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Checklist for metastasis

1) generates own growth signals
2) insensitive to antigrowth signals (loss of Rb, p21, p16)
3) able to evade apoptosis
4) immortalization
5) sustained angiogenesis
6) ability to invade basement membrane

E cadherin inactivation

loosens site of attachment; aids in metastasis

Protease expression

cuts through basement membrane

Metastasis

when tumor cells leave their organs of origin and spread elsewhere

Invasion

capability to transgress epithelial basement membrane; lesion now considered cancer; invasion does not equal metastasis

Size for angiogenesis

2mm beyond their site of origin - need O2 and nutrients

Ways for neovascularization

1) tumor cells, macrophages, stromal cells
2) production of NF-kB

Neoplastic vessels

1) disorganized
2) bleed easily, even without trauma
3) dilated and highly permeable
4) premature lack of mural cells
5) sluggish blood flow

Carcinoma-associated fibroblasts (CAF)

help to degrade basement membrane and interstitial tissues

How to get through basement membrane

1) loosen up cell junction
2) degrade BM and interstitial tissues
3) expression of receptors for stromal elements
4) get the cells moving

Stromal fibroblasts

aid in carcinogenesis; promote desmoplasia

Desmoplasia

dense fibrosis of stroma of a tumor; so much so that FNA cannot be performed

Tumor Spread Methods

1) direct invasion into adjacent tissue
2) invade lymphatics
3) seeding of body cavities
4) intravascular dissemination (hematogenous)

Seed and soil hypothesis

means tumor has metastasize and a tissue has to the right receptors/conditions/fertile ground for the tumor cells to take up residence

Benign neoplasm characteristics

1) usually well-circumscribed
2) push, don't infiltrate
3) may have capsule/pseudocapsule
4) respect borders
5) sometime hang out (leiomyoma)

Intraepithelial neoplasia

transformed epithelium with some cytologic features of malignancy but lacking the biological ability to invade and metastasize

Hypervascular neoplasms

1) hepatocellular carcinoma
2) renal cell carcinoma
3) carcinoid tumors
4) paragangliomas

Basal cell carcinoma of skin

Invades locally and can destroy large parts of the area it evolves in if it isn't treated, but rarely metastasizes

Papillary carcinoma of the thyroid

cancer tends to do nothing or spread locally to the nodes of the neck. one of the more benign cancers

Ductal carcinoma of the breast

highly aggressive

Renal cell carcinoma

usually invades renal veins

Hepatocellular carcinoma

invades portal and hepatic veins

Hematogenous spread

typically appear circumscribed as apposed to the appearance of the primary malignancy; can be a number of metastases in the same area (lung slide); look at cell type to confirm it is from another organ

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