STAGING

AND
GRADING CANCER
PATHOLOGY DEPARTMENT,
FACULTY OF MEDICINE,
GADJAH MADA UNIVERSITY
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The stage of cancer is a measure how much the cancer
has grown and spread
The grading of cancer is determined by looking at certain
features of the cancer cells under the microssope
The aim: help to predict how a cancer might behave, how
advanced it is, how well it may respond to treatment.

THE EARLY THE STAGE AND THE
LOWER THE GRADE OF CANCER, THE
BETTER THE OUTLOOK (PROGNOSIS)
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GROWING AND SPREADING OF CANCER
A cancer if untreated
1. Growing from one cell divides and multiplies
primary tumor invade surrounding tissue
2. Some cancer cells get into local lymph channel
lymph node(s) entrapped multiply enlargement
of lymph node
3. Some cancer cells get into local small blood vessel
into bloodstream spread to other areas multiply
secondary tumor may then grow and invade
nearby tissue spread again
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GROWING AND SPREADING OF CANCER
Each type of cancer differs in the speed of
growing and spreading

Some cancer may spread easily and quickly,
other may grow slowly and remain in the
primary site for a long times
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CANCER STAGING
A way of describing how much a cancer has grown and
spread
the stage is based on 3 factors
Primary tumor size and whether or not the tumor has grown
into other nearby areas
Whether or not the cancer has spread to the nearby lymph
nodes
Whether or not the cancer has spread to distant areas of the
body
Leukemia, and other some cancer of the blood are not
formally staged they are assumed to be in all parts of
the body

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CANCER STAGING
TYPE OF STAGING
1. Clinical staging, based on
1. Phisical exam
2. Imaging test (x-rays, CT scan, etc.)
3. Sometimes biopsies
4. Blood test (for certain cancers)
2. Pathologic staging (only on patient who have had
surgery to remove or explore the extent of the cancer)
1. Combines: clinical staging + results from the surgery
2. The pathology stage may be different from the clinical
staging
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CANCER STAGING
STAGING SYSTEMS

There were many different systems.
Sometimes different systems were used to stage
the same type of cancer.

Although some of the better ones are still
used, many of these systems did not give doctors
very useful information
T(tumor)N(nodule)M(metastasis)
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CANCER STAGING
STAGING SYSTEMS
TNM system
1. Developed by AJCC (the American Joint Commitee on Cancer)
2. Replaced many of the older systems

The T category describes the primary tumor
1. Tx: tumor cant be measured
2. T0: there is no evidence of primary tumor
3. T1s: the cancer is in situ (has not started growing into the surrounding
structures)
4. T1 T4: describes the size and/or level of invasion. The higher the T
number, the larger the size and/or the further it have may grown into the
nearby structures
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CANCER STAGING
STAGING SYSTEMS
TNM system

The N category describes whether or not the cancer has reached nearby lymph
nodes
Nx: the nearby lymph nodes cant be measured or found
N0: nearby lymph nodes do not contain cancer
N1 N3: the size, location, and/or the number of lymph nodes involved.
The higher N number, the more involved the lymph nodes are

The M category tells whether there are distant metastasis
Mx: metastasis cant be measured or found
M0: there are no known distant metastasis
M1: distant metastasis are present
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CANCER STAGING
STAGING SYSTEMS
TNM system

Note:
Each cancer type has its own classification system.
Letters and numbers do not always mean the same thing for every
kind of cancer

For example:
Some cancer may have subcategories, s.a. T3a and T3b, while other
may not have an N3 category

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CANCER STAGING
STAGING SYSTEM
STAGE GROUPING
T, N, M are combined overall stage I, II, III, IV
Sometimes stages are subdivided s.a. IIIA, IIIB
For example, for breast cancer
T1, N0, M0: primary tumor <2cm, no lymph node involvment, no spread
to distant parts of body STAGE I
T2, N1, M0: primary >2cm - <5cm, has metastised in axillar lymph node,
no spread to distant parts STAGE IIB

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BREAST CANCER
Stage I
T1a: T 0.5 cm

T1b: 0.5 cm < T 1 cm

T1c: 1 cm < T 2 cm
T1 N0 M0
T 2 cm
T1

N0 = no regional lymph node metastasis
M0 = no distant metastasis
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BREAST CANCER
Stage IIA
T2 N0 M0
N1 = metastasis to movable ipsilateral axillary lymph node(s)
M0 = no distant metastasis
2 cm < T < 5 cm

No evidence
of tumor

T0

T0
T1
N1 M0
}
T2

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BREAST CANCER
Stage IIB
T3 N0 M0
N1 = metastasis to movable ipsilateral axillary lymph node(s) (p) N1a, N1b
M0 = no distant metastasis
T > 5 cm

T2 N1 M0
T3

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BREAST CANCER
Stage IIIA
T0
T1
T2
T3
Metastasis to ipsilateral axillary lymph node(s)
N1 = movable
N2 = fixed to one another or to other structures
M0 = no distant metastasis
T3 N1 M0
N2 M0
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BREAST CANCER
Stage IIIB
Any T N3 M0
N3 = metastasis to ipsilateral internal mammary lymph node(s)
M0 = no distant metastasis
Tumor of any size
with direct extension
to chest wall or skin




T4d = inflammatory
carcinoma
T4 any N M0
T4

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BREAST CANCER
Stage IV
M1 = distant metastasis (including metastases to ipsilateral supraclavicular,
cervical, or contralateral internal mammary lymph nodes)
Any T any N M1
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CANCER STAGING
STAGING SYSTEM
Other Staging System
1. Duke system (for colorectal cancer)
Stage A: the cancer is just in the bowel wall
Stage B: the cancer has grown to the outer surface of
the bowel wall
Stage C: the cancer has spread to the lymph nodes
near to the bowel
Stage D: the cancer has spread to other parts of the
body (metastases, or secondary tumors hane
developed)
2. Other than TNM system used for lymphoma, some
childhood cancers, cancer in some female reproductive
organs
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Modified Duke A The tumor penetrates into the mucosa of the bowel wall but no further.
Modified Duke B
B1: tumor penetrates into, but not through the muscularis propria (the
muscular layer) of the bowel wall.
B2: tumor penetrates into and through the muscularis propria of the bowel wall.
Modified Duke C
C1: tumor penetrates into, but not through the muscularis propria of the bowel
wall; there is pathologic evidence of colon cancer in the lymph nodes.
C2: tumor penetrates into and through the muscularis propria of the bowel wall;
there is pathologic evidence of colon cancer in the lymph nodes.
Modified Duke D The tumor, which has spread beyond the confines of the lymph nodes
(to organs such as the liver, lung or bone).
Modified Duke Staging
System
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Staging system for
renal cancer
Stage I:
in the kidney only, < 7.0 cm
FYS > 90%
Stage II:
in the kidney only, >7.0 cm
FYS > 75%
Stage III:
in the kidney, may be any
size, does not extend beyond
Gerota's fascia.
Additionally, cancer has
spread to the renal vein, to
the inferior vena cava, or to
the adjacent adrenal gland
FYS >65 % depending on
involved sites
Stage IV:
extends beyond Gerota's
fascia, and/or has spread to
> 1 lnn. near the kidney
spread to other organs in the
body: lungs, liver, brain,
bones, intestines or pancreas
FYS <10%
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GRADING CANCER
TUMOR GRADE

Degree of abnormality of cancer cells
compared with the normal counterpart cell

Estimate how quickly the tumor is likely to grow
and spread (degree of malignancy and
aggresiveness)
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GRADING CANCER



Benign or
malignant
Tumor grade
Degree of cell differentiation
Tissue (biopsy)
Pathologist
DETERMINING THE TUMOR GRADE
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GRADING CANCER
THE SIGNIFICANCY OF CANCER GRADE
Cancer grade is determined based on microscopic
appearances of:
1. Degree of resemblance to the normal tissue (degree
of differentiation)
2. Mitotic activity
3. Nuclear size and pleomorphisme

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GRADING CANCER
THE SIGNIFICANCY OF CANCER GRADE

Cancer grade recommended by AJCC (the American
Joint Commission on Cancer)

GX: grade can not be assed (undetermined grade)
G1: well differentiated (low grade)
G2: moderately differentiated (intermediate grade)
G3: poorly differentiated (high grade)
G4: undifferentiated (high grade)
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GRADING CANCER
THE SIGNIFICANCY OF CANCER GRADE

Grade 1: tumor cells resemble normal cells, tend to grow
and multiply slowly generally considered the least
aggressive in behavior

Grade 2 : tumor cells appears between 1 and 3

Grade 3 4: tumor cells do not look like normal cells,
tend to grow rapidly and spread faster than tumor
with a lower grade
Well grade
squamous cell carcinoma
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Keratin pearl
Keratin pearl
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Moderate to poorly grade
Squamous Cell Carcinoma
Individual keratine
Well differentiated adenocarcinoma
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Tubular/ glandular pattern
Poorly grade adenocarcinoma
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Anaplastic tumor
Pleomorphic Rhabdomyosarcoma
Bizzare cell
Multinucleated giant cell
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Cancer grade + other factors (s.a., cancer stage)
treatment plan and to predict the prognosis.
Generally: a lower grade -- a better prognosis
(the likely outcome or course of a disease; the chance of
recovery or recurrence)
Tumor grade is very important for certain types of
cancers:
soft tissue sarcoma
primary brain tumors
Lymphomas
breast cancer
and prostate cancer
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GRADING CANCER
APPLYING THE GRADING SYSTEM

Grading systems are different for each
type of cancer, for example:
1. Gleason system for prostate cancer
2. Bloom-Richardson (Nottingham)
system for breast cancer
3. Furhman system for kidney cancer
Breast cancer
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DIAGNOSIS LABORATORIK
MORFOLOGIK :
- biopsi - IHC
- Frozen Section - Flowytometry
- AJH
BIOKIMIAWI : Tumor marker
MOLEKULAR : DNA microanalysis
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MARKER TUMOR
Hormon
HCG (Human Chorionic Gonadotropin)
Kalsitonin
Katekolamin dan metabolit
Hormon ektopik

Antigen onkofetal
Alfa-fetoprotein
CEA (carcinoma embryonic
antigen)

Isoenzim
Prostatic Acid Phosphatase
Neuron specific enolase (NSE)

Protein spesifik
Imunoglobulin
PSA

Musin & glikoprotein lain
CA-125
CA-19-9
CA-15-3

Tumor trofoblastik dan testis non-seminoma
Ca medular tiroid
Feokromositoma dan tumor yang berhubungan
Paraneoplastic syndrome


HCC, tumor testis sel benih non seminomatosa
Ca kolon, pankreas paru, gaster, mama



Ca prostat
Ca sel kecil paru, neuroblastoma


Mieloma multipel dan gamopati lain
Ca prostat


Ca ovarium
Ca kolon, pankreas
Ca mama
TUMOR MARKER / PETANDA TUMOR