ETIOLOGY OF

TUMORS
Etiology of tumor

1. Predisposing factors
2. Carcinogenic agents

Note:
 Mutation of a cell leads to development of
neoplasm.
 Mutation may occurs by carcinogens or may be
inherited.
Predisposing factors

1. Geographic and racial factors:

 i. Stomach cancer-Japan >> United States
 ii. Breast cancer-United States> > Japan
 iii. Liver hepatoma - Asia> > United States
 iv. Prostate cancer-African American> Caucasian
2. Occupational exposures:
 Plastic industry (vinyl chloride) = Angiosarcoma of liver
 Dye makers and rubber industry = Bladder cancer
 Predisposing factors
3. Age:
 Carcinomas usually occurs

at older age where as

sarcomas occurs at
younger age Multiple
4. Heredity predisposition: Polyp in
colon
 In some cases there is
strong link between Adenocarcinoma
hereditary genetic Of colon
abnormality and
development of cancer. E.g;
 Familial retinoblastoma

(Abnormality in
chromosome 13)
 Familial polyposis coli
Predisposing factors
5.. Preneoplastic disorders: Acquired
 Cervical dysplasia (HPV)
 Cirrhosis
 Chronic atrophic gastritis
Carcinogens
 These are the acquired environmental agents
that causes tumor by mutation
 Chemical carcinogens
 Radiation
 Micro-organism
 Oncogenic Virus
 Helicobacter pylori.
Chemical carcinogens
 Carcinogenesis is a multistep process involving
a sequence of initiation (mutation) followed by
promotion (proliferation).
 Chemical carcinogens are of two types;
 Direct-acting chemical carcinogens.
 These are mutagens that cause cancer directly by
modifying DNA.
 Indirect-acting chemical carcinogens
(procarcinogens).
 These require metabolic conversion to form active
carcinogens.
 Clinically important chemical
carcinogens
 Nitrosamines: gastric cancer
 Cigarette smoke: multiple malignancies
 Polycylic aromatic hydrocarbons: bronchogenic carcinoma
 Asbestos: bronchogenic carcinoma, mesothelioma
 Chromium and nickel: bronchogenic carcinoma
 Arsenic: squamous cell carcinomas of skin and lung, angiosarcoma
of liver
 Vinyl chloride: angiosarcoma of liver
 Aromatic amines and azo dyes: hepatocellular carcinoma
 Benzene: leukemia
 Napthylamine: bladder cancer
 Radiation
1. Ultraviolet radiation
 UVB sunlight is the most carcinogenic.

 Produces pyrimidine dimers in DNA leading to transcriptional

errors and mutations of onogenes and tumor suppressor genes

2. Ionizing radiation
 X-rays and gamma rays, alpha and beta particles, protons,

neutrons.
 Cells in mitosis are most sensitive

 Causes cross-linking and chain breaks in nucleic acids

Radiation
Oncogenic virus
 Viruses producing tumors are known as Oncogenic
viruses.
 RNA oncogenic viruses:
 The human T-cell leukemia virus (HTLV-l) causes adult T-cell
leukemia/lymphoma.
 DNA oncogenic viruses:
 i. Hepatitis B and C virus causes hepatocellular carcinoma
 ii. Epstein-Barr virus (EBV) .
 Burkitt lymphoma
 B-cell lymphomas in immunsuppressed patients
 Nasopharyngeal carcinoma
Oncogenic virus

DNA oncogenic viruses (contd…)

 iii. Human papilloma virus (HPV)
 Benign squamous papillomas (warts)
 Cervical cancer
 iv. Kaposi-sarcoma-associated herpes virus
(HHV8)
 Kaposi sarcoma.
Helicobacter pylori

 Associated with
 Gastric carcinoma
 Gastric lymphoma
Tumor biology
(Carcinogenesis)
Introduction
 Carcinogenesis is a multistep process.
 Development of all human cancers requires
mutation
 Most important mutations involve
 i. Growth promoting genes (proto-oncogene).
 ii. Growth inhibiting tumor suppressor genes.
 iii. The genes regulating apoptosis
 IV. The genes that repair the damaged DNA
 A tumor is derived from a monoclonal
expansion of a mutated cell
1.Activation of growth
promoting oncogenes
 Protooncogenes are normal cellular genes
involved with growth and cellular
differentiation.
 Oncogenes are derived from proto-
oncogenes by mutation.
 Activated oncogenes lack regulatory control
and are over expressed, resulting in
unregulated cellular proliferation
Clinically important
oncogenes
ONCOGENES TUMORS
Erb-B1 Squamous cell Ca of lung

Erb-B2 Breast , ovary and lung

Erb-B3 Breast

Ki-ras Lung, pancreas and colon

C- myc Burkitt Lymphoma

L- myc Small cell lung Ca

N- myc Neuroblastoma
2. Inactivation of tumor
suppressor genes
 Definition:
 Tumor suppressor genes
encode proteins that
regulate and suppress
GENE TUMORS
cell Proliferation. P 53 Lung, breast,
 Mutation of tumor colon etc
suppressor genes Rb Retinoblastoma
leads to excessive cell
WT 1,2 Wilms tumor
growth
BRCA 1 , 2 Hereditary
breast cancer
3. Alteration of gene
Regulating apoptosis
 Apoptosis:
 Programmed cell death.
 This is a Physiological process by which abnormal
cell die and eliminated.
 Loss of apoptosis results in immortality of the
cell.
 Example:
 bcl-2 gene
 Prevents apoptosis
 Over expression occurs in Non-Hodgkin's Lymphoma
CLINICAL
DIAGNOSIS OF
TUMOR
Symptoms

CHARACTERS BENIGN MALIGNANT

1.Growth Slow growing Rapid growing

2.Pain Usually absent May be painful at late

stage

3.Loss of weight Never seen A feature of

malignant growth

4.Loss of function Usually not seen Seen quite early

 Signs
CHARACTERS BENIGN MALIGNANT
1. Anaemia,Asthenia, Usually absent Usually present
Cachexia
2.Mobility Freely Mobile Fixed early due to
infiltration
3. Surface Usually smooth Usually irregular
4. Margin Definite and smooth Not definite and irregular
5.Consistancy Usually firm Either hard or variable
6. Regional Lymph node Absent Early involved and
enlarged
7.Clincal features of Never seen Feature of malignancy
metastasis.
8.Secondary changes Not seen Hemorrhage, Ulceration
and infection may be seen
9. Recurrence Never recurs after Often recurs after excision
complete excision
 PARANEOPLASTIC

SYNDROME
A paraneoplastic syndrome is a disease or symptom that is the
consequence of the presence of cancer in the body, but is not due
to the local presence of cancer cells .
 These phenomena are mediated by 
 Humoral factors (by hormones or cytokines) excreted by tumor
cells.
 An immune response against the tumor.

 Examples;
 Cushing syndrome
 Small cell Ca of Lung , Pancreatic carcinoma
 Caused by secretion of ACTH by tumor cells
 SIADH ( Syndrome of inappropriate ADH secretion)
 Small cell Ca of lung
 Trousseau sign of malignancy ( Migratory thrombophlebitis)
 Pancreatic cancer
 Caused by mucin secretion
STAGING AND
GRADING OF
MALIGNANT TUMORS
STAGING OF CANCER
 The stage of a tumor is the extent of spread.
 It determines the severity of the lesion and is of
clinical significance.
 Different staging systems are used
 TNM – general use
 Duke’s for colorectal cancer
 TNM staging
 T (extent of the primary tumour)
 Tx—primary tumour cannot be assessed.

 T0—no evidence of primary tumour.

 Tis—carcinoma in situ.

 T1, T2, T3, T4—increasing size and/or local extent of primary

tumour.
 N (absence or presence and extent of regional lymph node
metastases)
 Nx—regional lymph nodes cannot be assessed.

 N0—no regional lymph node metastases.

 N1, N2, N3—increasing involvement of regional lymph nodes.

 M (absence or presence of distant metastases)

 Mx—presence of distant metastases cannot be assessed.

 M0—no distant metastases.

 M1—distant metastases.
 GRADING OF CANCER
 The grade of cancer is an assessment on its degree of malignancy.
 Grading is done on
 differentiation ( degree of resemblance to normal tissue)
 Nuclear size and pleomorphism
 Grade I :
 more than 75% of cells are differentiated
 Grade II:
 50-75 % of cells are differentiated
 Grade III:
 25-50 % of cells are differentiated
 Grade Iv:
 Less than 25 % cells are differentiated.
LAB
INVESTIGATIONS
FOR TUMORS
Introduction
AIMS FOR INVESTIGATIONS:
 Investigations for diagnosis.
 Investigations for staging of tumors
 Investigations for metastasis
Lists of investigations :
 Histological diagnosis
 Cytology
 Biopsy and histopathology
 Others
 Immunocytochemistry , Frozen section , Molecular diagnosis
 Serum tumor markers
 Radiology
 X-Ray
 USG
 CT scan
 MRI
 ERCP
 Cytology
 Cytology is a branch
of pathology that studies
and diagnoses diseases
on the cellular level.
1.Exfoliative cytology:
 Cells are extracted from fluid
shed from the body and
used to prepare smear and
staining.
 Materials are
 PAP smear (Cervix) ,
Sputum , urine , fluids
of body cavities
 Cytology

2.FNAC (Fine needle

aspiration cytology)
 A needle attached to
a syringe is used to aspirate
cells from lesions or masses
in various organs of the body.
 FNAC can be done directly
on a mass in superficial
regions like the neck, thyroid
or breast; or it may be
assisted by ultrasound or CT
scan.  FNAC of parotid gland showing
Clusters of pleomorphic cells
Biopsy and histopathology

Biopsy:
 Removal of tissue from a living subject to

determine the presence or extent of a disease.

 Different technique of biopsy are applied like;

Core needle biopsy ,Incision biopsy, Excision

biopsy.
Examination:
 Gross ( Naked eye ) examination.

 Histopathological examination after staining.

Serum tumor markers
 Tumor markers are usually normal cellular
components that are increased in neoplasms
but may also be elevated in non-neoplastic
conditions.
 Use of tumor markers
 i. Screening (e.g., prostate specific antigen [PSA]).
 ii. Monitoring treatment efficacy.
 iii. Detecting recurrence.
List of clinically important serum
markers
1.Antigens:
 PSA (prostate specific antigen) :
 prostate cancer
 Alpha-fetoprotein ( AFP):
 These are oncofetal antigen; i.e. synthesized normally in fetal
life.
 Markedly increased in
 Hepatocellular carcinoma , Non seminomatous germ cell tumor of testis.
 Carcinoembryonic antigen ( CEA)
 These are oncofetal antigen.

 Elevated plasma CEA is found in

 Carcinoma of colon, carcinomas of the lung, pancreas, stomach, breast
 Carbohydrate antigen- 125 ( CA-125)
 ovarian cancer

 Carbohydrate antigen – 19-9 ( CA 19-9 )

 Pancreatic cancer
List of clinically important serum
markers
2. Hormones
 Human chorionic gonadotropin ( HCG)
 Hormone produced in pregnancy that is made by the
developing embryo after conception and later by
the syncytiotrophoblast (part of the placenta).
 Hence tumor of chorionic tissue secrets hCG
 Choriocarcinoma , Hydatidiform mole ,
Teratocarcinoma of testis and ovary.
 Calcitonin
 Medullary carcinoma of thyroid
 Ectopic hormones
 ACTH and ADH by small cell carcinoma of lung.
List of clinically important serum
markers

3. Serum enzymes:
 Placental alkaline phosphatase:
 seminoma of testis
 Prostatic acid phosphatase:
 prostate cancer
4. Other markers:
 Bence-jones protein in urine and blood
 Multiple myeloma.
Radiology in tumor Dx
 The radiologist is involved at every stage from the
 initial diagnosis
 Staging
 Radiotherapy planning
 patient management and follow-up.
 Common tumors such as those of the lung, breast,
and colon are often initially diagnosed by imaging
(chest X-ray, mammography, and barium enema), to
be confirmed by cytology or histology.
 Radiological imaging technique involves
 X-Ray ,USG ,CT scan ,MRI,ERCP , Radioisotope scanning
etc.
X-ray of Distal femur of X-ray chest showing a large, round soft-tissue
Osteosarcoma mass is present at the right apex
(Codman's triangles, Lytic (Bronchogenic Ca)
Lesion at metaphysis)
 CT scan of abdomen showing
metastatic liver cancer

CT scan of lung showing lung

cancer