Neoplasia

objectives
• Define neoplasia
• Describe the NOMENCLATURE of benign
and malignant neoplasms
• Discuss the biology of tumor growth
• Define dysplasia and describe its
pathological features
 NEOPLASIA
• Why is it important to study of neoplasia?

•The terms “neoplasm” and “tumor” are

used interchangeably, why?

• There are three essential statements that

cover the definition of neoplasia, what are
they?

•What is the definition of stem cell (T-IC) in

the context of neoplasia.
 NEOPLASIA
• Neoplasm = a new growth/ interchangeable with Tumor
• Oncology (Gr. oncos = tumor): study of neoplasms
• Cancer: all malignant tumors
• Neoplasm:
- an abnormal tissue proliferation
- exceeds that of adjacent normal tissue
- Proliferation continues even after removing inciting stimulus
(Tumor autonomous)
Heritable genetic changes in stem cell (T-IC)

Progeny of tumor cells (growth advantage)

• Tumors, in general consists of
two basic components
a.what are they?
b.There is a mutual interest between them,
explain?

• Some tumors are describe as being

encephaloid whereas others are termed
scirrhous, what do these two terms
signify? Give one example of each.
 NOMENCLATURE
• Tumors c/o two basic components
1. Proliferating neoplastic cells
2. Stroma: CT + BVs: vital
Providing B. supply Offering support
Cross-talk with neoplastic cells influence growth
• Variable proportions of two components

Determines consistency

↑↑Neoplastic cells ↑↑fibrotic stroma

desoplasia: hard tumor
Soft/fleshy (encephaloid)

• Nomenclature based on neoplastic cells

• What does the designation “leiomyoma” refer to?

• What does the designation “rhabdomyosarcoma”

refer to?
• Characteristics of benign neoplasms include all
of the following EXCEPT
a. slow growth
b. resemblance to tissue of origin
c. circumscription
d. invasion
NOMENCLATURE OF
NEOPLASMS
A 14-year-old male complained of pain of his Lt. knee joint. A radiograph was
taken to the joint. It showed an abnormality of upper metaphysis of the tibia.
Describe*.

The mass was excised and displayed for you in the Rt photo. It was bony hard in
consistency. Describe the excised mass?
 This is another example of the
same tumor, but excised from a rib.
In what way it differs from the
previous lesion*?
whole-mount appearance of the lesion on the Lt and HP view of the
surface on the Rt. Describe. What you call this lesion?
 Chondroma

The tumor has lobules of benign-looking

chondrocytes
A 25-year-old female presented with a thyroid nodule. Hemithyroidectomy
performed. A cross section of the mass is shown below. Describe. What would you
expect the lesion to be on microscpic examination, benign or malignant? Why?

This is a benign tumor of the thyroid gland. It is surrounded by a thin white capsule.
This is a microscopic section from a similar mass. Describe
This is a section from another but similar lesion. Describe.
A 15-year-old boy had almost 50 resections of multiple laryngeal, tracheal and
bronchial lesions, beginning at seven years of age, and finally he died of
suffocation. Below are post-mortem specimens of the larynx & trachea displaying
the multiple abnormalities. Describe.
Below is a histological section of one of the lesions,
describe.
These are masses excised from the ovary (A & B), describe each.
How you name this neoplasm?

B
This is a microscopic section from one of the warty projections seen
in the gross specimen B. Describe
This is a part of the large intestine displaying multiple abnormalities, describe?
Below is a histological section from one of the polyps. Describe.
 NOMENCLATURE OF BENIGN TUMORS
• By attaching suffix -oma to cell of origin
• Tumors of mesenchymal cells follow this rule
-fibroma -chondroma -osteoma

• Benign epithelial tumors more complex

- variously classified according to

Cells of origin Microscopic &/or macroscopic

appearance
• Adenoma
1. Forming glandular structures e.g. Renal cell adenoma
Thyroid follicular adenoma
2. Tumors derived from glands but not necessarily
reproducing glandular structures e.g. Thyroid follicular
adenoma

• Papilloma: producing micro- or macro- visible finger-like

(warty) projections from epithelial surfaces, e.g. laryngeal
papilloma

• Cystadenoma: adenoma forming large cystic space (es) e.g.

ovarian cystadenoma
• Papillary cystadenoma as above + papillary projections e.g.
ovarian papillary cystadenoma
• Polyp: benign/producing macro. visible projection above mucosa e.g.
Adenomatous polyp of stomach & colon
.1Reversible disorderly maturation with
variability in size, shape, and polarity of cells is:

(A) metaplasia.
(B) dysplasia.
(C) anaplasia.
(U) hyperplasia.
(E) desmoplasia.
.1Reversible disorderly maturation with
variability in size, shape, and polarity of cells is:

(A) metaplasia.
(B) dysplasia.
(C) anaplasia.
(U) hyperplasia.
(E) desmoplasia.
A 70-year-old
female has had
for decades
slowly but
progressively
enlarging a mass
in the Rt parotid
area. What do
you think the
most-likely
possibility?
This is an identical
but smaller mass
removed together
with the related
parotid gland.
Describe
This is a histological section from the same tumor, describe.
Another area from the same tumor, what does it show?
 NOMENCLATURE OF MALIGNANT TUMORS
• Follows essentially same scheme used for benign neoplasms
+certain additions
• Sarcomas (Greek sar = fleshy:)
-malignant tumors arising from or differentiating towarsd
mesenchymal cells
- generally scant CT stroma fleshy consistency
• Nomenclature of sarcomas relies on either
a. cell of origin
b. differentiation
- fibrosarcoma (fibroblasts)
- liposarcoma (lipocytes)
- leiomyosarcoma (SMCs)
- rhabdomyosarcoma (striated muscle cells)
• Carcinoma: malignant neoplasm of epithelial cell origin derived from
any one of three germ layers
- arising in epidermal epithelial cells (ectoderm)
- derived from renal tubules (mesoderm)
- originating from epithelial cells line GIT (endoderm)
• Further qualified according to morphology e.g.
- with a glandular growth pattern: adenoca
- with squamous cells arising in any epithelium: squamous cell ca.
• Specify organ of origin e.g.
- Renal cell Ca.
- Bronchogenic squamous cell Ca.
Undifferentiated malignant tumor c/o undifferentiated cells (no
enough criteria to point to site of origin or differentiation

Mixed tumor: due to divergent differentiations of a single line of

neoplastic cells into other tissues e.g.

e.g. mixed tumor of salivary glands

Benign epithelial/myoepithelial cells

Squamous nests
glands/strands/sheets
scattered within Cartilage/bone
myxoid stroma

-They are in reality adenomas (pleomorphic adenoma)

A 20-year-old female presented with severe Rt iliac fossa pain, it was thought clinically that
she was having appendicitis. Instead an ovarian mass was discovered on laparotomy. The
mass as shown below showed externally a hemorrhagic dark red-blue wall. What do you
think had happened to the patient?* The photo to your right showed a cross section of the
same mass, describe?
This is a close up view of the mass after removing some of the sebum.
Describe the findings. What is your provisional diagnosis?
Histological sections from the ovarian tumor, describe. What is your
final dia nosis?
---------------------
Teratomas
- c/o of variety of neoplastic cell types representative of > one germ
layer/usually all the three
- Arise from totipotent cells (located in gonads)
- Gonads principal site
-Totipotent cells differentiate along various germ lines
producing different tissues

skin (ectodermal) muscle/fat (mesodermal) gut epith (endodermal)

-tooth/brain tissues/bronchial structures etc,

• A common example cystic teratoma (dermoid cyst)
- seen in ovary
- commonly cystic
- skin & adenexae predominant component
Melanoma skin
Testicular Seminoma
Hepatoma (Hepatocellular ca)

The neoplasm is large and bulky and has a greenish

cast because it contains bile. To the right of the main
mass are smaller satellite nodules.
• Inappropriate designations/do not follow above principles
-usage continues conventionally e.g.

Melanoma (melanocarcinoma)

Seminoma (type of testicular carcinoma)

Hepatoma (hepatocellular carcinoma)

Ectopic pancreas wall of jejunum (arrow)
 Ectopic pancreatic tissue esophagus

Figure 1.Nest of pancreatic acinar tissue

covered by squamous esophageal mucosa
(hematoxylin-eosin, original magnification
.)250×
Figure 2.Immunostaining for the pancreatic
exocrine component of PAT. Yellow-brown–
stained cells represent positive staining for
trypsin (A), lipase (B), and amylase (C)
●Identify the organ?
●Describe the pathological changes
Hamartoma: is a growth in an organ that is composed
of:
●Tissue elements normally found at that site, but
●Growing in a haphazard mass.
.3Which of the following terms refers to a
malignant tumor of mesenchymal tissue?

(A) Carcinoma.
(B) Choristoma.
(C) Hamartoma.
(D) Sarcoma.
(E) Teratoma.
.3Which of the following terms refers to a
malignant tumor of mesenchymal tissue?

(A) Carcinoma.
(B) Choristoma.
(C) Hamartoma.
(D) Sarcoma.
(E) Teratoma.
The microscopic appearance of a
neoplasm from a 58-year-old female is
shown in the figure. This neoplasm is
best described as a(an:)

(A)Adenoma.
(B)Well-differentiated
adenocarcinoma.

(C) Squamous cell carcinoma.

(D) Leiomyoma.
(E) Anaplastic carcinoma.
The microscopic appearance of a
neoplasm from a 58-year-old female is
shown in the figure. This neoplasm is
best described as a(an:)

(A)Adenoma.
(B)Well-differentiated
adenocarcinoma.

(C) Squamous cell carcinoma.

(D) Leiomyoma.
(E) Anaplastic carcinoma.
BIOLOGY OF TUMOR
GROWTH

Differentiation and anaplasia

 BIOLOGY OF TUMOR GROWTH
• Malignant tumors differ from benign ones by
natural history (expected behavior)

I. Malignant transformation

II. Growth rate

III. Local invasion

IV. istant metastases

What would you expect the
microscopic sections from this
tumor reveal?
 Leiomyoma uteri
Here is the microscopic appearance of
a benign leiomyoma. Normal
myometrium is at the left, and the
neoplasm is well-differentiated so that
the leiomyoma at the right hardly
appears different. Why?

Bundles of smooth muscle are

interlacing in the tumor mass.
Leiomyoma
A pedunculated mass 'vith soft, greasy feeling, attached to the serosa
of the small intestine. Below is a histological section. Describe.
Differentiation and anaplasia:
Differentiation signifies:
The extent to which neoplastic cells resembl comparable
normal cells. e

The degree of tumor differentiation is represented by a

spectrum according to which neoplasms are divided in to:

●Very well differentiate.

●Well differentiated.
●Moderately differentiated.
●Poorly differentiated.
●Undifferentiated (Anaplastic.)
I. MALIGNANT TRANSFORMATION
Well-differentiated squamous cell carcinoma of the skin
 Degrees of differentiation in various colonic tumors

Normal

adenoma

carcinoma
Poorly differentiated carcinoma

Very little evidence to suggest site of origin

 Undifferentiated (Anaplastic) Cancer

Complete loss of differentiation

(primitive cells.)

Frequent mitoses including abnormal

ones

Cells/nuclei show marked pleomorphism /

sometimes multinucleated tumor
giant cells

Extreme nuclear hyperchromasia

Marked nuclear enlargement N:C may

reach 1:1 (instead of 1:4 or )1:6

The chromatin is coarsely clumped and

irregularly distributed

Usually large, prominent nucleoli

Morphologic features of undifferentiated (anaplastic)
malignant cells include:
.1Pleomorphism:
variations in the size and shape of the neoplastic cells and
their nuclei.
In anaplastic cancers, some cancerous cells are many times
larger than their neighboring extremely small cancerous cells.
2.Abnormal nuclear morphology: characteristically the nuclei
display:
a. Hyperchromatism.
b. High nuclear-cytoplasmic ratio (high N/C.)
c.Variations in nuclear shape and abnormal chromatin
clumping and distribution.

d. Large prominent nucleoli.

.3Frequent mitoses including abnormal ones: Undifferentiated
malignant cells usually possess large number of mitoses,
reflecting their high proliferative activity.
The presence of mitoses, however, does not necessarily
indicate that a tumor is malignant or that the tissue is

neoplastic.
More important as a morphologic feature of malignancy is the
presence of atypical mitotic figures:
Tripolar, quadripolar, or multipolar mitoses (instead of the
normal bipolar spindles)
.4Loss of polarity:
This means disturbed orientation of the cells.
In malignancy, sheets of tumor cells grow in disorganized
fashion.
5. Other changes:
a. Formation of tumor giant cells.
Some of these abnormally large cells possess only a single huge
pleomorphic nucleus; others have two or more nuclei.
b. Foci of ischemic necrosis.
 Undifferentiated/Anaplastic Carcinoma

This neoplasm is so poorly differentiated that it is difficult to tell the cell of origin. Note that nucleoli
are numerous and large in this neoplasm. Neoplasms with no differentiation are designated anaplastic.
 Abnormal Mitoses

Here are three abnormal mitoses. Mitoses by themselves are not indicators of malignancy. However,
abnormal mitoses are highly indicative of malignancy. The marked pleomorphism and
hyperchromatism of surrounding cells also favors malignancy.
 Rhabdomyosarcoma

Pleomorphic rhabdomyosarcoma
showing prominent pleomorphism,
frankly malignant nuclei &
malignant multinucleated giant
cells.
Foci of ischemic necrosis
.4A biopsy of the stomach reveals an area of
normal-appearing pancreatic tissue. This is an
example of which of the following lesions?

(A) Adenoma.
(B) Choristoma.
(C) Hamartoma.
(D) Metastatic carcinoma.
(E) Teratoma.
4. A biopsy of the stomach reveals an area of
normal-appearing pancreatic tissue. This is an
example of which of the following lesions?

(A) Adenoma.
(B) Choristoma.
(C) Hamartoma.
(D) Metastatic carcinoma.
(E) Teratoma.
Dysplasia
This is a section from a laryngeal biopsy of a heavy smoker. What
type of epithelium is this? How does it differ from normal? Describe.
This is a similar lesion showing more severe changes. What is your
diagnosis?
Cervix uteri severe dysplasia amounting to carcinoma in situ
 DYSPLASIA
• “disordered growth”.
• encountered principally in epithelia
• characterized by
1. Pleomorphism
2. Loss of polarity
3. Nuclear Changes
a. hyperchromasia
b. ↑N/C
c. ↑Mitotic figures:
- Almost invariably normal
- Frequently appear in abnormal locations
• Mild/moderate/severe CIS invasion
• Dysplastic changes often found adjacent to foci of invasive ca
II. GROWTH RATE OF THE TRANSFORMED CELLS
The growth rate of neoplasms (i.e. how rapidly they increase
in size) influences:
●Their clinical outcome.
●Their response to therapy.
Neoplasms are now considered clonal i.e. originating from one
(or at most few) initially transformed cells (I-TC.)
For the tumor to be clinically detectable (at least 1 g in wt), the
I-TC and its progeny (collectively referred to as tumor cell
population) must undergo at least 30 population doublings.

By the time a solid tumor is clinically detected it has already

completed a major portion (75%) of its life cycle.
 Biology of tumor growth and evolution

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The growth rate of a tumor is determined by three main
factors:
1.The doubling time of tumor cells (length of the cell cycle.)
2.The size of. (Replicative pool refers to that part of the tumor
made up of exclusively of dividing cells.)
3. The rate at which cells leave the growing tumor.
As tumors continue to grow, cells leave the replicative pool
in ever-increasing numbers due to:
1. Shedding.
2. Necrosis due to lack of nutrients.
3. Apoptosis.
4. Differentiation.
5. Reversion to G.0
Schematic representation of tumor growth
 Practical lessons deduced from studies of tumor cell kinetics

.1 Fast-growing tumors: have a high cell turnover

-High rates of proliferation & apoptosis
-Rate of proliferation > rate of apoptosis ↑↑tumor growth

2. Growth fraction a determinant of susceptibility to chemotherapy*

3. GR correlates inversely with level of differentiation

-most malignant Ts grow > rapidly than benign Ts
4. Factors affecting GR include
a. Hormonal stimulation b. Blood supply c. unknown influences**
5. Cancers show wide variations of GR: dedifferentiation phenomenon
 CANCER STEM CELLS
• Cancer stem cell (T-IC) mitoses daughter cells (clonal)
Different./specialization heterogeneous cells

• Stem cells initiate & sustain tumor

• Cancer stem cells (T-IC)
- identified in breast cancers & AML
- constitute 1- 2% of cell population
- initial targets of neoplastic transformation
- have low rate of replication
- probably responsible for recurrence after treatment
END