CHARACTERISTICS

OF
BENIGN
AND
MALIGNANT NEOPLASMS
Overview
 Characteristics of neoplasms compared to normal tissues
 Rate of growth
 Size
 Cellular differentiation
 Anaplasia
 Local invasion
 Microscopic features
 Metastases
 Pathways of spread
1. Rate of Growth:

Malignant neoplasms generally grow more rapidly

than benign ones, but there is no critical rate that
distinguishes malignant from benign.

Assessment of the growth rate is based upon:

-Clinical information (eg, change in size of the mass
in serial examinations).
-Histology (increased mitoses, atypical mitoses)
.
2. Size:

The size of a neoplasm usually has no bearing on its biologic

behavior.
Many benign neoplasms become very large; conversely,
highly malignant neoplasms may be lethal by virtue of
extensive dissemination even though the original primary
tumor is still small.
In a few neoplasms (such as endocrine neoplasms),
however, size is the deciding factor in distinguishing benign
from malignant growths.
3. Degree of Differentiation:

Denotes the degree to which a neoplastic cell resembles the

normal mature cells of the tissue in question; this meaning is
distinct from the more general use of the word to describe
passage of a cell down a particular maturation pathway.
Benign neoplasms are fully (well) differentiated, i.e. they closely
resemble normal tissue.
Malignant neoplasms, show variable degrees of differentiation
and frequently demonstrate little resemblance to normal tissue
(i.e. they are poorly differentiated).
Differentiation
Resembles adult tissue in
 Cell morphology
 Architecture
 Function
Cellular differentiation
 Tumors are often “graded” as to how closely they resemble
the normal parent tissue that they are derived from.
 Well-differentiated means the cells are very similar in
appearance and architectural arrangement to normal tissue
of that organ
Differentiation
 “Poorly-differentiated” refers to tumors that show only
minimal resemblance to the normal parent tissue they are
derived from.
 “Anaplastic” means the tumor shows no obvious similarity
to it’s parent tissue, usually associated with aggressive
behavior
So what??????
 Differentiation often provides clues as to the clinical
aggressiveness of the tumor
 Tumors often lose differentiation features over time as they become
more “malignant” and as they acquire more cumulative genetic
mutations
 Differentiation often predicts responsiveness to certain therapies,
eg estrogen receptors and Tamoxifen in breast cancers
 ANAPLASIA:
In anaplasia, the neoplastic cells have no morphologic
resemblance whatsoever to normal tissue.

The importance of these individual criteria varies with

different neoplasms. For example, the mitotic rate is the
major factor distinguishing benign from malignant smooth
muscle neoplasms in the uterus; in many other neoplasms,
the mitotic rate is of little relevance.
 Microscopic features of tumors
 Loss of normal architectural arrangement –
The malignant looking tumor cell
has;
Increased nuclear size
Increased nuclear/cytoplasmic ratio
Hyperchromatic nucleus
Coarsening of chromatin
Wrinkled nuclear edges
Multinucleation
Prominent/Macronucleoli
Numerous and bizarre mitotic figures
Failure to mature along normal functional lines
Cells of widely varying sizes
Loss of orientation of cells to one another
 Microscopic features of tumors
 Pleomorphism – variation in size and shape
of cells within the neoplasm
Microscopic features of tumors
 Mitotic activity - Increased in more malignant
tumors and often abnormal in shape
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.
 4. Changes in Deoxyribonucleic Acid
(DNA):

 Neoplasms are associated with abnormalities in their DNA

content; this abnormality increases with the degree of
malignancy.
 The degree of hyperchromatism (increased staining of the
nucleus) provides a crude assessment of DNA content on
microscopic examination; malignant cells are
hyperchromatic.
 When measured precisely by flow cytometry, the DNA
content of malignant cells correlates well with the degree of
malignancy in malignant lymphoma, bladder neoplasms, and
astrocytic neoplasms.
 Metaplasia, dysplasia, neoplasia
 Metaplasia – an adaptive
change in differentiation,
reversible, no mutations
necessary.
 e.g- change of esophageal
mucosa from squamous to
gastric type in the setting
of acid reflux
(“heartburn”). Better able
to withstand the corrosive
effects of the acid.
 Metaplasia is fertile
ground for development of
“dysplasia” (disordered
growth)
Metaplasia, dysplasia, neoplasia
 Dysplasia refers to recognizable morphologic changes in cells
that indicate the presence of genetic mutations beginning the
development of a neoplasm
 Often graded, eg PAP smears for uterine cervical cancer are low
and high grade (carcinoma in situ)
This is the next step toward neoplasia. Here, there is normal cervical
squamous epithelium at the left, but dysplastic squamous epithelium
at the right. Dysplasia is a disorderly growth of epithelium, but still
confined to the epithelium. Dysplasia is still reversible.
5. Infiltration and Invasion:

Benign neoplasms are generally non-infiltrative and are

surrounded by a capsule of compressed and fibrotic
normal tissue.
Malignant neoplasms, have infiltrating margins. Some
exceptions to this rule exist, and some benign
neoplasms (eg, granular cell tumor, dermatofibroma,
and carcinoid tumors) lack a capsule and have an
infiltrative margin.
Gross (macroscopic)
features of two breast
neoplasms
Benign – circumscribed,
often encapsulated,
pushes normal tissue
aside

Malignant – infiltrative
growth, no capsule,
destructive of normal
tissues
 Malignant
neoplasms are also
characterized by
the tendency to
invade
surrounding
tissues. Here, a
lung cancer is
seen to be
spreading along
the bronchi into
the surrounding
6. Metastasis:

The occurrence of metastasis (noncontiguous or

distant growth of tumor) is absolute evidence of
malignancy.

The major reason for distinguishing benign from

malignant neoplasms is to be able to predict their
ability to metastasize before they do so.
 Metastasis…..

Gross and microscopic examination of a neoplasm usually

enables a trained pathologist to classify most neoplasms as
benign or malignant.

In some instances, however, this identification is difficult,

and the only reliable evidence of a neoplasm's biologic
behavior is the occurrence of metastasis; about 90% of
pheochromocytomas are benign, but there are no reliable
criteria for identifying the 10% that will metastasize.
Metastases—metastatic cascade
 70% of newly diagnosed cancers have
metastases
 Millions of tumour cells circulate daily
 Less than 0.01% initiate colonies

1. Adhere to endothelium: fibrin platelets, clotting factors,

receptors basement membrane
2. Dissolve basement membrane: proteases, collagenases
IV, cathepsins
3. Locomotion: initiation (random), directed by autocrine
and host growth factors
Site of metastases
Anatomic factors
 Sarcoma: ˛ lung ˛ general circulation
 Carcinoma: ˛local lymph nodes ˛ lung, bone, brain
 GI primary: ˛ liver
 Prostate, breast: ˛ local venous plexus
 Ovary: ˛ peritoneum

Humoral factors (homing, soil)

 Local; preferential adhesion, preferential growth, local
diffusion of attractants (migratory directors)
 Pathways of Spread
 Lymphatic spread: permeate lymphatics,
metastasize to lymph node (sentinel LN, skip
metastases)
 Hematogenous spread: anatomical location,
portal (liver)/ systemic (lung), venous, typical of
sarcomas
 Intracavity: meningeal, serosal cavity
(peritoneal, pleural, pericardial, subarachnoid)
 Neoplasms can spread by seeding along body cavities, and this
pattern is more typical for carcinomas than other neoplasms.
 Note the multitude of small tan tumor nodules seen over the
peritoneal surface of the mesentery shown here.
Both lymphatic and hematogenous spread of malignant neoplasms is
possible to distant sites.
Here, a breast carcinoma has spread to a lymphatic in the lung.
 Effects of cancer
 Expansion- compression of surrounding tissue, forming
pseudocapsule
 Local invasion (infiltration):
 Follow lines of least resistence
 Damages or obstruct critical/surrounding structures
 Alters function
 Makes excision difficult
 Causes pain- infiltrate nerves
 Infarct
 Ulcerate- infected
 Bleeding
 Cachexia and Paraneoplastic syndromes
 Summary
 Benign and malignant tumors can be
distinguished on the basis of degree of
differentiation, rate of growth, local
invasiveness and distant spread.
 Benign tumors resemble the tissue of
origin and are well differentiated;
malignant tumors differentiation varies
from less well differentiated to
undifferentiated.
 Benign tumors usually retain function of
the cell of origin; malignant tumors may
acquire unexpected functions.
 In most tumors its behaviour can be predicted on the basis
of gross features and histologic findings.
 Metastases is an absolute evidence of malignancy.
MCQ’s
1- 44 year old women consult her physician for
lumps right breast and in the right axilla. On
examination physician noted hard lump in the
right breast and enlarged, firm, nontender right
axillary lymph nodes. Which of the following is
the most likely diagnosis?
 a. Ductal carcinoma of the breast
 b. Acute mastitis with breast abscess
 c. Leiomyosarcoma of the uterus
 d. Cerebral glioblastoma multiforme
 e. Fibroadenoma breast
 MCQ’s..Answer
1- 44 year old women consult her physician for
lumps right breast and in the right axilla. On
examination physician noted hard lump in the
right breast and enlarged, firm, nontender right
axillary lymph nodes. Which of the following is
the most likely diagnosis?
 a. Ductal carcinoma of the breast
 b. Acute mastitis with breast abscess
 c. Leiomyosarcoma of the uterus
 d. Cerebral glioblastoma multiforme
 e. Fibroadenoma breast
SEQ’S
 1- Define Leiomyoma uterus. Describe its
differentiating biological and morphological
features from Leiomyosarcoma.
SEQ’s..Answer
 Small size
 Well demarcated
 Slow growing
 Well differentiated
 Non-invasive
 Non-metastasising
 No/rare mitoses, no necrosis
SEQ’s
 2-What are the various microscopic nuclear changes seen
in a malignant cell?
 SEQ’s..Answer
 Increased nuclear size
 Increased N/C ratio
 Hyperchromatic
 Coarse chromatin
 Irregular nuclear membrane
 Macronucleoli
 Increased number of mitoses
 Bizarre/ Atypical mitoses
SEQ’s
 1- a) Define metastasis.
b) Describe pathways of dissemination of cancer.
 a) Metastasis is defined as spread of a tumor to sites that
are discontinuous with the primary tumor.
 b) 1. Direct seeding of body cavities or surfaces.
2. Lymphatic spread
3. Hematogenous spread