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Neoplasia, means new growth.

Group of disorders that occur in various tissues in the


body that are the consequence of excessive uncontrolled or sometimes controlled mitosis.
These are mitotically active diseases in which normal cell cycle is accelerated.
Differentiated cells dont normally divide, unless they are injured and need to repair. No
wound in this case, no cause.

Proliferations into subcategories (any tissue that continues to grow):


1) Reactive proliferations, hyperplasias, increase in size of tissue due to increase in
mitotic activity, however, we can find a cause, and the cause is usually an irritant
and the host is reacting to that irritant by causing a proliferation of cells.
Example: lesion that occurs more commonly in women, if they get something
stuck in sulcus then that irritant causes the connective tissue to proliferate, get big
gum bump, pyogenic granuloma. Increase in fibroblasts, vascular channels,
laying down more collagen. Easily treated.
2) Neoplasms: just happen. Some cells decide to start proliferating. Clinical
assessment, cant find irritant. No apparent etiology. There are mutations in key
genes that regulate cell division and ability of cells to move and invade into other
tissues. Genetic lesions that underlay the neoplastic lesion we see clinically
a. Benign, tumors that dont kill you, just grow and reach a certain size,
dont spread. Rarely deadly.
b. Malignant, tumors that spread to other parts of the body so the cells that
make up a malignant tumor, proliferating, have a marked increase in cell
cycle, mitotic rate. Second, ability to migrate away from center of the
tumor, invasiveness. Third, they penetrate vessels. Cause are mechanism
that govern cell cycling, that involve mutations in genes that regulate
migration of cells, stratified squamous epithelium as they divide, stack, in
cancer what they do is go south instead of north. Moving south show
invasiveness, change that occurs in the motility proteins of the cell,
cytoskeleton and motility components like actin filaments that cause the
clels to move. Adhere to vessel and penetrate and once they are in there,
flow with blood stream or lymphatic network. Nodal metastasis, when
they get into lymph nodes, or regional. Stays in region of head and neck.
Second, small veins, dont penetrate arteries, that thick muscular coat does
not allow them to penetrate. Enter venous system, go to vena cava, and
lungs. Most head and neck malignancies go into veins and lungs. Most
go to nodal metastasis. Hematogenous metastasis.
c. Indeterminate, type of neoplasm that metastasizes in some people not in
others. Low grade malignancies.
Carcinoma

Ectoderm epithelial cells


Entoderm GI tract, stratified columnar epithelium

Glandular cells derived from either of these two, specialized into salivary tissue or
pancreatic tissue. All are epithelial. Tumor arising from basal cell in oral epithelium or
ductal cell in salivary gland, then if its a malignant tumor, the term is carcinoma. All are
carcinomas here. In oral mucosa, stratified squamous, squamous cell carcinoma
Parotid gland epithelial tumor, then its adenoma. Adenocarcinoma, malignant tumors of
breast, Secretory glands of GI tract. Colon carcinoma is adenocarcinoma. Prostate
carcinoma is also adenocarcinoma.

Third germlayer in between these is mesoderm fat muscle collagen bone, connective
tissues. Tumor from fibroblast, then its mesodermal derived cell. Those kinds of cancers
are sacromas. Specifically, if it looks like fibroblast, then its a fibrosacroma. Lipid
material produced, lipo sarcoma.

Term for benign tumor from one of these germ layers, name of cell and then put on the
term oma on the end. Fibroma, lipoma. Epithelial, grow out like cauliflower,
papilloma. Dont metastasize and have a slow growth pattern. Benign grow slowly and
usually have capsule around them, connective tissue around the tumor, and usually
moveable, and fairly soft. Malignant are the opposite, grow rapidly, no capsule, and they
tend to be hard, not moveable, fixed.

How do we diagnose them: all of these behave differently, have different treatments
effective for one kind of malignancies but not another. Leukemia, cancer of white blood
cells. In reality, leukemia is a type of sarcoma because white blood cells come from
mesoderm. The way you treat is with chemotherapy, very effective anticancer drug, but
squamous cell carcinoma is not chemotherapy, have to cut it out surgically and then treat
it with radiation. Every tumor has a different name, different type, different forms of
treatment.
Histopathology oral histopathology, recognize patterns under microscope by taking a
biopsy. Remove or take a portion of it, and looking for what cell type. Fibroblastic,
epithelial, glandular. Decide the origin first. Fat cell in liposarcoma doesnt look like a
fat cell, but has characteristics. Tissue of differentiation. Second, benign or malignant.
Changes in cell that lets us know if something behaves benignly or malignant.
Malignant: chromosomes are changed, the cells may show different sizes or shapes
depending on how much chromatin they have, normal cells are diploid but in cancer they
are anaploid, may have 8 times the content of chromatin. Check the nuclei. Dividing
rapidly, mitosis. Changes in the nucleus is they can become enlarged, increased DNA
content, nuclear to cytoplasm ratio is increased, nuclei are to big compared to normal
cells. Cells have different shapes and sizes, pleomorphism. Die to stain cells stain the
DNA darker, cell nucleus will be very dark blue hyperchromatism. Those are the
nuclear changes to see if its benign or malignant for individual cells.
Then, under low mag, look at borders. If its well defined or of it infiltrates away from the
center. Round and well defined then its benign, cancer cells everywhere then its
malignant, infiltration. Cytologic features and also pattern of tumor growth. All need
a blood supply, tissue that supplies the tumors, fibrous tissue with capillaries and blood
cells, stroma of the tumor. Not proliferating, just supplying. Malignant tumors may be
differentiating along some pathway or pattern but they dont make a lot of product, they
spend more time making baby tumor cells then a product like a fibroblastst, that makes a
lot of collagen, a lot of product compared to cells, whereas a malignant turmor makes a
lot of cells and not so much collagen. There will be more cells per unit area,
hypercellularity. Point to more aggressive malignant behavior. When you put all that
together, put a name on the tumor. If collagen is the product, and cells are fibroblasts,
and thats all you see, minus vessels. Fibroblasts and lots of collagen then its a fibroma.
See a tumor that has hypercellualr, not a lot of product, all you find are a few foci of
osteoid, starting to form bone, lots of mitotic figures, hyperchromatis, all these features of
malignancies, then its osteosarcoma. See a well circumscribed mass of epithelial cells,
all forming ductal structures then its a adenoma. Glandular tumor, benign, well
encapsulated. See a tumor thats infiltrated, very cellular, making a few ducts here and
there, with mitotic figures, cells are hyperchromatic, then its adeno carcinoma. No such
thing as adeno sarcoma, all adenos are carcinomas.

Molecular genetics of cancer. At molecular level do see causes, cancer is caused by one
of two events: germline mutations, inherit a predisposition to cancer from parents, due to
mutation in a gene that governs mitotic division or some other activity thats related to
ability to invade or become motile. Key to all is proliferation. Something has to activate
cell cycles. Most germline mutations are heterozygous and recessive so that the good
gene overrides the bad gene and you dont get a tumor. Then, we have spontaneous
mutations that occur after birth and these are just during the normal process of cell
turnover and so on, sometimes you end up getting some DNA defects, DNA repair genes
that fix those but sometimes they persist. Other times, viruses that get in and cause
mutaitons, and also carcinogens, chemicals in environment, that cause point mutations.
Other tumors in which genes are translocated, so chromosome on one gets transposed to
another location, if they are near a gene that governs mitotic division, may speed up
mitosis. One of the key factors in almost all tumors are tumor suppressor genes, and they
are genes that arrest mitosis, prevent the cell from dividing, these are also involved in
apoptosis, get rid of cells that have damaged DNA> they are tumor suppressor genes that
counteract the cell cycle, going form Go to G1 to M phase and then the cell divides, there
are check points along the way where there are proteins that activate the cell cycle, those
are overridden by tumor suppressor genes. If the gene is suppressed, will arrest and the
cell wont divide. These are tumor suppressing genes. If you inherit mutation in one of
these from one parent, mother provides you with defective tumor suppressor but father
provides you with normal, have that check point thats necessary when you dont want it
to go, but what happens if something comes into that cell and damages the good gene?
Now, you have no breaks on mitosis, like an automobile, step on gas, cell goes into
division, break it stops, cut the break, nothing to stop cell division, key underlying cause
of almost all cancers in the body, some mutation in a tumor suppressor gene that prevents
it from operating. If we say that what happens is you inherit a bad gene and a good gene,
and then alter the good gene gets mutated from a carcinogen or virus, tow you have two
bad genes, what you did is went from heterozygous state to a homozygous state. Loss of
heterozygosity. Referring to tumor suppressor genes.
P53, tumor suppressor gene, has a loss of heterozygosity in 90% of oral cancer. You need
about 7 different mutations to get a malignancy, in 7 different genes. Oncogenes, one
becomes activated. May have gene that governs motility of cell, whatever holds the cell
in check moves around.
Very rare for a benign tumor to become malignant. Neurofibromatosis. Elephant man.
Nerve tumors all over his face, inherited. Those are benign but some can turn into
neurogenic sarcomas.

Precancerous, meaning that it is a disease or a lesion that has a much higher chance of
turning into cancer than if you didnt have that lesion. Doesnt mean its a lesion that will
definitely become cancer, just has a higher risk. once the cancer begins, begins in the
stratified squamous epithelium, and some of the cells towards the basal layer start to
show all these features, increased mitotic activity, large nuclei, atypical looking cells,
then that is the very first beginning of cancer. Not cancer yet, hasnt invaded. Terms is
dysplasia. Some are reversible, spontaneously resolves. Others go on and start to
proliferate and go south, begin to invade. At that point its squamous cell carcinoma.
Dysplasia is earliest stage of cancer, if you dont take it out, has a high chance of
becoming a malignant tumor. Most cancers begin from one single cell that shows the
appropriate mutations, colonal expansion.