Neoplasia Flashcards
neoplasms
1) tumor or swelling
2) new growth
- abnormal mass of tissue which is uncoordinated with normal tissues and persists in same excessive manner after cessation of stimuli
fundamental to neoplasm
1) loss of responsiveness to normal growth controls
2) and compete with normal cells and tissues for metabolic needs
oncology
1) study of tumors
tumors have 2 components
1) parenchyma
- transformed or neoplastic cells
2) stroma
- non neoplastic CT and blood vessels
benign tumors
1) suffix -oma
2) lipoma, adenoma, polyp, cystadenomas
- designated by cell type and pattern
know the roots
:(
fibroma
lipoma
rhabdomyoma = skeletal muscle
leiomyoma = smooth muscle
angioma
hemangioma
lymphangioma
neuroma
chrondroma
osteoma
squamous epithelium
1) squamous papilloma
- reactive?
glandular epithelium
1) adenoma
connective tissue
fibroma
- reactive, not uncontrolled
lymphoid
lymphoid hyperplasia
- reactive
melanocytic
1) nevus, mole
-oma misnomers that are NOT benign
1) hematoma
2) hamartoma
- usually controlled
3) choristoma
- abnormal location
4) teratoma
- tumors, benign or malignant
- all three germ cell layers
5) lymphoma, melanoma, mesothelioma, seminoma
- all malignant
cancer
1) can invade and destroy adjacent tissues and metastasize to cause death
- carcinoma (epithelium)
- sarcoma (soft tissue or bone)
- lymphoma (lymphoid)
villous adenoma
1) polyp of the colon
2) can become cancer
pleomorphic adenoma
1) benign mixed tumor of salivary glands
cystic teratoma
1) all three germ cells
2) can be taken out of ovary
3) hair and tooth
uterine leiomyoma
1) common in uterus
2) spindle cells
thyroid adenoma
1) lots of thyroid follicles
monoclonality and divergent differentiation
1) tumor from one cell
2) monoclonal origin
3) stem cell may undergo divergent differentiation
- tumor of mixed cell population
- mixed tumors
differentiation
1) extent to which tumor cells resemble tissue of origin
- well vs poorly
2) grading
- morphologically and functionally
- pleomorphic (look different)
- mitotic activity
- infiltration
- necrosis
anaplasia
1) lack of differentiation
2) if its anaplastic YOU WILL DIE
3) mitotic rate super high, pleomorphic, nucleus to cytoplasm ratio high, don’t mature and polarize
rhabdomyosarcoma
1) often in children
2) the cells look very different from others
- pleomorphic, deadly tumor
anaplastic tumor cell
1) hard to tell what it is
2) antibody stain
3) high NC ratio
dysplasia
1) precursor
2) intraepithelial neoplasia
3) can have it in the skin, epithelial
4) increased NC ratio, pleomorphism, not much mitosis (so it is malignant potential)
rate of growth
1) benign - slow
2) malignant - faster
- correlated with level of differentiation, if it is poorly diff. it is faster
3) cancers take years to evolve
4) rapidly growing tumors may contain areas of ischemic necrosis
- need blood supply, so if it outgrows it
local invasion
1) benign is typically localized with capsule
2) but if there is pleomorphic with no room, it will look slightly invasive
3) cancers grow by progressive infiltration
fibroadenoma of the breast
most common tumor of the breast
- likely benign
- fibrous component and ductal structures
invasive ductal carcinoma of the breast
1) extensions because it invades and can get into blood vessel
metastasis
1) neoplasm will be MALIGNANT
2) not all cancers have same ability to metastasize
- the more anaplastic, the more potential
3) 30% with solid tumors will metastasize
three modes of metastasis
1) seeding
- seeding into cavity
2) lymphatic spread
- carcinomas tend to do this
3) hematogenous spread
- favored by sarcomas
- liver and lungs
comparison of beign and malignant
1) benign is well differentiated and slow, well demarcated
2) malignant is anaplastic, erratic growth, locally invasive, often metastasize
epidemiology of cancer
1) dietary fat and fiber in africa and western societies
2) preneoplastic diseases
3) cigarette smoking and lung cancer
incidence rates of cancers by sex
1) men with lung cancer is coming down
- stopped smoking
2) breast cancer is rising
heredity
1) predisposition to a few uncommon cancers
- childhood retinoblastoma
- colon, ovary, prostate, uterus, and sometimes melanoma cancer
- xeroderma pigmentosum (sunburn damage)
- adenomatous polyposis coli (familial)
preneoplastic disorders
1) in the setting of these disorders, more tumors
- persistent regenerative cell replication
- hyperplastic and dysplastic proliferation
- chronic atrophic gastritis
- leukoplakia
- villous adenoma of the color
carcinogenesis
1) nonlethal genetic damage lies at the heart of cancer
- 4 genes
a) growth promoting proto-oncogenes
b) growth inhibiting cancer suppressor genes
c) genes that regulate apoptosis
d) genes involved in DNA repair
molecular basis of cancer
1) failure of DNA repair
2) mutations in genes can then activate growth promoting oncogenes or alteration of genes that suppress cancer
3) malignant cell can become clonal and acquire mutations
*p53 is the guardian of the genome (DNA damage repair and halts cell cycle)
oncogenes
1) discovered through transforming animal retroviruses
2) 2 points
- normally, they promote cell proliferation
- mutations promote UNCONTROLLED proliferation
3) DNA of spontaneously arising cancers contain these
growth factors
1) mutations can make them oncogenic
2) PDGF necessary, but it can make tumors
2) ras over expression of GF genes
- TGF-alpha which bind to GF receptor to promote growth
growth factor receptor
1) mutations can mean overexpression of continuous signals
2) EGR receptor family
- c-erb B-1 / B-2 (her-2-neu is seen in 15-20% of breast cancer)
- targets for new treatments
c-ras and c-abl
1) 30% of all tumors contain mutated ras
- which tell nucleus to keep replicated
2) activated downstream kinases that flood signals to continue replication
3) lives on chromosome 9
- normal
- translocation to chromosome 22 is bad
brc-c-abl
1) mutations also keeps signaling just like ras
myc
1) causes cell cycle progression
2) active in nucleus
- binds to DNA causing transcriptional activation of growth genes
- overexpression contributes to overproliferation
3) part of chromosome 8
- translates to chromosome 14 which is BAD
activation of oncogenes
1) mutations cuause inappropriate production of growth promoting protein
a) point mutation
- ras oncogene and seen in many tumors
b) chromosomal translocations
c) gene amplification
brc-abl
1) potent tyrosine kinase => proliferation
N-myc
1) can be amplified in neuroblastoma
antioncogenes
1) apply brakes to cell-proliferation
2) retinoblastoma
- gene that prevents DNA synthesis by binding to TFs
- on chromosome 13
- if it is inactivated (cyclin phosphorylation) will cause tumor to form
- mutant must occur on both alleles
TP53
1) cancer suppressor gene that inhibits cell cycle when DNA is damaged by chemicals or radiation
2) if no repair possible, APOPTOSIS
3) homozygous loss of P53 for malignant transformation
- seen in almost every types of cancer
4) mutation reduces efficacy of anti-cancer therapy
bcl-2
1) prototypic anti apoptosis gene
- mutation t(18;14)
- seen in 80% of B cell lymphomas
bax
1) opposes bcl-2 and accelerated cell death
- transcription is influenced by p53 (upregulated)
BRCA1 gene
1) mutations predispose to breast cancer
xerodoma pigmentosum
1) UV light causes DNA damage and prevent normal replication
multistep oncogenesis
1) no single oncogene can transform cells
2) several must be activated
3) loss of 2 or more cancer suppressor genes are necessary for cancer to form
adenoma - carcinoma sequence
1) normal epithelium is hyperproliferative
- loss of APC locus
- loss of DNA methylation
2) early adenoma => intermediate => late
- loss of tumor supressor, loss of p53
3) carcinoma
angiogenesis
1) tumors cannot enlarge beyond 1-2 mm without vessels
- cannot metastasize without this
2) tumor cells secrete basic fibroblast GF and vascular endothelial GF cause vessel to grow
tumor progression
1) more aggressive over time
mechanisms of local and distant spread
1) migration to vessel
2) tumor embolus
3) extravasion at different site
4) make new blood supply for them
classes of carcinogenic agents
1) chemical carcinomas
2) radiation
3) viral
chemicals
1) highly reactive electrophiles and can be augmented by promoters
2) can act in concert with other carcinogens
3) direct
- weak
4) indirect
- metabolic conversion required
radiation
1) chromosomal breakage, translocation, point mutation
2) latent period is long, which can accumulate additional mutations
- UV
- x-rays
- nuclear fusion
ionizing
1) means of clinical diagnosis and curative mode of therapy for some tumors
- mutagen and destroyer of cells
2) electromagnetic or high energy neutrons and charged particles
3) both forms displace electrons
4) DNA (direct and indirect damage), cell membranes
DNA damage is survivable
1) if cell is remained in the intermitotic phase
2) depends on repair and effect of oxygen
3) effect of radiation is cumulative
molecular
1) formation of pyrimidine dimers
cellular
chromatin clumping
cytoplasmic
mitochrondria and cell swelling
radon
1) short range DNA damage
2) certain US region with uranium in the soil
total body radiation
1) 50-100 rads can cause nausea
2) 700 rads can cause death
viral oncogenesis
1) can get into DNA
2) RNA oncogenic viruses
- human T-cell leukemia virus
3) DNA oncogenic
- HPV
- epstein barr
- hepatitis B
burkitts lymphoma
1 )EBV get on lymphocytes and proliferate
2) translocation mutations from getting into the DNA
tumor antigens
1) tumor treatment
2) immunohistochemistry is used to classify neoplasms
3) S-100 is on all neuroectodermally derived
- LCA on leukocytes
- cytokeratins
-PSA
- actin
effects of tumors on the host
1) location is very improtant
2) hormone production in endocrine tumores
3) cachexia
- metabolic rate is increased despite decreased food intake
4) paraneoplastic syndromes
- hypercalcemia
- cushings
grading of cancer
1) grade I
- differentiated
2) grade 4
- undifferentiated, spreading rapidly
staging
1) T1 - T4 (tumor size and expansion)
2) N1-N3 (cancer in lymph nodes)
3) M0-M1 (metastasis)
tissue sampling
1) tissue diagnosis of any mass is necessary before therapy is implemented
2) biopsy
3) fine needle aspiration
4) cytologic smears
