EPIDEMIOLOGY OF NEOPLASM

1. Faculty of Medicine
NEOPLSIA
2019
King Abdulaziz University
Rabigh Branch
EPIDEMOLOGY

2. Epidemiology

3. Neoplasia
• Cancer is the 2nd leading cause of death in the United
States, behind heart disease
• More than 1.3 million estimated new cancer cases occur
annually (female - 43.2% and male - 56.8%) resulting in
more than 560,000 deaths (excluding non-melanoma skin
cancer)
• The probability of dying of cancer is estimated at 20-25%
for individuals born in 1985, which has increased from ~15-
19% for those born in 1975

4. Why epidemiology is useful
• It allows you to know what is common and what is
rare.
• It can provide clues to aetiology
• Can facilitate planning of preventative measures
• It underpins the development of screening methods
for early diagnosis

5. A range of factors can influence
the epidemiology of a disease
Age variation
Gender differences
Historical variation
Geographic variation
Social and economic factors
Occupational factors
Dietary factors
Genetic factors
etc . . . . . . . .

6. Incidence
may be related to ethnic & geographic
differences in community:
• Cervical Cancer: Hispanic women are significantly more
likely to be diagnosed with cervical cancer than the
general population
• Multiple myeloma: is twice as common in African-
Americans as it is in white Americans.
• Chronic lymphocytic leukemia: is more common among
the Jewish people of East European descent and is
rather uncommon in Asia

7. Geographic Location
• Gastric CA -- High in Japan
• Skin CA------ High in New Zealand
• Hepatocellular CA --- High in Africa, China
• Breast CA ---- High in USA
• Prostatic CA ---- High in USA
• Colorectal CA ----High in USA
• Nasopharyngeal CA--- Far East
• Burkitt Lymphoma ----- Africa

8. Genetic polymorphism
is responsible for :
• Individual predisposition to disease
• Individual response to environmental agents
• Individual response to drugs

9. Environment
* Diet
* Occupation
* Sunlight
* Personal habits

10. Age
• In general , cancer incidence ≈ AGE
• However, certain cancers occur more in children
* Acute Leukemia
* Some Lymphoma
* Some CNS Tumors
* Bone & soft tissue Sarcomas

11. Heredity
• 5-10% of tumors
• Inherited Cancer Syndromes : Presence of defined genetic
abnormality, usually AD, often specific phenotype e.g.
– APC gene : Familial Adenomatous Polyposis Coli
– MEN1 & RET genes : MEN syndrome
– NF1 & NF2 genes : Neurofibromatosis
– RB gene : Retinoblastoma
• Familial cancers : No specific phenotype & multifactorial
• Family members have higher incidence to common cancers
– CA of COLON, BREAST, OVARY
– Younger age groups, multiple or bilateral, two or more family
members are affected.
– Some linked to inheritance of mutant genes e.g. BRCA-1 &
BRCA-2

12. Acquired Preneoplastic Syndromes
• These are associated with increased risk for CA and
most are related to rapid or abnormal cell proliferation.
– Endometrial Hyperplasia & carcinoma
– Cervical Dysplasia & Cervical CA
– Bronchial dysplasia & lung CA
– Liver Cirrhosis & Hepatocellular
– Chronic healing proces
– Ulcerative Colitis & Colorectal CA
– Villous Adenoma & Colorectal CA
– Leukoplakia & Squamous cell CA

13. Mortality statistics
the big 5 in men and women
Males Females
Lung Lung
Prostate Breast
Colorectal Colorectal
Oesophagus Ovary
Pancreas Pancreas

14. Invasion and Metastasis
• The two properties (Invasion and Metastasis)
accounts for most of the serious (and lethal)
consequences of neoplasia.
• Metastasis is the process whereby malignant tumor
cells spread from their site of origin (Primary site) to
some other distant site in the body (Secondary site).
• Size and differentiation of the primary neoplasm may
play role in metastatic potential.
• All tumors can potentially metastasize except
– BASAL CELL CA ., GLIAL TUMORS

15. Invasion and Metastasis
• Not all cancer have equivalent ability to metastasize:
– basal cell carcinoma of the skin and most primary
tumors of the CNS (glial) are highly invasive at
their primary sites but rarely metastasize.
– osteogenic sarcomas usually have metastasized
to the lungs at the time of initial discovery.

16. Local invasion
• Benign tumors remain localized at its site of origin
• They expand slowly and develop an enclosing fibrous
capsule (adenomas and fibromas).
– Exception: leiomyoma of the uterus separated
from the surroundings by a zone of compressed
normal myometrium
• Cancers grow by progressive infiltration, invasion,
destruction, and penetration of the surrounding
tissue.
• Local invasiveness is the most reliable feature that
distinguishes malignant from benign tumors.

17. Basal cell carcinoma of the skin
• Basal cell carcinomas of the skin,
the most common malignant tumor
in the human body.
• It is a locally invasive malignant
tumor, which, if untreated, could
ultimately kill the host.
• These tumors are usually diagnosed
early and removed adequately, so
that they almost never metastasize
• The neoplastic cells extend
downward into the dermis. Note the
pleomorphism of the cells, and there
is little keratinization. Compare with
the normal skin at the right. An
intense inflammatory infiltrate is
present.

18. Microscopic view of fibroadenoma of the breast .
The fibrous capsule (below) sharply delimits the
tumor from the surrounding tissue.

19. breast carcinoma illustrates the invasion of breast stroma
and fat by nests and cords of tumor cells.
The absence of a well-defined capsule should be noted.

20. Routes of spread
• Seeding within body cavities
• Lymphatic spread (typical of carcinoma)
• Haematogenous spread (favored by sarcomas)
• Direct transplantation of tumor cells (artificial mode of
dissemination)
– surgical instruments or the surgeon’s
gloves

21. • Peritoneal surfaces (colon carcinoma, ovary
cancers)
• Pleural cavities (lung cancers)
• Cerebral ventricles and then be carried by
cerebrospinal fluid to reimplant on the meningeal
surfaces (medulloblastoma)
Seeding within body cavities
Transcoelomic Spread

22. Pseudomyxoma Peritonei
• Pseudomyxoma of the ovary usually results (as a
complication) from peritoneal seeding of mucin-
secreting tumors of the ovary (Mucinous cystadenoma
of the ovary) or the gastrointestinal tract, and most
often the appendix.
• Although the ovarian tumor is benign, the implants of
the tumor cells seeding the peritoneal cavity can be
difficult to eradicate.
• The cells continue to secrete mucin and fill the
abdominal cavity, colloquially known as "jelly-belly."

23. Lymphatic spread (typical of carcinoma)
lymph node involvement depends on :
• The site of the primary
• The natural lymphatic pathways of drainage of the site.
Examples:
• lung carcinomas: regional bronchial lymph nodes then
tracheobronchial and hilar nodes.
• breast carcinoma: axillary nodes then supraclavicular
and infraclavicular Nodes.

24. Haematogenous spread
(favored by sarcomas)
Penetration of arteries are less readily than are veins.
In venous invasion,
• The bloodborne cells follow the venous flow, draining the
site of the neoplasm.
• The liver and lungs are the most frequently involved
secondary sites.
• Certain carcinomas invade veins early e.g.
RENAL Carcinoma  renal vein IVA
Hepatocellular Carcinoma Portal & Hepatic v.

25. Metastatic Pathway

26. Metastases occurs in two phases
• 1- Invasion of Extracellular Matrix (ECM)
• 2- Vascular dissemination

27. The main steps in the formation of a metastasis

29. 1- Mechanism of invasion of
ECM
1- Detachment of tumor cells
Inactivation of E-Cadherin OR activation of 
catenin detachment of tumor cells
Loss of function E-Cadherin in most CAs
2- Degradation of ECM by proteases :e.g.
Matrix Metalloproteinase (MMPs) such as
Cathepsin D, Type IV collagenase

30. 1- Mechanism of invasion of
ECM
3- Attachment of tumor cells to matrix
components by laminin & integrin receptors to
basement membrane & ECM
4- Migration of tumor cells :
Tumor derived cytokines e.g. Autocrine
motility factor
* Cleavage products of matrix & GF have
chemotactic activity for more tumor cells

31. 2- Vascular dissemination
1- Invasion of the circulation :
Adhesion to endothelium retraction of
endothelium  vessel
2- Attack by NK cells, some escape by
formation of a thrombus
3- Escape from circulation :
Adhesion to endothelium retraction of
endothelium  escape to tissue

32. What influences site of
metastases ?
• Anatomical Location
• Complimentary adhesion molecule between
tumor cells & target organs
• Chemoatractants liberated by target organs
• Protease inhibitors present in certain tissues

33. Examples of Tropism (Homing)
• Prostatic Carcinoma  Bone
• Lung Carcinoma  Adrenals & Brain
• Neuroblastoma  Liver & Bone
– Less common sites of metastases include skin,
muscle, thyroid, breast….etc.
– Spleen, Cartilage, Heart are almost never
involved by metastatic tumors.

34. CARCINOGENESIS IS A MULTISTEP PROCESS

35. Cancer is a disease of the cell cycle
Do you agree

36. What Is the Connection Among Cancer,
the Cell Cycle, and Genetics?
Cells either grow and divide with control ...or
not!
All kinds of malignant growth that the term
"cancer" represents, all have one lethal
attribute in common:
The cells of the malignancy go through the
cell cycle without control.
These cells disobey control mechanisms that lie
with them.

37. What Is the Connection Among
Cancer, the Cell Cycle, and Genetics?
 Many protein molecules involved in the cell
cycle, each is the product of a single gene.
 When there is a mutation in one of these genes,
it can:
 increase the likelihood that a cell will become
cancerous and eventually, through repeated,
unrestrained division, overtake the normal
cells, become malignant;
 possibly spread, or metastasise throughout
the body

38. What Is the Connection Among
Cancer, the Cell Cycle, and Genetics?
Cancer can develop at almost any stage in life.
Some forms of cancer develop very early, such as
retinoblastoma (a cancer of the eye)
Others tend to develop in childhood, such as
various forms of leukaemia, a cancer of the blood
There are many forms that develop during
adulthood.
In each case, cancer is the result of a mutated gene,
or a series of mutated genes, that lead to unregulated
cell growth and haphazard controls over cell
proliferation.

39. MALIGNANT NEOPLASM
(CANCER)
• Is multifactorial disease (genetic, environmental)
– Types of genes which may mutate to cause
cancer: (tumour suppressor genes,
oncogenes, DNA repair genes, telomerase,
p53)
– Environmental agents associated with cancer
such as viruses, tobacco smoke, food,
radiation, chemicals, pollution

40. • Cancer is considered as a genetic disease;
occurs sporadically (somatic mutations), or as a
hereditary trait.
• Genes in which mutations cause cancer fall into
two distinct categories:
– Oncogenes
– Tumor suppressor genes (TSGs) fall into two
types Gatekeepers and Caretakers
GENETIC BASIS OF CANCER

41. • Oncogene is a mutant allele of a proto-oncogene,
whose altered function or expression results in
abnormal stimulation of cell division and
proliferation.
– Proto-oncogene is normal gene that has
physiologic function via its protein that regulate
cell growth (proliferation & apoptosis) and
differentiation
ONCOGENES

42. ONCOGENES
• Oncogenes facilitate malignant transformation
by stimulating proliferation or inhibiting
apoptosis.
• Oncogenes have a dominant effect at the
cellular level
– when it is activated or overexpressed, a single
mutant allele is sufficient to initiate the change
in phenotype of a cell from normal to
malignant.

43. ONCOGENES
• The mutation can be an activating gain-of-
function mutation in the coding sequence of the
oncogene itself, a mutation in its regulatory
elements, or an increase in its genomic copy
number, leading to unregulated ectopic function
of the oncogene product.

44. ONCOGENES
• Activated oncogenes encode proteins such as:
– proteins in signaling transduction pathways
for cell proliferation (K-Ras, H-Ras, N-Ras)
– receptors and cytoplasmic proteins that
transduce signals
– transcription factors that respond to the
transduced signals and control the
expression of growth-promoting genes (myc)
– inhibitors of programmed cell death
machinery

46. Proto-oncogene activation

47. Proto-oncogene activation
• Point mutation: Ras oncogene point mutation
results in decreased GTPase activity.
– GTPase: enzyme that hydrolyze guanosine
triphosphate.
• Chromosomal rearrangement: (translocation and
inversion) Philadelphia chromosomes, Burkitt’s
lymphoma gene arrangement
• Gene amplification

48. • Fig 16-3. Mechanisms
of tumorigenesis by
oncogenes of various
classes. Unregulated
growth factor signaling
may be due to
mutations in genes
encoding growth factors
themselves (1), their
receptors (2), or
intracellular signaling
pathways (3).
Downstream targets of
growth factors include
transcription factors (4),
whose expression may
become unregulated.
Both telomerase (5)
and antiapoptotic
proteins that act at the
mitochondria (6) may
interfere with cell death
and lead to
tumorigenesis.

49. • TSGs are normal genes and their normal function is to
regulate cell division, so can suppress the development of
cancer
– TSGs encode a proteins which are part of the system that
regulates cell division (keeping cell division in check).
• When mutated, TSGs lose their function, and as a
result uncontrolled cell growth may occur
– This may contribute to the development of a cancer
• Both alleles need to be mutated or removed in order to
lose the gene activity.
– The first mutation may be inherited or somatic.
– The second mutation will often be a gross event
leading to loss of heterozygosity
TUMOR SUPPRESSOR GENES
(TSGS)

50. Knudsen’s “two hit” hypothesis
explain why certain tumors can occur in both hereditary and
sporadic forms

51. The Two-Hit Origin of Cancer
• For example, it was suggested that the
hereditary form of the childhood cancer
retinoblastoma might be initiated when a cell in
a person heterozygous for a germline mutation
in a tumor-suppressor retinoblastoma gene,
required to prevent the development of the
cancer, undergoes a second, somatic event that
inactivates the other allele.

52. The Two-Hit Origin of Cancer
• As a consequence of this second somatic event,
the cell loses function of both alleles, giving rise
to a tumor. The second hit is most often a
somatic mutation, although loss of function
without mutation, such as occurs with
transcriptional silencing (epigenetic changes),
has also been observed in some cancer cells.

53. The Two-Hit Origin of Cancer
• In the sporadic form of retinoblastoma, both
alleles are also inactivated (two somatic events
occurring in the same cell).
• familial polyposis coli, familial breast cancer,
neurofibromatosis type 1 (NF1), hereditary
nonpolyposis colon carcinoma, and a rare form
of familial cancer known as Li-Fraumeni
syndrome.

54. • Gatekeeper TSGs regulate the cell cycle and
control cell growth directly
– they block tumor development by regulating
the transition of cells through checkpoints
("gates") in the cell cycle or by promoting
apoptosis and, thereby, controlling cell division
and survival.
– loss-of-function mutations of gatekeeper genes
lead to uncontrolled cell proliferation.
TUMOR SUPPRESSOR GENES
(TSGS)

55. TUMOR SUPPRESSOR GENES
(TSGS)
• Gatekeeper TSGs encode:
– regulators of various cell-cycle checkpoints
– mediators of programmed cell death

56. • Caretaker TSGs are involved in repairing DNA
damage and maintaining genomic integrity.
– Loss of function of caretaker genes permits
mutations to accumulate in proto-oncogenes
and gatekeeper genes, which, in concert, go
on to initiate and promote cancer.
TUMOR SUPPRESSOR GENES
(TSGS)

57. • Caretaker TSGs encode:
– proteins responsible for detecting and repairing
mutations
– proteins involved in normal chromosome
disjunction during mitosis
– components of programmed cell death
machinery
TUMOR SUPPRESSOR GENES
(TSGS)

58. • Loss of both alleles of genes that are involved in
repairing DNA damage or chromosome breakage
leads to cancer indirectly by allowing additional
secondary mutations to accumulate either in
proto-oncogenes or in other TSGs.
TUMOR SUPPRESSOR GENES
(TSGS)

59. Gene Gene product and possible
function sporadic
DISORDERS IN WHICH THE GENE IS
AFFECTED
Gatekeepers Familial Sporadic
RB1 p110
Cell cycle regulation
Retinoblasto
ma
Retinoblastoma, small cell lung
carcinomas, breast cancer
TP53 p53
Cell cycle regulation
Li-Fraumeni
syndrome
Lung cancer, breast cancer,
many others
Selected Tumor-Suppressor Genes
Caretakers Familial Sporadic
BRCA1,
BRCA2
Brca1, Brca2
Chromosome repair in response to double-
stranded DNA breaks
Transcriptional regulation and DNA repair
Familial breast and
ovarian cancer
Breast cancer,
ovarian cancer
MLH1,
MSH2
Mlh1, Msh2
Repair nucleotide mismatches between
strands of DNA
(Microsatellite instability, a marker of
DNA mismatch repair)
Hereditary
nonpolyposis colon
cancer
Colorectal cancer

60. • The p53 protein is a DNA-binding protein that
appears to be an important component of the
cellular response to DNA damage.
• In addition to being a transcription factor that
activates the transcription of genes that stop cell
division and allow repair of DNA damage, p53
also appears to be involved in inducing apoptosis
in cells that have experienced irreparable DNA
damage.
TP53

61. TP53
• Loss of p53 function, therefore, allows
cells with damaged DNA to survive and
divide, thereby propagating potentially
oncogenic mutations. The TP53 gene can
therefore be considered to also be a
gatekeeper TSG.

62. • Different types of genetic alterations are responsible for
initiating cancer. These include mutations such as:
– activating or gain-of-function mutations, including gene
amplification, point mutations, and promoter mutations,
that turn one allele of a proto-oncogene into an
oncogene
– chromosome translocations that cause misexpression
of genes or create chimeric genes encoding proteins
with novel functional properties
– loss of function of both alleles, or a dominant negative
mutation of one allele, of TSGs.
Tumor Initiation & Progression

63. • Once initiated, a cancer progresses by accumulating
additional genetic damage, through mutations or epigenetic
silencing, of caretaker genes that encode the cellular
machinery that repairs damaged DNA and maintains
cytogenetic normality.
• A further consequence of genetic damage is altered
expression of genes that promote vascularization and the
spread of the tumor through local invasion and distant
metastasis.
Tumor Initiation & Progression

64. • Stages in the evolution of cancer. Increasing degrees of
abnormality are associated with sequential loss of tumor-
suppressor genes from several chromosomes and
activation of proto-oncogenes, with or without a
concomitant defect in DNA repair.
• Multiple lineages carrying somewhat different mutational
spectra and epigenetic changes are likely, particularly once
metastatic disease appears.

65. Transformation is
a multistep
process

66. • Some tumor-suppressor genes directly regulate proto-oncogene function
(gatekeepers); others act more indirectly by maintaining genome integrity
and correcting mutations during DNA replication and cell division
(caretakers). Activation of an antiapoptotic gene allows excessive
accumulation of cells, whereas loss of function of apoptotic genes has the
same effect.
• Activation of oncogenes or antiapoptotic genes is dominant. Mutations in
tumor-suppressor genes are recessive; when both alleles are mutated or
inactivated, cell growth is unregulated or genomic integrity is compromised.
Loss of pro-apoptotic genes may occur through loss of both alleles or
through a dominant negative mutation in one allele.

67. Tumor Initiation & Progression
• The development of cancer (oncogenesis)
results from mutations in one or more of the vast
array of genes that regulate cell growth and
programmed cell death.

68. Tumor Initiation & Progression
• When cancer occurs as part of a hereditary
cancer syndrome, the initial cancer-causing
mutation is inherited through the germline and is
therefore already present in every cell of the
body.
• Most cancers, however, are sporadic because
the mutations occur in a single somatic cell,
which then divides and proceeds to develop into
the cancer.

69. Micro-RNA Genes
• The catalogue of genes involved in cancer also
includes genes that are transcribed into
noncoding RNAs from which regulatory
microRNAs (miRNAs) are generated.
• There are at least 250 miRNAs in the human
genome that carry out RNA-mediated inhibition
of the expression of their target protein-coding
genes, either by inducing the degradation of
their targets' mRNAs or by blocking their
translation.

70. Micro-RNA Genes
• Approximately 10% of miRNAs have been found
to be either greatly overexpressed or down-
regulated in various tumors, and are referred to
as oncomirs.
• One example is the 100-fold overexpression of
the miRNA miR-21 in glioblastoma multiforme, a
highly malignant form of brain cancer.

71. Micro-RNA Genes
• Overexpression of some miRNAs can suppress
the expression of tumor-suppressor gene
targets, whereas loss of function of other
miRNAs may allow overexpression of the
oncogenes they regulate.
• Since each miRNA may regulate as many as
200 different gene targets, overexpression or
loss of function of miRNAs may have
widespread oncogenic effects because many
genes will be dysregulated.

72. Carcinogenic agents
(carcinogens)
Three Major types of Carcinogens
– Chemical
– Radiation
– Viral and Microbial

73. Chemical Carcinogens
• Direct Carcinogens :Directly produce damage
without prior metabolic conversion
• Indirect Carcinogens (Procarcinogen): Metabolic
conversion in liver by microsomal cytochrome P-
450 dependent mono-oxygenases (found in the
smooth endoplasmic reticulum of hepatocytes)
 ultimate carcinogen

74. Action of chemical carcinogens
• Initiator - Chemical inducing irreversible DNA
damage
• Promoter -Augment effect of initiator by
promoting cell growth, e.g. phorbol ester (PTA)
activate signal transduction or GF secretion,
hormones, saccharine …..etc
• No tumor develops unless the promoter is
applied AFTER the initiator.

75. Mode of action in chemical Carcinogens
• Chemical carcinogens contain highly reactive
electrophil groups that combine to DNA, RNA, or
proteins producing mutations
• Genes commonly affected are RAS & P53
• May be very specific‘ Signature Mutation’
• Some strong chemicals act as Initiator &
Promoter e.g. polycyclic hydrocarbon

76. CHEMICAL CARCINOGENS
• Alkylating Agents: Direct, used in chemotherapy
of cancer
– Cyclophosphamide: can cause leukemia,
lymphoma
• Polycyclic aromatic hydrocarbons: Indirect &
very strong, can cause cancer in the region of
contact (lung and bladder cancer), it is found in
tobacco smoke, smoked meats and fish.
• Aflatoxin B1: Naturally occurring carcinogen
present in fungus (Aspergillus flavus 
Hepatocellular CA)

77. CHEMICAL CARCINOGENS
• Nitrosamines: Endogenous or food preservatives,
it is converted to nitrites in the GI tract, which
may cause gastric cancer and other GI cancers.
• Aromatic Amines & Azo dyes: Rubber & Food
Industry e.g.  naphthylamine  Bladder CA
• Asbestos (ships insulation): lung Ca,
mesotheliomas, GI Ca
• Vinyl chloride - rare type of liver Ca
• Chromium, nickel - lung Ca
• Arsenic - skin cancer

78. PHYSICAL CARCINOGENS
• U-V light:
– Effect depends on intensity of exposure &
quantity of melanin
– Production of pyrimidine dimers in DNA 
MUTATION in RAS, P 53
– Failed repair  Skin CA
• Skin cancer includes: Squamous Cell CA,
Basal Cell CA, Melanoma

79. PHYSICAL CARCINOGENS
• Ionizing Radiation
– Explosions  Leukemia after 7 yrs, Latent
period  Breast, colon, thyroid, lung CA
• Leukemias (for example Chronic lymphocytic
leukemia) represent the most common radiation-
induced cancer in humans
– Therapeutic exposure  Thyroid CA,
Leukemia
– Mechanism: Free radical injury  Mutations
in RAS, RB. P53

80. VIRAL & MICROBIAL
CARCINOGENESIS
• Emerging Field
– DNA viruses
– RNA viruses
– other organisms

81. Viral & Microbial Carcinogenesis
Viruses
RNA Oncogenic viruses
Human T-Cell Leukemia Virus type 1 (HTLV-1)
• RNA retrovirus targets / transforms T-cells
causing T-Cell leukemia/Lymphoma
• Transmitted like HIV but only 1% of infected
develop T-Cell leukemia/Lymphoma
• No cure or vaccine exists for HTLV-I, treatable
with chemotherapy, but relapse is common

82. Viral & Microbial Carcinogenesis
Viruses
DNA Oncogenic Viruses such as:
• Human Papilloma Viruses (HPV).
– sexually transmitted
– Two types: Benign HPV and Malignant HPV
• Low risk groups (6, 11)  Genital
Squamous Cell Papilloma
• High risk group ( 16, 18 )  Squamous
Cell CA in cervix, vulva, perianal &
oropharyngeal regions

83. Viral & Microbial Carcinogenesis
Viruses
• Epstein-Barr (EBV) infects B lymphocytes and
epithelial cells of oropharynx and may result in
malignancy
• Burkitt’s Lymphoma
• B cell lymphoma in immunosuppressed
• Nasopharyngeal carcinoma
• Hepatitis B virus (HBV) has strong association
with Liver Cancer.
• Herpes virus 8 causes Kaposi sarcoma

84. Viral & Microbial Carcinogenesis
Helicobacter Pylori
• Bacteria infecting stomach implicated in:
– peptic ulcers
– gastric carcinoma
– marginal zone lymphomas (mucosa-
associated B-cell lymphomas (MALTomas) )
• The best and strongest evidence links
Helicobacter pylori infection with the onset of
mucosa-associated B-cell lymphomas
(MALTomas) of the stomach, which are also
known as marginal zone lymphomas.

85. Viral & Microbial Carcinogenesis
Helicobacter Pylori
• It is thought that H. pylori activates T cells, which
in turn promote polyclonal proliferation of B cells
in the gastric mucosa. In this process, some
cells obviously become malignant and give rise
to T-cell independent low-grade monoclonal
lymphomas

86. Tumor’s Effects on host
Tumours cause problems because of:
• Location and effects on adjacent structures:
– 1cm pituitary adenoma can compress and
destroy the surrounding and cause
hypopituitarism).
– 0.5 cm leiomyoma in the wall of the renal
artery may lead to renal ischemia and serious
hypertension).
• Tumors may cause bleeding and secondary
infections
(lesion ulcerates adjacent natural surfaces)

87. Tumor’s Effects on host
• Effects on functional activity such as Hormone
synthesis
– adenomas and carcinomas of B cells of the
islets of the pancreas produce hyperinsulinism.
• Cancer cachexia (wasting due to cancer):
manifests with weakness, weight loss, anorexia,
anemia and infection.
– The principal cytokine responsible for such
changes is Tumor necrosis factor-a.

88. Tumor’s Effects on host
Paraneoplastic syndromes
• They are diverse symptoms associated with many
different tumors that occur in patients and cannot
be explained.
– Could be earliest manifestation of hidden cancer
in some cases
• Bronchogenic and breast cancers and hematologic
malignancies are the most often neoplasms
associated with these syndromes.

89. Examples of Paraneoplastic
Syndromes
• Small Cell CA lung increased ACTH (Cushing
syndrome), increased ADH, Bone changes,
nervous system disorders
• Squamous Cell CA lung & Breast CA 
Parathormone related & others  Hypercalcemia
• Hepatic & Renal CA  Polycythemia
• Pancreatic, Gastric CA  Carcinoid S.

90. Examples of Paraneoplastic
Syndromes
• Advanced Cancers Nonbacterial thrombotic
endocarditis.
• Colonic Adenocarcinoma  Acanthosis
nigricans
• Pancreatic & lung CA  clotting factors  Deep
vein thrombosis
– N.B. Hypercalcemia is commonly produced by
lytic bone metastases

91. Tumor Diagnosis:
• History and Clinical examination
• Imaging: X-Ray, US, CT, MRI
• Biochemical assays
– Tumor markers Laboratory analysis
• Morphologic methodes (Histological diagnosis)
– Cytology: Pap smear, FNAB
– Biopsy: Histopathology, markers.
• Molecular Tech: Gene detection.

92. Histological diagnosis
Microscopic tissue examination is the gold
standard of cancer diagnosis.
• The specimen must be adequate,
representative and properly preserved.
Several sampling approaches are available:
• Excision or biopsy
• fine-needle aspiration
• Cytologic (papanicolaou) smears
• Immunocytochemistry
• Flow cytometry

93. Excision or biopsy
• Awareness in selecting appropriate site for biopsy
• In case of large mass: the margins may not be
representative and the center may be largely
necrotic.
• Frozen-section: quick technique permits histologic
evaluation within minutes
– determining the nature of lesion
– Evaluating the margins of an excised cancer to
ascertain that the entire neoplasm has been
removed.

94. Excision or biopsy
• in breast biopsy, frozen-section allows
determination of whether the lesion is malignant
and may require wider excision or sampling of
axillary lymph nodes for possible spread

95. Fine-needle aspiration
• It involves aspiration of cells from a mass,
followed by cytologic examination of the smears.
• Useful for palpable lesions affecting the breast,
thyroid, lymph nodes, and salivary glands
• With modern imaging techniques it can be
extended to deeper structures (liver, pancreas,
and pelvic lymph nodes)

96. Cytologic (papanicolaou) smears
• It is used widely for detecting cervix carcinoma
at an in situ stage.
• It is also used for endometrial carcinoma,
bronchogenic carcinoma, bladder and prostate
tumors.
• Neoplastic cells are less cohesive than others
and so are shed into fluid or secretion
• The shed cells are evaluated for anaplastic
features

97. Immunocytochemistry
tumor markers
• Monoclonal antibodies against cytokeratin
present in epithelial cells (undifferentiated tumor
rather than large cell lymphoma)
• PSA for prostatic metastasis
• Estrogen receptor and Her2 in breast cancer
• Carcinoembryonic antigen (CEA): abnormal
increase are seen in colorectal Ca, Gastric CA,
Pancreatic Ca, Breast Ca.
• Alpha fetoprotein: increased in liver cancer,
colorectal Ca, pancreatic Ca, lung Ca, and
cancer arised from germ cells of testes.

98. Flow cytometry
• Routine classification of leukemias and
lymphomas
• Fluorescent antibodies against cell surface
molecules and differentiation antigens.
• Assessing DNA content of the tumor cell

99. Biochemical assays
• Useful for measuring the levels of tumor
associated enzymes, hormones, and tumor
markers in serum.
• Useful in determining the effectiveness of
therapy and detection of recurrences after
excision

100. Molecular diagnosis
• Polymerase chain reaction (PCR)
example: detection of BCR-ABL transcripts in
chronic myeloid leukemia.
• Fluorescent in situ hybridization (fish)
it is useful for detecting translocation characteristic
of many tumors
• Both PCR and Fish can show amplification of
oncogenes (HER2 and N-MYC)

101. Bilateral Cystadenoma Ovary

102. Lipoma Intestine

103. Meningioma

104. Lung carcinoma

105. Hepatic Adenoma

106. Carcinoma Breast

107. Carcinoma Lung

108. Osteo-sarcoma

109. Colon Polyp

110. Hepatic Adenoma
Normal Adenoma

111. Metastatic Adenocarcinoma

112. Hepatic Adenocarcinoma