AETIOLOGY, SPREAD,GRADING,STAGING & MANAGEMENT OF TUMORS

1. Aetiology, Spread,
Grading, Staging and
management of tumors
By
Dr Ankit Kumar
under guidance of
Dr Dharmraj Meena Sir

2.  Study of neoplastic diseases:
 ONCOS = tumor LOGOS = study
Neoplasm:
 Altered cell population characterized by
an excessive, non-useful proliferation
of cells that are unresponsive to normal
control mechanisms and to organizing
influences of adjacent tissue.

3. Neoplasm:
1. Malignant:
 Cancer cells that exhibit uncontrolled
proliferation and impair the function of
normal organs by local tissue invasion
and metastatic spread to distant
anatomic sites.
2. Benign:
 Composed of normal appearing cells
that do not invade locally or
metastasize to other sites

4. EPIDEMIOLOGY:



Overall cancer death rates shows
slow steady increase
Lower death rates during past
50yrs:
1. Stomach
2. Uterus
Increase death rates:
1. Lung
2. Pancreas

5. EPIDEMIOLOGY:
Cancer incidence by sites and sex:
Male Female
Lung 20% Breast 27%
Prostate 20% Colon & Rectum 16%
Colon & Rectum 14% Lung 11%
Urinary 10% Uterus 10%
Leukemia &
Lymphoma
8%
Leukemia &
Lymphoma
7%
Skin, pancreas
and oral
3-4%
Skin, pancreas
and oral
3-4%

6. EPIDEMIOLOGY:
Cancer death by sites and sex:
Male Female
Lung 36% Lung 20%
Colon & Rectum 11% Breast 18%
Prostate 10% Colon & Rectum 14%
Leukemia &
Lymphoma
9%
Leukemia &
Lymphoma
9%
Pancreas &
Urinary
5%
each
Pancreas & Ovary 5%
Urinary & Uterus
4%
each

7.  The most significant 5 yrs survival
rates are achieved in patients w/
cancer of skin, thyroid, cervix,
uterus and bladder; while the
lowest survival with pancreatic
cancer

8. ETIOLOGY:
Chemical carcinogens:
a. Hydrocarbons from coal tar = skin,
larynx & bronchial CA
b. Aromatic amines = urinary tract CA
c. Benzene = leukemia
d. Asbestos = mesothelioma
Physical carcinogens:
a. Ionizing radiations = bone cancer
 Multiple x-rays = skin/thyroid CA
b. Atomic bomb (Japan) = leukemia

9. ETIOLOGY:
Mechanical (chronic irritation):
 Marjolin’s ulcer = burn scar cancer
Infection:
 Parasitic:
 Schistosomas – Liver & bladder CA
 Viruses:




Hepatitis B – hepatocellular CA
Epstein-Barr virus – Burkitts lymphoma
Herpes simplex virus 2 – cervical CA
Aids

10. ETIOLOGY:
Precancerous conditions:
a. Leucoplakia
b. Actinic keratosis
c. Polyps of colon & rectum
d. Neurofibromas
e. Dysplasia of cervix, bronchial
f. Chronic ulcerative colitis
Hereditary factors:
 Familial polyposis – colonic CA

11. ETIOLOGY:
Oncogenes & Growth Factors:


RNA tumor viruses cause:
1. Carcinomas
2. Sarcoma
3. Leukemia
4. Lymphomas
Retrovirus have an enzyme that alters
genomic RNA resulting to abnormal
growth and differentiation of the cell.
Multi-factorial:
 Lung / breast CA

12. Breast Cancer Risk Factors
 Having first period before age12
 Not having children or having first children after
age 30
 Late age at menopause
 Family history of breast cancer
 Use of menopausal hormone therapy
 Exposure to radiation, especially at a young age
 Increrase body weight
 Alcohol intake,even low level of alcohol

13. Colorectal cancer Risk Factors
• Age- much more common after age 50
• Risk is higher for those with relatives who have
had colorectal cancer or polyps.
• A personal history of adenomatous polyp, if the
polyp is large,if there are many of them,or if any
of them shows dysplasia.
• A personal history of inflammatory bowel disease
• Long term tobacco use
• Excessive alcohol use(specially among men)
• Obesity
• Diets low in vegetables, fruits, and whole grains
• Diets hight in red meats(such as beef,pork or
liver) and processed meats(frying,grilling)
• Low level of physical activity

14. Stomach cancer Risk Factors
 Age – sharp increase in stomach cancer rates in
people over age 50
 Geography- world wide more common in japan,
china, south and central America.
 Helicobacter pylori infection
 Stomach lymphoma-MALT Lymphoma
 Obesity (causes gestric reflux)
 Lower intake of fruits and vegetables
 High intake of salt and salt-preserved foods
 Processed meat
 Physically inactive
 Previous stomach surgery
 Pernicious anemia
 Family history

15. CANCER BIOLOGY
1. Morphologic changes:





Rise from a single cell
Revert to more primitive cell types
Normal orderly tissue patterns are lost
or replaced by the random pilling up
of malignant cells w/o definite pattern
High index of mitoses
Invasion of adjacent structures

16. CANCER BIOLOGY
2. Biochemical changes:


Changes in DNA, RNA and chemical
architecture results to LOSS of
CONTACT INHIBITION to proliferation
and intercellular adhesiveness
Reversion of normal cellular
biochemistry to that of the embryonal
cells that produces EMBRYONAL subs.
(CEA, alpha fetoprotein)

17. CANCER BIOLOGY
Effector mechanism in tumor
immunity:
 Host provides a number of effector
mechs. that destroys the tumor:






Tumor-antigen-specific antibodies
Mononuclear phagocytes
Natural killer cells
Cytotoxic T lymphocytes
Neutrophils
K cells

18. CANCER BIOLOGY
Effector mechanism in tumor
immunity:
 Tumor Necrosis Factor (TNF):


Cytokines produced by monocytes,
machrophage, endothelial cells, large
granular lymphocytes and neutrophils
Properties:
a. Direct cytotoxicity for certain cells
b. Stimulation of procoagulant activity by
vascular endothelial cells
c. Induction of fever by direct effect on the
hypothalamic thermoregulatory center

19. CANCER PATHOLOGY
Classification of Neoplasm:
Carcinoma – arising from epithelial cells
Sarcoma – arise from connective tissue
and cells of mesenchymal origin
(fibrous, muscular, fatty, vascular &
skeletal).

20. CANCER PATHOLOGY
Grading of malignancy:
 Broders classified carcinoma into
4 grades according to:
1. Degree of differentiation
2. Appearance of cells, their nuclei and
the number of mitotic figures
Grade I
Grade IV
– least malignant
– most malignant

21. CANCER PATHOLOGY
Carcinoma in Situ:
Has cytologic characteristic of
malignant tumors but with no
detectable invasion into the
surrounding tissue or infiltration
into deeper cell layers

22. ROUTES OF SPREAD:
 Metastasis may entirely dominate
the clinical picture, while the
primary tumor remains latent and
asymptomatic
1. Direct extension
2. Lymphatic spread
 Common in epithelial
neoplasms of all types (except
for basal cell CA)

23. ROUTES OF SPREAD:
3. Vascular spread



Either thru the thoracic duct or by the
invasion of blood vessels
Capillaries are almost invaded, veins
invaded frequently but arteries rarely.
More common in sarcomas
4. Spread through serous cavities
 Peritoneal seedings (gastrointestinal CA)

24. CLINICAL MANIFESTATION:
Seven Danger Signals of Cancer
(Direct manifestation):
1. Change in bowel or bladder habits
2. A sore that does not heal
3. Unusual bleeding or discharge
4. Thickening or lump in breast or
elsewhere
5. Indigestion or difficult in swallowing
6. Obvious change in wart or mole
7. Hoarseness of voice.

25. CLINICAL MANIFESTATION:
Indirect or Systemic Manifestation:
1. Secondary to metastasis
 Cachexia
2. Secondary to none metastatic:
a. Ectopic production of known hormones
b. Secretion of unidentified, hormone like
substances
c. Toxic substances secreted from the tumor
d. Autoimmune – host is sensitized to an
antigen from the tumor

26. CLINICAL MANIFESTATION:
Signs of Expansile growth:
1. Obstruction
2. Destruction
Signs of Infiltrative Growth:
 Tumor infiltrates the nerves
1. Pain
2. Numbness
3. paralysis

27. CLINICAL MANIFESTATION:
Signs of Tumor necrosis (Bleeding &
Infection):



Tumor may become necrotic, ulcerate
and bleed
Fatigue and weakness in right colon
cancer is due to anemia
Inflammation caused by cecal CA can
mimic the clinical symptoms of acute
AP or cholecystitis.
Unknown primary tumors presenting
as metastases

28. DIAGNOSIS OF CANCER:
A. Clinical History:
1. Weight loss
2. Loss of Appetite
3. Bleeding or a discharge from any
body orifice or nipple
4. Sore that is slow to heal

29. DIAGNOSIS OF CANCER:
5. Persistent cough or wheeze
6. Change in voice
7. Difficulty of swallowing
8. Change in bowel habit
9. Growing lump in the skin, breast,
abdomen or muscle

30. DIAGNOSIS OF CANCER:
B. Physical Examination:


Palpable masses (movable, non-
movable)
LN enlargement
C. Laboratory Examination:


Blood examination
Radiological procedure:
 X-ray, esophagoram, Barium enema,
mammography, thyroid scan, CT scan,
MRI

31. DIAGNOSIS OF CANCER:
Biopsy:


o
To document presence of malignancy
Types:
1. Needle biopsy (cytological)
2. Incisional biopsy
3. Excisional biopsy
Rapid frozen biopsy / exfoliative
cytology (Pap smear)

32. NEEDLE BIOPSY
A needle biopsy is procedure to obtain a sample of
cells from the body for diagnose a medical condition
or disease or to assess the progress of a treatment
.
Common needle biopsy procedure include Fine
Needle aspiration and core needle biopsy.
Needle biopsy may be used to take tissue or fluid
samples from muscles, bones and other organs,
such as the liver or lung.

33. NEEDLE BIOPSY
Fine needle aspiration- This type of needle biopsy
uses a thin, hollow needle to draw cells from the
body.
Core needle biopsy- This type of needle biopsy
uses a wider needle then does FNAC. The needle
used during core needle biopsy is a hollow tube that
allows to extract a core of tissue.
Pathology report includes -
A description of the biopsy sample
A description of the cells
A pathologists diagnosis

34. Incisional & Excisional Biopsy
An Incisional Biopsy is a test to remove a piece of
tissue from a lesion or mass. The tissue is then
tested to find out what it is.
An excisional biopsy is a test in which the whole
lesion or mass is removed and tested.
The tissue sample is reviewed by a pathologist
and a report is written.

35. STAGING OF CANCER:
Most cancers are staged in five broad groups.
These are usually referred to with Roman
numerals. Other kinds, like blood cancers,
lymphoma and brain cancer have their owen
staging system.
Physical examination and several tests are used
to determine the clinical stage- an estimate of
how far the cancer has spread and helpfull in
treatment plan . These test may includes Blood
and other test and scans like MRI,CT,USG, PET
or nucler scan .

36. STAGING OF CANCER:
Clinical Staging of Cancer:
TNM:
Stage 0 = means there is no cancer , only
abnormal cells with the potential to become
cancer . Also called carcinoma in situ.
Stage I = cancer confined to it’s primary site
Stage II = more locally advanced disease
Stage III = metastasis to regional LN
Stage IV = metastasis to distant sites


37. STAGING OF CANCER:
TNM System- Short form of tumor, node and
metastasis.
Tumor(T)- T, followed by number from 0-4 tells
how large the tumor is, T0 means no
measureable tumor. The higher the number, the
bigger the tumor.
Node(N)- N, followed by number from 0-3 tells
us if the cancer has spread to the lymph node,N0
means lymph nodes are not involved. A higher
the number means the cancer is in more lymph
nodes.

38. STAGING OF CANCER:
Metastasis(M)- M, is followed by either 0 or 1. It
says if cancer has spread to organs and tissues in
other part of body. A 0 means it hasn’t, and a 1
means it has.
If a cancer is localized to one area of body, then
surgery or radiotherapy could be enough to
remove it completely. If a cancer has spread,
chemotherapy, harmone therapy or biological
therapies that circulate throughout the
bloodstream are required.

39. Staging of Carcinoma of the colon
Tumor Stage (T)
Tx – Can not be assess
T0 – No evidence of tumor
T1 – Tumor invades submucosa
T2 – Tumor invades muscularis propria
T3 – Tumor invades through muscularis propria in
to subserosa or nonpetritonealized pericolic or
perirectal tissue.
T4 – Tumor directly invades other organs or
structures and /or perforates visceral peritoneum

40. Staging of Carcinoma of the colon
Regional nodal metastasis(N)
Nx – Regional lymph node can not be assessed
N0 – No nodal metastasis
N1 – Metastasis in 1 to 3 pericolic or perirectal
nodes
N2 – Metastasis in 4 to more pericolic or perirectal
nodes
N3 – Metastasis in any node along course of a
named vascular trunk and /or metastasis to apical
nodes

41. Staging of Carcinoma of the colon
Distant metastasis(M)
Mx – Presence of distant metastasis cannot be
assessed
M0 – No distant metastasis
M1 – Distant metastasis

42. Staging of Carcinoma of the colon
AJCC DUKES TNM
0 Tis
I A T1-2N0M0
II B T3-4N0M0
III C AnyT,N1-3,M0
IV D AnyT,AnyN,M1

43. STAGING OF CANCER:
A. Post-surgical Resection Staging:

The extent of disease using all data available at the
time of surgery and on examination of a
completely resected specimen.
B. Re-treatment Staging:

Restaging is necessary for additional or secondary
definitive treatment after a (disease-free) interval
following 1st treatment.
C. Autopsy Staging:
 Used only when the cancer is 1st diagnosed at
autopsy.

44. CANCER TREATMENT:
1. Surgical resection
2. Radiation therapy
3. Chemotherapy


Surgery & radiation tx represents
treatment of cancers that remains
localized to it’s primary site or regional
LN.
Chemotherapy and Immunotherapy
– tx effective against tumor cells already
metastatic to distant organ sites.

45. CANCER TREATMENT:
GOALS of Therapy:
 Vary with extent of the cancer:
1. Localized w/o evidence of spread:
 Eradicate the cancer and CURE
THE PATIENT
2. Spread beyond the local site:
 Control patient’s symptoms and
to maintain maximum activity
for the longest possible period
of time.

46. CANCER TREATMENT:
CRITERIA of Incurability:
1. Distant metastasis (most common)
2. Evidence of extensive local
infiltration of adjacent organs or
structures


Pt’s general condition and the presence
of any co-existing disease must be
considered in planning therapy.
The PSYCHOLOGICAL makeup of the
patient and the patient’s life situation
must be considered.

47. CANCER TREATMENT:
SURGICAL RESECTION:
A. Surgical Curative Resection:
 Wide local resection:


Low grade malignancy
Basal cell CA of the skin
 Radical Local Resection:


High grade malignancy
En Bloc LN dissection for breast,
esophagus, gastric, colorectal CA
B. Surgical Palliative Resection:
1. To relieve symptoms
2. To prolong a useful comfortable life
3. Gastrojejunostomy, colostomy

48. CANCER TREATMENT:
RADIOTHERAPY:


Destroy tumor with preservation of
anatomic structures
Direct toxic effect to cells due to
ionization of water

49. CANCER TREATMENT:
CHEMOTHERAPY:
Antimetabolites:
Methotrexate & 5-FU
Alkylating agents:
cyclophosphamide
Ifosfamide
Chlorambucil
Melphalan
Busulfan
Carmustine, Lomustine
Dacarbazine, Procabazine

50. CANCER TREATMENT:
CHEMOTHERAPY:
Antibiotics:
Actinomycin D, Doxorubicin, Bleomycin
Vinca Alkaloids:
Vincristine & Vinblastine

51. CANCER TREATMENT:
IMMUNOTHERAPY:



Inhibit proliferation of cancer cells w/o
affecting function of normal cells
Stimulates the host to generate specific
immune response to its tumor-vaccine from
tumor cells
TUMOR SPECIFIC ANTISERUM:


Murine monoclonal antibodies
Immunotoxins
 None-specific immunotherapy=BCG vaccine

52. CANCER TREATMENT:
HIPEC (Hyperthermic Interperitonial
chemotherapy)– is a highly
concentrated, heated chemotherapy
treatment that is delivered directly to
the abdomen during surgery.
• Heating (41 to 43 degree
Celsius)the solution may also
improve the absorption of
chemotherapy
• The procedure treats tumors in the
abdomen ( peritoneal) lining that
stem from
colon,gastric,ovarian,appendix
tumors

53. CANCER TREATMENT:
TACE(Transarterial chemoembolization therapy)
is a localised method of administrating
chemotherapy directing to a liver tumor via a
catheter.
• TACE is most commonly used in the treatment
of hepatocellular carcinoma & selective
metastasis disease (most commonly from
colorectal carcinoma ) , it may also be used in
cholangiocarcinoma.
• It can be used as palliative treatment for a
patient with unresectable HCC or as a bridge
to a liver transplant.

54. CANCER TREATMENT:
TAE (Transarterial embolism) i.e.
without a chemotherapy agent added,
is also used.
This may be just as effective as TACE

55. PROGNOSIS:
DETERMINANTS:
1. Site of origin of primary tumor
2. Stage of the disease
3. Histologic features of the cancer
4. Host immune factors
5. Age of the patients

56. THANK YOU