Oncology

Cancer is a disease where cells

grow out of control and
invade, erode and destroy
normal tissue.
These cells are now termed
neoplasm.
Tumor

Benign Tumors Malignant Tumors

(noncancerous) (cancerous)
• Enclosed in a fibrous • Not usually contained –
shell or capsule. metastasis
• Take up space • Invade and emit clawlike
• Concerned if they protrusions that disrupt
interfere with the RNA and DNA of
surrounding tissues or normal cells (these
vessels or impede the cancerous cells act like
function of the body. a virus).
 CATEGORIES OF CANCER
Carcinoma
 Arises from the epithelial cells lining the
internal
surface of various organs (e.g. mouth,
esophagus,
uterus)
 Sarcoma
 Arises from the mesodermal cells constituting the
various connective tissues (e.g. fibrous tissue,
bone)
Lymphoma, myeloma and leukemia
 Arising from the cells of the bone marrow and
immune
system
• Epidemiology of cancer.
• Most common cancer in developed
countries are lung,breast,prostate and
colorectal
• Most common cancer in developing
countries are liver,cervical and oesophageal.
• Following life-style factor attributing cancer
worldwide:
• Tobacco use, alcohol abuse, obesity,physical
inactivity,low fiber diet, unprotected
sex ,polluted air, indoor household smoke
and contaminated injections.
• Five most common primary cancers in the
world.
• Men women Children
• 1 Lung Breast Acute leukeamia

• 2 Prostate Lung CNS tumor

• 3 Colorectal Colorectal Bone sarcoma
• 4 Urinary Endometrial Endocrine
bladder
• 5 Lymphoma Lymphoma Soft tissue
• sarcoma
•
 THE NINE WARNING SIGNS
C •Change in bowel or bladder habits.
A •A sore that does not heal.
U •Unusual bleeding or discharge.
T •Thickening of a lump in breast or elsewhere.
I •Indigestion or difficulty in swallowing.
O
•Obvious change in a wart or mole.
N
•Nagging cough or hoarseness.
U
•Unexplained anemia.
S
•Sudden, unexplained weight loss.
• Epidemiologic factors
• 1 Predisposing factors
• A) Familial and genetic factors
• B) Racial and geographic factors
• C) Environmental and cultural factors
• D) Age and gender
• 2 Chronic non-neoplastic(pre-malignant)conditions
• A) Carcinoma in situ
• B) Benign tumors
• C) Miscellaneous conditions
• 3 Role of hormones in cancer
• A) Oestrogen
• B) Contraceptive hormones
• C) Anabolic steroids
• D) Hormone-dependent tumor
Precancerous lesion it is a
morphologically altered tissue in wich
cancer is more likely to occur than in its
apparently normal counterpart.
Lesion that is not itself malignant, but
has greater probability of becoming so
than normal tissue.
Cancer evolve through a series of
intermediate lesions which have greater
premalignant potential than one that
preceded it
 Cancer Genes
• Proto-oncogenes – normally promote normal
cell growth; mutations convert them to
oncogenes(c-myc, bcl-2,EGFR, HER2, SRC, ABL, RAS
etc)
• Tumor suppressor genes – normally restrain cell
growth; loss of function results in unregulated
growth(р53, RB1, BRCA1, BRCA2, MLH1, MSH2 etc)
• DNA repair genes – when faulty, result in an
accumulated rate of mutations(BER, PARP etc).
 CARCINOGENS
• Occupation related causes
• Lifestyle related causes
– Tobacco
– Diet
– Sexual practices
• Multifactorial causes
• Viral carcinogens
• Chemical carcinogens
• Ionizing radiation
 Occupational Risk Factors

Etiology Site of Malignancy

Arsenic Lung, skin, liver
Asbestos Mesothelium, lung
Benzene Leukemia
Benzedine Bladder
Chromium cpds Lung
Radiation (mining) Numerous locations
Mustard gas Lung
Polycyclic hydrocarbons Lung, skin
Vinyl Chloride Angiosarcoma of liver
 Diet-Related Risk Factors
Nitrates
Salt
Low vitamins A, C, E
Gastric Cancer
Low consumption of
yellow-green vegetables Esophageal
Cancer
 Diet-Related Risk Factors

High fat Colon Cancer

Low fiber Pancreatic Cancer
Prostate Cancer
Low calcium
Breast Cancer
High boiled or
Uterine Cancer
fried foods

Mycotoxins Liver Cancer

 Sexual Practices Risk
Factors

Sexual promiscuity
Multiple partners
Unsafe Sex Cervical Cancer
Human Papillomavirus
 Radiation Carcinogenesis

• Radiation-induced mutation in the

host cell
• Transmits irreversible changes in
gene expression to cell progeny
 Sources of Potentially
Carcinogenic Radiation
• Sunlight
• Artificial sources of UV light
• X-rays
• Radio-chemicals
• Nuclear fission
 Viral Carcinogenesis
• Viral carcinogens are classified into RNA and
DNA viruses.

• Most RNA oncogenic viruses belong to the

family of retroviruses that contain reverse
transcriptase mediates transfer of viral
RNA into virus specific DNA.
Sequence of Disease Progression

Leukoplakia / Erythroplakia

Dysplasia

Carcinoma in situ

Invasive Carcinoma

Regional / Distant Metastasis

STAGING AND GRADING
OF
TUMORS
•

Histology provides a definitive diagnosis and also

allows grading and assessment of spread
(staging) in cases of malignant tumors.
• Histological diagnosis requires biopsy which
may
• be either incisional or excisional.

•
• Incisional biopsy-Removal of small portion of
tumor.This is for tumors that are thought to be
inoperable .This includes endoscopic biopsy,
core needle biopsy, fine needle aspiration biopsy.
• Excisional biopsy-This is the most important type of
biopsy which allows to assess the extent of
spread.
• Grading and staging are 2 systems to determine
prognosis and choice of treatment after a malignant
tumor is detected.
• These two methods of evaluating malignant tumors
(grading and staging) are based on different
parameters.
• The curability of a tumor usually is inversely
 Staging-Staging is defined as the extent of disease
evaluated by a variety of noninvasive and invasive
diagnostic tests and procedures.
 Stage can be assesed by 3 ways –by clinical
examination, investigations and by pathologic
examination of the tissue removed.
 Types of staging-There are two types-
a) Clinical staging is based on physical examination,
radiographs, isotopic scans, CT scans, and other
imaging procedures;
b) Pathologic staging takes into account
information obtained during a surgical
procedure,
1. intraoperative palpation,
2.resection of regional lymph nodes and/or
3. tissue adjacent to the tumor, and inspection and
biopsy of organs commonly involved in disease
• Pathologic staging includes histologic examination
of all tissues removed during the surgical
procedure.
• Knowledge of the predilection of particular
tumors for spread to adjacent or distant organs
helps direct the staging evaluation.
• Information obtained from staging is used to
define the extent of disease either as localized, as
exhibiting spread outside of the organ of origin to
regional but not distant sites, or as metastatic to
distant sites.
• Staging systems-2 important staging
systems currently followed are-TNM staging
and AJC staging.
• The most widely used system of staging is the
TNM (tumor, node, metastasis) system originally
developed by Pierre Denoix in France in 1940 and
adopted by the International Union Against
Cancer and the American Joint Committee on
Cancer (AJCC) in 1950s.
• During the 1990s the importance of TNM staging of
cancer was heightened by the mandatory
requirement that Commission on Cancer-
approved hospitals use the UICC or AJCC TNM
system as the major language for cancer reporting.
• General rules of the TNM system-
The TNM system is an expression of the anatomic extent of
the disease and is based on the assessment of 3
components:as
T-The extent of primary tumor .
N-The absence or presence and extent of regional
lymph node metastasis.
M-The absence or presence of distant
metastasis.
• Definitions of TNM-
• Primary tumor-(T)-
Tx-Primary tumor cannot be assesed.
T0-No evidence of primary tumor.
Tis-Carcinoma in situ.
T1,T2,T3,T4-Increasing size and/or local extent of
• Regional lymph nodes-(N)-
Nx-Regional lymph nodes cannot be assesed.
N0-No regional lymph node metastasis.
N1,N2,N3-Increasig involvement of regional lymph nodes.
Direct extension of the primary tumor into a
lymph node is
classified as lymph node metastasis.
Metastasis in any lymph node other than regional is classified
as distant metastasis.
• Distant metastasis-(M)-
Mx-Distant metastasis cannot be assesed.
M0-No distant
metastasis. M1-Distant
metastasis.
For pathologic Stage grouping ,if sufficient tissue to evaluate
the highest T and N categories has been removed for
pathological examination ,M1 may be either clinical(cM1) or
pathologic(pM1).If only the metastasis has had microscopic
Size of primary tumor (T) in cm
TX No information available on primary
tumor
T0 No evidence of primary tumor
Tis Carcinoma in situ at primary site
T1 Tumor less than 2 cm
T2 Tumor 2-4 cm in diameter
T3 Tumor greater than 4 cm
T4 Tumor has invaded adjacent structures
Lymph node involvement (N)

NX Nodes not assessed

N0 No clinically positive nodes (not palpable)

N1 Single clinically positive ipsilateral (on same side) node

less than 3 cm

N2 Single clinically positive ipsilateral node 3 to 6 cm; or

Multiple ipsilateral nodes with all less than 6 cm; or
bilateral or contralateral nodes with none greater
than 6 cm

N3 Node or nodes greater than 6 cm

Distant metastasis (M)

MX Distant metastasis not assessed

M0 No distant metastasis

M1 Distant metastasis is present

Stage TNM Classification

0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3 N0 M0 TNM
T1 N1 M0
T2 N1 M0 Staging
IV
T3 N1 M0
T4 N0 M0
System
T4 N1 M0
Any T N2 M0
Any T N3 M0
Any T Any N M1
 Stage grouping-The various permutations of T, N, and
M scores (sometimes including tumor histologic
grade
G) are then broken into stages, usually designated by
the roman numerals I through IV.
 AJC staging-( American Joint Committee Staging)-
divides all cancers into stage 0 to 4 and takes into
account all 3 components of the preceeding system in
each stage.
 Significance of staging-
1. Tumor burden increases and curability decreases
with increasing stage.
2.Staging serves to estimate the chances of survival in
the
individual patient.
• Some cancers, like squamous cell carcinomas of the
uterine cervix, are staged by the clinical examination
alone; for others, like transitional cell carcinomas of
the bladder and adenocarcinomas of the large bowel,
the stage is determined on the basis of the findings in
the resected specimens.
 In both cases, there is an excellent correlation with the
prognosis.
 Other staging systems-
Other anatomic staging systems are used for some
tumors, e.g.,
Dukes classification for colorectal cancers,
FIGO(International Federation of Gynecologists and
Obstetricians ) classification for gynecologic cancers,
Ann Arbor classification for Hodgkin's disease.1
• The staging of bladder neoplasms, devised by Jewett, is
as follows:
stage A, invasion of submucosa,five-year survival
rate of 53.7 percent;
stage BI, superficial half of the muscle, 52.6 percent;
stage B2, deep half of muscle, 28.6 percent; and
stage C,perivesical tissues, 17.9 percent.
• Large bowel cancers are staged,according to Dukes, as:
stage A, tumor restricted to the wall of the bowel, with
a five-year survival rate of 90 percent;
stage B, with invasion through the wall into the
peritoneum or perirectal fat, 65 percent; and
stage C, with regional lymph node metastases, 20
percent.
• Staging of melonomas of the skin has shown to
correlate very closely with incidence of lymph
node metastasis and patient survival,whether it is done
with the Clark or by measuring the maximum
thickness of the tumor in millimeters, as recommended
by Breslow.
In the series of Holmes et al. metastatic lymph nodes
were present in 32 percent of Level III cases and in over
65 percent of Levels IV and V cases.
 Drawbacks of staging-
Certain tumors cannot be grouped on the basis of
anatomic considerations.
For example, hematopoietic tumors such as leukemia,
myeloma, and lymphoma are often disseminated at
presentation and do not spread like solid tumors. For
these tumors, other prognostic factors have been
identified.
• Grading-Grading is defined as the macroscopic and
microscopic degree of differentiation of the tumor.
• Cancers can be graded grossly and
microscopically.
• Gross features like exophytic or fungating appearance
are indicative of less malignant growth than diffusely
infiltrating tumors.
• However grading is largely based on 2 important
histologic features-the degree of anaplasia and rate of
growth.
• Based on these features cancers are categorised from
grade 1 as the most differentiated to grade 3 ,4 as
the most undifferentiated or anaplastic.
• Many systems of grading have been proposed but the
one described by Borders for dividing squamous cell
carcinoma into 4 grades depending upon degree of
differentiation is followed for other malignant
• When grading a tumor, the pathologist is referring to the
appearance of the tumor cells, specifically to their degree
of anaplasia.
• Von Hanseman and Borders were leaders in popularizing this
approach.
• For most tumors,four grades are used.
Grade I tumors are so well-differentiated that they
closely resemble the normal parent cells, whereas
Grade IV tumors are so anaplastic that even the
recognition of
their cell of origin becomes difficult.
Grades II and III are intermediate.
• Instead of using a numerical system, some pathologists
prefer to indicate that the tumor is well-differentiated,
moderately differentiated, poorly differentiated or
undifferentiated .
•
• Borders grading is as follows-
1-Well differentiated(<25% anaplastic
cells) 2-Moderately differentiated (25-50 %)
3 Moderately differentiated (50-75%)
4 Poorly differentiated or anaplastic (>75%)
• This is reported as:
Gx-Grade cannot be
assesed. G1-Well
differentiated
G2-Moderately
differentiated
G3-Poorly
• However grading of tumors has several
shortcomings.
• It is subjective and the degree of differentiation
may
vary from one area of tumor to the other.
• If different areas of a given neoplasm show
different grades of malignancy, the tumor should
be graded according to the more undifferentiated
area (prostatic cancer being an exception).
• Because of this focal variation in the degree of
differentiation, the grade assigned to a small
biopsy of a tumor may not always be
representative of the whole neoplasm.
• Therefore it is common practice to grade cancers in
descriptive terms (eg-well differentiated
undifferentiated, keratinising non keratinising ,etc)
rather than giving
the tumors grade numbers.
• Grading has no prognostic value in certain types of
cancers, such as ofmelanoma the skin, and in others it
is of questionable value.
• Grading of salivary malignancies is not standardised and
may vary according to histologic type.In some instances
histologic type defines grade;for eg-myoepithelial carcinoma
and basal cell adenocarcinoma are low grade while salivary
duct carcinoma is usually high grade.
• In some tumors, such as transitional cell carcinoma of the
urinary bladder, the grading has a direct relationship to the
prognosis. The five-year survival rate of Grade I tumors is
80 percent, whereas for Grade III neoplasms it is only 20%.
• In the central nervous system, grading is useful
for astrocytomas, but not for ependymomas or
oligodendrogliomas.
• In bone sarcomas, grading is of value for
chondrosarcomas, since the five year survival rate
is 78 percent for the well-differentiated tumors, 53
percent for the moderately differentiated and only
22percent for the poorly differentiated ones.
• Grading is of no value for osteosarcomas, except
for
some distinct subtypes of this tumor.
• Gleason has shown a remarkable correlation
between a five grade system of prostatic
• Other grading systems used-
1.Scarff Bloom Richardson Grading system for Ca
breast based on degree of tubule formation , nuclear
grade and mitotic rate.Points are asigned to each
parameter. The histologic grade is
determined by summing the points.
2.Albores Saavedra grading system for papillary
intraductal carcinomas of pancreas is based on nuclear
typia and mitotic figures.
3.Because of poor correlation of cytologic features ,pattern
of growth and biologic behavior in most endocrine tumors
they are not graded.
4.No grading is currently available for Ca parathyroid.
5.Gleasons grading system is used for prostate Ca which
proposes that Ca prostate may show one or several of 5
histologic patterns. Gleasons score has prognostic