neoplasm I Flashcards
What is a neoplasia
“New Growth”; lack of responsiveness to normal growth controls
what is the study of neoplasms
Oncology
what is a benein neoplasms
a localized, non spreading neoplasm
what is a malignant neoplasm
Cancer
with the potential to invade and destroy adjacent normal tissue and spread to distant sites
survivability to benign and malignant neoplasm
Benign can be fixed via surgical removal
Malignanat neoplasms can lead to death, especially without treatment
spread of mailgnant neoplasms to distant sites
Metastasis
what is the parenchyma
transformed or neoplastic cells
what is a stroma
The supporting tissue of the tumor i.e. the non-neoplastic blood vessels and connective tissue supplied by the host
can benein tumors be lethal
yes, can crush important parts of brain or body
how would one name a nenign tumor
Adding the suffix “-oma” to the end
what is an Adenoma
A benign gland-forming epithelial tumor or tumor derived from glandular tissue
what is a papilloma
A benign surface epithelial tumor characterized by numerous finger-like progections
how would one name a malignant mesenchymal neoplasms
Add the suffix Sarcoma to the root word describing the parenchymal tissue of origin
how would one name a malignancy of epithelial origin
Carcinomas
what is a lymphoma
A malignancy of lymphocytic origin
what is melanoma
Malignancy of melanocytic origin
what is a hamartoma
Proliferation of tissue normally found at the site
- still dissordered
how series is a Hamartoma
Can regress, and will self heal
what is a choristoma
A collection of tissue not normally found in that anatomic site
what is a teratoma
A neoplasm derived from more than 1 germ layer
how bad is a teratoma
Can range from benign to aggressive
what is melanoma
malignancy of melanocytes
what is mesothelioma
pleural malignancy
what is seminoma
testicular malignancy
what are more differentiated, benign or malignant neoplasms
Beneign are generally well-differentiated (look like the cells from which they rose)
- rare and normal appearance of mitosis
Malignant neoplasms: can be well differentiated to poorly differentiated
what are malignancies composed of poorly differentiated cells
Anaplastic
what characterizes anaplasia
Pleomorphism Nuclear hyperchromatism increased nuclear/cytoplasmic ratio compared to normal cels Atypical nuclei numerous and atypical mitoses
what is pleomorphism
variation in cell shape and size
what is nuclear hyperchomatism
Intensely baseophilic nuclei
what is dysplasia
Altered growth pattern
what does dysplasia normally refer to
Epithelium that is not neoplastic but may become cancerous eventually.
what do dysplasia cells normally look like
microscopic alterations similar to cancer cells
what is the most severe form of epithelial dysplasia
Carcinoma-in-situ
what is carcinoma-in-situ
has all the microscopic features of cancer , but the atypical cells have not invaded into the host
what is the benifit of well differentiated tumors compared to undifferentiated tumors
Still able to retain some functional capability
what grows faster, benign or maliganant tumors
Malignant grow much faster
- well differentiated grow slow
- poorly differentiated grow fast
how can dysplasia causes problems
slowly grow as dysplasia to become carcinoma in situ
eventually cross the basement membrane as a seed bed from which cancer can occur
what happens if tumors outgrow their blood supply
results in areas of ischemic necrosis
what would someone say by saying something is paraneoplastic
can cause problems due to secondary effects of the neoplasms such as PR
what type of tumor tends to have a capsule
Benign tumors
what is the capsule that tends to form around a benign tumor made of
A compressed band of fibroud connect tissue at the periphery of the tumor
do all benign tumors have a capsule
No (hemangioma and neurofibroma are exceptions
how do cancers grow
progressive infiltration
invasion
destruction
penetration of surrounding tissues
what is the most reliable means of distinguishing the malignant nature of a tumor
infiltrative quality
what is metastasis
the process in which portion of a malignancy break free and travel to distant sites where they form new tumor masses
what establishes a tumor as being malignant unequivovally
metastasis
what determines if a tumor can metastasize
the type of tumors
which tumors metastasize
osteosarcoma
melanoma
what tumors tend not to metastasize
basal cell carcinoma
how often do tumors tend to metastases
30% are large
20% have small metastases
what increases the tendency of metastasis
greater anaplasia
how do malignancies spread
Seeding within body cavities
spreading within the Lymphatic
Hematogenous spread
wheree do lymphatic spread
seen with carcinomas, resulting in lymph node metastases
what preferes hematogenous spread
Sarcomas
where do metastics deposites spread via hematogenous spread
lung and liver
what is hematogenous spread
spread via the blood
what is the incidence of cancer
1.69 million new cases
600,00 deaths a year
what gender is increasing in cancer
leveled for males
More females have taken up smoking, so greater rate
what gender is dying more via cancer
more Cancer deaths in males over 50 years
less deaths in females
- due to papsmears (decreased uterine cervix cancer)
at what age does cancer frequency increase
greater than 55 years
does the environment have an effect on cnacer
Yes
how much does cancer affect children under `15 years old
account for 10% of deaths in us (second to car accidents)
what are the hereditary aspects of cancer
Inherited cancer syndroms
Defective DNA repair syndromes
Familial cancers
what kind of dissorder is an inhereted cancer syndrom
autosomal dominant
examples of inherited cancer syndroms
Retinoblastoma
Multiple endocrine neoplasia (Men)
what kind of dissorder is defective DNA repair syndromes
Autosomal recessive
examples of Defective DNA repair sydromes
xeroderma pigmentosum
ataxia telangiesctasia
what are examples of familial cancers
Breast
Ovarian
colon
when do hereditary disease tend to show themselves
early age of onset(especially defective DNA repair)
how often do Hereditary disases tend to have an identifiable basics
about 10%
- most often a co roll
why do familial cancers tend to show themsevlves
early age at onset
what are characters of familial cancers
tumors arising in 2+ close relatives of the index case
Multiple or bilateral tumors
what is an acquired preneoplastic disorder
Persistent regenerative cell replication
where does acquired preneoplastic disorders tend to show themselves
Squamous metaplasia and dysplasia of bronchial mucosa
Endometrial hyperplasia and dysplastic proliferation
Leukoplakia of oral mucosa, vulva, or penis
Vilous adenomas of the colon
what lies at the heart of cancinogenesis
Nonlethal genetic damge
how many cells does Cancers come from
arise from one geneticall altered cells
what are the normal regulatory genes that are the principle targets of genetic damge
Protooncogenes
Cancer suppressor genes
Apoptosis regulatory genes
what happens if DNA repair genes are disables
the frequency of mutations increases
rate of neoplastic transformation increases
can carciongenesis occur with one mutation
No, a multistep process both photypicaly and genetically
what do cancers tend to produce that encourages their own growth
Self-sufficiency in growth signals
what are the protein products of oncogenes
Oncoproteins
what are protooncogenes
Growth promoting genes
what tends to be included/neded from cancer to occur
Evade apoptosis Self-sufficincy in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiogenesis
what is the difference between proto-oncogenes and oncogenes
Proto-oncogenes lack reguatlion
what happens when a proto-oncogen is mutated, or its regulator is mutated
uncontrolled promotion of cell growth
what oncogenes can lead to uncontrolled promotion of cell growth
Growth factors GRowth factor receptors signal transuding proteins nuclear transcription factors Cyclins and cyclin-dependent kinases
how might a protooncogene be transformed to an oncogenes
- Structural mutation of the gene, resulting in an abnormal product
- altered regulation of gene expression, resulting in increased production of a normal growth promoting protein
what is growth factor needed for
Stimulation to undergo proligeration
what is Glioblastoma
Platelet derived growth factor (PDGF)
what does Some sarcomas need for growth and self-sufficiency
TGFa (tumor growth factor alpha)
how can receptors aid in growth signal self-sufficiency
Mutation and overexpression of growth factor receptors (ERB B1 and B2
- lead to response even if no growth factor
what do mutant receptor proteins cause
Deliver continuous mitogenic signal
what does overexpression of growth factors lead to
Makes cancer cells hyperresponsive to even normal GF
what is often times mutated to lead to growth factor protblems
RAS oncogenes(30% of tumors have this mutation)
how does Mutant RAW cause a problem
Growth signals are normally turned off quickly, but mutant RAS remains active leading to constant cell proliferation
what nuclear transcription factor tends to be the most affected to cause GRowth self-sufficiency
MYC
what does MYC gene dysregulation lead to
- overexpression, leading in continuous activation of cyclin-dependent kinases (CDKs) driving the cell to devide
- repressed CDK inhibitors
how Does Burkitt lumphoma lead to an increase in MYC oncogene
- chromosome 8 and 14 switch a little bit and MYC is found on chromosome 14 next to the Ig gene
- Ig is constanatly being synthesized so MYC is also then synth often
what is the roll of Cyclins/cyclin-dependent Kinases
Orderly progresssion of cell cycle after activation by binding to cyclins
what regulates CDK’s
two families of CDK inhibitors
dysregualtion of CDK’s leads to what
Favors cell proliferation
- more and more transcription factors
what do tumor suppressor genes do
Inhibit cell proliferation
what was the first tumor suppressor gene found
RB gene
what does the RB gene product do
Regulates transcription
what is the Knudson’s two hit hypothesis
Two mutation in the genome of a cell required to induce retinoblastoma
what is needed for retinoblastoma to develop
Both of the normal allels of the RB locus must be inactivated
how does RB mutation pass in familial cases
Childinherits one defective copy of the RB gene and the other allele is normal
-normal RB gene undergoes somatic mutation leading to a tumor developing
where do most retinoblastomas come from
60% of retinoblastomas are sporadic
others are familail, inhherited as autosomal dominant
what do we understand better, tumor suppressor genes or oncogenes
we better understand oncogenes
what do tumor suppressor genes regulate
Cell cycle
cell adhesion
singal transduction
what does Active PRb do
binds transcription factors that regulate the cell cycle
what happens when pRb is phosphorylated
transcription factors are released, leading to DNA synthesis
what happens if pRb is mutated
cell cycle has no breaks, and transcription factors go wild
what genes is the single most common target for genetic alteration in human tumors
TP53 tumor suppressor gene
commonness of tp52 tumor suppressor gene genetic alteration in human tumors
single most common target,
- homozygous loss of TP52 in nearly all cancers
what usually leads to loss of TP53 gene
somatic mutation
- or -
one aberrant TP53, leading to increased rate of cancer
what is Fraumeni syndrom
having one aberrant TP53 gene
what is the action of TP53
- slow down DNA replication when mutations have affected the DNA
- activates the transcription of DNA repair enzymes
- apoptosis if cell cannot be repaired
what happens without a normal TP53 gene
cell incorporates the mutation in its genome and results in cancer
does one gene aid in evading apoptosis
No, many genes
what is the prototypic anti-apoptosis gene
BCL2
(other genes are TP53 and c-myc)
what are the characteristisc of tumors that grow via apoptotic evasion
slow grwoing and low grade due to not ding, instead of quick prolieration
why would there be a surplus of BCL2
translocation from chromsome 18 to Ig heavy chain locus on chromosome 14
how large can tumors get without vasculatur
cannot exceed 1-2 mm
what does angiogenesis facilitate that is bad
metastases to provide access to the vasculature
what are the major 2 phases of metastasis
- Invasion of the ECM
- vascular dissemination and adhesion/homing of tumor cells
what are the steps of invasion of the ECM
- tumor cells detach from each other
- attach to ECM components (BM and CT) including collagens, glycoproteins and proteoglycans
- Degrade matrix components and basement membrane
- Migrate to vascular channels
what may happen to a tumor once in circulation
- vulnerable to destruction by the host immune cells
- Adhere to vascular endothelium, following by basement membrane transmigration
how can distribution of tumor metases be predicted
by location of the primary tumor and its vascular or lymph drainage
how often is organ tropism seen in metastasis
Sometimes, but never involved skeltal muscle
why does organ tropism seen in skeletal muscle
- Organ-specific endothelial adhesion molecules bind tumor cell lingants
- Chemokine receptors on tumor cells home to sites where specific ligands and readily produced.
what are some environmental carcinogens
ionizing radiation
Sunlight
Dietary agents
what is hereditary nonpolyposis colon cancer syndrome
familial cancer of the colon
- result from defective genes involved in DNA mismtach repair and evidence of microsatellite instability
what does xeroderma pigmentosum lead toc
increase in skin cancers
what is xeroderma pigmenosum
the inability to repair UV damage
what are examples of fragile DNA diseases
Bloom syndrome
Ataxia telangiectasia
Fanconi anemia
Familial breast cancer
what does sunlight normmaly due to DNA
pyrimidine(thymadine) cross-linking in DNA which halts replication
does fragile DNA need only a couple mutations to induce cancer
No, still needs lots
how do tumors change after time
More aggressive locally and hreater metastatic potential
what are some karyotypic changes that occur
Balanced translocation
Deletions
GEne amplifactaions
how common are balanced transolocations
extremely common
- especially in hematopoietic neoplasms
how similar are tumor cells in one tumor mass
may be heterogeneous
benifit of tumors being heterogeneous
able to survive certain therapies, invade host tissue or metastasize with greater efficiency
what is the second most prevalent form of keryotypic abnormality
Deletions
what deletions are most common in oral cancer
3p, 9p, and 17p
what did percival pott do
Described scotal skin cancer in chimney sweep, attributing it to chronic exposure to soot
are chemical carcinogens natural or synthetic
both
what are the actions of carcinogens
directly with DNA (direct-acting agents)
most are indirect with some metabolic conversion
what are indirect carcinogens called
Procarcinogens
what are the active end-products of procarcinogens
Ultimate carcinogens
what are the characteristics of tumors that survive chemo
Low control
Need little to grow
non antigenic/ recognixable
3 major classes of cariogenic agents
Chem
Radiant energy
Oncogenic viruses
are chemical carcinogens electrophiles or neutralphiles
electrophiles
what do chemical carcinogens react with
DNA
RNA
cell proteins
what are chemicals called promoters
have little inherent mutagenicity
drive cells to divide and immortalize DNA alterations
how do alcohol and cigarates work together to increase cancer
alcohol makes it easier for the carcinogens to enter
what happened to dentists that help patients film for radiographs
Developed squamous cell carcinoma of the index finer
how has cancer affected those who mine radioactive ores
10x high lunger cancer
what happened to the survivors of the atomic bomb
had markedly increased incidence of leukemia as well as other cancers
how long is the latent periods for radiation exposure and time of cancer
long (7-12 years)
latency of atomic bomb survivor cancer
8-12 years
what kind of virus is Human T-cell leukemia virus Type I
RNA oncogenic virus
how often does Human T-cell leukemia virus type I cause leukemia
only in 3-5% of individuals who are infected after 20-50 years of latency
what do f DNA oncogenic viruses do
transforming DNA viruses that form stable associations with the host cell genome
what cancers can HPV cause
some types do benign squamous papillomas or veruca vulgaris
ulterine cnacer and oropharyngeal cancer
what can Epstein barr virus do
Burkitt lymphoma
B cell lymphoma in immunosuppressed patients
Hodgkin lymphoma
nasopharyngeal carcinoma
what can Hep B do
Linked to hepatocelular carcinoma
what are tumor antigens
Tumor-specific antigens and tumor associated antigens
what are the antitumor effector mechanisms
Cytotoxic T cells (CD8+)
Nat Killer cells
Macrophages
Humoral factors
what shows that immunosurveillance is a real thing
Increased frequency of cancer observed in immunocompromised
what are tumor specific antigens
antigens only associated with tumor cells
what is the cancer-testis antigens
MAGE-1 (melanoma-associated antigen)
what are tumor associated antigens
found on normal cells
overexpressed on tumors
what are antigesn that represent a specialized function of cells
Differentiation-specific antigens
what kind of antigen is prostate specific antigen
Tumor associated antigen
where is prostate-specific antigen
in association with both normal and enoplastic prostatic epithelium, but more in neoplastic state
what does Cytotoxic T lymphocytes do to fight cancer (CD8+)
play a role against virus-induced neoplasms
- burkitt’s lymphoma
what do Natural Kiler cells do
Lymphocytes that kill tumor cell without prior sensitization
the first line of defnse against tumors
Natural killer cells
what is the action of macrophages
Collaborate with T cells and NK cells to destroy tumor cells
how do macrophages kill tumors
Act by using mechs that destroy microbes
Produce TNF-alpha
how much do immunocompromised people have cancer
200x more often
why do immunocompromised tend to have more cancer
- selective outgrowth of antigen-negative variants
- loss or reduced expression of histocompatibility antigens
- lack of co-stimulation
- Immunosuppression
what does it mean by saying that selective outgrowth of antigen negative nariants in immunocompromised people lead to more cancer
Subclones that are most immunogneic to host are destroyed, leading to relatively antigen-negative subclones
what does it mean by saying that loss or reduced expression of histocompatibility antigens in immunocompromised people lead to more cancer
tumor cells dont express normal levels of HLA class I, escaping attack of cytotoxic T cells
what does it mean by saying that loss of costimulation in immunocompromised people lead to more cancer
t cells need co-stimulatory molecule to initate immune response to foreign antigen
can carcinogenic agents suppress the immun system
Yeh
can benign tumors be serious
Yeh
When can cancer lead to a change in hormone prouction
adenomas and carcinomas arising from beta cells can produce hyperinsulinism
- fetal
what kind of tumors tend to produce too much insulin
Well differentiated benign tumors
when would a tumor cause ulveration
when a tumor expands to the point of breaking through the epithelium surface
when can ulceration cause a problem
bleeding and secondary infection
where is cachexia seen
In cancer patients
what does Cachexia lead to
Progressive loss of body fat and lean body mass
accompanied by profound weakness, anorexia, and anemia
- wasting
when does Cachexia present itself
terminal
how often are paraneoplastic syndroms found
10-15% of cancer patients
why are paraneoplastic syndroms important
May represent an early manifestation of occult disase
May pose significant clinical problems for affected patients
May mimic metastatic disease and thereby confound treatment
what is a prognosis
defining a grade and stage of a malginicy to predict the course of a disease
what does grading cancer show
Assess aggressiveness of a malignancy
- differentiation
- number of mioses
what is grade I vs Grade IV cancer
Grade I: most differentiated
Grade IV: least differentiated
what is staging of cancer
estimating cancer size of extent
- size of primary lesion
- presence of metastatic lesion
- presence of lymph node involvement
what unit is used for squamous cell carcinoma of head and neck staging
T: primary tumor diameter(1-4)
N: regional lymph node involvement (0-3)
M: metastases (0-1)
what is more valuable for prognosis staging of Grade
Staging
what is incisional biopsy
Portion of lesion taken for microscopic examination
excisional biops
Entire lesion was removed for microscopic examination
how useful is electron microscopy
Only for a limited number of cases
when is frozen section biopsy done
Done at time of definitve surgery in the hospital
Pros and cons of Frozen section biopsy
Quick but prone to erros
pros and cons of fine needle aspiration biopsy
Needs expertise in obtaining
Expertese in analyzing
when is fine needle aspiration biopsy useful
evaluating superficial and deep seated masses
when is cytologic (papanicolaou) smears done
Screening for cervical Ca
Supplemnted by HPV test
what is Immunocytochemistry
Specific antibody-guided detection of tumor-specific or associated antigens to determine the precise classifciation or subclass of a tumor
when is Flow cytometry done
Classifcation of leukemias and luymphomas
what is done for Flow cytometry
Surface markers and DNA ploidy analysis
what do biochemical assays look for
Tumor associated enzymes, hormones and other tumor markers in blood
- prostate-specific antigen
what is molecular diagnosis
Use of fluorescent in-situ hybridization or PCR to create personalized medicine
