for Undergraduate Medical Students (MBBS)

1. NEOPLASIANEOPLASIA
Dr.CSBR.Prasad, M.D.,Dr.CSBR.Prasad, M.D.,

16. Neoplasia
• Definition
• Nomenclature
• Biology of tumor growth
• Benign and malignant neoplasms
• Epidemiology
• Molecular basis of cancer
• Carcinogens
• Host defense against tumor
• Clinical Features of Tumors
• Lab Diagnosis of cancer

17. Nomenclature
• Neoplasia
• Neoplasm
• Tumor
• Oncology
• Clonal / Clonality
• Benign
• Malignant
• Cancer

18. Neoplasia - Definition
• Neo = New
• Plasia = Growth Neoplasia = New growth
• Tumor = Swelling
• Cancer = Crab (L)
• Oncology = Study of tumor / Neoplasm
(Oncos = Tumor)

19. Nomenclature
• Normal
• Abnormal
– Non neoplastic
• Hyperplasia
• Metaplasia
– Precancerous (dysplasia)
– Neoplastic
• Benign
– Epithelial
– Mesenchymal
• Malignant
– Epithelial
– Mesenchymal

20. Neoplasia - Definition
• Neo = New
• Plasia = Growth Neoplasia = New growth
• Tumor = Swelling
• Cancer = Crab
• Oncology = Study of tumor / Neoplasm
(Oncos = Tumor)

21. Cancer (L. Crab)
• Any malignant growth of cells (clonal)
• Second most common cause of death
in US
• One in 3 Americans will die of cancer
Gross features Microscopic featuresGross features Microscopic features

22. Normal – Hyperplasia – Dysplasia -
Carcinoma

23. Definition
• “Willis” definition of Neoplasia - (new growth)
abnormal mass of tissue, the growth of
which exceeds and is uncoordinated with
the normal tissues and continues to grow
even after the cessation of the stimulus
that evoked the initial response
• New Definition: (Robbins Path) a neoplasm
can be defined as a disorder of cell growth
that is triggered by a series of acquired
mutations affecting a single cell and its clonal
progeny

24. Neoplasm
The causative mutations give the
neoplastic cells a survival and growth
advantage, resulting in excessive
proliferation that is independent of
physiologic growth signals
(autonomous)

25. Makes an interesting reading…

26. Neoplasia
• It is autonomous, purposeless
• Proliferation is uncontrolled
• Competes with normal cells for its needs
• It is a clonal disorder
• It is a genetic disorder
– In 95% of cases acquired genetic disorder
– In 5% of cases inherited

27. Nomenclature
• All tumors have two components
– Parenchyma
• Represents tumor proper; the growth of the tumor
is due to proliferation of these cells
– Stroma
• Provides the framework, blood supply and nutrition
for the parenchymal cells

28. ParenchymaParenchyma
StromaStroma

29. Desmoplasia
• Formation of abundant collagenous stroma
• Stimulated by parenchymal cells
• Ex: Schirrous. ca of breast
Linitus plastica (ca stomach)
Carcinoma prostate

30. Scirrhous carcinoma of breast

31. Scirrhous carcinoma of breast

32. Linitus plastica

33. Nomenclature
• Tumors are designated by attaching suffix “–oma”
to the cell or tissue of origin
– Fibroma, chondroma, lipoma, osteoma etc
– Benign tumor arising from glandular structure is called
adenoma
– Benign tumor arising from epithelial surface having finger
like projections is called papilloma
– Malignant tumor arising from epithelial tissue is called
Carcinoma
– Malignant tumor arising from mesenchymal tissue is
called Sarcoma

34. Papilloma / Polyp / Adenoma

35. Papilloma / Polyp / Adenoma
Pedunculated polyp
Sessile polyp

36. Papilloma / Polyp / Adenoma

37. Tissue of Origin Benign Malignant
Composed of One Parenchymal Cell Type
Tumors of mesenchymal origin
Connective tissue and
derivatives
Fibroma Fibrosarcoma
Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Synovium Synovial sarcoma
Mesothelium Mesothelioma
Brain Coverings Meningioma Invasive
meningioma

38. Tissue of Origin Benign Malignant
Blood cells and related cells
Hematopoietic cells Leukemias
Lymphoid tissue Lymphomas
Muscle
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarcoma

39. Tumors of epithelial origin
Stratified
squamous
Squamous cell
papilloma
Squamous cell carcinoma
Basal cells of skin
or adnexa
Basal cell carcinoma
Epithelial lining of
glands or ducts
Adenoma Adenocarcinoma
Papilloma Papillary carcinomas
Cystadenoma Cystadenocarcinoma
Respiratory
passages
Bronchial
adenoma
Bronchogenic carcinoma
Renal epithelium Renal tubular
adenoma
Renal cell carcinoma
Liver Cell Adenoma Hepatocellular carcinoma
Urothelial cell Papilloma Urothelial carcinoma

40. Placental epithelium Hydatidiform mole Choriocarcinoma
Testicular epithelium
(germ cells)
Seminoma
Embryonal carcinoma
Melanocytic Tumors Nevus Malignant melanoma
More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from
One Germ Cell Layer
Salivary glands Pleomorphic adenoma
(mixed tumor of salivary
origin)
Malignant mixed tumor
of salivary gland origin
Renal anlage Wilms’ tumor
More Than One Neoplastic Cell Type Derived from More Than One Germ
Cell Layer-Teratogenous
Totipotential cells in
gonads or in embryonic
rests
Mature teratoma, dermoid
cyst
Immature teratoma,
teratocarcinoma

41. Tissues with NO benign tumors
• Synovium
• Mesothelium
• Lymphoid tissue
• Hematopoietic cells
• Basal cells of skin or adnexa

42. Nomenclature
• Malignant tumor arising from epithelial
structures is called “Carcinoma”
• Malignant tumor of the mesenchymal
tissues is called “Sarcoma”
• Embryonal tumors usually have the suffix
“Blastoma”
• Malignant lesions of the blood are called
“Leukemia”
• Malignant lesions of the lymphoid tissue is
called “Lymphoma”

44. Neoplasms of
Totipotent Cells

45. Neoplasms of Embryonic
Pluripotent Cells
• Pluripotent cells can mature into several
different cell types
• These neoplasms are generally called
Embryomas or Blastomas

46. Blastoma
• All blastomas are childhood tumors
• All blastomas are malignant tumors
Except:
–Chondroblastoma
–Osteoblastoma
–Pulmonary blastoma

47. Neoplasms of pluripotent embryonic-type cells
(BLASTOMAs)

48. Nomenclature of Neoplasms of
Differentiated Cells

49. Exceptions to These Rules
• Neoplasms That Sound Benign But Are
Really Malignant
• Neoplasms That Sound Malignant But Are
Really Benign
• Leukemias
• Mixed Tumors
• Neoplasms Whose Cell of Origin Is
Unknown

50. Nomenclature
• Some malignant tumors named like
benign tumors
– Melanoma, Hepatoma, Lymphoma
• Some benign tumors named like
malignant tumors
– Cystosarcoma phylloides, chondroblastoma
• Some unusual tumors
– Mixed tumor of salivary gland (pleomorphic
adenoma)
– Teratoma

51. Mixed tumor
• Tumors with single type of
parenchymal cells that differentiates
into many cell lines
–Eg: Pleomorphic adenoma of salivary
gland.

52. Pleomorphic adenoma - Parotid

53. Teratoma
• Tumor arising from totipotent cells (germ
cells) showing differentiation towards
tissues derived from all the three germ cell
layers
– Seen usually along the midline
– Common sites
• Ovary, testis, sacro-coccygeal region, retro-
peritoneum, mediastinum, base of the brain etc

54. What are the common sites for teratomas ?
• Gonads
• Mid line
• Lines of fusion

57. Along the lines of fusion

58. Neoplasms of
Totipotent Cells

60. Sacrococcygeal teratoma

61. Teratoma

62. Teratoma

63. Named tumors

64. Hamartomas & Choristomas
• A hamartoma is composed of tissues that are
normally present in the organ in which the tumor
arises
– Eg: a hamartoma of the lung consists of a
disorganized mass of bronchial epithelium and
cartilage that may become so large that it presents as
a lung mass. Its growth is coordinated with that of the
lung itself
• A choristoma resembles a hamartoma but
contains tissues that are not normally present in
its site of origin
– Eg: A orderly mass of pancreatic acini and ducts in
the wall of the stomach is properly called a
choristoma.

65. Hamartoma
• Definition - Jumbled mixture of tissue native to
the site / organ
• Eg: Hamartoma of lung

66. Choristoma
• Definition – Normal organized tissue at an abnormal
site (ectopic rest of normal tissue)
• Eg: adrenal cells under kidney capsule, pancreas in
stomach

67. Biology of tumor growth
(Natural history of malignant tumor)
Four phases
1. Malignant change in the target cell,
referred to as transformation
2. Growth of the transformed cells
3. Local invasion
4. Distant metastasis

68. Characteristics of benign &
malignant tumors
• Differentiation and anaplasia
• Rate of growth
• Local invasion
• Distant spread (metastasis)

69. Differentiation
• Refers to the extent to which neoplastic
cells resemble comparable normal cells,
both morphologically and functionally
• Anaplasia is lack of differentiation
“to form backwards”

70. Differentiation and Anaplasia
• Benign tumors are well differentiated (they
resemble very closely the tissues from
which they arose)
• Malignant tumors are variably
differentiated (some are well differentiated
and others are poorly differentiated)
• Greater the malignancy, poorer the
differentiation
• Highly malignant tumors are anaplastic

71. Differentiation & Anaplasia
Adenocarcinoma Normal & benign lesion

72. Differentiation and anaplasia
LipomaLipoma LiposarcomaLiposarcoma

73. Differentiation and anaplasia
Two thyroid tumors
Follicular carcinoma Anaplastic carcinoma

74. Characteristics of a malignant cell
• Nucleus is large and hyperchromatic
• Irregular nuclear membrane
• Nuclear – cytoplasmic ratio is high
– Normal cell 1:4-1:6
– Cancer 1:1
• Mitosis: Increased and often atypical
• Tumor giant cells
• Loss of polarity or organization of cells
• Loss of normal function (functional
dedifferentiation)
• Development of new function (sometimes)

75. Characteristics of a malignant cell
Hyperchromatism, Irregular nuclear
membrane

76. Pleomorphism
• Variation in size and shape of nuclei
• Many times larger than the neighboring
cells or extremely small and primitive
appearing

77. Abnormal mitosis
• Atypical bizarre mitotic figures
• Tripolar, quadripolar or multipolar

78. Abnormal Mitosis

79. Loss of polarity
• Orientation of normal cells markedly
disturbed
• Sheets of cells grow in anarchic,
disorganized fashion

80. Loss of
polarity

81. Tumor giant cells
• Single huge polymorphic nucleus
• Two or more nuclei
• Nuclei are hyper chromatic &
large in relation to cell

82. Tumor giant
cells

83. Tumor necrosis
• Anaplastic tumors show large central
ischemic necrosis
• Anaplastic tumors - grow fast - require
more blood supply
• Often the vascular stroma is scant

84. Tumor necrosis

85. Dysplasia
• Disordered growth
• Principally seen in epithelia
• Loss of uniformity of individual cells
• Loss in their architecture orientation
• Exhibit pleomorphism, hyper chromatic
nuclei to the size of cell
• Mitotic figures more abundant than usual

86. Dysplasia
• Severe dysplasia
Antedates invasive cancer
• Mild to moderate dysplasia
Do not involve entire thickness
May be reversible

87. Carcinoma in situ
• Dysplastic changes are marked and
involve entire thickness of epithelium
• Lesion confined to the normal site( i.e.,
confined to BM)
• Considered preinvasive neoplasm
• Invasion of BM – invasive
• Foci are found near invasive carcinoma
• Cervix, Barretts esophagus, smokers lung

88. Carcinoma ‘in situ’

89. Lobular carcinoma ‘in situ’

90. Rate of growth
• Benign tumors show slow regular growth.
• Malignant tumors exhibit rapid, erratic
growth
• It is infiltrative in nature

91. Burkitt’s lymphoma

92. Growth pattern
Benign MalignantMalignant

93. Local invasion
• Benign tumors are generally well circumscribed
and are frequently encapsulated. The pattern of
growth is expansile (like a balloon) and do not
invade.
• Malignant tumors are poorly circumscribed and
show infiltrative pattern of growth. They invade
surrounding tissues. This is one of the most
important characteristics of malignancy

94. Benign tumors
- gross
LeiomyomaLeiomyoma
Hepatic adenomaHepatic adenoma
Lipomatous polypLipomatous polyp

95. Benign tumors - micro
LipomaLipoma LeiomyomaLeiomyoma
AdenomaAdenoma

96. Papilloma / Adenoma
• Benign epithelial neoplasm producing
microscopically or macroscopically visible
finger like projection from epithelial
surface
• Cystadenoma: adenomas producing large
cystic masses.
• Papillary cystadenoma: adenomas
producing large cystic masses with
papillary projections into the lumen

98. Polyp
(Restricted to benign lesion)
• Tumor producing macroscopic visible
projection above mucosal surface and
projects into the gastric or colonic lumen
• Polyps can be
– Sessile (without stalk)
– Pedunculated (with stalk)
• Malignant polyps are better designated
as polypoid cancers

99. Polyp
Pedunculated polyp
Sessile polyp

100. Invasion
• Associated with activated motility and
local tissue independence in vitro
• Balance between tissue destruction and
synthesis
• Cell surface and extracellular matrix
play important roles

101. Local invasion
Hepatic adenomaHepatic adenoma
Hepatocellular carcinomaHepatocellular carcinoma

102. Spread (metastasis)
• Benign tumors do not metastasize
• Malignant tumors almost always
metastasize
– Exceptions: basal cell carcinoma and
gliomas)
• This is probably the most important
characteristic of malignancy

103. Exceptions:
Benign metastasizing tumors
• Atrial myxoma
• Pleomorphic adenoma
• Osteoclastoma
• Leiomyoma

104. Metastasis

105. Metastasis
• Require acquisition of additional tumor
characteristics beyond those necessary
for invasion
• Multiple lesions
• Organ specificity

106. Development ofDevelopment of
Metastatic cloneMetastatic clone

107. Metastasis
 Tumor implants discontinuous from the
primary
 30% of solid tumors at diagnosis
 Most of the malignant tumors
 Except: Basal cell ca, Glial tumors

108. Modes of Spread
• Seeding the body cavities
– The cavity most often involved is peritoneal cavity
(Krukenberg tumor, Pseudomyxoma peritonei)
• Lymphatic spread
– Most carcinomas
– Deposits will be in the regional or distant nodes
• Hematogenous (through blood stream)
– Most sarcomas and some carcinomas

109. Direct seeding of body cavities or
surfaces
• Penetration of
malignant neoplasm
into a natural “open
field”
– Ca. Stomach
– Ca. Ovaries

110. Peritoneal
deposits

111. Krukenberg tumor

112. Krukenberg tumor

113. Pseudomyxoma
peritonei

116. Lymphatic Spread
• Epithelial tumors
(Carcinoma)
• LN in natural route of
lymphatic drainage
(Eg: Breast – upper outer quadrant –
axilla)
• Effective barrier at
least for some time

117. Lymphatic Spread

118. Lymphatic Spread

119. Lymphatic Spread ?

120. Skip metastasis
• Usually Lung carcinoma first metastasizes
to perihilar, tracheobronchial and
mediastinal LNs
• This may not be followed always
• Causes:
– Lymphovascular anastomosis
– Fibrosis (old infections, radiation)

121. Sentinel LN biopsy
• To avoid complications of block dissection
of lymphnodes
• Complications:
– Lymphedema
– Lymphangiosarcoma
• Used in breast carcinoma
– Oral cancers
– Melanomas
– Colonic carcinomas

123. Lymphangiosarcoma
secondary to lymphedema

125. Hematogenous Spread
• Mesenchymal
tumors (Sarcoma)
• Predominantly veins
(RCC, HCC)
• Lung, Liver &
Vertebra

126. Common sites of metastatic
deposits (hematogenous spread)
• Liver
• Bones
• CNS
• Lung

127. Some tumors prefer certain sites
• Adrenals prefered by Br.carcinoma (Lung)
• Bone metasizing tumors:
– BK.Patil
• Liver & bone by Neuroblastoma
• Bone seeking kidney tumor
– Clear cell sarcoma

128. Rare sites for mets
• Skeletal muscle
• Spleen
• Pancreas

129. Carcinomas that prefer blood spread
• HCC
• RCC
• Choriocarcinoma

130. Sarcomas that prefer lymphatic spread
“CARES”
• Clear cell sarcoma
• Angiosarcoma
• Rhabdomyosarcoma
• Epithelioid sarcoma
• Synovial sarcoma

131. Other mechanisms of spread
• Direct extension
• Surgical or procedural transplantation
(iatrogenic)

132. Unusual modes of spread
• Carcinomas arising close to vertebral
column spread via paravertebral venous
plexus giving rise to early bone metastasis
• Renal cell carcinoma grows inside renal
vein in a snake like fashion
• Carcinoma lung gives rise to metastatic
deposit in adrenals very frequently!

133. Tumor spread
Lymphatic embolusLymphatic embolus Metastasis in lymphnodeMetastasis in lymphnode

134. Metastasis – Liver

135. Perineural Spread
Eg: Adenoid cystic carcinoma

136. Peritoneal Spread

137. Pleural Seeding – Carcinoma Breast

138. The process of
Metastasis

139. The process of Metastasis
• Metastasis is defined by the spread of a
tumor to sites that are physically
discontinuous with the primary tumor
• Unequivocally marks a tumor as malignant,
as by definition benign neoplasms do not
metastasize

140. The process of Metastasis
The metastatic cascade is divided into
two phases:
1.Invasion of the extracellular matrix (ECM)
and
2.Vascular dissemination, homing of tumor
cells and colonization

141. The process of Metastasis
The metastatic cascade is divided into
two phases:
1.Invasion of the extracellular matrix (ECM)
– Interactions between cells and the ECM
– ECM: basement membrane and interstitial
connective tissue
– ECM is made up of collagens, glycoproteins,
and proteoglycans

142. The process of Metastasis
• A carcinoma must first breach the
underlying BM, then traverse the
interstitial connective tissue, and ultimately
gain access to the circulation by
penetrating the vascular BM
• This process is repeated in reverse when
tumor cell emboli extravasate at a distant
site

143. The process of Metastasis
Invasion of the ECM:
• “Loosening up” of tumor cell–tumor cell
interactions
• Degradation of ECM
• Attachment to novel ECM components
• Migration and invasion of tumor cells

144. “Loosening up” of
tumor cell–tumor cell interactions
• Normal epithelial cells are tightly glued to
each other and the ECM by a variety of
adhesion molecules
• Cell-cell interactions are mediated by the
cadherin family of transmembrane
glycoproteins esp. E- Cadherin
• E-cadherin function is lost in many of the
malignant tumors
NOTE: Loss of adhesion in normal cells leads to induction
of apoptosis

146. Degradation of the BM and interstitial connective
tissue is the second step in invasion
• This is achieved by secreting proteolytic
enzymes
– By the tumor cell themselves or
– By inducing stromal cells to do so
• Different families of proteases that are
implicated in tumor cell invasion:
– Matrix metalloproteinases (MMPs)
– Cathepsin D
– Urokinase
– Plasminogen activator

147. The third step in invasion involves
changes in attachment of tumor
cells to ECM proteins
• Normal epithelial cells have receptors,
such as integrins, for BM laminin and
collagens

149. Locomotion is the final step of invasion,
propelling tumor cells through the degraded
BMs and zones of matrix proteolysis
• Cells must attach to the matrix at the leading edge,
detach from the matrix at the trailing edge, and contract
the actin cytoskeleton to ratchet forward
• This is brought about by:
– Tumor cell-derived cytokines, such as autocrine motility factors
– Cleavage products of matrix components and some growth
factors (e.g., IGFs I and II) have chemotactic activity for tumor
cells
– Stromal cells also produce paracrine effectors of cell motility,
such as hepatocyte growth factor (HGF)

150. Vascular Dissemination and
Homing of Tumor Cells
• Within the circulation, tumor cells tend to
aggregate in clumps
– Homotypic adhesions
– Heterotypic adhesion
• Tumor cells and PLTs
• Tumor cells and fibrin

151. Vascular Dissemination and
Homing of Tumor Cells
• Arrest and extravasation of tumor emboli
at distant sites involves adhesion to the
endothelium, followed by egress through
the BM
– Adhesion molecules (integrins, laminin
receptors) and
– Proteolytic enzymes

152. Vascular Dissemination and
Homing of Tumor Cells
• The site at which circulating tumor cells
leave the capillaries to form secondary
deposits is related to the anatomic
location and vascular drainage of the
primary tumor and the tropism of particular
tumors for specific tissues

153. Such organ tropism may be related to
the following mechanisms:
• Tumor cells may have adhesion molecules to bind to
ligands expressed preferentially on the endothelial cells
of the target organ
• Chemokines have an important role in determining the
target tissues for metastasis.
– For instance, some breast cancer cells express the chemokine
receptors CXCR4 and CCR7.
• In some cases, the target tissue may be a nonpermissive
environment—“unfavorable soil,” so to speak, for the
growth of tumor seedlings.
– For example, although well vascularized, skeletal muscle and
spleen are rarely sites of metastasis.

157. Benign vs Malignant
Characteristics Benign Malignant
Growth pattern Expansive Infiltrative
Rate of growth Slow Fast
Differentiation Good Atypical, poor
Metastasis Absent Usually
Present

158. Benign vs Malignant

159. Desmoplasia
The formation and proliferation of connective
tissue in response to neoplastic growth (e.g..
Scirrhous carcinoma of breast)

160. Invasion and Metastasis
• Characteristics that are unique to
malignant neoplasms (cancer)
• The major cause of morbidity and mortality

161. Neoplasia - Epidemiology
• Cancer incidence
• Cancer mortality rate
• Geographic & environmental factors
• Age
• Genetic predisposition to cancer
• Nonhereditary predisposing conditions

162. Cancer Incidence
• National Incidence
• Men
– Prostate
– Lung
– Colorectal
• Women
– Breast
– Lung
– Colorectal
Jemal A etal Cancer J Clin 53:5,2003

163. Cancer Mortality Incidence
• Increased in men
• Decreased in women
(reduced Ca. Cx)
• Ca Stomach – low
mortality
(better food habit)
• Lung is leading cause in
both sex
Jemal A etal Cancer J Clin
53:5,2003

164. Evidence for role of environmental agents
• Epidemiological
– scrotal cancers in chimney sweeps
– HBV, HCV, aflotoxin B & hepatoma in Uganda
– Dietary factors & oesophageal cancer in China
– Lung cancer in smokers and asbestos handlers
– Bladder cancer in dye industry workers
• Direct
– Radiation in children and thyroid carcinoma
– Thorostrat and angiosarcoma of liver

165. Geographic And Environmental
Factors
• Ca. Stomach = Japan
• Ca. Lung = USA
• Melanoma = New
Zealand
• ? Genetic
• Also environmental &
cultural

166. Cancer Mortality Incidence
• Increased in men
• Decreased in women
(reduced Ca. Cx)
• Ca Stomach – low
mortality
(better food habit)
• Lung is leading cause in
both sex
Jemal A etal Cancer J Clin
53:5,2003

167. Occupational Cancers
Agents or Groups of
Agents
Human Cancer Site Typical Use or
Occurrence
Arsenic and arsenic
compounds
Lung, skin, hemangiosarcoma Byproduct of metal smelting.
Component of alloys, electrical
and semiconductor devices,
medications and herbicides,
fungicides, and animal dips
Asbestos Lung, mesothelioma;
gastrointestinal tract
Construction, Roofing, flooring
tiles
Benzene Leukemia, Hodgkin's Printing and lithography, paint,
rubber, dry cleaning,
adhesives and coatings, and
detergents
Beryllium Lung Aerospace applications and
nuclear reactors
Cadmium Lung Component of metal alloys,
paints, pigments, and
preservatives

168. Agents or Groups of
Agents
Human Cancer Site Typical Use or
Occurrence
Chromium Lung Component of metal alloys,
paints, pigments, and
preservatives
Ethylene Oxide Leukemia Ripening agent for fruits and
nuts. Used in rocket propellant
and chemical synthesis, in
fumigants for foodstuffs and
textiles, and in sterilants for
hospital equipment
Nickel Nose, Lung Nickel plating. Component of
ferrous alloys, ceramics, and
batteries. Byproduct of
stainless steel arc welding
Radon Lung Decay of minerals containing
uranium
Vinyl chloride Liver - Angiosarcoma Refrigerant. Monomer for vinyl
polymers. Adhesive for
plastics. Formerly inert aerosol
propellant in pressurized
containers
Occupational Cancers

169. Other Risk Factors
• Overweight
• Alcohol
• Smoking
• Age of sexual activity and number of
partners (Ca. Cervix)
(everything one does for pleasure is fattening,
immoral, illegal, or, even worse,
oncogenic !!!!!)

170. Age
• Later years of life (≥ 55 years)
• Children under age 15
– Acute leukemia
– Neoplasms of the central nervous system
• Common neoplasms of infancy and childhood
– Neuroblastoma
– Wilms tumor
– Retinoblastoma
– Acute leukemias
– Rhabdomyosarcomas

171. Genetic Predisposition To
Cancer
• Autosomal Dominant Inherited Cancer
Syndrome
• Defective DNA Repair Syndromes
• Familial Cancers
• Interactions Between Genetic and Non-
Genetic Factors

172. Inherited Predisposition to
Cancer• Inherited Cancer Syndromes (Autosomal
Dominant)
Gene Inherited Predisposition
RB Retinoblastoma
p53 Li-Fraumeni syndrome (various tumors)
p16INK4A Melanoma
APC Familial adenomatous polyposis/colon
cancer
NF1, NF2 Neurofibromatosis 1 and 2
BRCA1, BRCA2 Breast and ovarian tumors
MEN1, RET Multiple endocrine neoplasia 1 and 2
MSH2, MLH1, MSH6Hereditary nonpolyposis colon cancer
PATCH Nevoid basal cell carcinoma syndrome

173. Inherited Predisposition to
Cancer
• Familial Cancers
Familial clustering of cases, but role of inherited predisposition not
clear for each individual (early age, multiple or bilateral tumors)
Breast cancer
Ovarian cancer
Pancreatic cancer
• Inherited Autosomal Recessive Syndromes of Defective DNA
Repair
Xeroderma pigmentosum
Ataxia-telangiectasia
Bloom syndrome
Fanconi anemia

174. Nonhereditary Predisposing
Conditions
• Chronic inflammation
– UC, Crohn Disease, H. pylori gastritis, Viral
hepatitis
• Cytokines – growth of transformed cells
• Increase in tissue stem cells
• ROS (reactive oxygen species) and genome
instability
• Practical implication (COX – 2 inhibitor in colon
cancer prevention)

175. Nonhereditary Predisposing
Conditions
• Precancerous Conditions
– Chronic atrophic gastritis
– Solar keratosis
– Chronic ulcerative colitis
– Leukoplakia

176. Acquired preneoplastic disorders
• Endometrial
hyperplasia
• Cervical dysplasia
• Cirrhosis
• Dysplasia of bronchial
mucosa in smokers
• Solar keratosis
• Villous adenoma
• Chronic atrophic
gastritis
• Ulcerative colitis
• Leukoplakia of oral
cavity, vulva, penis

177. Morbidity and Mortality
• Metastases
• Rupture into major vessels, structure
• Starvation
• Infection
• Compression of vital organs
• Organ failure

180. Paraneoplastic syndrome
• Occurs when a neoplasm elaborates a
substance that results in an effect that is not
directly related to growth, invasion, or
metastasis. Most paraneoplastic syndromes
result from elaboration of hormone-like
substances, but a variety of effects are possible.
Sometimes the paraneoplastic syndrome may
precede diagnosis of the neoplasm and may
give a clue to its presence.

181. Syndrome Mechanism Example
Cushing's
Syndrome ACTH-like substance
Lung (oat cell)
carcinoma
Hypercalcemia
Parathormone - like
substance
Lung (squamous cell)
carcinoma
Hyponatremia
Inappropriate ADH
secretion
Lung (oat cell)
carcinoma
Polycythemia
Erythropoietin-like
substance
Renal cell carcinoma
Paraneoplastic syndromes
Trousseau's
Syndrome Hypercoagulable state Various carcinomas
Hypoglycemia Insulin-like substance
Various carcinomas and
sarcomas
Carcinoid
Syndrome
5-hydroxy-indoleacetic
acid (5-HIAA)
Metastatic malignant
carcinoid tumors

182. Prognosis
• Prediction of Outcome
–Criteria are different for each cancer
type
–Grade, stage, histology routine criteria
–Patient characteristics are important
–Treatment considerations critical

183. Prognostic Factors
• Grade
• Stage
• Tumor type
• Biomarkers (slide based and molecular
techniques)

184. Grading of Malignant Neoplasms
Grade Definition
I Well differentiated
II Moderately differentiated
III Poorly differentiated
IV Nearly anaplastic

185. Cancer Grade
• Alternate term “tumor grade”
• Based on microscopic features
(cytology or histology)
low grade moderate high

186. Cancer Stage
• Reflects degree of spread, for an individual
cancer patient
• Assigned at the time of diagnosis, may be
updated as patient progresses
T Tumor characteristics
N Nodal involvement
M Metastasis

187. Staging of Malignant Neoplasms
Stage Definition
Tis In situ, non-invasive (confined to epithelium)
T1 Small, minimally invasive within primary organ site
T2 Larger, more invasive within the primary organ site
T3 Larger and/or invasive beyond margins of primary organ site
T4 Very large and/or very invasive, spread to adjacent organs
N0 No lymph node involvement
N1 Regional lymph node involvement
N2 Extensive regional lymph node involvement
N3 More distant lymph node involvement
M0 No distant metastases
M1 Distant metastases present

188. Summary
• Cancer is synonymous with malignant
neoplasia
• It is usually a clonal disorder
• Precursor/precancerous lesions exist
• Anaplasia, Invasion and metastasis are
the hallmark of malignancy
• Cancer typing and subtyping is pre-
requisite for patient treatment