Principles of Neoplasia Flashcards
what is cancer
genetic disorder caused by DNA mutations
what can cancer causing DNA mutations be caused by
- hereditary
- environmental exposure
- aging
genetic alterations are _____
inheritable
describe neoplasia
- independent of regulatory influences, increase in size
- require host nutrients, blood supply, hormones
- can be benign or malignant
what is a benign tumor
gross and microscopic characteristics are often innocuous; lesion is localized
what is a malignant tumor
ability to invade and destroy adjacent structures and metastasize
what is the nomenclature for benign tumors
attached suffix ending in -oma
what is the nomenclature for a malignant tumor
mesenchymal tissue: sarcoma
- blood: leukemia/lymphoma
what is the nomenclature for epithelial tissue
- carcinoma
- squamous: squamous cell carcinoma (SCC)
- glandular: adenocarcinoma
what is the benign and malignant tumors of connective tissue and derivatives
- benign: fibroma, lipoma, chondroma, osteoma
- malignant: fibrosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma
what are the benign and malignant tumors for blood vessels
- benign: hemangioma
- malignant: angiosarcoma
what are the benign and malignant tumors of lymph vessles
- benign: lymphangioma
- malignant: lymphoangiosarcoma
what is the malignant tumor of mesothelium
mesothelioma
what is the benign and malignant tumor of brain coverings
- benign: meningioma
- malignant: invasive meningioma
what is the malignant tumor of hematopoietic cells
leukemias
what is the malignant tumor of lymphoid tussue
lymphomas
what is the benign and malignant tumor of smooth muscle
- benign: leiomyoma
- malignant: leiomyosarcoma
what is the benign and malignant tumor of striated muscle
- benign: rhabdomyoma
- malignant: rhabdomyosarcoma
what is the benign and malignant tumor of stratified squamous cells
- benign: squamous cell papilloma
- malignant: squamous cell or epidermoid carcinoma
what is the malignant tumor of basal cells of skin or adnexa
basal cell carcinoma
what is the benign and malignant tumor of tumors of melanocytes
- benign: nevus
- malignant: malignant melanoma
what is the benign and malignant tumors of epithelial lining of glands or ducts
- benign: adenoma, papilloma, cystadenoma
- malignant: adenocarcinoma, papillary carcinoma, cystadenocarcinoma
what is the benign and malignant tumor of lung
- benign: bronchial adenoma
- malignant: bronchogenic carcinoma
what is the benign and malignant tumor of the kidney
- benign: renal tubular adenoma
- malignant: renal cell carcinoma
what is the benign and malignant tumor of the liver
benign: liver cell adenoma
malignant: hepatocellular carcinoma
what is the benign and malignant tumor of the bladder
- uroethelial papilloma
- uroethelial carcinoma
what is the benign and malignant tumor of the placenta
- hydatidiform mole
- choriocarcinoma
what is the malignant tumor of the testicle
- seminoma
- embryonal carcinoma
what is the benign and malignant tumor of the salivary gland
- pleomorphic adenoma
- malignant mixed tumor of salivary gland
what is the malignant tumor of the renal anlage
Wilms tumor
what is differentiation
refers to the extend a tumor resemble their tissue of origin morphologically and functionally
what is anaplasia
lack of differentiation
what are benign tumors
usually well differentiated cells that resemble normal parent tissue
what are malignant tumors
wide range of parenchymal cell differentiation
- well- differentiated tumors to poorly differentiated tumors
what is local invasion
progressive infiltration, invasion, and destruction of surrounding tissue
what do benign tumors grow as
cohesive expansile masses and remain localized to site of origin
where do malignant tumors grow
locally invasive and destructive
what is metastasis
spread of tumor with sites that are physically discontinuous with the primary tumor
do benign tumors metastasize
no
what do malignant tumors invade
blood vessels, lymphatics, body cavities to spread to distant sites
what are the types of metatastic spread
- seeding within body cavities
- lymphatic spread/hematogenous
describe seeding within body cavities and give example
- invasion of natural body cavity
- ovarian tumors commonly invade peritoneum
what is lymphatic spread/hematogenous
- invasion through lymph nodes/lymphatic system or vascular system
- involvement depends on tumor’s primary location and access to lymphatics/vascular
- sentinel lymph node: first regional lymph node that receives lymph flow from a primary tumor
what is the leading cause of death worldwide
cancer
cancer accounts for _____ deaths
10 million
between ______ of cancers can be prevented by avoiding risk factors
30-50%
what are the most common cancers
breast, lung, colon, rectum and prostate cancers
incidence of cancer in men are _____ as women
twice as high
where do cancers associated with HPV occur
oropharynx
what are the risk factors for cancer of oral cavity and pharynx
- tobacco use
- alcohol consumption
- HPV infection
frequency of cancer ____ with age
increases
most cancer deaths occur between ____ years of age
55-75
in children, most common tumors are:
leukemias, CNS cancer, lymphoma, soft tissue, and bone sarcoma
what environmental factors can be controlled to prevent cancer
- diet
- smoking
- alcohol
- sun exposure
- infectious agents
what cancer is arsenic responsible for
lung carcinoma, skin carcinoma
what cancer is asbestos responsible for
lung, esophageal, gastric, and colon carcinoma; mesothelioma
what cancer is benzene responsible for
acute myeloid leukemia
what cancer is beryllium responsible for
lung carcinoma
what cancer is cadmium responsible for
prostate carcinoma
what cancer is chromium compounds responsible for
lung carcinoma
what cancer is nickel compounds responsible for
lung and oropharyngeal carcinoma
what cancer is radon responsible for
lung carcinoma
what cancer is vinyl chloride responsible for
hepatic angiosarcoma
what types of radiation are established carcinogens
- UV light
- radiographs
- nuclear fission
- radionuclides
what are exposure examples of radiation carcinogenesis
- unprotected mineworkers of radioactive elements- 10x risk
- survivors of hiroshima and nagasaki bomb, increased risk of leukemia, increased mortality rates of thyroid, breast, lung carcinomas
- chernobyl accident- increased risk of thyroid cancer
- therapeutic radiation to head and neck
- UV light
what can radiation to the head and neck area cause
- mutagenic effects
- may give rise to papillary thyroid carcinoma
what can UV light cause
- may form pyrimidine dimers in DNA
- nucleotide excision repair pathway may be overwhelmed
- SCC, melanoma
many chronic inflammatory conditions create a supportive environment for:
the development of malignant tumors
immunodeficiency states predispose:
to viral- induced cancer, including specific types of lymphoma
what are precursor lesions
localized disturbances of epithelial differentiation, elevated risk of developing carcinoma
what is an example of precursor lesions in the oral cavity
leukoplakia
what are oncogenes
genes that promote independent cell growth in cancer cells
what are proto-oncogenes
unmutated precursor cellular counterpart of an oncogene
what are oncoproteins
products of oncogenes which usually lack regulatory elements and do not need external signals to function
what are growth factors
substances that link to growth factor receptors on cells and signal internal cell signaling pathways to stimulate growth
what are tumor suppressor genes
genes which produce products which limit cell proliferation, often transcription factors
what are the stages of carcinogenesis and what are they
- initiation: genetic damage occurs due to a carcinogen
- promotion: exposure to a factor which allows for clonal expansion
- transformation: point at which a cell does not respond to normal controls for growth
- progression: growth of the tumor
what are the hallmarks of cancer
- self- sufficiency in growth signals
- insensitivity to growth- inhibitory signals
- altered cellular metabolism
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- invasion and metastasis
- evasion of immune surveillance
what does self- sufficiency in growth stem from
gain of function mutations that convert protooncogenes to oncogenes
what are the normal cell proliferation steps
- growth factor binding to its receptor on cell membrane
- limited activation of growth factor receptor -> activates several transducing proteins
- transmission of transduced signal across cytosol into nucleus by second messengers
- activation of nuclear regulatory factors -> initiate DNA transcription, other cellular components necessary for cell division
- cell cycle progression -> ultimately results in cell division
what do cell cycle checkpoints do
ensure there is not progress if there is damage or unfavorable cell condition
what are the cell cycle checkpoints
- G1/S checkpoint
- G2/M checkpoint
cancer may acquire the ability to secrete their own _____
growth factors
what cells does cancer induce to make growth factors
stromal cells
in cancer RAS is kept in ____ state
active
oncogenes allow for ______, whereas tumor suppressor genes dont
cell growth and progression
in cancer, oncogenes are turned____ and tumor suppressor genes are turned _____
on; off
what is RB
- retinoblastoma gene
- tumor suppressor gene inactivated in many cancers
- regulates G1/S checkpoint
what is TP53
tumor suppressor gene
- most commonly mutated gene in cancer
- important for DNA repair
what is Warburg effect
- cancer cells demonstrate a distinctive form of cellular metabolism through the glycolytic pathway- high levels of glucose uptake and conversion to lactose
- less efficient: produced 2 ATP/glucose vs 35 ATP/glucose in oxidative phosphorylation
- the glycolytic pathway produced metabolic intermediates necessary for synthesis of cellular components
tumor cells contain mutations in genes that regulate _____
apoptosis
what is the result of tumor cells regulating apoptosis
cell survival during times of intrinsic stress
what can p53 do
stop cell cycle if theres damage
most normal cells have a capacity of ____ divisions
70
how do cells get a capacity to replicate
- telomeres shorten, the cells enter replicative senescence
what makes cancer cells immortal and have limitless replicative potential
telomere maintenance
- telomerase is upregulated
what is neoangiogenesis
vessel formation from existing capillaries
what does neoangiogenesis do
- supplies nutrients and oxygen
- newly formed endothelial cells stimulate growth of adjacent tumor cells
- secrete growth factors
- vessels form haphazard connections,may leak
what does invasion and metastasis result from
- interactions between cancer cells, stromal cells, and the ECM
what are the steps in invasion and metastasis
- invasion of ECM
- vascular dissemination and homing of tumor cells
what happens in the invasion of ECM
- loosening of tumor cell- cell interactions
- degradation of ECM
- migration of tumor cells
what is immune surveillance
immune system scans the body for emerging malignant cells and destroys them
immune response to established tumors is______
ineffective
what are neoantigens
mutations may generate new protein sequences that the immune system is unfamiliar with
what is immunoediting
the ability of the immune system to promote darwinian selection of the tumor subtypes that are most able to avoid host immunity
what are immune checkpoints
inhibitory pathways that are crucial for maintaining self-tolerance
cancer cells reduce expression of ___ and minimize _____ response
MHC; CD8 T cell
what are some of the incidence and mortality changes in cancer detection and which cancers in each
- screening and early detection: colon cancer, cervical cancer
- identification of risk factors: lung cancer, breast cancer
- treatment improvements: childhood leukemia and lymphoma
what is immunohistochemistry
- the use of monoclonal antibodies via special stains on tissue samples from biopsy or aspirational biopsy to subclassify types of tissue based on the expression of cell products or surface markers
what does immunohistochemistry help determine
- tissue of origin
- site of origin of metastatic tumors
- markers may indicate behavior of lesion or response to treatment
what is IHC: S100 staining used for
neurofibroma
describe H pylori
- first bacterium classified as a carcinogen
- implicated in gastric carcinomas and gastric mucosal lymphomas
- pathway to adenocarcinoma through chronic gastritis, atrophy, metaplasia, dysplasia and carcinoma
h pylori infection leads to a monoclonal B cell tumor over time ->
MALT lymphoma
gastric lymphomas may regress with:
antibiotic treatment
what are the oncogenic DNA viruses
- human papilloma
- Epstein Barr virus
- Hep B virus
- Hep C virus
describe human papilloma virus
- most commonly transmitted STI
- strains most often associated with cancer are 16 and 18
- low risk types cause squamous papillomas
- high risk types cause SCC of the cervix, anogenital region, oropharyngeal region
- HPV viral genes: E6 and E7- prooncogenic
describe epstein barr virus
- herpesvirus
- infects mostly B lymphocytes
- implicated in Burkitt lymphoma, nasopharygneal cancer, T cell lymphomas, gastric carcinoma
- enters B cells via CD21 molecule and may remain latent in the nucleus
- abnormally regulates proliferative and survival signals of the cells
describe hepatitis B and C viruses
- 70-85% of hepatocellular carcinoma is associated with HBV or HCV
- HBV: DNA virus
- HCV: RNA virus
- chronic inflammation results in hepatocyte death, leading to regeneration with genomic damage -> tumor formation
- HBV - HBx protein and HCV- core protein can activate signal transduction pathways that may contribute to carcinogenesis
