#6 Neoplasm

Question 1

Neoplasia

Answer 1

Disorder of cell growth
Triggered by series of acquired mutations of single cell and its clones
monoclonal, autonomous (does not follow normal cell cycle regulations), irreversible
unregulated

Question 2

two components of all tumors (both benign and malignant)

Answer 2

parenchyma and stroma

Question 3

Parenchyma

Answer 3

Neoplastic cells (display genetic changes leading to abnormal growth)
Largely determines biologic behavior
Source for the name of the neoplasm
Neuroectodermal, epithelial or mesenchymal in origin

Question 4

Stroma

Answer 4

Connective tissue, blood vessels, immune system cells

“Support” growth and spread of neoplasm

Question 5

Mixed Tumors- derived from 1 germ layer

Answer 5

Single neoplastic clone capable of divergent differentiation
*Derived from 1 germ cell layer
More than 1 neoplastic cell type
common example in the salivary gland

Question 6

teratoma

Answer 6

mixed tumor from more than one germ layer. Totipotential germ cells differentiate into any cell types found in human body
Neoplasms often originate in gonads, abnormal midline embryonic rests

Question 7

benign neoplasms

Answer 7

tumors that do not spread, may cause deleterious effects due to compressing nearby tissues. Often contained within a capsule

Question 8

malignant tumors

Answer 8

cancers. Invade locally into adjacent tissues and can metastasize

Question 9

-oma

Answer 9

benign tumor of mesenchyme or epithelium orgin

Question 10

-sarcoma

Answer 10

malignant tumor of mesenchyme orgin

Question 11

-carcinoma

Answer 11

malignant tumor of epithelial orgin

Question 12

differentiation

Answer 12

the extent to which parenchymal tumor cells resemble their normal tissue counterpart. well differentiated looks very similar to “normal” cells of that type

Question 13

anaplasia

Answer 13

“backward differentiation” loss of the structural and functional differentiation of the cells from which a neoplasm is dervived

Question 14

pleomorphism

Answer 14

variation in the size and shape of cells. Anaplastic neoplasms usually have marked pleomorphisim. Cells are not uniform and all look different

Question 15

Nuclear to cytoplasmic ratio (N:C ratio)

Answer 15

normally 1:4 or 1:6 indicates small nucleus and large cytoplasm. In malignant cells it approaches 1:1 indicating a large nucleus and small cytoplasm

Question 16

dysplasia

Answer 16

disordered growth often within the epithelium. results from mutations. Cells have many characteristics of malignancy (pleomorphism, hyperchromatic nuclei, high N:C ratios, disordered maturation, mitosis above the basal layer) but DO NOT PENETRATE THE BASEMENT MEMBRANE
reversible- especially if the trigger is removed (smoking)

Question 17

Carcinoma in-situ

Answer 17

dysplastic cells involving the entire layer (full thickness) of an epithelial surface but has not yet crossed the basement membrane

Question 18

metastasis

Answer 18

secondary implants of a malignant tumor that are discontinuous with the primary tumor and may be in remote tissues. identifies a neoplasm to be malignant

Question 19

3 pathways of dissemination

Answer 19

1. seeding within body cavities- deposits from origional site common with ovarian carcinoma (cake the cavity)
2. via lymphatics - more typical of carcinomas, initially spread to regional draining lymph nodes (breast cancer)
3. via blood vessels- hematogenous spread. More typical of sarcomas but can be seen with carcinomas as well.

Question 20

characteristics of benign tumors

Answer 20

well differentiated to dysplastic, grow slowly, most are encapsulated and stay localized

Question 21

characteristics of malignant tumors

Answer 21

can be well differentiated to very de-differentiated (anaplastic), Pleomorphic (variations in nuclear size and shape), hyperchromatic nuclei, mitosis, prominent nucleoli

grow at variable and unpredictable rates, usually varies with the degree of differentiation (less differentiated= faster)

infiltrates and destroys locally and is able to metastasize

Question 22

Familial adenomatous polyposis

Answer 22

autosomal dominant cancer syndrome. Patients get thousands of polyps throughout the bowel that eventually become dysplastic and then carcinoma in-situ and eventually cancerous

Question 23

proto-oncogenes

Answer 23

normal cellular genes whose products promote cell proliferation

Question 24

oncogenes

Answer 24

mutant over-expressed versions of normal proto-oncogenes. function autonomously, encode growth factors, growth factor receptors, signal transducer, cell cycle regulators. Only need one allele mutated to form a tumor (dominant)

Question 25

RAS

Answer 25

oncogene that is most commonly mutated in tumors signal transducer that relays receptor activation to the nucleus. Controls movement from G1 to S phase. A point mutation causes RAS to be permanently in the active form (bound to GTP) by inhibiting its GTPase activity or mutating GAP. causes a continuously proliferating state

Question 26

tumor suppressor genes

Answer 26

normally prevent uncontrolled growth

Question 27

Knudson's two-hit hypothesis

Answer 27

both copies of a tumor suppressor gene must be mutated in order for cancer to develop

Question 28

Retinoblastoma gene

Answer 28

Tumor suppressor gene (basis of knudson's hypothesis) Rb controls G1->S transition of the cell cycle when active it binds E2F (preventing E2F from activating transcription). When phosphorylated it releases E2F activating transcription. The mutated form is inactive and cannot bind E2F which is therefore always active. sporadic RB mutations= unilateral retinoblastomas germline RB mutations result in bilateral retinoblastomas and osteosarcomas

Question 29

p53

Answer 29

"guardian of the genome" regulates progression from G1 to S If it senses DNA damage it will either cause quiescence (pause) and activate repair enzymes or if the damage is too extensive cause senescence (permanent stop) and apoptosis via the BAX protein

Question 30

Li-Fraumeni

Answer 30

a germline p53 mutation causes pts to have a 25 greater risk of developing cancer by age 5

Question 31

caspases

Answer 31

mediate apoptosis by activating proteases which break down the cell cytoskeleton and endonucleases that break down DNA. 8 & 9 are activators and all others are executioners

Question 32

2 pathways to activate caspases

Answer 32

1. intrinsic mitochondrial pathway | 2. Extrinsic receptor ligand pathway

Question 33

intrinsic mitochondial pathway

Answer 33

DNA damage leads to inactivation of BCL2 (normally stabilized the mitochondrial membrane) which causes cytochrome c to leak out of the inner mitochondial matrix into the cytoplasm and activates caspases

Question 34

BCL2

Answer 34

anti-apoptotic protein that stabilizes the mitochondrial membrane ( preventing cytochrome c from leaking out) in follicular lymphoma BCL2 is over expressed preventing apoptosis of the B-cells in the lymph nodes and they begin to build up. Could be activated by a t(14;18)

Question 35

extrinsic receptor ligand pathway

Answer 35

aka death receptor pathway. FAS ligand binds to the FAS receptor (CD95) on the target cell which activates caspases and other proteins which begin to break down the cell. used to eliminate self reactive lymphocytes

Question 36

telomerase

Answer 36

stabilizes telomer length to avoid senescence. often upregulated in cancer. P53 can also recognize shortened telomers and kill the cell.

Question 37

angiogenesis

Answer 37

production of new blood vessels vascularization of neoplasms is necessary for growth bc it supplies nutrients and oxygen. new endothelial cells produce growth factors such as PDGF and insulin-like growth factor

Question 38

VEGF

Answer 38

induces angiogenesis vascular endothelial growth factor normally involved in healing but commonly produced by tumor cells hypoxia inducible factor (HIF-1a) increases VEGF

Question 39

Von Hippel Lindau (VHL)

Answer 39

tumor suppressor gene inhibits HIF-1a when VHL is lost it leads to an increase in VEGF

Question 40

Process of metastasis

Answer 40

1. down regulation of E-cadherin (normally attaches epithelial tumor cells together) leads to dissociation of attached cels 2. cells attach to laminin and destroy/degrade the basement membrane vial collagenase (main component is collagen IV) 3. cells invade the vascular and/or lymphatic spaces

Question 41

ionizing radiation

Answer 41

results in chromosome breakage, translocations, point mutations which leads to genetic damage and carcinogenesis. Turnoble

Question 42

Non-ionizing radiation

Answer 42

UV light damages DNA by forming nicks within pyrimidine dimers. Normally repaired vial the nucleotide excision repair pathway

Question 43

Xeroderma Pigmentosum

Answer 43

Autosomal Recessive Syndrome of Defective DNA Repair Defect in nucleotide excision repair pathway Markedly increased predisposition to skin cancers

Question 44

Cancers can evade the immune system

Answer 44

Eliminate strongly immunogenic subclones Fail to express HLA class I, escape CTL attack Suppress host immune response (Secrete TGF-β, Express FasL, Activate regulatory T cells) Produce thicker coat of glycocalyx molecules blocking access to immune cells

Question 45

cancer cachexia

Answer 45

pt with cancer may experience loss of body fat, lean body mass, weakness, anorexia, anemia. due to the tumor and immune system producing cytokines particulary TNF and proetolysis inducing factor. Only way to get rid of it is to cure the cancer

Question 46

paraneoplastic syndromes

Answer 46

symptom complexes that cannot be readily explained by local or distant spread of the neoplasms. May be mediated by hormone elaboration which is not indigenous to the tumor parenchyma. (not due to the tumors location or type)

Question 47

grading of cancer

Answer 47

based on cytologic differentiation (anaplasia, pleomorphism, loss of normal architecture, mitoses) of the tumor cells. Well differentiated = low grade; poorly differentiated = high grade

Question 48

staging of cancer

Answer 48

based on the size/depth of the primary tumor, extent of spread to egional lymph nodes and the presence or absence of metastases. greater clinical value than grading for most cancers. Done after the tumor is removed. TNM system: T =tumor size, N= nodes, M=metastases(most important).

Question 49

Immunohistochemistry

Answer 49

uses monoclonal antibodies labeled with peroxidase. helpful for a poorly differentiated cancer. stains for the different types of intermediate filaments

Question 50

protein markers

Answer 50

elevations of particular proteins can be indicative of a cancer. Used mostly for detecting recurrence of cancer not an initial diagnosis