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 Why we have to learn about cancer/ tumor?

 Cancer is the second leading cause of death
 In the year 2000,
 10 million new cases of cancer

 6 million cancer deaths worldwide.

 In the United States 2003,

 Cancer caused 556,000 death/year

 1500 cancer deaths per day.

1. Definition of Neoplasm
2. Nomenclature
3. Characteristic of Neoplasms
4. Epidemiology
 Neoplasm means “ new growth”

Tumor originally means swelling caused by


 Tumor is now equated with Neoplasm

 Oncology is the study of tumors or

neoplasms (Greek ‘oncos’ = tumor)

 Cancer is the common term for all malignant

tumors. (Cancer = latin for crab)

British oncologist Sir Rupert Willis

A neoplasm is an abnormal mass of

tissue, the growth of which exceeds and
is uncoordinated with the normal tissues and
persists in the same excessive manner after
cessation of the stimuli which evoked the
(Causative agent of cancer)
 Chemical agent
 Nitrosamin Colon Cancer
 Viral
 HPV Cervical Cancer
 HCV, HBV Liver Cancer
 Epstein Barr Nasopharyngeal Cancer
 Radiation
 Bomb in Hiroshima Lung Cancer
 Chernobil Thyroid Cancer
 Hormonal agent
 Estrogen Breast cancer
 Loss of responsiveness to normal growth controls,
continue replicative

Becomes autonomous (independent of physiologic

growth stimuli)

Behave as parasites and compete with normal

cells and tissue for their metabolic need.

Depend on host for nutrition and blood supply.

Flourish in patients who are wasting and cachexia.

 Progressive, Purposeless, Pathologic, Proliferation
of cells characterized by loss of control over cell
 DNA damage at growth control genes is central to
development of neoplasm.
 Carcinogens – Chemical, physical & genetic  DNA
damage  Neoplasm.
Language of Oncology
 Neoplasm: (meaning new growth that is
“autonomous”); scientific term for a tumor.
 May be “malignant or benign”
 Other “plasias”:
 Hyperplasia: an increase in cell number
 Hypertrophy: an increase in cell size but not number
 Metaplasia: a reversible process where one cell type
changes into another cell type
Pathogenesis of Neoplasia:
 Normal  Hyperplasia  Metaplasia (DNA damage)
 Dysplasia  (DNA damage)  (DNA damage) Anaplasia
(DNA damage) Infiltration  (DNA damage)  Metastasis….

 Progressive DNA Damage – features of neoplasia.

Pathogenesis of Neoplasia:
 Non lethal DNA Damage leading to
uncontrolled cell division.
2. Nomenclature

Neoplasm has categorized into two part

based on potential clinical behaviour:

1. Benign tumor

2. Malignant tumor

Some neoplasms fall in the gray area

which we call “borderline tumor”
 Microscopic and gross are relatively
 It remains localized
 It can not spread to other sites
 Respons to local surgical removal
 Prognosis is generally good
 Tumors are usually obstinate manner
like the crab
 Invade and destroy adjacent structures
 Spread to distant sites
 Prognosis is bad
Giant fibroadenoma mamma with malignant degeneration
• All tumors have 2 basic components:

1. Proliferating neoplastic cells that

constitute their parenchyma
2. Supportive stroma made up of
connective tissue and blood vessels

The nomenclature is based on the

parenchymal component, which determine
biologic behaviour.
Nomenclature Benign Tumor
• A. In general, Attaching the suffix “oma” to the cell
type of tumor origin, denotes benign neoplasm
ex -fat tissuelipoma
-fibrous tissuefibroma
• B. Based on microscopic/ gross pattern
ex -Growing as finger-like pattern papilloma
-Form gland pattern/derived from glands
-A mass project above mucosaPolyp
• C. Other classified by cells of origin
Papilloma is benign epithelial

Papilloma of the colon with finger-like projections into the lumen .

Benign tumor:Adenomatous polyp of the colon,

A, Gross appearance of several colonic polyps B, This benign

glandular tumor (adenoma) is projecting into the colonic lumen and is
attached to the mucosa by a distinct stalk
Nomenclature Benign Tumor
• The tumor origin composed of more than one of
neoplastic cell types, but derived from one germ
layer mixed type
• Ex. Pleomorphic adenoma, mixed tumor of salivary origin

This mixed tumor of

the parotid gland
contains epithelial
cells forming ducts
and myxoid stroma
that resembles
Nomenclature Benign Tumor
• The tumor origin composed of more than one of
neoplastic cell types and derived from more than one
germ layer teratogenous
• Ex. Mature teratoma
Gross appearance
of an opened cystic
teratoma of the
ovary. Note the
presence of hair,
material, and tooth
Nomenclature of Malignant Tumor
• A. follow nomenclature of benign tumor with certain
• If arising from mesenchymal tissue sarcoma
»fat tissue liposarcoma
»fibrous tissuefibrosarcoma

• If arising from epithelial cells carcinoma

»bile ductcolangiocarcinoma
»Renal renal cell carcinoma
Nomenclature of Malignant Tumor
• Carcinomas are qualifed further:
– If resemble squamos epithelium squamos cell
– If grow in gland pattern adenocarcinoma
– If undifferentiated pattern poorly differentiated
Some with suffix oma, but not benign
» Lymphoma
» Melanoma
» Mesothelioma
» Seminoma
3. Characteristic of Neoplasms
A. Differentiation and anaplasia
B. Rate of growth
C. Local invasion
D. Metastasis
A. Differentiation and anaplasia
 Apply in parenchymal cells of neoplasm
 Differentiation (diff.) refers to extent which
parenchymal cells resemble comparable normal cells,
both morphologically and functionally.

 In general, all benign tumor are well diff.

 Malignant tumor, ranges from well diff to undiff.
 Well diff.
 If more resemble to mature normal cells
 Moderately diff.
 Poorly diff. / undifferentiated
 If appeared like unspecialized cells, and far resemble to cell
Leiomyoma uteri, benign smooth muscle tumor

Leiomyoma of the uterus. This benign, well-differentiated

tumor contains interlacing bundles of neoplastic smooth
muscle cells that are virtually identical in appearance to
normal smooth muscle cells in the myometrium
Benign tumor of thyroid gland

Normal thyroid

Benign tumor (adenoma) of the thyroid. Note the normal-

looking (well-differentiated), colloid-filled thyroid follicles.
A. Anaplasia
 Anaplasia means lack of differentiation, marked
changes of morphologic and function.
 Anaplasia, is marked by a number of morphologi

1. Pleomorphism.
Both the cells and the nuclei show variation in
size and shape
2. Abnormal nuclear morphology.
The nuclei contain an abundance of DNA and are
extremely dark staining (hyperchromatic).
The nuclear shape is very variable and larger
The nucleus-to-cytoplasm ratio may 1:1
normal ratio 1:4 or 1:6.
3. Mitoses
Large numbers of mitoses (bizarre mitotic figures),
reflecting the higher proliferative activity of the cells.
The presence of mitoses, however, does not
necessarily indicate that a tumor is malignant or that the
tissue is neoplastic. Ex normal in bone marrow,
4. Loss of polarity.
the orientation of anaplastic cells is markedly
disturbed (i.e., they lose normal polarity). Sheets or
large masses of tumor cells grow in an anarchic,
disorganized fashion.
5. Other changes.
formation of tumor giant cells, some possessing only
a single huge polymorphic nucleus and others having two
or more nuclei.
Anaplastic tumor showing cellular and nuclear variation in size
and shape. The prominent cell in the center field has an
abnormal mitotic tripolar spindle (arrow).
Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma).

Note the marked cellular and nuclear pleomorphism,

hyperchromatic nuclei, and tumor giant cells.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 11 November 2005 02:05 PM)
© 2005 Elsevier
B. Rate of Growth
 The rate of growth of a tumor is determined by
three main factors:

1. the doubling time of tumor cells

2. the fraction of tumor cells that are in the

replicative pool

3. the rate at which cells are shed and lost/ apoptosis

in the growing lesion.


of genetically
Unstable cells

Tumor cells

The left panel shows minimal estimates of tumor cell doublings untill tumor mass can be detectable
clinically. The right panel illustrates clonal evolution of tumors and generation of tumor cell heterogeneity.
New subclones arise from the descendants of the original transformed cell, and becomes enriched for
thosevariants that are more adept at evading host defenses.
Rate of Growth
 Benign tumor
 Usually progressive and slow, may come to a
standstill or regress,
 mitotic figures are rare and normal

 Malignant tumor
 Usually grow much faster
 Erratic and may be slow to rapid; mitotic figures
may be numerous and abnormal
C. Local Invasion


 Nearly all benign tumors remain localized to their site of

 Do not have the capacity to infiltrate, invade, or
metastasize to distant sites
 They grow and expand slowly, and usually develop a rim
of compressed connective tissue, sometimes called a
fibrous capsule, which separates them from the host
 Note: not all benign tumors encapsulated, leiomyoma
 Lack of capsule does not imply malignant
A. Fibroadenoma of
the breast. The tan-
colored, encapsulated
small tumor is sharply
demarcated from the
whiter breast tissue.

B. Microscopic view
of fibroadenoma of
the breast. The
fibrous capsule (right)
delimits the tumor
from the surrounding
C. Local Invasion


 Cancer grow by progressive infiltration, invasion,

destruction, and penetration of the surrounding
 penetrate the wall of the colon or uterus, or fungate through
the surface of the skin.

 Do not develop well define capsule

 Next to the development of metastases, invasiveness

is the most reliable feature that differentiates
malignant from benign tumors.
Ulcus carcinomatosa mamma
A. Cut section of an invasive
ductal carcinoma of the
breast. The lesion is
retracted, infiltrating the
surrounding breast
substance, and would be
stony hard on palpation.

B. The microscopic view of the

breast carcinoma seen in A
illustrates the invasion of
breast stroma and fat by
nests and cords of tumor
cells. Note the absence of
a well-defined capsule.
Carcinoma In situ
 A preinvasive stage of cancer referred to as carcinoma in situ.
 Occurs in tumors of the skin, breast, uterine cervix
 In situ epithelial cancers display the cytologic features of
malignancy (marked nuclear and cellular pleomorphism, and
numerous mitotic figures extending toward the surface)
without invasion of the basement membrane.
Illustrated carcinoma in situ in
the uterine cervix
I. Very Mild Grade 1 Grade 2 Gradet 3
Normal I II III IV V
II. Mild

III. Moderate

IV. Severe
V. Carsinoma membrane
In Situ

Microinvasive carcinoma
D. Metastasis

Metastasis is a hallmark for malignant tumors,

because benign do not metastasize.

Metastasis are tumor implants discontinuous with

the primary tumor

Almost all cancer can metastasize, except

malignant glioma (glial cells) and basal cell
carcinoma of the skin.

Ability of cancer to metastasize is different

D. Metastasis

Liver metastatic cancer from pancreatic adenocarcinoma

Pathway of Spread Metastatic tumor

1. Direct seeding of body cavities or surfaces

ex. Ovarian cancer
2. Lymphatic spread
ex. Breast cancer
3. Hematogenous spread
ex thyroid and prostat > vertebrae/scull

Direct transplantation through surgical instrument or

on surgeon’s gloves may occur theoritically, but its very
rare in clinical practice
1. Seeding of Body Cavities and Surfaces.
 Malignant neoplasm penetrates into a natural body
 Most often involved is the peritoneal cavity, but any
other cavity-pleural, pericardial, subarachnoid, and
joint space-may be affected.
 Ex in ovarian cancer, all peritoneal surfaces become
coated with a heavy layer of cancerous glaze.

2. Hematogenous Spread.
 Hematogenous spread is typical of sarcomas but is also
seen with carcinomas.
 Arteries, with their thicker walls, are less readily
penetrated than are veins
3. Lymphatic Spread.

 Transport through lymphatics is the most common

pathway for the initial dissemination of
 The pattern of lymph node involvement follows the
natural routes of lymphatic drainage
 For ex. Breast Cancer, metastatic to axillary lymph
 The regional nodes serve as effective barriers to
further dissemination of the tumor.
 Tumor Cells, may be destroyed by a tumor-specific
immune response.
 Enlargement of nodes may be caused by
(1) the spread and growth of cancer cells or
(2) reactive hyperplasia
Comparison between a benign tumor of the myometrium (leiomyoma)
and a malignant tumor of similar origin (leiomyosarcoma).
 Benign and Malignant Tumor

Characteristic Benign Malignant

Differentiation Well differentiation, structure Lack of differentiation/

may be typical of tissue origin anaplasia
Structure is often
Rate of growth Usually progressive and slow Erratic, may be slow to
growth, rapid,
Mitotic figures are rare and Abnormal and
normal Numerous mitotic figure
Local invasion Usually well demarcated and Locally invasive,
no infiltration to the infiltration to the
surrounding tissue surrounding tissue
Metastasis Absent Frequently present
Benign Malignant:
 Slow growing,  Fast growing,
 capsulated,  non capsulated,
 Non-invasive  Invasive & Infiltrate
 do not  Metastasize.
metastasize,  poorly differentiated,
 well differentiated,  Suffix “Carcinoma”
 suffix “oma” eg. or “Sarcoma”

 The metastatic cascade is divided into two phases:

(1) invasion of the extracellular matrix

(2) vascular dissemination and homing of tumor
Invasion of extracellular matrix
 The structural of normal tissues is determined by interactions
between cells and the extracellular matrix (ECM)
 There are two types of ECM: basement membrane and interstitial
connective tissue.
 ECM is made up of collagens, glycoproteins, and proteoglycans.
 Invasion of the ECM is an active process that can be resolved into
four steps.
1) Detachment ("loosening up") of the tumor cells from each other
2) Attachment to matrix components
3) Degradation of ECM
4) Migration of tumor cells
Invasion of extracellular matrix, 4 steps

A. Loose of surface adhesion

molecule, ex cadherins

Cells able to migrate

B. To penetrate the
surrounding ECM, the tumor
cells attach to the basement
membrane via the laminin
C. Tumor cells must create
passageways for
migration, by degradation
of the ECM components
These requiare proteolytic
enzymes, including type IV
collagenase (MMP2 and
MMP9) and plasminogen
activator to digest
connective tissue

D. Cells enable to migrate

and this is influenced by
cellular motility
MMP (Matrix Metallo Proteinases)

•Collagenases that cleave type IV collagen

of epithelial and vascular basement

•Obviously increase in several cancer

•MMP also promote angiogenesis, tumor

growth, and tumor cell motility .
Four mechanisms of
metastasis development within
a primary tumor.

A, Metastasis is caused by rare

variant clones that develop in the
primary tumor;
B, by the gene expression
pattern of most cells of the
primary tumor,
referred to as a metastatic
C, Combination of A and B,
D, Metastasis development is
greatly influenced by the tumor
stroma, which may regulate
angiogenesis, local invasiveness
and resistance to immune
elimination, allowing cells of the
primary tumor to become
Metastatic cascade
Metastatic of thyroid cancer to the skull
 Studying cancer epidemiology contribute substantial
knowledge origin of cancer.

 Cigarette smoking is casually associated with lung

 Dietary fat and less fiber content are associated with
colon cancer

1. Geographic and environmental factors

2. Age
3. Heredity
4. Acquired Preneoplastic disorder
Geographic and Environmental Factors
Many Gastric Cancer in Japan, a few in US
 Most Cancer Mortality occured between ages 55-75

 The rising incidence with age may be explained by

accumulation of somatic mutation associated

 Decline immune competence that accompanies aging

 Heredity forms of cancer divided into 3 categories

1. Inherited Cancer Syndrom (Autosomal Dominant)

Familial retinoblastoma
Familial adenomatous poliposis

2. Familial Cancer
Breast Cancer
Ovarian cancer

3. Autosomal Recessive Syndromes of Defective DNA Repair

Xeroderma pigmentosum
Some clinical condition are recognized as predispodition to
development of neoplasia and these condition are acuired,
not genetic influence

 Skin fistula or skin woundSquamous cell carcinoma

 Cirrhosis of the liver  Hepatocellular
 Chronic Gastritis  Gastric Cancer
 Chronic Colitis  Colon Cancer
 Neoplasm is the uncontrolled and abnormal new

 Differentiated in to benign and malignant neoplasm

with different nomenclature.

 Malignant tumor can metastasize to other organ.

 Cotran Kumar Robin, Robbins Pathologic Basis of
Disease, 7th ed,2004, WB. Saunders Company