2018. 10. 14.

Oncology
Livia Vida 2018

Definitions
Tumors (neoplasms) may be considered
new, useless tissues. Neo-plasm means
new growth.
Cancers (malignant neoplasms) invade
and spread to remote sites (metastasize).
The original tumor is called the PRIMARY.
Benign tumors cannot invade or spread to
remote sites, but they can cause problems
by compressing local structures.
Tumors arise from a single cell (it is one
clone), and they recapitulate, more or
less, the things that cell did in health. The
cell of origin gives its name to the tumor. Figure from the article of 1851 of Rudolf Virchow headed, “The endogenous formation of
cells in cancer”. The original legend reads: “Epidermoid cancroid of the lip: 3 large rooms
for breeding with endogenous formations and a concentric wall, surrounded by nucleated,
flat epidermoid cells that, at the edge, have a striped appearance.”
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Benign vs malignanat tumors

• A tumor is either BENIGN or MALIGNANT.
• Benign: (1) A neoplasm that will
compress but not invade the surrounding
tissue. (2) Loosely, any non-cancer, non-
precancer diagnosis.
• Malignant: A neoplasm that will invade
the surround tissue. A synonym for
"malignant neoplasm" is "cancer". Most
types of cancer will also eventually spread
(metastasize) to remote sites; hence the
importance of timely detection and cure.

Characteristics of BENIGN ("good") tumors:

Cells resemble normal cells and tumor architecture resembles that of the
parent organ ("well-differentiated").
Usually are spherical and compress the surrounding tissues (giving rise to the
appearance of a "capsule")
Grow slowly and have few mitotic figures.
Never metastasize. (If it metastasizes, it has turned malignant.)
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Caracteristics of MALIGNANT tumors

• Malignant tumors generally grow more
rapidly than benign tumors.
• However, no malignant tumor grows as
rapidly as an embryo, nor do cancer cells
divide nearly as fast as cells in normal bone
marrow or intestinal epithelium.
• Cells differ morphologically and functionally
from normal cells, and tumor architecture is
less organized than that of parent tissue.
• Tumor cells are locally invasive; the tumor
grows into the surrounding tissue and
destroys it.
• The tumor will eventually metastasize,
spreading to another site remote from the
original tumor (exceptions: basal cell
carcinomas of skin, cancers of glial origin).
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Definitions
Cancers that arise from epithelium are called
"carcinomas". Cancers that arise from
mesenchyme/mesoderm are called
"sarcomas".
Most cancers arising from ectoderm and
endoderm are carcinomas, since these cells
primarily become surface epithelium and gland
parenchyma.
Cancers arising from mesoderm can be
carcinomas (i.e., adrenals, genitourinary),
sarcomas (solid connective tissue and all sorts
of muscle), or cells of hematopoietic origin
(leukemias, lymphomas).

Tumor characteristics
Tumors are LIKE organs:
• All have parenchyma and stroma.
• Cells usually look similar to cells in the organ where the
tumor arose.
• Cells will continue to perform some of the functions of the
parent organ and express most of the same proteins.
Tumors are DIFFERENT from organs:
• They don't contribute to the homeostasis of the body.
• They usually grow more rapidly than surrounding tissues.
• Some benign and all malignant tumors never cease to grow.
• Malignant tumors are locally invasive and have metastatic
potential.
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Grade and stage

• The grade of a cancer is a
function of how bizarre the
cells look. The higher the
grade, the more likely to
cancer is to behave
aggressively.
• The stage of a cancer is
how far the clinician knows
it has spread.

What do cancers look like?

• Macroscopy:
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What do cancers look like?

The malignant-looking cell has:
Increased nuclear DNA
increased nuclear/cytoplasmic ratio,
hyperchromatic nucleus,
coarsening of chromatin,
macronucleoli,
weird-shaped nucleoli.
Multinucleation is a marker for
cancer only if the nuclei within an
individual cell are obviously
different from one another.
Numerous and bizarre mitotic
figures.
Tripolar mitoses are only the most
familiar of the many weird patterns
you may see.

How will I see malignant

tumors invading?
1. Local infiltration
• Invasion of surrounding tissues
2. Intraepithelial spread is possible and may take the
form of single cells or of DYSPLASIA / CARCINOMA IN
SITU, in which an epithelial surface is replaced by a layer
of dysplastic cells that has not (yet) penetrated the
basement membrane.
3. Metastatic spread:
• Seeding of serosal surfaces
• Via lymphatics: tumors spread first to regional lymph
nodes, then (because of disruption of directions of
lymph flow) to any lymph nodes or organs
• Via blood vessels
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papilloma melanoma

Macroscopic basal cell carcinoma

epithelial lesions

SCC
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Tumor nomenclature – papilloma -carcinoma

Melanoma – basal cell carcinoma

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CARCINOGENESIS
• CARCINOGENESIS is a generic term for
a series of events leading up to
expression of full malignant potential.
• TRANSFORMATION is the term for this
process as applied to cells themselves.
• Tumors are CLONAL OVERGROWTHS,
generally monoclonal.
• By the time a tumor is visible, the
changes have been underway for a
long time (at least months, usually
years).

MULTI-STEP CLONAL EVOLUTION MODEL OF TUMORIGENESIS

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THE ABILITY TO INVADE AND SPREAD

• Self-sufficiency in growth signals. Tumors have the capacity to
proliferate without external stimuli, usually as a consequence of
oncogene activation.
• Insensitivity to growth-inhibitory signals. Tumors do not respond to
molecules that inhibit the proliferation of normal cells, usually
because of inactivation of tumor suppressor genes that encode
components of these growth inhibitory pathways.
• Altered cellular metabolism.
• Evasion of apoptosis.
• Limitless replicative potential (immortality).
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CHEMICAL CARCINOGENESIS
• Cyclophosphamide: Transitional epithelial (mostly bladder)
cancers
• Alkylaters: nitrogen mustard, bischloromethyl ether, benzyl
chloride
• Polycyclic hydrocarbons: Tobacco smoking-related cancers
• Azo dyes: Bladder cancer
• Aflatoxin: Eaters of moldy grain and peanuts
• Vinyl chloride
• Chromium, nickel
• Cadmium
• Asbestos
• Arsenic
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RADIATION CARCINOGENESIS
• Exposure to high-energy photons (ultraviolet,
ionizing radiation) is well-known as a cause of
cancer.
• Atomic bomb survivors (Japan) have greatly
increased incidences of all the common leukemias
(except CLL; the incubation time is a few years),
and minor increases in many (but not most) solid
tumors (thyroid, breast, salivary gland, lung).
• Nobody's shown an increased risk from living near
nuclear power plants.
• Ultraviolet radiation is the principal risk factor in
most skin cancers (basal cell, squamous cell,
malignant melanoma).

ONCOGENIC VIRUSES
• Wart virus ("human papilloma virus", HPV) causes warts ("benign tumors") in humans,
and certain strains cause cancer of the uterine cervix, vulva, and penis in humans.
• Epstein-Barr virus is necessary (but not sufficient) to cause Burkitt's lymphoma, and is
etiologic in nasopharyngeal cancer.
• Hepatitis B virus has been known for decades to be a major cause of hepatocellular
carcinoma. It became clear in the 1990's that hepatitis C virus is also important.
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P53 – The guardian of the genome

• The most common known genetic
injury in human cancer is damage to
the p53 (TP53) gene.
• The p53 gene product is a sequence-
specific binder to DNA that prevents
mitosis during times of cell injury, so
that there will be more time for DNA
repair. Sometimes p53 even tells an
injured cell to undergo apoptosis.

ONCOGENES
• By now, about 200 different proto-oncogenes
are known.
• Many proto-oncogenes are the genes for
hormone receptors, while others seem to be
general turn-ons.
• When a proto-oncogene is altered to become
an oncogene, we speak of its being ACTIVATED.
• This is by one of three mechanisms:
• POINT MUTATION: The gene product is probably
stuck on the "on" position ("gain of function").
• TRANSLOCATION: The gene product is under the
control of the wrong promoter, or a FUSION GENE
(half-one gene, half-another) produces a FUSION
GENE PRODUCT that promotes cell division.
• AMPLIFICATION: There are too many copies of the
gene. Sometimes there are so many copies that
"double minute" chromosomes are formed from
them
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