Transcript Neoplasia (Dr. Ismiil)

NEOPLASIA
Nadia Ismiil, MD, FRCPC



Neoplasia: “New Growth” and a new
growth is called “neoplasm”
Oncology: The study of tumors or
neoplasms
Cancer: Malignant Tumor
Neoplasm


An abnormal mass of tissue, the
growth of which exceeds and is
uncoordinated with that of the normal
tissues and persists in the same
excessive manner after cessation of
the stimuli which evoked the change
The persistence of tumors, even after
the inciting stimulus is gone, results
from heritable genetic alterations that
are passed down to the progeny of the
tumor cells


These genetic changes allow excessive
and unregulated proliferation that
becomes autonomous, although
tumors generally remain dependant
on the host for their nutrition and
blood supply
The entire population of cells within a
tumor arises from a single cell that
has incurred genetic change, and
hence tumors are said to be clonal

All tumors benign and malignant
have two basic components:
1. Proliferating neoplastic cells that
constitute their parenchyma
2. Supportive stroma made up of
connective tissue and blood vessels


Benign tumors are generally
designated by attaching “oma” to the
cell of origin, e.g. Tumor of Fibrous
tissue is “fibroma.”
This is generally true to tumors of
stromal origin


Nomenclature of Benign tumors of
epithelial origin is more complex. The
suffix “oma” may follow cell of origin,
microscopic or macroscopic features.
A benign cystic tumor is
“cystadenoma”, a papillary tumor is
“papilloma”


The nomenclature of malignant
tumors follows the same schema.
Malignant tumors of the connective
tissue are called “sarcoma”.
Examples include fibrosarcoma for
malignancy of the fibrous tissue and
liposarcoma for malignancy of the
adipose tissue.


Malignant tumors of epithelial cell
origin , derived from any of the three
germ cell layers are called
“carcinoma”, ectodermal, mesoderm
or endoderm.
Examples include squamous cell
carcinoma and adenocarcinoma.






The natural history of most malignant
tumors can be divided into four phases:
Transformation which is the malignant
change happening in the target cell.
Growth of the transformed cell.
Local invasion
Distant metastases.
The differences between benign and
malignant tumors correspond to these
characteristics.
Colonic polyp, benign
Metastatic carcinoma of the liver
Differentiation



The extent to which the neoplastic
cells resemble comparable normal
cells, both morphologically and
functionally.
Benign and well differentiated
malignant tumors are composed of
cells resembling the cells of origin.
Poorly differentiated tumors have
primitive unspecialized cells.
differentiation



Leiomyoma is a benign tumor of the
smooth muscle. Can be seen in
uterine fibroids.
The tumor cells closely resemble the
cells of origin that it may be
impossible to recognize it as a tumor
microscopically.
The only way to recognize it , is
because it forms a mass.
Leiomyoma, gross and microscopy
Anaplasia




Definition: Lack of differentiation.
Malignant tumors may be well
differentiated.
Malignant tumors may be anaplastic,
ie, undifferentiated. The cells are
primitive.
There is mounting evidence that in
most cancers, the cells of origin is a
stem cell (an undifferentiated cell).
Anaplasia


In well differentiated cancers, the
stem cells will undergo specialization
and maturation first then undergo
malignant transformation.
In undifferentiated cancers, the stem
cell stem cell will proliferate directly
without undergoing the cycle of
maturation first.
Anaplasia



It is marked by a number of morphologic
changes:
Pleomorphism, variation in size and shape.
It applies to the cells and nuclei.
Abnormal nuclear morphology: high
nuclear cytoplasmic ratio,
hyperchromatism (abundance of DNA),
variability of the nuclear shape and
prominence of the nucleoli.
Anaplasia (cont.)

Mitoses: large number of mitoses
reflecting the high proliferative
index. Its presence by itself is not
diagnostic of malignancy since
mitoses can be seen in benign
tumors. However, the presence of
abnormal mitoses is indicative of
malignancy.
Anaplasia (cont)


Loss of polarity: The orientation of
the malignant cells is markedly
disturbed.
Other changes, presence of giant
cells is an example. These may al;so
be present in inflammatory
conditions.
Anaplasia
Dysplasia




Definition: disordered growth.
Encountered principally in epithelia
such as cervix and esophagus.
Characterized by constellation of
changes that include loss of
uniformity of the individual cells and
loss in their architectural orientation.
The dysplastic cells are pleomorphic,
high N/C ratio and lots of mitoses.
Dysplasia (cont)




When dysplastic changes involve the
entire thickness of the epithelium, they
are considered peri-invasive tumors with
no invasion (yet). The process is called
carcinoma in situ.
Dysplasia may be found next to an
invasive cancer.
The detection of early dysplastic changes
in cervix by pap smear is one of the
greatest success stories in medicine.
Dysplastic changes in esophagus can be
seen in cigarette smokers.
Cervical dysplasia
Dysplasia in the intestinal epithelium
Genetic predisposition to cancer


Evidence now indicates that for a
large number of cancer types, there
exists not only an environmental
influences but also hereditary
predisposition.
Less than 10% of cancer patients
have inherited mutations that
predispose to cancer.
Continued


Genetic predisposition to cancer can
be divided into three categories:
Autosomal dominant inherited cancer
syndrome, in which the inheritance
of a single mutant gene increases
the risk of developing a tumor.
Retinoblastoma, a malignant tumor
of the eye is an example.
Continued


Defective DNA repair syndrome. There will
be a defect in the repair process leading to
DNA instability. Example is hereditary non
polypoid cancer syndrome (HNPCC).
Familial cancers. Cancer may occur more
frequently in some families, so far non
clearly defined pattern. Example, breast,
colon and ovarian cancer.
Molecular basis of cancer


Non lethal genetic damage lies at the
heart of carcinogenesis.Such genetic
damage (mutation) may be environmental
such as chemicals, radiation or viruses or
may be inherited in the germ line.
A tumor is formed by the clonal expansion
of a single precursor cell that has incurred
the genetic damage, tumors are
monoclonal.
continued

Four classes of regulatory genes, the
growth promoting protooncogenes,
the growth inhibiting tumor
suppressor genes, genes that
regulate apoptosis and genes
involved in DNA repair ARE THE
PRINCIPLE TARGETS OF GENETIC
DAMAGE.
Molecular basis of cancer

WHAT ARE THE ESSENTIAL
ALTERATIONS FOR MALIGNANT
TRNSFORMATION??





1.Self sufficiency in growth signals ,
tumors have the capacity to
proliferate without external stimuli.
2.Insensitivity to growth inhibiting
signals.
3.Evasion of apoptosis
4.Defects in DNA repair
5.limitless replicative potential


6. Sustained angiogenesis, vascular
supply.
7.ability to invade and metastasize
Examples of occupational
associated cancers




Asbestos: lung mesothelioma
Nickel: nose and lung cancer
Vinyl chloride: liver tumors
Ethylene oxide: Leukemia
Lung cancer