2. Definition of Neoplasm
A neoplasm is an abnormal mass of tissue, the growyh of
which exceeds and is uncoordinated with that of the normal
surrounding tissue and persists in the same excessive
manner even after cessation of stimuli which evoked the
change
3. At the molecular level, neoplasm is disorder of growth
regulatory genes ( the activation of growth regulatory genes
and inactivation of tumour suppressor genes)
It develops in a multistep fashion
Different neoplasms, even of the same histologic type, may
show different genetic changes
4. The causative mutations give the neoplastic cells a survival
and growth advantage, resulting in excessive proliferation
that is independent of physiologic growth signals
(autonomous)
5. Structural Characteristics
The gross appearance of tumour is varied
May be polypoid, papillary, nodular, lobulated, cystic,
fungating and ulcerated etc
6. Two basic components of tumours—
• Parenchyma – made up of proliferating neoplastic cells, largely
determines the biologic behaviors of the tumour. The
classification, nomenclature and histological diagnosis are also
made according to the parenchymal cells
• Supporting stroma – made up of connective tissue, blood
vessels and lymphatics
10. Nomenclature
Neoplasms are named according to a binomial system
according to
the histogenic origin of the parenchymal
component and
the biologic behavior
Benign tumours - ‘~oma’ eg. Lipoma, fibroma
Malignant tumours – ‘~ carcinoma’ , ‘~sarcoma’ eg.
Adenocarcinoma, liposarcoma
11.
12.
13. More than one neoplastic cell type, mixed
tumour, usually derived from one germ layer
Tissue of origin Benign Malignant
Salivary gland Pleomorphic
adenoma
Malignant mixed
tumor of salivary
gland origin
Renal anlage Wilms tumour
14. More than one neoplastic cell type, derived
from more than one germ layer- teratogenous
Tissue of origin Benign Malignant
Totipotential cells in
gonads or in
embryonic rests
Mature teratoma Immature teratoma
15. Adenoma – benign epithelial neoplasms producing gland
patterns – derived from glands but not necessarily exhibiting
gland patterns
16. Papillomas – Benign epithelial neoplasms, growing on any
surface, – Produce microscopic or macroscopic finger-like fronds
17. Polyp – a mass that projects above a mucosal surface, as in the
gut, to form a macroscopically visible structure
18. Cystadenomas – hollow cystic masses; typically they are seen in
the ovary
21. Tumours with Aberrant differentiation (Not true neoplasm)
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 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.
23. Pluripotent cells can mature into several different cell types
Neoplasms of pluripotent or precursor cells are generally
called Embryomas or Blastomas( small blue round cell
tumour)
Example:
- Retinoblastoma (occular growth)
- Neuroblastoma (common in adrenal gland)
- Nephroblatoma (renal tumour)
- Hepatolastoma (hepatic growth)
- Acute lymphoblastic lymphoma (hematological
malignancy)
24. All blastomas are childhood tumors
All blastomas are malignant tumors
Except:
– Chondroblastoma
– Osteoblastoma
– Pulmonary blastoma
25. Benign vs Malignant Features
Features Benign Malignant
Rate of growth Progressive but
slow. Mitoses
few and normal
Variable. Mitoses
more frequent
and may be
abnormal
Differentiation Well
differentiated
Well differentiated to
various degrees of
anaplasia
Capsule Common Less common
Local invasion
Metastasis
Cohesive growth.
Capsule & BM
not breached
Absent
Poorly cohesive
and infiltrative
May occur
26. Differentiation and Anaplasia
‘Differentiation’ denotes to the degree to which a neoplastic
cell resembles the normal mature cells of the tissue both
morphologically and functionally
Benign tumours are usually well differentiated. They
resemble closely their normal counterpart
Malignant tumours on the other hand, show variable degree
of differentiation
27. Malignant tumours that are composed of undifferentiated cells
are said to be anaplastic, that means no morphological
resemblance to normal tissue
‘Anaplasia’ denotes to the lack of differentiation
28. ANAPLASIA
Pleomorphism and anisonucleosis
Size
shape
Abnormal nuclear morphology
Hyperchromasia
High nuclear cytoplasmic ratio (upto 1:1)
Chromatin clumping
Prominent nucleoli
Irregular nuclear membrane
Abnormal mitoses tripolar, quadripolar and multipolar spindles
Loss of polarity
29.
30. Characteristics of a single
malignant cell
Abormal size – usually larger than normal
Large nuclei
Small cytoplasm
Altered nuclear: cytoplasm ratio (1:1)
Hyperchromatic nuclei / coarse chromatin
Chromatin clumping
Irregular nuclear membrane
Multiple nuclei
Prominent nucleoli
Bizarre (tri-, quadri- or multipolar) mitotic spindle
31. Features of Malignant Tumors
Cellular features
Local invasion
Malignant: expand, invade and infiltrate the surrounding
tissue (basement membrane)
Whereas Benign tumours expand and push aside without
invading, infiltrating surrounding capsule or
basement membrane
Metastasis
Unequivocal sign of malignancy
32.
33. Dysplasia
Literally means abnormal growth, the term implies disordered
growth of epithelim
In dysplasia some but not all of the features of
malignancy are present
Dysplastic cells may show a degree of pleomorphism,
hyperchromasia, increased mitosis and loss of architectural
orientation or polarity
Dysplasia may develop into malignancy
Uterine cervix
Colon polyps
Graded as low-grade or high-grade
Dysplasia may NOT develop into malignancy
34.
35.
36.
37. Tumours grading
Grading is based on
(1) the degree of anaplasia
(2) number of mitoses
• Grade-I : Well-differentiated (less than 25% anaplastic
cells)
• Grade-II : Moderately-differentiated (25-50% anaplastic
cells)
• Grade-III : Moderately-differentiated (50-75% anaplastic
cells)
• Grade-IV : Poorly-differentiated or anaplastic (more than
75% anaplastic cells)
38. Criteria for grading vary in different types of tumour
39. Tumours staging
International TNM system is commonly used for solid
tumours– T: Tumour (size of primary tumour), N: Nodes
(local/ regional node involvement), M: Metastases (distant
metastases)
T0 No evidence of tumour Tis Carcinoma in situ T1-4
Progressive increase in tumour size
40. NX Regional lymph nodes can’t be assessed
N0 Regional lymph nodes not involved
N1-4 Progressive increase in number of local/ regional
lymph nodes involved
M0 No evidence of distant metastases
MX distant metastases can’t be assessed
M1-3 Increasing involvement of distant metastases
41.
42. Natural History Of Malignant
Tumors
Malignant change in the target cell, referred to as
transformation
Growth of the transformed cells
Local invasion
Distant metastases
43. METASTASIS
Metastasis is the process by which a tumor cell leaves the
primary tumor, travels to a distant site via the circulatory
system, and establishes a secondary tumor
Routes of Metastasis: Mainly 3 types
Through the circulatory (blood) system (hematogenous)
:Common route for sarcomas but certain carcinomas also
frequently metastasiseby this mode.
•Ex: liver, lungs, brain, bones, kidney and adrenals
44. Through the lymphatic system : commonly carcinoma
Through the body wall into the abdominal and chest
cavities (transcoelomic)
eg. Pseudomyxoma peritonei , Cruckenberg tumour of
ovary
47. Locally malignant tumours
Groups of malignant tumours that spread only locally by
direct infiltration but rarely metastasize
Examples:
- Basal cell carcinoma of skin
- Osteoclastoma/ giant cell tumour of bone
- Adamantinoma of jaw
- Carcinoid tumour
- Astrocytoma of brain
- Craniopharyngioma in pituitary fossa
48. Molecular basis of cancer
Non- lethal genetic damage (mutation) lies at the heart of
carcinogenesis (initiation and transformation)
Clonal expansion of a single progenitor cell that incurred the
genetic damage
Carcinogenesis results from the accumulation of complementary
mutations in a stepwise fashion over time (progression)
49. Normal growth regulatory genes
Three normal regulatory genes
- Growth promoting proto-oncogenes
- Growth inhibiting tumour suppressor genes
- Apoptosis regulatory genes
- Apoptosis inducer
- Apoptosis suppressors
4th – DNA repair genes
50. Normal Cell Growth
Proto-oncogene product leads to cell growth with external
stimuli
This growth stimuli should be balanced by the products of
tumour suppressor genes
Any mutated genes will either be repaired by DNA repair
genes (maintains genomic integrity) or killed by products of
apoptosis regulatory genes
51. Principles of carcinogenesis
Cancer is caused by alteration or mutations in genetic code
Induced in somatic cells by
- carcinogenic chemicals
- radiation
- some viruses
Herediary/ germline mutations
5-10 %
52. Principles of carcinogenesis
Neoplastic transformation is a progressive process involving
multiple hits or genetic damages
Mutation affects one or more of the following genes
Proto-oncogenes
Tumour suppressor genes
Genes that regulate apoptosis
DNA repair genes
Approximately 90- 90% of all cancers are sporadic
5-10% are inherited
53. Proto-oncogenes
uncontrolled growth
Tumour suppressor genes
Uncontrolled growth
DNA repair genes
unable to recognize and repair non lethal genetic
damage Mutator phenotype/ Genomic instability
Gain of function mutation
Loss of function mutation
Loss of function mutation
54.
55.
56. Driver mutations :
Mutations that contribute to the development of the
malignant phenotype are reffered to as ‘driver mutations’.
Passenger mutations:
Mutations that have no phenotypic consequence, are called
‘passenger mutations’
The first driver mutation that starts a cell on the path to
malignancy is termed ‘initiating mutation’
57. Initiated cell acquires a number of additional driver mutations ,
each of which contributes to the development of cancer
Mutation in DNA repair genes is a common early step on the road
to malignancy , it leads to genomic instability
By the time a cell acquires all of the driver mutations needed for
malignant behavior, it may bear hundreds or even thousands of
additional mutations (tumour progression, diagnosis)
58.
59. Cellular and molecular
hallmarks of cancer
All cancers display eight fundamental changes in cell
physiology , which are considered the hallmarks of cancer
60. Hallmarks
Self – sufficiency in growth signals
Insensitivity to growth inhibitory signals
Altered cellular metabolism
Evasion of metastasis
Limitless replicative potential (immortality)
Sustained angiogenesis
Ability to invade and metastasize
Ability to evade the host immune response
61. Germline mutations are changes to your DNA that you
inherit from the egg and sperm cells during conception.
Somatic mutations are changes to your DNA that happen
after conception to cells other than the egg and sperm.
Mutations can lead to genetic conditions
and familial cancer syndromes.
62.
63. Proteins involved in normal cellular
growth :
Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators
71. RADIATION CARCINOGENS
UV:BCC, SCC, MM
IONIZING:
alpha, beta, gamma ray, X-ray
Hematopoetic and Thyroid (90%/15yrs) tumors in
fallout victims
Solid tumors either less susceptible or require a longer
latency period than LEUK/LYMPH
BCCs in Therapeutic Radiation
76. How do tumor cells
escape immune surveillance?
Mutation, like microbes, like “evolution”
↓ MHC molecules on tumor cell surface
Lack of CO-stimulation molecules, e.g., (CD28, ICOS),
not just Ag-Ab recognition
Immunosuppressive agents
Antigen masking
Apoptosis of cytotoxic T-Cells (CD8)
77. Effects of TUMOR on the HOST
Location anatomic ENCROACHMENT
HORMONE production
Bleeding, Infection
ACUTE symptoms, e.g., rupture, infarction
METASTASES
78. CACHEXIA
Individuals with cancer commonly suffer progressive loss
of body fat and lean body mass accompanied by profound
weakness, anorexia and anaemia referred to as cancer
cachexia.
TNF α
IL-6 by tumor cells
PIF (Proteolysis Inducing Factor) by tumor cells
79. PARA-Neoplastic Syndromes
Some cancer bearing individuals develop signs and
symptoms that cannot readily be explained by the anatomic
distribution of the tumor or by the elaboration of hormones
indigenous to the tissue from which the tumor arose –
paraneoplastic syndromes
80. PARA-Neoplastic Syndromes
May be the earliest manifestation of an occult neoplasm
Can cause significant clinical problems and may even be
lethal
May mimic metastatic disease and therefore confound
treatment
85. Flow cytometry
FISH –fluorescent in situ hybridization
DNA micro-arrays
86. Tumor markers
Biochemical assays
Not definitive diagnosis of cancer
Caontribute to the detection of cancer
Useful in determining the effectiveness of therapy
Or the appearance of a recurrence
89. TUMOR MARKERS
HORMONES: (Paraneoplastic Syndromes)
“ONCO”FETAL: AFP, CEA
ISOENZYMES: PAP, NSE
PROTEINS: PSA, PSMA (“M” = “membrane”)
GLYCOPROTEINS: CA-125, CA-195, CA-153
MOLECULAR: p53, RAS
NOTE: These SAME substances which can be measured in
the blood, also can be stained by immunochemical methods
in tissue