characteristic features of tumours

2. • The characteristics of tumours are described under the
following headings:
I. Rate of growth.
II. Cancer phenotype.
III. Clinical and Gross features.
IV. Microscopic features
V. Spread of tumours
a. Local invasion or direct spread
b. Metastasis or distant spread

3. I. RATE OF GROWTH
• The tumour cells generally proliferate more rapidly
than the normal cells.
• In general, Benign tumours grow slowly and
Malignant tumours rapidly.
• In general, malignant tumour cells have increased
mitotic rate (doubling time) and slower death rate and
are IMMORTAL.

4. • 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.

5. • 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
i) Epidermal growth factor (EGF)
ii) Fibroblast growth factor (FGF)
iii) Platelet-derived growth factor (PDGF)
iv) Colony stimulating factor (CSF)
v) Transforming growth factors-b (TGF-b)
vi) Interleukins 1 and 6 (IL-1, IL-6)
vii) Vascular endothelial growth factor (VEGF)
viii) Hepatocyte growth factor (HGF)

6. II. CANCER PHENOTYPE (behaviour):
Cancer cells exhibit anti-social behaviour as under:
- Disobey the growth controlling signals in the body and thus
proliferate rapidly.
- Escape death signals and achieve immortality.
- Perform little or no function.
- Genetically unstable and develop newer mutations.
- Invade locally.
- Colonise and establish distant metastasis.

7. III. CLINICAL AND GROSS FEATURES
Clinically: BENIGN TUMOURS
MAY PRODUCE SERIOUS SYMPTOMS
(E.G. MENINGIOMA IN THE NERVOUS
SYSTEM).
MAY REMAIN
ASYMPTOMATIC
(E.G. SUBCUTANEOUS
LIPOMA)
depending upon the location

8. Clinically:
may spread to distant sites
(METASTASIS), and
also produce systemic features such as
WEIGHTLOSS, ANOREXIA AND
ANAEMIA.
may ulcerate on the surface,
INVADE LOCALLY into deeper
tissues.
MALIGNANT TUMOURS GROW RAPIDLY

9. Gross appearance:
BENIGN TUMOURS
 Spherical or ovoid in shape.
 Encapsulated or
 Well-circumscribed,
 Freely movable,
 Firm and Uniform, unless secondary changes like
haemorrhage or infarction supervene

10. Gross appearance:
MALIGNANT TUMOURS
 Irregular in shape,
 Poorly-circumscribed
 Extend into the adjacent
tissues.
 Secondary changes like
Haemorrhage, Infarction and
Ulceration are seen more often.

11. SARCOMAS TYPICALLY HAVE FISH
FLESH LIKE CONSISTENCY
CARCINOMAS ARE GENERALLY
FIRM.

12. IV. MICROSCOPIC FEATURES
• The microscopic characteristics of tumour cells help in
recognizing and classifying the tumours.
They are studied under following sections:
1. Microscopic Pattern.
2. Cytomorphology of neoplastic cells (differentiation and
Anaplasia)
3. Tumour angiogenesis and stroma
4. Inflammatory reaction

13. 1. MICROSCOPIC PATTERN
Epithelial tumours:
• Generally consist of
ACINI SHEETS CORDS

14. Mesenchymal tumours :
Tumour cells arranged as
Whorls
FasciclesInterlacing Bundles

15. 2. CYTOMORPHOLOGY OF NEOPLASTIC CELLS
(DIFFERENTIATION AND ANAPLASIA)
• The neoplastic cell is characterized by structural and
functional changes.
• The most significant of which are ‘Differentiation’
and ‘Anaplasia’.

16. Differentiation
• It is defined as the extent of morphological and functional resemblance of
tumour cells to corresponding normal cells.
WELL-DIFFERENTIATED:
• 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:
• ‘Poorly differentiated’, ‘undifferentiated’ or ‘dedifferentiated’ are
synonymous terms for poor structural and functional resemblance to
corresponding normal cell as in malignant tumours.

17. Anaplasia
• It 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.

18. Features of Anaplasia are as follows:

19. i) Loss of polarity
• Early in malignancy, tumour cells lose their
basal polarity so that the nuclei tend to lie
away from the basement membrane.

20. ii) Pleomorphism
• Variation in size and shape of the tumour cells.

21. iii) N:C ratio
• Nuclei are enlarged disproportionate to the cell size
so that the nucleocytoplasmic ratio is increased from
normal 1:5 to 1:1

22. iv) Anisonucleosis/Nuclear Pleomorphism
• Just like cellular pleomorphism, the nuclei too,
show variation in size and shape in malignant
tumour cells.

23. v) Hyperchromatism
• The nuclear chromatin of malignant cell is increased
and coarsely clumped.
• This is due to increase in the amount of nucleoprotein
resulting in dark-staining nuclei, referred to as
hyperchromatism.

24. vi) Nucleolar changes:
• Malignant cells frequently have a prominent
nucleolus or nucleoli in the nucleus reflecting
increased nucleoprotein synthesis.

25. vii) Mitotic figures:
• The parenchymal cells of poorly differentiated tumours often
show large number of mitoses as compared with benign
tumours and well-differentiated malignant tumours.
• Abnormal or atypical mitotic figures: seen in Malignant cells

26. viii) Tumour giant cells
• Multinucleate tumour giant cells or giant cells
containing a single large and bizarre nucleus,
possessing nuclear characters of the adjacent tumour
cells, are another important feature of Anaplasia in
malignant tumours.

27. x) Chromosomal abnormalities
• The chromosomal abnormalities are more marked in
more malignant tumours which include deviations in
both morphology and number of chromosomes.
• Most malignant tumours show DNA aneuploidy

28. 3. TUMOUR ANGIOGENESIS AND STROMA
TUMOUR ANGIOGENESIS
ANGIOGENIC FACTORS elaborated by
tumour cells (e.g. Vascular endothelium
growth factor or VEGF)
NEW BLOOD VESSELS ARE FORMED
NOURISHMENT TO GROWING TUMOUR
MORE THE DENSITY OF THE BLOOD
VESSELS GREATER THE RATE OF GROWTH
OF TUMOURS

29. IF THE TUMOUR OUTGROWS ITS
BLOOD SUPPLY
(IN RAPIDLY GROWING TUMOURS OR IF
ANGIOGENESIS FAILS)
ITS CORE
UNDERGOES ISCHAEMIC NECROSIS.

30. TUMOUR STROMA
IF THE COLLAGEN TISSUE IS SCANTY
IN THE STROMA
IF COLLAGENOUS TISSUE IN THE
STROMA IS EXCESSIVE
TUMOUR WILL BE
SOFT AND FLESHY
TUMOUR WILL BE
HARD AND GRITTY
EG: MOSTLY SARCOMAS
LIKE LYMPHOMAS.
EG: MOSTLY CARCINOMAS
LIKE INFILTRATING
DUCTAL CARCINOMA OF BREAST

31. LYMPHOMA
INFILTRATING DUCTAL
CARCINOMA OF BREAST

32. IF A EPITHELIAL TUMOUR CONTAINS
MORE PARENCHYMAL CELLS
THAN STROMA
MEDULLARY TUMOR
because the tumor is a
SOFT FLESHY mass
that resembles a part of
the brain called the
medulla
MORE FIROUS TISSUE (LIKE
COLLAGEN) IN STROMA
SCIRRHUS TUMOR
HARD SLOW-
GROWING
malignant tumor having
a preponderance of
fibrous tissue.
IT IS NAMED AS

33. SCHIRRUS CARCINOMA OF BREASTMEDULLARY CARCINOMA OF BREAST

34. V. SPREAD OF TUMOURS
• Cardinal features of malignant tumours:
 ABILITY TO INVADE AND DESTROY
ADJOINING TISSUES (LOCAL INVASION
OR DIRECT SPREAD)
 ABILITY TO DISSEMINATE TO DISTANT
SITES (METASTASIS OR DISTANT SPREAD).

35. 1. LOCAL INVASION (DIRECT SPREAD)
BENIGN TUMOURS
Encapsulated or
circumscribed masses
expand and push aside the
surrounding normal tissues
without actually invading,
infiltrating or metastasising.

36. MALIGNANT TUMOURS
Malignant tumours INVADE, INFILTRATE AND CAUSE
DESTRUCTION of the surrounding tissue.
1. Thin-walled capillaries and
veins are more easy for invasion
than thick-walled arteries for
Malignant tumours.
2. Dense compact collagen,
elastic tissue and cartilage are
resistant to tumour invasion
FACTORS AFFECTING INVASION, INFILTRATION AND DESTRUCTION:

37. 2. METASTASIS (DISTANT SPREAD)
• Metastasis is defined as spread of tumour by invasion
in such a way that discontinuous secondary tumour
mass/masses are formed at the site of lodgment.
• Besides Anaplasia, invasiveness and metastasis are
the two other most important features to distinguish
malignant from benign tumours.

38. • Benign tumours do not metastasise.
• All the malignant tumours can metastasise,
EXCEPT few exceptions like
- Gliomas of the central nervous system
- Basal cell carcinoma of the skin.
• More aggressive and rapidly growing tumours are
more likely to metastasise (except few malignant
tumours).

39. Glioma Basal Cell Carcinoma

40. MECHANISM AND BIOLOGY OF INVASION &
METASTASIS.
Following are sequential steps of INVASION & METASTASIS:
1. Aggressive Clonal proliferation and angiogenesis.
2. Tumour cell loosening
3. Tumour cell-ECM interaction
4. Degradation of ECM
5. Entry of tumour cells into capillary lumen
6. Thrombus formation
7. Extravasation of tumour cells
8. Survival and growth of metastatic deposit

42. 1. AGGRESSIVE CLONAL PROLIFERATION AND ANGIOGENESIS
• CLONAL PROLIFERATION : The first step in the
spread of cancer cells is the development of rapidly
proliferating clone of cancer cells.
• ANGIOGENESIS: Tumour angiogenesis plays a very
significant role in metastasis since the new vessels
formed as part of growing tumour are more vulnerable
to invasion because these evolving vessels are directly
in contact with cancer cells.

43. CANCER CELLS
NEW BLOOD VESSEL FORMATION
(ANGIOGENESIS)
INCREASE IN CELL COUNT
(CLONAL PROLIFERATION)

44. 2. TUMOUR CELL LOOSENING
• Normal cells remain glued to each other due to
presence of cell adhesion molecules (CAMs)
i.e. E (epithelial)-cadherin.
• In epithelial cancers, there is either loss or
inactivation of E-cadherin and also other
CAMs results in loosening of cancer cells.

45. CANCER CELLS
BLOOD VESSEL
E-cadherin
integrins
fibronectin

46. CANCER CELLS
BLOOD VESSEL

47. 3. TUMOUR CELL-ECM INTERACTION
• Loosened cancer cells are now attached to ECM
proteins, mainly laminin and fibronectin.
• This attachment is facilitated due to profoundness
of receptors on the cancer cells for both these
proteins.
• There is also loss of integrins further favouring
invasion.

48. CANCER CELLS
NEW VESSEL
Laminin part of BM
fibronectin
integrins

49. CANCER CELLS
NEW VESSEL
Laminin part of BM
fibronectin

50. 4. DEGRADATION OF ECM
• Tumour cells over express proteases and matrix-degrading
enzymes, metalloproteinases (e.g. collagenases and
gelatinase), while the inhibitors of metalloproteinases are
decreased.
• These enzymes bring about dissolution of ECM—firstly
basement membrane of tumour itself, then make way for
tumour cells through the interstitial matrix, and finally
dissolve the basement membrane of the vessel wall.

51. CANCER CELLS
BLOOD VESSEL
BM
fibronectin

52. 5. ENTRY OF TUMOUR CELLS INTO CAPILLARY
LUMEN:
• Following mechanisms play a role in entry of tumour cells into lumen.
i) Autocrine motility factor (AMF), a cytokine derived from tumour cells
which stimulates receptor-mediated motility of tumour cells.
ii) Cleavage products of matrix components which are formed following
degradation of ECM have properties of tumour cell chemotaxis, growth
promotion and angiogenesis in the cancer.
After the malignant cells have migrated through the breached basement
membrane, these cells enter the lumen of lymphatic and capillary
channels.

53. 6. THROMBUS FORMATION
• The tumour cells protruding in the lumen of the capillary are now
covered with constituents of the circulating blood and form the
thrombus.
• Thrombus provides nourishment to the tumour cells and also
protects them from the immune attack by the circulating host cells.
• In fact, normally a large number of tumour cells are released into
circulation but they are attacked by the host immune cells.
• Actually a very small proportion of malignant cells (less than 0.1%)
in the blood stream survive to develop into metastasis.

54. CANCER CELLS
CAPILLARY BLOOD VESSEL
BM
Thrombus

55. 7. EXTRAVASATION OF TUMOUR CELLS:
• Tumour cells in the circulation (capillaries, venules,
lymphatics) may mechanically block these vascular
channels and attach to vascular endothelium and then
extravasate to the extravascular space.
• In this way, the sequence similar to local invasion is
repeated and the basement membrane is exposed.

56. CANCER CELLS
CAPILLARY BLOOD VESSEL
BM
Thrombus

57. 8. SURVIVAL AND GROWTH OF METASTATIC DEPOSIT
• The malignant cells on lodgment in extravascular
region grow further under the influence of growth
factors produced by
- Host tissues,
- Tumour cells and
- by cleavage products of matrix components.
• Some of the growth promoting factors are: PDGF, FGF,
TGF-b and VEGF.

58. • The metastatic deposits grow further if the host
immune defense mechanism fails to eliminate
it.
• Metastatic deposits may further metastasise to
the same organ or to other sites by forming
emboli.

59. CANCER CELLS
CAPILLARY BLOOD VESSEL
BM
EMBOLUS

60. CAPILLARY
BLOOD VESSEL
EMBOLUS

61. Routes of Metastasis
• Cancers may spread to distant sites by
following pathways:
1.Lymphatic spread.
2.Haematogenous spread.
3.Spread along body cavities and natural
passages.

63. 1. LYMPHATIC SPREAD
• In general, carcinomas metastasise by lymphatic
route while sarcomas favour haematogenous
route.
• However, some sarcomas may also spread by
lymphatic pathway.
• Lymph nodes provide fertile soil for growth of
tumour cells.

64. • The involvement of lymph nodes by malignant cells may be of
two forms:
i) 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.

65. ii) 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.

66. • The tumour emboli enter the lymph node at its
convex surface and are lodged in the
subcapsular sinus where they start growing.
• Later the whole lymph node may be replaced
and enlarged by the metastatic tumour

67. CHARACTERISTICS OF
LYMPHATIC SPREAD OF MALIGNANT TUMORS
1. REGIONAL NODAL METASTASIS:
• Regional lymph nodes draining the tumour produce regional
nodal metastasis
e.g.
i. From carcinoma breast to Axillary lymph nodes
ii. From cancer of the thyroid to lateral cervical lymph nodes,
iii. Bronchogenic carcinoma to hilar and para-tracheal lymph
nodes etc…

69. 2. SKIP METASTASIS:
• Sometimes lymphatic metastases do not develop
first in the lymph node nearest to the tumour due
to obliteration of lymphatics by inflammation or
radiation called as skip metastasis.
• Seen in Osteosarcoma, & Papillary Carcinoma
of Thyroid.

70. N1
N3
N2

71. N1
N3
N2

72. 3. RETROGRADE METASTASES:
• Other times, due to obstruction of the lymphatics by tumour
cells, the lymph flow is disturbed and tumour cells spread
against the flow of lymph causing retrograde metastases at
unusual sites.
E.g.
1. Metastasis of carcinoma prostate to the supraclavicular
lymph nodes.
2. Metastatic deposits from bronchogenic carcinoma to the
Axillary lymph nodes.

73. Direction of lymph flow.

74. 4. Virchow’s lymph node: is nodal metastasis
preferentially to supraclavicular lymph node
from cancers of abdominal organs
e.g. cancer stomach, colon, and gallbladder.

75. 2. HAEMATOGENOUS SPREAD
• Blood-borne metastasis is the common route for sarcomas.
• Certain carcinomas also frequently metastasise by this mode.
Especially those of
- Lung,
- Breast,
- Thyroid,
- Kidney,
- Liver,
- Prostate and Ovary.

76. • The sites where blood-borne metastasis commonly
occurs are:
- Liver.
- Lungs.
- Brain.
- Bones.
- Kidney and adrenals.
Provide ‘good soil’ for
the growth of ‘good
seeds’.

77. NOTE:
Spleen
Heart
Skeletal muscle
GENERALLY DO NOT ALLOW TUMOUR
METASTATIC CELLS TO GROW.
Spleen is unfavorable site due to open sinusoidal pattern
which does not permit tumour cells to stay there long
enough to produce metastasis.

78. CHARACTERISTIC FEATURES OF HAEMOGENOUS
METASTASIS:
1. Systemic veins drain blood into vena cavae from
limbs, head and neck and pelvis. Therefore, cancers
of these sites more often metastasise to the lungs.

79. 2. Portal veins drain blood from the bowel, spleen and
pancreas into the liver. Thus, tumours of these
organs frequently have secondaries in the liver.

80. 3. Blood in the pulmonary veins carrying cancer
cells from the lungs reaches left side of the
heart and then into systemic circulation and
thus may form secondary masses elsewhere in
the body.

81. 4. Arterial spread of tumours is less likely
because they are thick-walled and contain
elastic tissue which is resistant to invasion.
• Nevertheless, arterial spread may occur when
tumour cells pass through pulmonary capillary
bed or through pulmonary arterial branches
which have thin walls.

82. 3. SPREAD ALONG BODY CAVITIES AND
NATURAL PASSAGES:
Uncommon routes of spread of some cancers
I) TRANSCOELOMIC SPREAD
II) SPREAD ALONG EPITHELIUM-LINED SURFACES
III) SPREAD VIA CEREBROSPINAL FLUID
IV) IMPLANTATION

83. I) TRANSCOELOMIC SPREAD
Certain cancers invade
through the serosal wall of
the coelomic cavity so that
tumour fragments or clusters
of tumour cells break off to
be carried in the coelomic
fluid and are implanted
elsewhere in the body cavity.

84. • Peritoneal cavity is involved most often, but
occasionally pleural and pericardial cavities are also
affected.
Examples of transcoelomic spread are as follows:
a) Carcinoma of the stomach (Gastric Adenocarcinoma)
seeding to both ovaries (KRUKENBERG TUMOUR).

85. b) PSEUDOMYXOMA PERITONEI is the gelatinous coating of
the peritoneum from mucin-secreting carcinoma of the ovary
or appendix.

86. II) SPREAD ALONG EPITHELIUM-LINED SURFACES
• It is unusual for a malignant tumour to spread along
the epithelium-lined surfaces because intact
epithelium and mucus coat are quite resistant to
penetration by tumour cells.
• Exceptional to this, certain malignant tumours
spread through above method they are:

87. Eg:
1. Malignant tumour may spread through the fallopian tube from the
endometrium (endometrial carcinoma) to the ovaries or vice-versa;

88. 2. through the ureters from the kidneys into
lower urinary tract.

89. III) SPREAD VIA CEREBROSPINAL FLUID
• Malignant tumour of the ependyma and
leptomeninges may spread by release of tumour
fragments and tumour cells into the CSF and produce
metastases at other sites in the central nervous
system.

90. IV) IMPLANTATION
• Spread of some cancers by implantation by surgeon’s
scalpel, Needles, sutures, and direct prolonged
contact of cancer of the Lower lip causing its
implantation to the apposing upper lip.