Ch 7: Neoplasia Flashcards
what are the hallmarks of cancer
set of properties that produce certain cellular phenotypes that dictate the natural history of cancer and response to therapy
what is neoplasia
new tissue growth that is unregulated, irreversible, and monoclonal
what is monoclonal
neoplastic cells derived from a single mother cell
what is benign
microscopic and gross features are innocent, the humor is localized, and easily removable
what is malignant
lesion can invade and destroy nearby structures, can spread, and can cause death
what are the two basic microscopic components of neoplasia
parenchyma is made of transformed cells
supporting host stroma contains connective tissue, blood vessels, and inflammatory cells
what is a fibroma
benign growth of fibrous tissue
what is a chondroma
benign growth of cartilage
what is an adenoma
benign lesion that produced gland-like features
what is a papilloma
benign lesion on the surface that produces fronds
what is a cystadenoma
benign hollow cystic mass
usually in ovary
what is a sarcoma
malignant tumor of mesenchymal tissue
what are leukemias and lymphomas
malignant tumor of mesenchymal cells in the blood
what is a carcinoma
malignant tumor of epithelial cells
what is an adenocarcinoma
malignant, epithelial tumor with glandular pattern of growth
what is a squamous cell carcinoma
malignant, epithelial tumor that produces squamous cells
what does differentiation mean
when new growing parenchymal cells resemble the corresponding normal parenchymal cells
(does the cell still look and function like itself)
if poorly differentiated, suggestive of malignancy
what is divergent differentiation and what are three examples
mixed tumors due to the progenitor cell having the ability to differentiate into more than one lineage
ex. pleomorphic adenoma, fibroadenoma, and teratoma
what is a pleomorphic adenoma
mixed salivary gland tumor made of a epithelial component and fibromxyoid stroma
example of divergent differentiation
what is a pleomorphic tumor
tumor with more than one form; mixed tumors
what is a fibroadenoma
proliferating ductal elements and in loose fibrous tissue
example of divergent differentiation
what is a teratoma
mixed tumor of mature and immature elements derived from one or more germ layers
example of divergent differentiation
what is a solitary fibrous tumor
benign, lung pleural tumor made of solid dense fibrous tissue
not linked to asbestos exposure
what is malignant mesothelioma and what is it caused by
malignant lung pleural tumor with disseminated nodules or plaques
spreads
caused by homozygous deletion of chromosome 9p leading to loss of the tumor suppressor gene CDKN2A
what is a hamartoma
benign mass of proliferating cartilage outside of the bronchial tree in the lung parenchyma
appear as coin lesions
what is a choristoma
a benign congenital anomaly consisting of a heterotropic nest of cells in a place where they shouldn’t be
believed to occur during embryonic development
what is a lingual osseous choristoma
benign area of bone found in the tongue due abnormal folding during embryonic development
what is a choristoma of foregut
presence of pancreatic tissue in different places of the foregut or mesentery
what is anaplasia
lack of differentiation - cells don’t look like they should
indication of malignancy
what is hyperchromatic
darkly stained nuclei that is suggestive of malignancy
what is pleomorphism
variation in size and shape of tumor cells that is suggestive of malignancy
what is anisonucleosis
variation in size and shape of nuclei that is suggestive of malignancy
what is nuclei-cytoplasmic ratio
ratio of size of nucleus to cell (normal is 1:4 - 1:6)
can increase 1:1 and be suggestive of malignancy
what are nucleolar changes
prominent or lots of changes in the nucleolus which are suggestive of malignancy
what is loss of polarity
disrupted orientated of cells (they become crooked) which is suggestive of malignancy
what are mitotic figures
numerous mitotic figures which can be suggestive of malignancy
easiest thing to recognize malignancy through
what are tumor giant cells
multinucleate tumor giant cells with large bizarre nuclei that are suggestive of malignancy
what are functional changes
certain things like glands stop functioning which can be suggestive of malignancy
what are chromosomal abnormalities in relation to malignancy
those with certain chromosomal abnormalities are more susceptible to malignancy
what are a few of the main differences between a benign and malignant tumor
capsulated vs non-capsulated
slow vs fast growing
metastasis
cell morphology
necrosis vs no necrosis
invasive vs non-invasive
what are the three pathways of malignant dissemination (metastasis)
seeding
lymphatic spread
hematogenous spread
what is seeding within the body cavities
a metastasis mechanism where seeds of the tumor break off and spread to other areas
typical of ovarian cancers going to peritoneal surfaces
what is lymphatic spread and which cancers use it most
tumor travels through lymphatics
typical of carcinomas like breast cancer
what is hematogenous spread and which cancers use it most
tumor spreads through vascular supply
typical of sarcomas
what is a sentinel lymph node
the first node in a regional lymphatic basin that receives lymph flow from the primary tumor
what are the four steps of metastasis
1.) loosening of cell to cell contacts
2.) degradation of the extracellular matrix
3.) attachment to the novel extracellular matrix components
4.) migration of tumor cells
what is loss of cell-to-cell contacts
first step of metastasis which is caused by inactivation of E-cadherin by a variety of pathways
what is the breakdown of the extra-cellular matrix
second step of metastasis which is mediated by proteolytic enzymes secreted by the tumor and stroma
what is the attachment of extra-cellular matrix components
third step of metastasis where proteolytic enzymes release growth factors that cleave fragments from the ECM
what is the migration of tumor cells
fourth step of metastasis where tumor moves, usually to a specific site
what is organ tropism
when a primary tumor metastasizes to a specific site
where do breast, colon, kidney, and lung cancers like to metastasis to
liver and lung
what is skip metastasis
cancer reaches blood vessel by thoracic duct
which tumor tends to grow in veins
renal cell carcinoma
what is the relationship between age and cancer
as you age, you’re more likely to get cancer
cancer accounts for what % of all deaths in children under 15
10%
what are three acquired predisposing conditions to cancer
chronic inflammation (IBD)
immunodeficiency status (HIV)
precursor lesions (cervical dysplasia)
what are proto-oncogenes
genes that are essential for cell growth and differentiation
once mutated, become oncogenes which lead to unregulated cell growth
what is p53
protein produced by the tumor suppressor gene TP53 gene
regulates progression of cell cycle from G1 to S phase (guardian of the genome)
induces apoptosis if cells are beyond repair
what is the most frequently mutated gene in human cancers
TP53
50% of cancer cases have this gene mutated
what is Li-Fraumeni Syndrome
mutation in TP53 gene with one defective copy
gives a 25-fold greater chance of developing a malignant tumor before age of 50
can cause: sarcoma, breast cancer, leukemia, brain cancer, and adrenal cortex cancer
what is RB gene
tumor supressor gene that regulates progression of cell cycle from G1 to S phase
called governor of cell cycle
if both alleles are mutated, leads to retinoblastoma
what do tumor suppressor genes do
stop cell proliferation
what are some hallmarks of cancer
self sufficient in growth signals
insensitive to growth inhibitory signals
altered cell metabolism
won’t go through apoptosis
limitless replicative potential
angiogenesis
metastasis
evasion of immune surveillance
what is a point mutation
mutation in single nucleotide that can either activate or deactivate protein products
convert porto-oncogenes to oncogenes
can reduce suppressor genes ability to suppress
what is the most common, point mutated oncogene
KRAS (rat sarcoma)
seen in 30% of tumors
higher in pancreatic adenocarcinoma
what are passenger mutations
acquired genes that are neutral and do not affect cell behavior
occur randomly throughout genome
what are driver mutations
alter function of cancer genes and directly contribute to the development or progression of a given cancer
usually acquired but can be inherited
what are gene rearrangements
translocation or inversions
seen commonly in hemopoietic or mesenchymal derived malignancies
can activate proton-oncogenes
occur mostly in lymphoid tumors
what are gene deletions
deletion of specific regions of chromosomes can lead to loss of particular tumor suppressor gene
what are gene amplifications
porto-oncogenes converted into oncogenes during amplification
leads to over-expression of normal protein
what are epigenetic modifications
stable and heritable alterations in gene expression and cellular function without changes to original DNA sequence
regulate gene expression
what is APC gene
adenomatous polypsis coli - gatekeeper of colonic neoplasms
tumor suppressor genes that down regulate growth promoting signal pathways
what is von Hipple-Lindau gene
targets other proteins to be broken down when not needed
mutation causes von Hipple Syndrome which is associated with renal cell cancers
what is HNPCC (hereditary nonpolyposis colon cancer syndrome)
Lynch syndrome
mutation that causes deficits in the mismatch repair system leading to carcinomas of the colon
what is xeroderma pigmentosum
rare genetic syndrome with a defective DNA nucleotide excision repair
presents with extreme sensitivity to UV light and has a high risk of developing skin cancer
how is angiogenesis controlled/regulated/treated
triggered by hypoxia
regulated by p53 protein, RAS, and MYC
treated using VEGF inhibitors
what is VEGF
proangiogenic factor released by tumor cells
increases blood vessel expression and movement to tumor
what is cancer immunoediting
ability for a neoplasm to shape its immunogenic properties to avoid elimination
creates immune tolerance and immune suppression
what is the most important class of tumor antigens
oncogenic viruses
what are three stages of cancer enabling inflammation
anemia
fatigue
cachexia
how does inflammation effect the tumor microenvironment (TME)
causes:
proliferation
unregulated growth
invasion and metastasis
resistance to cell dead
resistance to therapy
explain the two steps of chemical carcinogenesis
initiation: cells exposed to sufficient dose of carcinogen to cause mutations (cells now initiated)
promotors: promotors cause cell proliferation of initiated (mutated) cells; cells pick up more mutations on the wall until they become cancer
what is a direct acting carcinogen
chemicals that require no metabolic conversion to become carcinogenic
most are weak as carcinogens
can cure cancers but cause a second form (acute myeloid leukemia)
what is an indirect acting carcinogen and give three examples
chemicals that require metabolic conversion to become active carcinogens (ultimate carcinogen)
ex. polycyclic hydrocarbons, aromatic amines, and azo dyes
what is a “hotspot”
clustered mutations in specific sequences or bases
what are promotors
chemical agents that stimulate cell proliferation and expansion of a clone of mutated cells
what is a quiescent tissue
one that is not actively dividing
what is a mitogenic stimulus
small protein that stimulates mitosis
what are three types of carcinogenic radiant energy
UV rays of sunlight
ionizing electromagnetic
particulate radiation
what is human T-cell Leukemia Virus Type 1
a type of retrovirus that causes adult T-cell leukemia/lymphoma
what is a retrovirus
virus that inserts a copy of its RNA genome into DNA of a host cell that it invades, thus changing the genome of that cell
which types of HPV cause benign squamous papilloma’s
1,2,4, and 7
high risk types of HPV, 16 and 18, are known to cause which three types of squamous cell carcinomas
cervix
anogenital region
head and neck
which strains of HPV are genital warts
6 and 11
what is Burkitt lymphoma
a disease caused by Epstein-Barr virus
causes nasopharyngeal and gastric cancers
what percent of hepatocellular carcinomas are caused by infection with Hep B or Hep C
70 to 85%
what are the oncogenic effects of Hep B and Hep C
chronic inflammation and hepatocyte death
what is Helicobacter pylori
bacteria that causes peptic ulcers, gastric adenocarcinomas, and gastric lymphoma of B cell origin
what is thought to be the cause of cachexia in cancer patients
TNFalpha (cachectin)
what is type 1 hypercoagulability
balance of endogenous heparin production and degradation is disturbed with increase degradation of heparin by tumor-secreting heperanse
what is type 2 hypercoagulability
procoagulant molecules secreted from tumor cells, leading to hypercoagulability
what are paraneoplastic syndromes
when cancer patients have signs and symptoms that cannot be explained by the tumor
occurs in 10% of patients
what types of cancers can cause cushings
small cell carcinoma of lung
pancreatic carcinoma
neural tumors
what 4 types of cancers can cause hypercalcemia
squamous cell carcinoma of lung
breast carcinoma
renal carcinoma
adult T-cell leukemia
what are the two processes involved in cancer-associated hypercalacemia
osteolysis (breaking down of bone cells)
production of calcemic humoral substances by extra osseous neoplasms
what is a tumor marker
present in or produced by cancer cells in response to cancer or other condition
provides information about a cancer like how aggressive it is or what kinda of treatment it needs
explain grading of a cancer
based on degree of differentiation of cells
ex. changing architecture in the cells (nuclei size)
low to high grade
explain staging of a cancer
based on size/invasion of the primary lesion, its spread, and metastasis
more helpful than grading
uses TNM system
what does T0 mean
no tumor
which staging system is used for prostate
Gleason’s grading pattern
which staging system is used for breast
Nottingham Histology scoring system
new tissue growth that is unregulated, irreversible, and monoclonal
what is neoplasia
neoplastic cells derived from a single mother cell
what is monoclonal
benign growth of fibrous tissue
what is a fibroma
benign growth of cartilage
what is a chondroma
benign lesion that produced gland-like features
what is an adenoma
benign lesion on the surface that produces fronds
what is a papilloma
benign hollow cystic mass
usually in ovary
what is a cystadenoma
malignant tumor of mesenchymal tissue
what is a sarcoma
malignant tumor of mesenchymal cells in the blood
what are leukemias and lymphomas
malignant tumor of epithelial cells
what is a carcinoma
malignant, epithelial tumor with glandular pattern of growth
what is an adenocarcinoma
malignant, epithelial tumor that produces squamous cells
what is a squamous cell carcinoma
when new growing parenchymal cells resemble the corresponding normal parenchymal cells
(does the cell still look and function like itself)
if poorly differentiated, suggestive of malignancy
what does differentiation mean
mixed tumors due to the progenitor cell having the ability to differentiate into more than one lineage
ex. pleomorphic adenoma, fibroadenoma, and teratoma
what is divergent differentiation and what are three examples
mixed salivary gland tumor made of a epithelial component and fibromxyoid stroma
example of divergent differentiation
what is a pleomorphic adenoma
tumor with more than one form; mixed tumors
what is a pleomorphic tumor
proliferating ductal elements and in loose fibrous tissue
example of divergent differentiation
what is a fibroadenoma
mixed tumor of mature and immature elements derived from one or more germ layers
example of divergent differentiation
what is a teratoma
benign, lung pleural tumor made of solid dense fibrous tissue
not linked to asbestos exposure
what is a solitary fibrous tumor
malignant lung pleural tumor with disseminated nodules or plaques
spreads
caused by homozygous deletion of chromosome 9p leading to loss of the tumor suppressor gene CDKN2A
what is malignant mesothelioma and what is it caused by
benign mass of proliferating cartilage outside of the bronchial tree in the lung parenchyma
appear as coin lesions
what is a hamartoma
a benign congenital anomaly consisting of a heterotropic nest of cells in a place where they shouldn’t be
believed to occur during embryonic development
what is a choristoma
benign area of bone found in the tongue due abnormal folding during embryonic development
what is a lingual osseous choristoma
presence of pancreatic tissue in different places of the foregut or mesentery
what is a choristoma of foregut
lack of differentiation - cells don’t look like they should
indication of malignancy
what is anaplasia
darkly stained nuclei that is suggestive of malignancy
what is hyperchromatic
variation in size and shape of tumor cells that is suggestive of malignancy
what is pleomorphism
variation in size and shape of nuclei that is suggestive of malignancy
what is anisonucleosis
prominent or lots of changes in the nucleolus which are suggestive of malignancy
what are nucleolar changes
disrupted orientated of cells (they become crooked) which is suggestive of malignancy
what is loss of polarity
certain things like glands stop functioning which can be suggestive of malignancy
what are functional changes
a metastasis mechanism where seeds of the tumor break off and spread to other areas
typical of ovarian cancers going to peritoneal surfaces
what is seeding within the body cavities
tumor travels through lymphatics
typical of carcinomas like breast cancer
what is lymphatic spread and which cancers use it most
tumor spreads through vascular supply
typical of sarcomas
what is hematogenous spread and which cancers use it most
the first node in a regional lymphatic basin that receives lymph flow from the primary tumor
what is a sentinel lymph node
when a primary tumor metastasizes to a specific site
what is organ tropism
cancer reaches blood vessel by thoracic duct
what is skip metastasis
genes that are essential for cell growth and differentiation
once mutated, become oncogenes which lead to unregulated cell growth
what are proto-oncogenes
protein produced by the tumor suppressor gene TP53 gene
regulates progression of cell cycle from G1 to S phase (guardian of the genome)
induces apoptosis if cells are beyond repair
what is p53
mutation in TP53 gene with one defective copy
gives a 25-fold greater chance of developing a malignant tumor before age of 50
can cause: sarcoma, breast cancer, leukemia, brain cancer, and adrenal cortex cancer
what is Li-Fraumeni Syndrome
tumor supressor gene that regulates progression of cell cycle from G1 to S phase
called governor of cell cycle
if both alleles are mutated, leads to retinoblastoma
what is RB gene
mutation in single nucleotide that can either activate or deactivate protein products
convert porto-oncogenes to oncogenes
can reduce suppressor genes ability to suppress
what is a point mutation
acquired genes that are neutral and do not affect cell behavior
occur randomly throughout genome
what are passenger mutations
alter function of cancer genes and directly contribute to the development or progression of a given cancer
usually acquired but can be inherited
what are driver mutations
stable and heritable alterations in gene expression and cellular function without changes to original DNA sequence
regulate gene expression
what are epigenetic modifications
targets other proteins to be broken down when not needed
mutation causes von Hipple Syndrome which is associated with renal cell cancers
what is von Hipple-Lindau gene
Lynch syndrome
mutation that causes deficits in the mismatch repair system leading to carcinomas of the colon
what is HNPCC (hereditary nonpolyposis colon cancer syndrome)
rare genetic syndrome with a defective DNA nucleotide excision repair
presents with extreme sensitivity to UV light and has a high risk of developing skin cancer
what is xeroderma pigmentosum
proangiogenic factor released by tumor cells
increases blood vessel expression and movement to tumor
what is VEGF
ability for a neoplasm to shape its immunogenic properties to avoid elimination
creates immune tolerance and immune suppression
what is cancer immunoediting
chemicals that require no metabolic conversion to become carcinogenic
most are weak as carcinogens
can cure cancers but cause a second form (acute myeloid leukemia)
what is a direct acting carcinogen
chemicals that require metabolic conversion to become active carcinogens (ultimate carcinogen)
ex. polycyclic hydrocarbons, aromatic amines, and azo dyes
what is an indirect acting carcinogen and give three examples
clustered mutations in specific sequences or bases
what is a “hotspot”
chemical agents that stimulate cell proliferation and expansion of a clone of mutated cells
what are promotors
one that is not actively dividing
what is a quiescent tissue
small protein that stimulates mitosis
what is a mitogenic stimulus
a type of retrovirus that causes adult T-cell leukemia/lymphoma
what is human T-cell Leukemia Virus Type 1
virus that inserts a copy of its RNA genome into DNA of a host cell that it invades, thus changing the genome of that cell
what is a retrovirus
a disease caused by Epstein-Barr virus
causes nasopharyngeal and gastric cancers
what is Burkitt lymphoma
bacteria that causes peptic ulcers, gastric adenocarcinomas, and gastric lymphoma of B cell origin
what is Helicobacter pylori
balance of endogenous heparin production and degradation is disturbed with increase degradation of heparin by tumor-secreting heperanse
what is type 1 hypercoagulability
procoagulant molecules secreted from tumor cells, leading to hypercoagulability
what is type 2 hypercoagulability
when cancer patients have signs and symptoms that cannot be explained by the tumor
occurs in 10% of patients
what are paraneoplastic syndromes
present in or produced by cancer cells in response to cancer or other condition
provides information about a cancer like how aggressive it is or what kinda of treatment it needs
what is a tumor marker