basics about neoplasia- classification of tumors cancer

1. NEOPLASIA
A brief presentation on general
aspects of neoplasia

2. Defination, nomenclature
and classification of tumours
Rate of growth and
features of tumours
02
INTRODUCTION
CHARACTERISTICS
OF TUMOUR
01
To predict tumour
behavior and guide
therapy
GRADING AND
STAGING OF
CANCER
04
SPREAD OF
TUMOUR
Local invasion/direct
spread and
metastasis/distant
spread
03
MAIN TOPICS

3. DEFINITION,
NOMENCLATURE AND
CLASSIFICATION
OF
TUMOURS

4. Definition: A mass of tissue formed as a result of abnormal, excessive,
uncoordinated, autonomous and purposeless proliferation of cells
even after cessation of stimulus for growth which caused it
NEOPLASIA

5. The branch of science dealing with neoplasms or tumours
is called oncology(oncos=tumour, logos=study).
Neoplasms may be ‘benign’ when they are slow-growing
and localized without causing much difficulty to the host, or
‘malignant’ when they proliferate rapidly, spread throughout
the body and may eventually cause death of the host.
The common term used for all malignant tumours is
cancer.
NOMENCLATURE

6. All tumours, benign as well as malignant, have 2 basic components:
‘Parenchyma’ comprised by proliferating tumour cells; parenchyma
determines the nature and evolution of the tumour.
‘Supportive stroma’ composed of fibrous connective tissue and blood
vessels; it provides the framework on which the parenchymal tumour
cells grow.
The tumours derive their nomenclature on the basis of the parenchymal
component comprising them-
The suffix ‘-oma’ is added to denote benign tumours.
Malignant tumours of epithelial origin are called carcinomas, while
malignant mesenchymal tumours are named sarcomas (sarcos = fleshy)
However, some cancers are composed of highly undifferentiated cells
and are referred to as undifferentiated malignant tumours.
NOMENCLATURE
cont…

7. Although, this broad generalization regarding nomenclature of tumours
usually holds true in majority of instances, some examples contrary to
this concept are:
melanoma for carcinoma of the melanocytes,
hepatoma for carcinoma of the hepatocytes,
lymphoma for malignant tumour of the lymphoid tissue, and
seminoma for malignant tumour of the testis
Leukaemia is the term used for cancer of blood forming cells.

8. These tumours are made up of a mixture of
various tissue types arising from totipotent
cells derived from the three germ cell
layers—ectoderm, mesoderm and
endoderm.
Most common sites for teratomas are ovaries and testis
(gonadal teratomas). But they occur at extra-gonadal
sites as well, mainly in the midline of the body such as
in the head and neck region, mediastinum,
retroperitoneum, sacrococcygeal region etc
SPECIAL CATEGORIES OF TUMOURS
2. Teratomas
1. Mixed tumours
When two types of tumours
are combined in the same
tumour, it is called a mixed
tumour
i) Adenosquamous carcinoma is the combination of adenocarcinoma and
squamous cell carcinoma in the endometrium.
ii) Adenoacanthoma is the mixture of adenocarcinoma and benign
squamous elements in the endometrium.
iii) Carcinosarcoma is the rare combination of malignant tumour of the
epithelium (carcinoma) and of mesenchymal tissue (sarcoma) such as in
thyroid.
iv) Collision tumour is the term used for morphologically two different
cancers in the same organ which do not mix with each other.
v) Mixed tumour of the salivary gland (or pleomorphic adenoma) is the
term used for benign tumour having combination of both epithelial and
mesenchymal tissue elements.

9. Hamartoma is benign tumour
which is made of mature but
disorganised cells of tissues
indigenous to the particular organ
e.g. hamartoma of the lung consists of
mature cartilage, mature smooth muscle and
epithelium. Thus, all mature differentiated
tissue elements which comprise the bronchus
are present in it but are jumbled up as a
mass.
5. Choristoma
Choristoma is the name given
to the ectopic islands of
normal tissue. Thus,
choristoma is heterotopia but
is not a true tumour, though it
sounds like one.
Blastomas or embryomas are a group
of malignant tumours which arise
from embryonal or partially
differentiated cells which would
normally form blastema of the organs
and tissue during embryogenesis.
These tumours occur more frequently
in infants and children
Some examples of tumours in this age
group: neuroblastoma, nephroblastoma
(Wilms’ tumour), hepatoblastoma,
retinoblastoma, medulloblastoma,
pulmonary blastoma.
3. Blastomas
(Embryomas) 4. Hamartoma

10. CLASSIFICATION
. Currently, classification of tumours is based
on the histogenesis (i.e. cell of origin) and
on the anticipated behaviour

11. CHARECTERISTICS
OF
TUMOUR
(INCLUDING SPREAD OF TUMOURS)

12. Majority of neoplasms can be categorised
clinically and morphologically into benign and
malignant on the basis of certain characteristics.
However, there are exceptions—a small proportion of tumours
have some features suggesting innocent growth while other
features point towards a more ominous behaviour. Therefore, it
must be borne in mind that based characteristics of neoplasms,
there is a wide variation in the degree of deviation from the normal
in all the tumours.

13. CHARECTERISTICS OF TUMOUR
RATE OF
GROWTH
Causes of, cancer cells
exhibiting antisocial
behaviour
CANCER PHENOTYPE
AND STEM CELLS
Features of benign and
malignant tumours
CLINICAL AND
GROSS FEATURES
MICROSCOPIC
FEATURES
SPREAD OF
TUMOURS
1.Rate of cell production,
growth fraction and rate
of cell loss
2.Degree of differentiation
of the tumour.
Patterns and
arrangement s of
tumour cells
Local invasion
and metastasis

14. RATE OF GROWTH
Doubling
time of
tumour cells
Growth
fraction
no. of cells remaining in
the proliferative pool
Rate of loss
of tumour
cells(cell
shedding)
In general, malignant tumour cells have
increased mitotic rate (doubling time) and
slower death rate i.e. the cancer cells do not
follow normal controls in cell cycle and are
immortal.
If the rate of cell division is high, it is likely
that tumour cells in the centre of the tumour
do not receive adequate nourishment and
undergo ischaemic necrosis.
At a stage when malignant tumours grow
relentlessly, they do so because a larger
proportion of tumour cells remain in
replicative pool but due to lack of availability
of adequate nourishment, these tumour
cells are either lost by shedding or leave the
cell cycle to enter into G0 (resting phase) or
G1 phase.

15. DEGREE OF DIFFERENTIATION
The rate of growth of malignant tumour is directly proportionate to the degree of differentiation. Poorly
differentiated tumours show aggressive growth pattern as compared to better differentiated tumours.
The regulation of tumour growth is under the control of growth factors secreted by the tumour cells.
Out of various growth factors, important ones modulating tumour biology are listed below.
Epidermal growth factor (EGF)
Fibroblast growth factor (FGF)
Transforming growth factors-β (TGF-β)
Platelet-derived growth factor(PDGF)
Colony stimulating factor (CSF)
Interleukins (IL)
Vascular endothelial growth factor (VEGF)
Hepatocyte growth factor (HGF)

16. CANCER PHENOTYPE AND STEM CELLS
Normally growing cells in an organ are related to the neighbouring cells—they grow under normal growth
controls, perform their assigned function and there is a balance between the rate of cell proliferation and
the rate of cell death including cell suicide (i.e. apoptosis). Thus normal cells are socially desirable.
However, cancer cells exhibit antisocial behaviour as under:
Cancer cells disobey the growth controlling signals in the body and thus proliferate rapidly.
Cancer cells escape death signals and achieve immortality.
Imbalance between cell proliferation and cell death in cancer causes excessive growth.
Cancer cells lose properties of differentiation and thus perform little or no function.
Due to loss of growth controls, cancer cells are genetically unstable and develop newer
mutations.
Cancer cells overrun their neighbouring tissue and invade locally.
Cancer cells have the ability to travel from the site of origin to other sites in the body where they
colonise and establish distant metastasis.

17. Cancer cells originate by clonal prolferation of a single
progeny of a cell (monoclonality). Cancer cells arise
from stem cells normally present in the tissues in small
number and are not readily identifiable
These cancer stem cells are called tumour-initiating
cells. Their definite existence in acute leukaemias has
been known for sometime and have now been found
to be present in some other malignant tumours.

18. CLINICAL AND GROSS FEATURES
Slow
growing
may remain
asymptomatic
(e.g. subcutaneous
lipoma),
or may
produce
serious symptoms
(e.g. meningioma in the
nervous system).
grow rapidly
may ulcerate
on the surface
, invade locally
into deeper tissues
may spread to
distant sites
(metastasis)
also produce
Systemic features
such as weightloss,
anorexia and anemia

19. They have a different colour, texture and
consistency. Gross terms such as papillary,
fungating, infiltrating, haemorrhagic, ulcerative and
cystic are used to describe the macroscopic
appearance of the tumours.
Benign tumours are generally spherical or ovoid in shape.
They are encapsulated or well-circumscribed, freely movable,
more often firm and uniform, unless secondary changes like
haemorrhage or infarction supervene
Malignant tumours, on the other hand, are usually irregular in
shape, poorly-circumscribed and extend into the adjacent
tissues. Secondary changes like haemorrhage, infarction and
ulceration are seen more often. Sarcomas typically have fish-
flesh like consistency while carcinomas are generally firm
Benign tumours
Malignant tumours

20. 01 03
02 04
MICROSCOPIC FEATURES
. microscopic pattern
cytomorphology of
neoplastic cells
(differentiation and anaplasia)
tumour angiogenesis and
stroma
inflammatory reaction.
For recognising and classifying the tumours, the microscopic characteristics of
tumour cells are of greatest importance. These features which are appreciated in
histologic sections are as under:

21. MICROSCOPIC PATTERN
The tumour cells may be arranged in a variety of
patterns in different tumours as under:
The epithelial tumours generally consist of acini, sheets,
columns or cords of epithelial tumour cells that may be
arranged in solid or papillary pattern.
The mesenchymal tumours have mesenchymal tumour
cells arranged as interlacing bundles, fasicles or whorls,
lying separated from each other usually by the
intercellular matrix substance
Certain tumours have mixed patterns e.g. fibroadenoma
of the breast, carcinosarcoma of the uterus and various
other combinations of tumour types.
Haematopoietic tumours such as leukaemias and
lymphomas often have none or little stromal support.

22. Cytomorphology of Neoplastic Cells (Differentiation and Anaplasia)
The neoplastic cell is characterised by morphologic and functional alterations
Differentiation is defined as the extent of morphological and functional resemblance of parenchymal tumour cells
to corresponding normal cells. If the deviation of neoplastic cell in structure and function is minimal as compared
to normal cell, the tumour is described as ‘well-differentiated’ such as most benign and low-grade malignant
tumours. ‘Poorly differentiated’, ‘undifferentiated’ or ‘dedifferentiated’ are synonymous terms for poor
structural and functional resemblance to corresponding normal cell.
Anaplasia is lack of differentiation and is a characteristic feature of most malignant tumours. Depending upon the
degree of differentiation, the extent of anaplasia is also variable i.e. poorly differentiated malignant tumours have
high degree of anaplasia. As a result of anaplasia, noticeable morphological and functional alterations in the
neoplastic cells are observed.

23. Tumour Angiogenesis and Stroma
TUMOUR ANGIOGENESIS. In order to provide nourishment to growing tumour, new blood vessels are formed
from pre-existing ones (angiogenesis),
TUMOUR STROMA. The collagenous tissue in the stroma may be scanty or excessive. In the former case, the
tumour is soft and fleshy (e.g. in sarcomas, lymphomas), while in the latter case the tumour is hard and gritty (e.g.
infiltrating duct carcinoma breast). Growth of fibrous tissue in tumour is stimulated by basic fibroblast growth
factor (bFGF) elaborated by tumour cells. If the epithelial tumour is almost entirely composed of parenchymal
cells, it is called medullary e.g. medullary carcinoma of the breast, medullary carcinoma of the thyroid. If there is
excessive connective tissue stroma in the epithelial tumour, it is referred to as desmoplasia and the tumour is
hard or scirrhous e.g. infiltrating duct carcinoma breast.
Inflammatory Reaction
At times, prominent inflammatory reaction is present in and around the tumours. It could be the result of
ulceration in the cancer when there is secondary infection. The inflammatory reaction in such instances may be
acute or chronic.This is due to cell-mediated immunologic response by the host The examples of such reaction
are: seminoma testis (Fig. 8.10), malignant melanoma of the skin, lymphoepithelioma of the throat, medullary
carcinoma of the breast, choriocarcinoma, Warthin’s tumour of salivary glands etc.

24. 01 02 03 04
SPREAD OF TUMOURS
BENIGN TUMOURS. Most benign tumours form
encapsulated or circumscribed masses that expand and
push aside the surrounding normal tissues without
actually invading, infiltrating or metastasising.
MALIGNANT TUMOUR. They are distinguished from benign
tumours by invasion, infiltration and destruction of the
surrounding tissue, besides distant metastasis. Tumours
invade via the route of least resistance, though eventually
most cancers recognise no anatomic boundaries.
Cancers extend through tissue spaces, permeate
lymphatics, blood vessels, perineural spaces and may
penetrate a bone by growing through nutrient foramina.
invasion infiltration Distant metastasis
destruction of the
surrounding tissue
LOCAL INVASION DIRECT SPREAD

25. METASTASIS (DISTANT SPREAD)
Metastasis (meta = transformation, stasis = residence) is defined as spread of tumour by invasion in such a way
that discontinuous secondary tumour mass/masses are formed at the site of lodgement. Metastasis and
invasiveness are the two most important features to distinguish malignant from benign tumours: benign tumours
do not metastasise while all the malignant tumours with a few exceptions like gliomas of the central nervous
system and basal cell carcinoma of the skin, can metastasise.
Routes of Metastasis
1.Lymphatic spread
2.Haematogenous spread
3.Spread along body
cavities and natural passages
Cancers may spread to distant sites by following
pathways:
Transcoelomic spread
Spread along epithelium-lined Surfaces
spread via cerebrospinal fluid
implantation
Lymphatic permeation. The walls of lymphatics are readily
invaded by cancer cells and may form a continuous growth in
the lymphatic channels called lymphatic permeation.
Lymphatic emboli. Alternatively, the malignant cells may
detach to form tumour emboli so as to be carried along the
lymph to the next draining lymph node.
SYSTEMIC VEINS
PORTAL VEINS
PULMONARY VIENS
ARTERIAL SPREAD
RETROGRADE
SPREAD

26. MECHANISM AND
BIOLOGY OF
INVASION AND
METASTASIS

27. GRADING AND
STAGING OF
CANCER

28. ‘Grading’ and ‘staging’ are the two systems to predict tumour behaviour and guide therapy
after a malignant tumour is detected.
Grading is defined as the gross and microscopic degree of differentiation of the tumour, while
staging means extent of spread of the tumour within the patient.
Thus, grading is histologic while staging is clinical.
GRADING
grading is largely based on 2 important histologic features: the
degree of anaplasia, and the rate of growth.
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).
However, grading of tumours has several shortcomings. It is subjective and the degree of differentiation may vary from one area of
tumour to the other. Therefore, it is common practice with pathologists to grade cancers in descriptive terms (e.g. well-differentiated,
undifferentiated, keratinising, non-keratinising etc) rather than giving the tumours grade numbers.
More objective criteria for histologic grading include use of flow cytometry for mitotic cell counts, cell proliferation Neoplasia markers
by immunohistochemistry, and by applying image morphometry for cancer cell and nuclear parameters

29. The extent of spread of cancers can be assessed by 3 ways—
-by clinical examination,
-by investigations, and
-by pathologic examination of the tissue removed.
Two important staging systems currently followed are:
-TNM staging
-AJC staging.
STAGING
TNM STAGING T for primary tumour, N for regional nodal
involvement, and M for distant metastases. For each of the 3
components namely T, N and M, numbers are added to indicate
the extent of involvement, as under:
T0 to T4: In situ lesion to largest and most extensive primary
tumour.
N0 to N3: No nodal involvement to widespread lymph node
involvement.
M0 to M2: No metastasis to disseminated haematogenous
metastases.
AJC staging. American Joint Committee staging divides all
cancers into stage 0 to IV, and takes into account all the 3
components of the preceding system (primary tumour, nodal
involvement and distant metastases) in each stage.
Currently, clinical staging of tumours does not rest on routine
radiography (X-ray, ultrasound) and exploratory surgery but more
modern techniques are available by which it is possible to ‘stage’ a
malignant tumour by non-invasive techniques like CT, MRI, PET etc

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