KMU (IPM&R) pathology

1. GRADING & STAGING
TUMOUR MARKERS
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2. • Prognosis of the course of the disease
• Determination of efficacy of various forms of cancer
treatment require a high degree of similarity among
the tumors being considered.

3. • Systems in semiquantitative terms,
• The level of differentiation, or grade
• Extent of spread of a cancer within the patient,
or stage,

4. Grading of a cancer is based
• Degree of differentiation of the tumor cells and the
number of mitoses within the tumor as presumed
correlates of the neoplasm's aggressiveness.

5. • Grades I to IV with increasing anaplasia.
• Criteria for the individual grades vary with
each form of neoplasia,
• To judge the extent to which the tumor cells
resemble or fail to resemble their normal
counterparts.

6. • The correlation between histologic appearance and
biologic behavior is less than perfect.
• Characterize a particular neoplasm in descriptive
terms,
• Well-differentiated, mucin-secreting adenocarcinoma
of the stomach, or
• Highly undifferentiated, retroperitoneal malignant
tumor-probably sarcoma.

7. Cytologic grading of squamous cell carcinoma of the lung.
A. Well-differentiated (grade 1) squamous cell carcinoma

8. Poorly differentiated (grade 3) squamous cell
carcinoma. The malignant cells are difficult to identify
as being of squamous origin.

9. • Grading of cancers has proved of less clinical
value than has staging

10. The staging of cancers
• Based on the size of the primary lesion,
• Its extent of spread to regional lymph nodes,
• Presence or absence of blood-borne
metastases

11. • Great importance in the selection of the best
form of therapy
• Staging has proved to be of greater clinical
value than grading

12. • Union Internationale Contre Cancer (UICC)
• American Joint Committee (AJC) on Cancer
Staging.

13. The UICC employs a classification called
the TNM system-
• T for primary tumor,
• N for regional lymph node involvement
• M for metastases.

14. The TNM staging varies for each specific form
of cancer, but there are general principles
• With increasing size, the primary lesion is
characterized as T1 to T4.
• T0 is added to indicate an in situ lesion. .

15. • N0 would mean no nodal involvement,
whereas N1 to N3 would denote involvement of
an increasing number and range of nodes

16. • M0 no distant metastases,
• M1 or sometimes M2

17. AJC divides all cancers into stages 0 to IV
• Incorporating within each of these stages the
size of the primary lesion , presence of nodal
spread & distant metastases.

18. • Stage 0. DCIS or LCIS (5-year survival rate: 92%).
• Stage I.
Invasive carcinoma 2 cm or less in diameter
(including carcinoma in situ with microinvasion)
without nodal involvement (5-year survival rate:
87%).

19. Stage II
• Invasive carcinoma 5 cm or less in diameter
with up to three involved axillary nodes or
• Invasive carcinoma greater than 5 cm without
nodal involvement (5-year survival rate: 75%).

20. Stage III
• Invasive carcinoma 5 cm or less in diameter with four
or more involved axillary nodes;
• Invasive carcinoma greater than 5 cm in diameter
with nodal involvement;
• Invasive carcinoma with 10 or more involved
axillary nodes;
• Invasive carcinoma with involvement of the
ipsilateral internal mammary lymph nodes; or
• Invasive carcinoma with skin involvement (edema,
ulceration, or satellite skin nodules), chest wall
fixation, or clinical inflammatory carcinoma (5-year
survival rate: 46%).

21. • Stage IV. Any breast cancer with distant
metastases (5-year survival rate: 13%).

23. Tumor Markers

24. Tumor Markers
Biochemical indicators of the presence of a tumor.
• A molecule that can be detected
in plasma or other body fluids
• Tumor markers cannot be
primary diagnosic modalities
• Utility to support the diagnosis.
• Response to therapy
• Indicating relapse during the
follow-up period.
•Cell-surface
antigens,
•Cytoplasmic
proteins,
•Enzymes,
•Hormones.

25. CEA A complex glycoprotein
Elevations in many benign
disorders
• Alcoholic cirrhosis,
• Hepatitis,
• Ulcerative colitis,
• Crohn disease
•60% to 90% of
colorectal,
•50% to 80% of
pancreatic
•25% to 50% of gastric
and breast carcinomas
Normally produced in embryonic
tissue of the gut, pancreas, and liver

26. Lack both specificity and the sensitivity required
for the detection of early cancers
• Preoperative CEA levels body burden of tumor.
• Elevated CEA levels 6 weeks after therapy indicates
residual disease.
• A rising CEA level indicates recurrence, with an
increase in tumor marker level often preceding
clinically detectable disease.
• Serum CEA is also useful in monitoring the treatment
of metastatic breast cancer.

27. AFP Glycoprotein
• Useful indicator of hepatocellular
carcinomas and germ cell tumors of the
testis.
• Decline rapidly after surgical resection
of liver cell cancer or treatment of germ
cell tumors.
• Less regularly in carcinomas of the
colon, lung, and pancreas
Early in Fetal Life,Yolk Sac,
Fetal Liver & Fetal Git
Adults with
cancer
arising
principally
in
Liver
Germ cells
of the testis.

28. Markers Associated Cancers
Hormones
Human chorionic
gonadotropin
Trophoblastic tumors,
nonseminomatous
testicular tumors
Calcitonin Medullary carcinoma of
thyroid
Catecholamine Pheochromocytoma
Ectopic hormones Paraneoplastic Syndromes

29. Oncofetal Antigens
α-Fetoprotein Liver cell cancer,
nonseminomatous germ
cell tumors of testis
Carcinoembryonic
antigen
Carcinomas of the colon,
pancreas, lung, stomach,
Isoenzymes
Prostatic acid
phosphatase
Prostate cancer
Neuron-specific enolase Small cell cancer of lung,
neuroblastoma

30. Specific Proteins
Immunoglobulins Multiple myeloma and other
gammopathies
Prostate-specific antigen and
prostate-specific membrane
antigen
Prostate cancer
Mucins and Other Glycoproteins
CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer

31. New Molecular Markers
p53, APC, RAS mutations in
stool and serum
Colon cancer
p53 and RAS mutations in
stool and serum
Pancreatic cancer
p53 and RAS mutations in
sputum and serum
Lung cancer
p53 mutations in urine Bladder cancer

32. Serologic Diagnosis
• Theoretically, it may be possible to diagnose cancer
by detecting cancer cell products in the serum,
whether these are molecules secreted by malignant
cells or antigens released by periodic death of such
cells.
• No general serologic screening methods exist for
cancer, but several tests are of value for certain
tumors

33. Radiologic Diagnosis
• CT & (MRI) scans, are invaluable for localizing
masses as part of the primary diagnosis or for staging
tumors.
• As a general rule, radiologic findings suggestive of
cancer must be confirmed by either cytologic or
histologic examination of biopsy material before
treatment can be started.