Neoplasia

Question 1

neoplasia

Answer 1

abnormal tissue mass with uncoordinated, excessive growth; 3 defining criteria:
1) autonomous
2) clonal
3) proliferative

Question 2

autonomous characteristic of neoplasia

Answer 2

growth independent of physiological signals

Question 3

clonal characteristic of neoplasia

Answer 3

series of acquired mutations affecting a cell and ALL of its progeny

Question 4

proliferative characteristic of neoplasia

Answer 4

mutations give neoplastic cells survival/growth advantage

Question 5

benign neoplasms

Answer 5

1) localized and well-defined (may be encapsulated)
2) do NOT spread to other sites
3) growth usually recapitulates normal structures (cells look normal, relative to the tissue they are in)

Question 6

benign neoplasms - nomenclature

Answer 6

-oma added to the cell of origin
*adenoma = benign glandular epithelial tumor
*fibroma = benign fibroblast tumor
*chondroma = benign cartilage tumor
*osteoma = benign bone tumor

Question 7

papillary

Answer 7

visible fingerlike projections

Question 8

polyp

Answer 8

visible projection above mucosa with a stalk

Question 9

cystic

Answer 9

cyst/cavitary centers

Question 10

malignant neoplasms

Answer 10

1) ill-defined growth
2) invasive (spread to and destroy adjacent structures)
3) metastasize (spread to non-contiguous, distant sites)
*requires interventional therapy

Question 11

malignant neoplasm - nomeclature

Answer 11

*carcinoma = epithelial origin
(ex. adenocarcinoma, squamous cell carcinoma)
*sarcoma = mesenchymal origin
(ex. fibrosarcoma, liposarcoma)

Question 12

differentiation of benign neoplasms

Answer 12

well-differentiated (close resemblance to normal)

Question 13

differentiation of malignant neoplasms

Answer 13

*wide range of differentiation:
-well differentiated = closest resemblance to normal
-moderate = some resemblance to normal
-poor = little resemblance to normal
-undifferentiated = anaplasia, NO resemblance to normal

Question 14

pleomorphism

Answer 14

variation in size/shape of cells (all cells look different from each other)

Question 15

anaplasia characteristics

Answer 15

-pleomorphism
-abnormal nuclear morphology
-mitoses (increased and atypical)
-loss of polarity
-ischemic necrosis

Question 16

metaplasia

Answer 16

replacement of one differentiated tissue with another
-chronic stress leads to reprogrammed stem cells
-typically reversible cell change
*precursor to malignancy

Question 17

dysplasia

Answer 17

-“disordered growth”
-increased pleomorphism and increased mitotic activity
-may be reversible
*precursor to malignancy

Question 18

typical sequence from normal to neoplastic

Answer 18

normal <-> hyperplasia <-> dysplasia <-> carcinoma

Question 19

invasion

Answer 19

infiltration or destruction of surrounding tissues
(ex. mucosal layer invading the serosa of a tissue)
-sign of malignant (benign are non-invasive)

Question 20

metastasis

Answer 20

spread of a tumor to physically distant, discontinuous sites
*unequivocally marks a neoplasm as malignant
*most reliable feature distinguishing malignant from benign

Question 21

pathways of dissemination of metastasis

Answer 21

1. seeding of body cavity or organ surfaces
2. lymphatic spread
3. hematogenous spread

Question 22

seeding & metastasis

Answer 22

*involving an open body cavity
*peritoneal cavity is most common, but could also be pleural, pericardial, subarachnoid, etc

Question 23

lymphatic spread & metastasis

Answer 23

*invade lymphatics to involve draining lymph nodes
**most common pathway for CARCINOMA dissemination
*pattern of nodal involvement follows natural lymphatic drainage (breast cancer to axillary nodes; lung cancer to hilar/mediastinal nodes)

Question 24

hematogenous spread & metastasis

Answer 24

*direct invasion of blood vessels
**most common pathway for SARCOMA dissemination
*follow blood flow (veins more common than arteries; liver and lungs are most frequent sites of metastasis)

Question 25

radiation and oncogenesis

Answer 25

UV radiation: mutations in oncogenes, tumor suppressor genes, formation of thymidine dimers ionizing radiation: depends on type, length of exposure, etc

Question 26

microbial agents and oncogenesis

Answer 26

-HPV & Epstein-Barre viruses (EBV) -H. pylori

Question 27

HPV oncogenesis

Answer 27

HPV can induce expression of oncoproteins -**E6: degrades p53, preventing apoptosis**; activates telomerase -**E7**: allows progression in cell cycle (**binds RB and displaces E2F; blocks p21 and p27**) OVERALL EFFECT: immortalizes epithelial cells

Question 28

EBV oncogenesis

Answer 28

-allows inappropriate expression of latency-phase genes -EBNA and LMP

Question 29

oncogenes

Answer 29

mutations in oncogenes turn them on and endow cell with self-sufficiency in growth; genes that accelerate cells and tell them to proliferate; "gain of function" process *ONLY ONE COPY NEEDS TO BE MUTATED

Question 30

growth factors

Answer 30

oncogenes that induce cellular growth -some tumors induce autocrine loop, in which they synthesize the same growth factors to which the cell is responsive -ex = PDGF (brain cancer)

Question 31

growth factor receptors

Answer 31

oncogenes that mediate growth factor signals -activation by growth factors cause dimerization and phosphorylation signaling cascade substrates *constitutively dimerized/activated mutant receptors can be on without growth factor *overexpression of normal forms of growth factor receptors

Question 32

signal transducers

Answer 32

oncogenes that mediate signals to nucleus into different cascade events; mutations become "trapped" in active form

Question 33

transcription factors

Answer 33

oncogenes that orchestrate the mitotic cycle

Question 34

cell cyclers

Answer 34

oncogenes that orchestrate the cell cycle

Question 35

tumor suppressor genes

Answer 35

mutations that lead to failed response to growth inhibitory signals; "loss of function" process that stops cellular proliferation *BOTH COPIES MUST BE MUTATED

Question 36

RB (retinoblastoma) gene

Answer 36

common tumor suppressor gene -normal function = regulate G1-S transition -mutations allow tumor cells to enter S phase unchecked **require a DOUBLE HIT (both copies must be knocked out)

Question 37

TP53 gene

Answer 37

common tumor suppressor genes -normal function = slow down cell cycling in response to DNA damage, allowing repair or apoptosis -mutations lead to no cell cycle arrest in tumor cells **requires a DOUBLE HIT (both copies must be knocked out)

Question 38

apoptosis regulators

Answer 38

disruption leads to immortalization of cells via evasion of cell death -ex = BCL2 inhibits apoptosis; normally turned OFF in cells, but tumors can upregulate this gene and therefore they don't undergo apoptosis

Question 39

other features of oncogenesis

Answer 39

-replicative immortalization via upregulated telomerase (allows cells to continue to proliferate over time) -angiogenesis to supply nutrients to tumor cells (tumor upregulates angiogenic factors) -escape of immunosurveillance (down-regulate MHC class I)

Question 40

warburg effect

Answer 40

tumor cells shift their metabolism to favor glycolysis, even with adequate oxygen, because it provides them a lot of other nutrients; provides a growth advantage in hypoxic tumor microenvironment; characteristic "glucose hunger" of tumor cells can be identified via PET scans

Question 41

local problems associated with neoplasms

Answer 41

-space-filling can lead to obstruction -tissue compression can lead to dysfunction and destruction -surface ulceration can lead to bleeding and secondary infection

Question 42

systemic problems associated with neoplasms

Answer 42

-cachexia -paraneoplastic syndromes

Question 43

paraneoplastic syndrome

Answer 43

clinical signs/symptoms that result from substances produced by the tumor and occurring remotely include: -hypercalcemia -endocrinopathies -hypercoagulability

Question 44

tumor grade

Answer 44

pathology morphologic assessment (level of differentiation) *low grade = well differentiated (better) *high grade = poorly differentiated / anaplastic

Question 45

tumor staging

Answer 45

determines the extent of SPREAD using the TMN system

Question 46

TNM system

Answer 46

T = tumor size N = node involvement M = metastases

Question 47

T (tumor size) of TMN system

Answer 47

T0 = in situ (non-invasive) T1-T4 = increasing tumor size

Question 48

N (node involvement) of TMN system

Answer 48

N0 = no regional lymph node involvement N1 to N3 = increasing number of involved lymph nodes

Question 49

M (metastases) of TNM system

Answer 49

M0 = no distant metastases M1 = distant metastases

Question 50

tumor markers

Answer 50

biochemical indicators of a tumor's presence that are detectable in plasma

Question 51

examples of tumor markers

Answer 51

-mucins (CA125, CA19-9) -oncofetal antigens (AFP, CEA) -specific proteins (PSA, immunoglobulins)