
Normal Lipoma

Fibroma

Bone –
NORMAL

Normal Fibroma

Bone (Benign)
OSTEOMA

Fibroma Fibrosarcoma Normal Benign

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Adenomatous Polyp

➢ If polyp has glandular tissue

Colonic Polyp

Uterus
- Myometrium

Myometrium
Leiomyolipoma

An adenomatous (glandular) Gross

polyp is projecting into the appearance of
colonic lumen and is several colonic
attached to the mucosa by polyps.
a distinct stalk
Benign Epithelial Tumors

- classified on their microscopic

appearance (histology), while others on Without stalk -
sessile
their macroscopic (gross) architecture:
1. Adenoma – applied to benign
epithelial neoplasms derived from
glandular tissues.
2. Papilloma – for those that produce
fingerlike or warty projections
(papillary structures).
3. Cystadenoma – forming large
By their gross or macroscopic appearance, these
cystic masses (cyst + adenoma),
tumors (assuming they are benign) are called?
like in the ovary
4. Papillary cystadenoma – cyst + • ADENOMA (because it is glandular)
adenoma + papillary projections
5. Polyp – if the tumor produces a Papilloma
grossly visible projection above a
• a benign (non-cancerous) tumor arising
mucosal surface (can be applied
from an epithelial surface and usually
also to malignant tumors)
known to grow in an outward direction.
o Adenomatous polyp is a
polyp that has glandular
tissue.
Large Intestine
(Transverse colon)

Polyp

➢ When a neoplasm—benign or malignant—

produces a grossly visible projection
above a mucosal surface, for example,
into the gastric or colonic lumen.

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Cytadenoma - EPITHELIAL
- Malignant epithelial tumors
• rare cystic tumors of epithelial origin that
a) Squamous cell carcinoma –
arise in the liver, the majority in the right
tumor cells resemble
lobe, or less commonly in the extrahepatic
stratified squamous
biliary system.
epithelium
b) Adenocarcinoma – the
neoplastic epithelial cells
grow in a glandular pattern

Squamous cell became cancer →

CARCINOMA
Glands becmae cancer → SARCOMA

MIXED TUMORS

• Classic example is the benign mixed tumor

of the salivary gland, that is composed of
epithelial components scattered within a
myxoid stroma, that may contain islands of
cartilage or bone (epithelial +
mesenchymal), called PLEOMORPHIC
ADENOMA
• Adenocarcinoma – GLANDS

Papillary Cyst Adenoma

Normal

MALIGNANT TUMORS

• Collectively referred to as cancers derived

from latin word crab because they tend to
adhere to any part that they seize on in an
Benign – OSTEOMA
obstinate manner.
• Follow the same schema used for benign
tumors, plus:
1. Sarcoma
- Greek sar = fleshy
- Fibrous
- MESENCHYMAL
- e.g., fibrosarcoma and
chondrosarcoma
2. Leukemia or Lymphoma
- Arising from blood-forming Malignant– OSTEOSARCOMA
cells
- Malignancy in blood cells
- e.g., Cancer in Lymphoid
Tissue
3. Carcinoma

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Squamous cell carcinoma

Mixed tumor of the parotid gland

(Mixed Pleomorphic Adenoma)

Teratoma

• Contains recognizable mature or

Adenocarcinoma (to be more
specific, colonic adenocarcinoma)
Pleomorphic adenoma, a classic example of a mixed tumor.
immature cells or tissues belonging to
more than one germ cell layer, and
sometimes all three are present
• Majority of neoplasms are composed of
cells from a single germ layer:
1) Mesoderm
2) Endoderm
3) Ectoderm
• Also called dermoid cyst.
o Mature teratomas are BENIGN.
o Immature teratomas are
MALIGNANT.
• Originates from totipotential germ cells
that are normally present in the ovary and
testis.
• Sometimes also found in abnormal midline
embryonic rests.

Cystic teratoma of
the Ovary

CASE ANALYSIS

• A 25 year old female came to the clinic

Leiomyoma presenting with a palpable movable, non -
tender mass on the upper outer quadrant
of her right breast. The skin over and
surrounding the mass does not show any
skin discoloration and there are no
abnormal discharge. The patient is also
negative for lymphadenopathy. She was
Normal Benign - Leiyomyoma scheduled for
surgery and
upon excision
this was the
mass:
BREAST

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• Microsection shows a well circumscribed Anaplasia
lesion composed of a proliferation of
- Lack of differentiation
glandular and stromal elements. The
glands appear to be compressed by the
• In general, benign tumors are WELL
proliferating surrounding stroma in some
DIFFERENTIATED.
areas. No atypia seen.
• Malignant tumors exhibit morphologic
alterations that betray their potential for
aggressive behavior, but these features
may not be obvious.
• MALIGNANT TUMOR
- Exhibit morphologic alterations that
betray their potential for aggressive
behavior, but these features may
not be obvious
- POORLY DIFFERENTIATED CELLS
➔ tumors exhibit little or no
1. Histopathologic diagnosis.
evidence of differentiation
FIBROADENOMA
• BENIGN TUMOR
2. Benign or malignant? BENIGN
- Well differentiated
• A 55 year old female came to the clinic
presenting with a palpable non-movable,
mass on the upper outer quadrant of her
right breast. There is skin discoloration and
the right axillary lymph node is palpable.
She was
scheduled
for surgery Striated Muscle Striated Muscle
and upon NORMAL ABNORMAL
excision
this was
the mass:

• Microsection shows a neoplasm

composed of proliferating duct structures
arranged in sheets and cords infiltrating
surrounding fibrotic stroma. The ductal Thyroid Gland Thyroid Gland –
cells exhibit nuclear atypia and mitotic (NORMAL) ABNORMAL
figures are frequent. (Adenoma – benign)

Adenomatous goiter – benign thyroid gland

Stratum Corneum

Stratum Basale
1. Histopathologic diagnosis.
INVASIVE DUCTAL CARCINOMA
Normal Squamous Cell
2. Benign or malignant? MALIGNANT

DIFFERENTIATION AND ANAPLASIA Well-differentiated

squamous
Differentiation epithelial cells of
the skin arranged
- Refers to the extent to which neoplastic in islands

parenchymal cells resemble the

Intercellular
corresponding normal parenchymal cells, bridges and nests
both morphologically and functionally. of keratin pearls
(differentiated
cancer cells)

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Glandular Epithelium

COLONIC GLANDS – Malignant Tumor

(adenocarcinoma)
Adenoma – still well differentiated
NOTE: Compared with the well-formed and
normal-looking glands characteristic of a benign
tumor, the cancerous glands are irregular in
shape and size and do not resemble the normal
colonic glands. This tumor is considered
moderately well differentiated because gland
formation is seen. The malignant glands have
invaded the muscular layer of the colon.

• In addition to anaplasia, malignant tumors

Adenocarcinoma – well differentiated
will exhibit:
1. Pleomorphism
- refers to variation in cell size
and shape.
2. Abnormal nuclear morphology
- Characteristically, cancer
cells have nuclei that are
disproportionately large, with
a nuclear-to-cytoplasm ratio
that may approach 1: 1
instead of the normal 1 :4 to Adenocarcinoma – poorly differentiated
1:6.
- Hyperchromatic: darkly
stained than normal
3. Mitoses
- Unlike benign tumors and
some well-differentiated
malignant neoplasms,
undifferentiated cancers often
contain many cells in mitosis, Abnormal Mitosis
(in Metaphase
reflecting their high rate of
stage)
proliferation
4. Loss of polarity
- In addition to cytologic
abnormalities, the orientation
of anaplastic cells with respect
to each other or to supporting
structures like basement
membranes is markedly
disturbed
5. Areas of necrosis may be seen due
to the rapid growth of tumor cells;
the blood supply may be
insufficient.
Pleomorphic tumor of the skeletal
muscle (Rhabdomyosarcoma)

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Pleomorphic rhabdomyosarcoma
Thyroid Gland – NORMAL

METAPLASIA, DYSPLASIA, AND CARCINOMA IN SITU

• Metaplasia
Poorly differentiated thyroid carcinoma - Is defined as the replacement of
one type of cell with another type
- Nearly always found in association
with tissue damage, repair, and
regeneration.
o Example: BARRETT
ESOPHAGUS
- Gastroesophageal
reflux damages the
squamous
Anaplastic thyroid carcinoma
epithelium of the
esophagus, leading
to its replacement
by glandular
(gastric or intestinal)
epithelium better
suited to an acidic
environment.
• Dysplasia
- Is a term that literally means
Striated Muscle – NORMAL “disordered growth.”
- Dysplastic cells may exhibit
considerable pleomorphism and
often contain large hyperchromatic
nuclei with a high nuclear-to-
cytoplasmic ratio.
- Dysplastic epithelial surfaces
typically show architectural disarray
and a loss of orderly differentiation.
Rhabdomyoma • Carcinoma in-situ
- Dysplasia that is severe, involving
full thickness of the epithelium, but
the lesion does not penetrate the
basement membrane.
- Often seen in the skin, breast,
bladder, and uterine cervix.

Normal

Rhabdomyosarcoma

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Carcinoma in-situ primary tumor, event that unequivocally

marks a tumor as malignant.

Fibroadenoma
of the breast

LOCAL INVASION VS. METASTASIS

• Benign (not cancer) – tumor cells grow Invasive Ductal Carcinoma of the Breast

only locally and cannot spread by

invasion or metastasis
• Malignant (cancer) – cells invade
neighboring tissues, enter blood vessels,
metastasize to different sites

Involvement of omentum by
metastatic ovarian carcinoma

Lymph node – NORMAL

Local Invasion

• The growth of cancers is accompanied by

progressive invasion, destruction of
surrounding tissue, and eventually systemic
spread, whereas nearly all benign tumors
grow as cohesive, expansile masses that
remain localized to their site of origin and
lack the capacity to invade or metastasize
to distant sites.

Metastasis

• Defined as the spread of a tumor to sites Axillary Lymph Node with

that are physically discontinuous with the METASTATIC BREAST CARCINOMA

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Liver studded with
metastatic cancer
Lung metastasis
Normal
Carcinoma in-situ
Local Invasion
Metastasis
Scenario in connection to METASTASIS:
❖ Imagine that the basement membrane is
the wall surrounding the school in the All of
Us are Dead
❖ As long as the infected are confined within
the school and has not gone beyond the
wall, they are inside or in-situ. The infected
are the cancer cells thus CARCINOMA IN-
SITU.
❖ Once the infected breaches or breaks
through the wall of the school (the
basement membrane), they are no longer
confined inside or no longer in-situ.
❖ But since the invasion of the infected is still
within the same town (same organ/tissue),
it is LOCAL, therefore, it is called LOCAL
INVASION because it is still locally confined
even if the infected broken through the
basement membrane (wall of the school).
❖ Imagine the side of the wall as surrounding
area of the tissue/organ outside the
basement membrane. Since the same
organ/tissue, it is still local, but no longer
carcinoma in-situ because it is now
invaded by the infected cancer cells thus
termed LOCAL INVASION.
❖ Now, imagine the infected students went
all the way to another town (different
tissue organ). They are no longer local;
they have gone beyond their town of
origin or have spread to different parts of
Korea. This is now METASTASIS or
METASTATIC SPREAD.
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Dysplasia
• Dysplastic cells exhibit considerable
pleomorphism.
• Cells often contain hyperchromatic nuclei
with a high nuclear-to-cytoplasmic ratio
• Dysplastic epithelial surfaces typically
show architectural disarray and a loss of
orderly differentiation.
IHC STAINS (Immunohistochemical stains for
Immunostains)
Immunohistochemistry (IHC)
• Is used in histology to detect the presence
of specific protein markers that can assist
with accurate tumor classification and
diagnosis
• Target antigens for IHC are proteins that
are within or on surface of a cell.
Pathologists look for the presence or
absence of particular antigens to assist
with diagnosis.
• There are many hundreds of antigens that
have been found to be diagnostically
useful. Often, a pathologist will use a
“panel” of multiple antigens to help fully
classify a particular tumor.
• Basically, IHC stain is the “ANTIBODY” that
binds to the target antigen (protein)
expressed by cell/tissue.
How the immune system works
• When an antigen (e.g., microorganism)
enters the body, the immune system as
activated to produce antibodies that is
specific for that antigen.
• When antibodies opsonize the antigen, it
will be neutralized.
• Now, you have circulating antibodies that
will now recognize that antigen if you get
exposed to it again.
• The result, again is neutralization of the
antigen.
For example
1) The B-cell finds an antigen which matches
its receptor
2) It waits until it is activated by a T-helper
cell
3) The B-cell divides to produce plasma and
memory cells.
4) Plasma cells produce antibodies that
attach to the current type of invades.
5) “Eater cells” prefer intruders marked with
antibodies and ‘eats” load of them.
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6) If the same intruder invades again, CK7 AND CK20
memory cells helps to activate the
CK7
immune system to activate much faster.
• Generally expressed (with some variations)
in adenocarcinoma of the lung, breast,
thyroid, endometrium, cervix, ovary,
salivary gland, upper GI tract, urothelial
carcinoma, papillary renal cell carcinoma
and Paget diseases.
• Generally negative (with some variation) in
colorectal carcinoma, Merkel cell
carcinoma, hepatocellular carcinoma,
prostatic adenocarcinoma,
• GPC (-) adrenocortical tumors and squamous cell
• Normal liver negative for glypican-3 carcinoma.
• No IHC CK20

• Positive staining (normal)

o Colon
o Merkel cells
o Small intestine
o Urothelium (umbrella cells)
o Uterus
• Positive staining (not malignant)
o Bladder intestinal metaplasia
o H-mole
• GPC (+) • Positive staining (malignant)
• Hepatocellular carcinoma positive for o Colon
glypican-3 o Stomach
• With IHC o Liver
o Ovary
No IHC + glypican-3 = Positive for glypican-3, o Merkel cells
which means this is from the liver or if this is • CK7+ / CK20+
a neoplasm (tumor), this neoplasm’s origin is o Carcinomas of bile duct
the LIVER. extrahepatic/gallbladder
o Carcinoma in lung (mucinous)
• CK7- / CK20+
So, if the neoplasm is not from the liver o In carcinoma of colon (particularly
and glypican-3 is used, there won’t be early stage
any reaction, and it would negative for To distinguish primary lung carcinoma
that IHC. (CK7+ / CK20-) from metastatic colonic
carcinoma to lung (CK7- / CK20+)
To help distinguish colon carcinoma (80%
are CK20+) and poorly differentiated
prostatic carcinoma (90% are ck20-)

Metastatic Ovarian Cancer, Malignant Ascites, Cell

Block: CK20 negative, Ck7 positive Ck7+ in lung adenocarcinoma and
normal alveolar cells

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Other examples of IHC: Environmental Factors

• CEA – expressed by lungs, stomach, • Play a dominant role in the development

pancreas, colon, heart of cancers.
• PSA – expressed by prostate 1) Infectious agents
• AFP, glypican-3 – expressed by ▪ hepatocellular carcinoma
hepatocytes (HCC) from HBV and HCV,
• LCA – expressed by lymphoid tissues. squamous cell carcinoma
• CD3 – expressed by T-lymphocytes from HPV, gastric
• CD20 – expressed by B lymphocytes adenocarcinoma from H.
• Desmin – expressed by mesenchymal pylori
tumors 2) Smoking
• NSE – expressed by neural tumors ▪ Single most important
environmental factor
EPIDEMIOLOGY OF CANCER
contributing to premature
• Epidemiologic studies have established death in the United States.
the causative link between smoking and 3) Alcohol consumption
lung cancer, and comparison of diet and ▪ Increases the risk of
cancer rates in different regions of the carcinoma of the
world has linked diets high in fat and low in oropharynx (excluding lip),
fiber to colon cancer. larynx, and esophagus and,
• The strong association of certain by the development of
inflammatory and other diseases with alcoholic cirrhosis,
cancer also provides clues to its hepatocellular carcinoma.
pathogenesis ▪ Risk of cancers in the upper
• Genetics airways and digestive tract
• In 2018 it was estimated that there were 4) Diet
over 9.5 million deaths caused by cancer ▪ Incidences of colorectal
worldwide, representing nearly 1 in 6 of all carcinoma, prostate
deaths. carcinoma, and breast
carcinoma has been
ascribed to differences in
diet
5) Obesity
6) Reproductive history
▪ Unopposed by
progesterone, increases the
risk of cancers of the breast
and endometrium
7) Environmental carcinogens
▪ Asbestos (lung cancer)
▪ UV radiation (skin cancer)
▪ Benzene (leukemia)

Age

• Most carcinomas occur in adults older

than 55 years of age.

Acquired predisposing conditions

• predispose to cancer can be divided into

chronic inflammatory disorders, precursor
lesions, and immunodeficiency states.
o Chronic Inflammation
o Precursor lesions
o Immunodeficiency and cancer

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MOLECULAR BASIS OF CANCER • Enabling replicative immortality
• Tumor-promoting inflammation
• Technologic advances in DNA sequencing
• Activating invasion metastasis
and other methods permit genome-wide
• Genomic instability (mutator phenotype)
analysis of cancer cells
• Resisting cell death
• Nonlethal genetic damage lies at the
• Inducing angiogenesis
heart of carcinogenesis
• Deregulating cellular energetics
o Initial damage (mutation) may be
• Sustaining proliferative signaling
caused by environmental
exposures, and may be inherited in
the germline, or may be
spontaneous and random.
o Refers to any acquired mutation
caused by exogenous agents such
as viruses or environmental
chemicals or by endogenous
products of cellular metabolism
that have the potential to damage
DNA (such as reactive oxygen
species) or alter gene expression
through epigenetic mechanisms
(e.g., so-called oncometabolite,
described later)
• A tumor is formed by the clonal expansion
• There are four classes of genes are the
of a single precursor cell that has incurred
principal targets of cancer-causing
genetic damage (i.e., tumors are clonal)
mutations.
• Carcinogenesis results from the
1) Growth-promoting proto-
accumulation of complementary
oncogenes
mutations in a stepwise fashion over time
2) Growth-inhibiting tumor suppressor
o Mutations that contribute to the
genes
acquisition of cancer hallmarks are
3) Genes that regulate programmed
referred to as driver mutations
cell death (apoptosis)
o Loss-of-function mutations in genes
4) Genes that are responsible for DNA
that maintain genomic integrity
repair
appear to be a common early
step on the road to malignancy,
particularly in solid tumors.
o Mutations in many other genes
contribute to tumorigenesis by
interfering with host immune
responses or altering interactions
with the stroma, or by other
mechanisms.
• Once established, tumors evolve
genetically during their outgrowth and Proto-oncogenes
progression under the pressure of
Darwinian selection (survival of the fittest). - Normal cellular genes whose products
• Selection of the fittest cells can explain not promote cell proliferation
only the natural history of cancer, but also
Oncogenes
changes in tumor behavior following
therapy. - Mutated genes that cause excessive cell
• DNA mutations, epigenetic aberrations growth, even in the absence of growth
also contribute to the malignant properties factors and other growth-promoting
of cancer cells. external cues.
- Have multiple roles, but virtually all encode
Cancer Hallmarks
constitutively active oncoproteins that
• Avoiding immune destruction participate in signaling pathways that
• Evading growth suppressors drive the proliferation of cells.

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Examples of genes if affected by mutations could • If there is no growth factor, what is the
lead to cancer: reason why the RAS gene is still active? If
the RAS gene remains active even in the
1. RAS – make proteins involved in cell
absence of a stimulating growth factor,
signaling pathways that control cell
what would happen to cellular growth?
growth and cell death
2. Rb – governor of proliferation
3. TP53 – guardian of the genome
o P21 – acts both as a tumor-
suppressor gene and an inhibitor
of apoptosis by interacting with
various molecules and transition
factors
o GADD45 – regulation of many
cellular functions including DNA
repair, cell cycle control,
senescence and genotoxic stress
o BAX – core regulators of the
intrinsic pathway of apoptosis

Retinoblastoma – cancer in the eyes

Yellow line in allele – NORMAL

Red line – MUTATED

Sporadic Form – sudden mutation without the

inheritance.

Familial Form – affected ancestor can be

manifested by the future generation.

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• Chromosomal rearrangements can

activate proto-oncogenes:
1. Inversions
o If there is growth factors RBG is mutated
2. Amplifications
3. Translocations – most common
4. Small deletions
5. Etc…
• Philadelphia Chromosome
- characteristic of CML and a subset
of B-cell acute lymphoblastic
leukemias.
- provides the prototypic example of
a chromosomal rearrangement
that creates a fusion gene
encoding a chimeric oncoprotein
- swapping of chromosome 9 and 22
- carries the bcr-abl gene.
➔ The bcr-abl gene
encodes for the enzyme
tyrosine kinase.
• Tyrosine kinase
- is an enzyme that is involved in
cellular growth and proliferation.
- From the creation of the bcr-abl
gene targets the myeloid cells of
o P53 the bone marrow, leading to
- Checker (before entering S phase, unregulated growth of immature
it will be checked by P53. myeloid cells.
- Prevents replication ➔ These immature
leukocytes proliferates
in the bone marrow
and goes out into the
circulation.

Review: what do you call the malignant

transformation of blood forming cells?

- Leukemia and Lymphoma

CML – Chronic myelogenous leukemia

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Other examples of carcinogens or conditions that

could develop into cancer:

1. UV radiation
2. Alcohol
3. Tobacco
4. Ulcers
5. Barrett esophagus
6. Benign neoplasms – tubular adenoma

CLINICAL ASPECTS OF NEOPLASIA

Questions: Can benign tumors cause morbidity

and mortality?

CML – increase in the number ▪ Mortality – sickness

of neutrophils or granulocytes ▪ Morbidity – death

Local Hormonal Effects

Few examples of Chemical Carcinogens
• Location – critical determinant of the
1. Benzene – leukemia
clinical effects of benign and malignant
2. Asbestos – lung cancer
tumors.
3. Vinyl chloride – angiosarcoma

Few examples of microorganisms that can cause A 1cm pituitary adenoma, can
cancer: compress and destroy the
surrounding normal gland and thus
1. HPV – SCC lead to hypopituitarism.
2. EBV – nasopharyngeal carcinoma, A neoplasm in the intestines may
lymphoma cause obstruction as they enlarge.
3. H. pylori – gastric adenocarcinoma Neoplasms arising in the endocrine
4. HTLV – leukemia glands can cause problems by
5. HHV-8 – Kaposi sarcoma producing hormones
Hematochezia – bright red blood in
stool
Melena – black stools
Hematuria – presence of blood in
urine
▪ Caused: kidney stone and
urinary bladder stone

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• Cancer cachexia
- Hypercatabolic state defined by a
loss of muscle mass that cannot be
explained by diminished food
intake.
- This occurs in about 50% of cancer
patients.
- Super skinny
• Paraneoplastic syndromes
- Signs and symptoms that cannot
readily be explained by anatomic
distribution of the tumor or by the
elaboration of hormones
indigenous to the tissue from which
the tumor arose.
- Occurs in about 10% of persons
with cancer.
• Grading and Staging of Tumors
o Grading – based on the degree of
differentiation of tumor cells, in
some cancers, the number of
mitoses or architectural features.
o Staging – for solid cancers, based
on size of the primary lesion,
whether it has spread to regional
lymph nodes, and the presence or
absence of blood-borne
metastases.
• AJCC (American Joint Committee on Cancer
Staging)
o TNM staging
▪ T – primary tumor
▪ T0 – in-situ lesion
▪ T1 to T4 – based on increase
size (or in some cancers,
depth of invasion)
▪ N – regional lymph node
involvement
▪ N0 – no lymph node
involvement
▪ N1 to N3 – increasing number
of regional lymph node
involvement
▪ M – metastases
▪ M0 – no distant metastases
▪ M1 (sometimes M2) –
presence of metastases

R.CHAN 18
 DGP_3101. GENERAL PATHOLOGY
MIDTERM
• Laboratory Diagnosis of Cancer
1. Histologic and cytologic methods.
2. Immunohistochemistry.
3. Flow cytometry.
4. Circulating tumor cells.
5. Molecular diagnostics and
cytogenetics.
6. Molecular profiles of tumors: the
future of cancer diagnostics.

Normal Papanicolaou smear from the uterine

cervix showing large, flat epithelial cells with
small nuclei

Typical histologic appearance of anaplastic

tumor cells showing variation in cell size and
shape with large, hyperchromic nuclei
Laboratory Diagnosis of Cancer

• Selected tumor markers:

o HCG – trophoblastic tumors
o Alpha-fetoprotein – HCC
o CEA – cancers of the colon, pancreas,
lung, stomach, and heart
o PSA – prostate cancer
o CA-125 – ovarian cancer
o CA-15-3 – breast cancer
Anti-cytokeratin immunoperoxidase
stain of a tumor of epithelial origin

R.CHAN 19