Characteristic of Neoplasms

1. Neoplasia
Characteristics
of Neoplasms
Dr Mohammad Manzoor Mashwani BKMC L2

2. Recall
• Def. Neoplasm: RA Willis & Molecular era
• Nomenclature of Neoplasms
• Adenoma
• Carcinoma: def, classification
• Sarcoma: def, classification
• Differentiation
• Hamartoma
• Choristoma
• Mixed tumors
• Teratoma

3. All tumors, benign and malignant, have two basic components:
(1) the parenchyma, made up of transformed or neoplastic cells, and
(2) the supporting, host-derived, nonneoplastic stroma, made up of
connective tissue, blood vessels, and host-derived inflammatory cells.
The parenchyma of the neoplasm largely determines its biologic
behavior, and it is this component from which the tumor derives its
name.
The stroma is crucial to the growth of the neoplasm, since it carries the
blood supply and provides support for the growth of parenchymal
cells.
Although the biologic behavior of tumors largely reflects the behavior of
the parenchymal cells, there has been a growing realization that
stromal cells and neoplastic cells carry on a two-way conversation
that influences the growth of the tumor.
1.Parenchyma 2. Stroma
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.
Parenchyma: Animal tissue that constitutes the essential part of an organ as contrasted with, e.g., connective tissue & blood vessels.

4. Characteristics of Neoplasms
Benign & Malignant tumors
There are four fundamental features by which benign and malignant tumors can be
distinguished:
1. Differentiation and anaplasia, (Cytomorphology)
2. Rate of growth,
3. Local invasion (Direct Spread), and
4. Metastasis (Distant Spread).
The characteristics of tumours are described under the following headings:
I.Rate of growth
II. Cancer phenotype and stem cells
III. Clinical and gross features
IV. Microscopic features
V. Local invasion (Direct spread)
VI. Metastasis (Distant spread).

5. Characteristics of Neoplasms
1. Differentiation and Anaplasia
Differentiation and anaplasia are characteristics seen
only in the parenchymal cells that constitute the
transformed elements of neoplasms.
The differentiation of parenchymal tumor cells refers to the
extent to which they resemble their normal forebears
morphologically and functionally.
Cytomorphology of neoplastic cells

6. Characteristics of Benign Neoplasms
Benign neoplasms are composed of well-differentiated
cells that closely resemble their normal
counterparts (e.g., Lipoma, chondroma).
In well-differentiated benign tumors, mitoses are
usually rare and are of normal configuration.

7. Characteristics of Malignant Neoplasms
Malignant neoplasms are characterized by a wide range of
parenchymal cell differentiation, from surprisingly well
differentiated (adenocarcinoma of thyroid) to completely
undifferentiated (rhabdomyosarcoma). Between the two
extremes lie tumors loosely referred to as moderately well
differentiated.
Variable: Well-differentiated, moderately differentiated and poorly or undifferentiated.

8. Desmoplasia
• Desmoplasia: Certain cancers
induce a dense, abundant fibrous
stroma (desmoplasia), making
them hard, so-called
scirrhous tumors e.g.
infiltrating duct carcinoma breast
, linitis plastica of the stomach.
Desmoplasia originates from the Ancient Greek desmos,
"knot", "bond" and plasis, "formation". It is usually used in
the description of desmoplastic small round cell tumors.
If the epithelial tumour is almost entirely composed of
parenchymal cells, it is called medullary

9. Anaplasia: Lack of differentiation
Malignant neoplasms that are composed of
undifferentiated cells are said to be anaplastic.
Lack of differentiation, or anaplasia, is considered a
hallmark of malignancy. The term anaplasia literally
means “backward formation”—implying
dedifferentiation, or loss of the structural and
functional differentiation of normal cells.
Anaplasia, Undifferentiation, dedifferentiation, loss of differentiation,
lack of differentiation

10. Anaplasia
Anaplastic cells display marked pleomorphism
(i.e., variation in size and shape). Often the nuclei are
extremely hyperchromatic (dark-staining) and
large resulting in an
increased nuclear-to-cytoplasmic
ratio that may approach 1 : 1 instead of the normal 1
: 4 or 1 : 6.
Giant cells that are considerably larger than their
neighbors may be formed and possess either one
enormous nucleus or several nuclei.
Pleomorphism, hyperchromatism, increased nuclear to cytoplasm ratio, Giant cells

11. Anaplasia
Anaplastic nuclei are variable and bizarre in size and shape.
The chromatin is coarse and clumped, and nucleoli
may be of astounding size.
More important, mitoses often are numerous and distinctly
atypical; anarchic multiple spindles may produce
tripolar or quadripolar mitotic figures.
Also, anaplastic cells usually fail to develop recognizable
patterns of orientation to one another (i.e., they lose
normal basal polarity).
They may grow in sheets, with total loss of communal
structures, such as glands or stratified squamous
architecture.

14. Dysplasia
• Dysplasia (from the Greek δυσπλασία
"malformation", δυσ- "mal-" + πλάθω "to create, to
form"), is a term used in pathology to refer to an
abnormality of development.
• Dysplasia is a term that literally means disordered
growth.
It is a loss in the uniformity of individual cells and in
their architectural orientation.
Dysplasia often occurs in metaplastic epithelium, but
not all metaplastic epithelium is also dysplastic

15. Microscopic changes
• Dysplasia is characterised by four major
pathological microscopic changes:
1. Anisocytosis (cells of unequal size)
2. Poikilocytosis (abnormally shaped cells)
3. Hyperchromatism (excessive pigmentation)
4. Presence of mitotic figures (an unusual
number of cells which are currently dividing).

16. Dysplasia
In dysplastic stratified squamous epithelium, mitoses
are not confined to the basal layers, where they
normally occur, but may be seen at all levels and
even in surface cells.

17. Dysplasia vs. carcinoma in situ vs.
invasive carcinoma
• These terms are related since they represent the
three steps in the progression of many
malignant neoplasms (cancers) of epithelial tissues.
• The likelihood of developing carcinoma is related to
the degree of dysplasia.
1. Dysplasia 2. Carcinoma In-situ 3. Invasive Carcinoma

18. Dysplasia
• Dysplasia is the earliest form of pre-cancerous
lesion which pathologists can recognize in a pap
smear or in a biopsy.
• Dysplasia can be low grade or high grade.
A Pap smear, also called a Pap test, is a procedure to test for cervical cancer in women.
The Papanicolaou test is a method of cervical screening used to detect potentially pre-cancerous
and cancerous processes in the cervix.
Dr. George Nicholaus Papanicolaou.

19. Dysplasia
• The risk of low grade dysplasia transforming into
high grade dysplasia, and eventually cancer, is low.
• High grade dysplasia represents a more advanced
progression towards malignant transformation.

20. Dysplastic changes are often found adjacent to foci
of invasive carcinoma, and in some situations, such
as in long-term cigarette smokers and persons with
Barrett esophagus, severe epithelial dysplasia
frequently antedates the appearance of cancer.
However, dysplasia does not necessarily progress
to cancer.
Dysplasia

21. • Mild to moderate changes that do not involve the
entire thickness of epithelium may be reversible,
and with removal of the inciting causes the
epithelium may revert to normal.
Even carcinoma in situ may take years to become
invasive.
Dysplasia

22. • When dysplastic changes are marked and involve
the entire thickness of the epithelium but the
lesion remains confined by the basement
membrane, it is considered a preinvasive
neoplasm and is referred to as carcinoma in situ
• Once the tumor cells breach the basement
membrane, the tumor is said to be invasive.
Dysplasia- Carcinoma in-situ

23. CIN or CIS
Epithelial dysplasia of the cervix (cervical
intraepithelial neoplasia (CIN) – a disorder
commonly detected by an abnormal pap smear)
consists of an increased population of immature
(basal-like) cells which are restricted to the mucosal
surface, and have not invaded through the
basement membrane to the deeper soft tissues.
Carcinoma in-situ

24. Dysplasia- Invasive carcinoma
• Invasive carcinoma is the final step in this sequence.
It is a cancer which has invaded beyond the
basement membrane and has potential to
metastasize.
1. Dysplasia 2. Carcinoma In-situ 3. Invasive Carcinoma

25. Normal Stratified Squamous Epithelium 1/3 ep CIN I 2/3ep CIN II 3/3ep CIN III Invas. Ca
I.Dysplasia II.CIS III. Inv. Ca
Normal
CIN I CIN II CIN III Inv. Ca
Stratified Squamous Epithelium of Cervix

26. 2. Rate of Growth
Most benign tumors grow slowly, and most cancers grow
much faster, eventually spreading locally and to distant
sites (metastasizing) and causing death.
There are many exceptions to this generalization,
however, and some benign tumors grow more rapidly
than some cancers. For example, the rate of growth of
leiomyomas (benign smooth muscle tumors) of the uterus is
influenced by the circulating levels of estrogens. They
may increase rapidly in size during pregnancy and
then cease growing, becoming largely fibrocalcific, after
menopause.

27. Rate of Growth
The rate at which the tumour enlarges depends upon 2 main
factors:
1. Rate of cell production, growth fraction and rate of cell loss
2. Degree of differentiation of the tumour.
1. Rate of cell production, growth fraction and rate of cell loss.
Rate of growth of a tumour depends upon 3 important parameters:
i) doubling time (mitotic rate) of tumour cells,
ii) number of cells remaining in proliferative pool (growth fraction), and
iii) rate of loss of tumour cells by cell shedding.

28. Rate of growth
The rate of growth of malignant tumors usually
correlates inversely with their level of
differentiation.
In other words, poorly differentiated tumors tend to
grow more rapidly than do well-differentiated
tumors. However, there is wide variation in the rate
of growth.

29. Rate of growth
Other influences, such as adequacy of blood supply or
pressure constraints, also may affect the growth
rate of benign tumors.
Adenomas of the pituitary gland locked into the sella
turcica have been observed to shrink suddenly.
Presumably, they undergo a wave of necrosis as
progressive enlargement compresses their blood
supply.

30. 3. Local Invasion= direct spread
A benign neoplasm remains localized at its site of
origin. It does not have the capacity to infiltrate,
invade, or metastasize to distant sites, as do
malignant neoplasms.
Benign tumors are encapsulated but not all benign
neoplasms are encapsulated (e.g. Leiomyoma).
Cancers grow by progressive infiltration,
invasion, destruction, and penetration of the
surrounding tissue.
Two of the cardinal clinical features of malignant tumours are:
invasiveness and metastasis

31. 4. Metastases=Distant Spread
Metastases are secondary implants of a tumor that are
discontinuous with the primary tumor and located in remote
tissues.
More than any other attribute, the property of metastasis
identifies a neoplasm as malignant. Not all cancers have
equivalent ability to metastasize, however.
At one extreme are basal cell carcinomas of the skin and most
primary tumors of the central nervous system, which are
highly invasive locally but rarely metastasize.
At the other extreme are osteogenic (bone) sarcomas, which usually
have metastasized to the lungs at the time of initial
discovery.
Two of the cardinal clinical features of malignant tumours are:
invasiveness and metastasis

32. Routes of Metastasis
Malignant neoplasms disseminate by one of three
pathways:
1. seeding within body cavities,
2. lymphaticspread, or
3. hematogenousspread.

33. Spread by seeding within body cavities
SPREAD ALONG BODY CAVITIES and NATURAL PASSAGES.
i) Transcoelomic spread (Spread along body cavities).
ii) Spread along epithelium-lined surfaces.
iii) Spread via cerebrospinal fluid (CSF).
iv) Implantation.
COELOM: A cavity in the mesoderm of an embryo that
gives rise in humans to pleural cavity, pericardial cavity &
peritoneal cavity.

34. 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.
Peritoneal cavity is involved most often, but
occasionally pleural and pericardial cavities are also
affected.
A few examples of transcoelomic spread are as
follows:

35. Transcoelomic spread
a) Carcinoma of the stomach seeding to both ovaries
(Krukenberg tumour).
b) Carcinoma of the ovary spreading to the entire peritoneal
cavity without infiltrating the underlying organs.
c) Pseudomyxoma peritonei is the gelatinous coating of the
peritoneum from mucin-secreting carcinoma of the ovary or
apppendix.
d) Carcinoma of the bronchus and breast seeding to the pleura
and pericardium.

36. 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.
However, exceptionally a malignant tumour may spread
through:
a) the fallopian tube from the endometrium to the ovaries or
vice-versa;
b) through the bronchus into alveoli; and
c) through the ureters from the kidneys into lower urinary
tract.
Fallopian tube, Bronchus, Ureter

37. iii) Spread via cerebrospinal fluid (CSF)
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.

38. iv) Implantation.
Rarely, a tumour may spread by implantation by
surgeon’s scalpel, needles, sutures, or may
be implanted by direct contact such as transfer
of cancer of the lower lip to the apposing
upper lip.

39. Lymphatic & Hematogenous Spread
Lymphatic spread is more typical of carcinomas,
whereas hematogenous spread is favored by
sarcomas.
There are numerous interconnections, however,
between the lymphatic and vascular systems, so all
forms of cancer may disseminate through either or
both systems.

40. Lymphatic Spread
• The pattern of lymph node involvement depends
principally on the site of the primary neoplasm
and the natural pathways of local lymphatic
drainage.
• Lung carcinomas arising in the respiratory passages
metastasize first to the regional bronchial lymph
nodes and then to the tracheobronchial and hilar
nodes.

41. Lymphatic Spread
Carcinoma of the breast usually arises in the upper
outer quadrant and first spreads to the axillary nodes.
However, medial breast lesions may drain through the
chest wall to the nodes along the internal mammary
artery. Thereafter, in both instances, the
supraclavicular and infraclavicular nodes may be
seeded.

42. Lymphatic Spread- Skip Metastasis
In some cases, the cancer cells seem to traverse the
lymphatic channels within the immediately
proximate nodes to be trapped in subsequent
lymph nodes, producing so-called skip metastases.
The cells may traverse all of the lymph nodes
ultimately to reach the vascular compartment by
way of the thoracic duct.

43. Lymphatic Spread: Sentinel Lymph node
A “sentinel lymph node” is the first regional
lymph node that receives lymph flow from a
primary tumor.
It can be identified by injection of blue dyes or
radiolabeled tracers near the primary tumor.
Biopsy of sentinel lymph nodes allows determination
of the extent of spread of tumor and can be used
to plan treatment.
Sentinel Lymph Node

44. Hematogenous Spread
Hematogenous spread is the favored pathway for
sarcomas, but carcinomas use it as well. As
might be expected, arteries are penetrated less
readily than are veins.
With venous invasion, the blood-borne cells follow
the venous flow draining the site of the neoplasm,
with tumor cells often stopping in the first capillary
bed they encounter.

45. Hematogenous Spread
Since all portal area drainage flows to the liver, and all
caval blood flows to the lungs, the liver and lungs are the
most frequently involved secondary sites in
hematogenous dissemination.
Cancers arising near the vertebral column often embolize
through the paravertebral plexus; this pathway
probably is involved in the frequent vertebral
metastases of carcinomas of the thyroid and prostate.
The most frequently involved secondary sites in hematogenous dissemination are Liver
& Lungs.

46. Hematogenous Spread
Certain carcinomas have a propensity to grow within
veins.
Renal cell carcinoma often invades the renal vein to grow
in a snakelike fashion up the inferior vena cava,
sometimes reaching the right side of the heart.
Hepatocellular carcinomas often penetrate portal and
hepatic radicles to grow within them into the main
venous channels.
Remarkably, such intravenous growth may not be
accompanied by widespread dissemination.

47. Hematogenous Spread
Many observations suggest that the anatomic
localization of a neoplasm and its venous drainage
cannot wholly explain the systemic distributions of
metastases.
For example, prostatic carcinoma preferentially
spreads to bone, bronchogenic carcinomas tend to
involve the adrenals and the brain, and
neuroblastomas spread to the liver and bones.
Conversely, skeletal muscles, although rich in
capillaries, are rarely the site of secondary deposits.

48. Gross or Macroscopic features
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.

49. MICROSCOPIC FEATURES
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:
1. Microscopic pattern;
2. Cytomorphology of neoplastic cells (differentiation and anaplasia);
3. Tumour angiogenesis and stroma; and
4. Inflammatory reaction.

50. 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

51. 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 such as
 hyaline material in leiomyoma,
 cartilaginous matrix in chondroma,
 osteoid in osteosarcoma,
 reticulin network in soft tissue sarcomas etc.

52. 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.

53. Medullary Carcinoma
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.

54. Desmoplasia
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 , linitis plastica of the stomach.

55. 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.

56. However, some tumours show chronic inflammatory
reaction, chiefly of lymphocytes, plasma cells and
macrophages, and in some instances
granulomatous reaction, in the absence of
ulceration. This is due to cell-mediated
immunologic response by the host in an attempt to
destroy the tumour. In some cases, such an immune
response improves the prognosis.

57. The examples of such reaction are:
Seminoma testis,
Malignant melanoma of the skin,
Lymphoepithelioma of the throat,
 Medullary carcinoma of the breast,
Choriocarcinoma,
Warthin’s tumour of salivary glands etc.

61. THANKS
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