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Flashcards in Lec10 Neoplasia Deck (63):
1

Is histopathological diagnosis necessary for neoplasia?

Yes

2

What is common etiology of neoplasia?

Cacinogens/hereditary

3

Definition of neoplasm

abnormal mass of tissue whose uncoordinated and excessive growth exceeds normal tissue and persists after cessation of stimuli that evoked change. Genetic changes allow excessive and unregulated proliferation that become autonomous [independent of physio stimuli] but tumors are dependent on host for nutrition and blood supply

4

6 Characteristics of neoplsam

- autonomous growth
- monoclonality
- histology phenotype
- genetic mutations
- mutagens/carcingoens [initiating cause]
- benign or malignant

5

Benign tumor characteristics

- cohesive, expansile [slow limited growth]
- well circumscribe, lobulated, encapsulated
- discrete, mobile [easily removed]

6

What are two examples of benign tumors than can be lethal

- brain meningioma
- atrial myxoma

7

Malignant tumor characteristics

- progressive infiltration [limitless growth]
- invasion/destruction of adjacent structures
- poorly demarcated [not clear margins]
- unfavorable prognosis

8

What is hamartoma?

Disorganized growth/mass of indigenous tissue
- excess of normal tissue in normal place
- usually benign
ex. extra bile duct tissue in liver

9

What is choristoma?

Congenital anomaly [heterotropic rest of cells]
- excess of normal tissue in abnormal place
- ex. pancreatic tissue in duodenum

10

Definition of Parenchyma

The tumor = transformed neoplastic cells

11

Definition of stroma

The host = surrounding supportive connective tissue

12

Definition of hyperplasia

increase in number of cells

13

Definition of metaplasia

replacement of one mature cell type by another

14

Definition of Dysplasia

loss of cell uniformity/orientation [epithelial]
disordered proliferation, lack of progressiver maturation, differentiation

15

Definision of Desmoplasia

Stromal reactions [fibrosis-collagen] to invasion

16

Definition of Anaplasia

Complete lack of differentiation [malignancy]
Only in malignant tumor

17

What are 4 histologic criteria of tumor?

1. uniformity of cells
2. nuclei
3. mitosis
4. architecture

18

Pleomorphism

variation in size and shape
Cells and nuclei become less uniform

19

How do nuclei change in cancer

abnormal nuclear morphology
large nuclei, irregular, hyperchromatic

20

How does proliferative activity change in cancer?

- higher proliferative activity
- more cells undergoing mitosis, atypical shapes

21

How does architecture change in cancer?

Loss of architecture
haphazard growth
irregular glands

22

How to measure differentiation in tumor cell

- extent of resemblance to normal
- evaluated on histologic sections
- morphologically and functionally

23

Grading of tumors

- quantitative evaluation of differentiation
- predicts future behavior [prognosis]
grade from 1-4
1-2 = low grade
3-4 = high grade

24

Benign tumor differentiation

- very well differentiated
- difficult to distinguish from normal
- mass may be only sign of neoplasia

25

Malignant tumor differentiation

- range of differentiation
- grading: well, moderately, poorly
- anaplasia: lack of differentiation

26

How is rate of tumor growth measured

- doubling time
- growth fraction
- rate of cell loss

[cell production > cell loss, malignant > benign]

27

At what stage clinically detectable? Incompatible with life?

clinically detectable: 10^9 cells [1gm], 30 doublings

incompatible with life: 10^12 [1kg], + 10 doublings

28

Local growth and invasion in benign vs malignant tumors

benign: remain localized in tissue of origin, have well-defined cleavage plane [enucleation]

malignant: invade host stroma and desmoplasia, wider margin needed for complete resection

29

What is carcinoma in situ? What is it characterized by?

- marked dysplasia involving entire thickness of epithelium
- pre-invasive

30

3 forms of metastatic spread

- lymphatic spread: regional lymph nodes
[carcinomas]

- hematogenous: liver, lungs
[carcinomas, sarcomas]

- seeding of cavities: peritoneum, pleura
[carcinomas]

31

Tumor staging

T = primary tumor: size or extent
-- T0-T4 [T0 = in situ]

N = regional node: number, location
-- N0-N3 [N0 = negative]

M = metastases: number, sites
-- M0-M2 [M0 = negative

32

Is staging or grading more important for prognosis?

Staging is more important

33

Risk factors for cancer

- geography and environment - ambient carcinogens
- diet and lifestyle - tobacco, obesity, alcohol
- age (>55 yrs) - more mutations, less immunity
- genetic predisposition (hereditary)
-- cancer syndromes, familial clustering
- chronic inflammation
- pre-malignant leisions

34

cancer cachexia

- loss of body fat, lean muscle
- weakness, anorexia, anemia
- high BMR, catabolic rate

35

paraneoplastic syndromes

- unexplained by local/distant spread of indigenous hormones
- 10-15% of malignancies
- can precede cancer diagnosis
- significant morbidity/mortality
- can be hematologic, endocrinopathy, neuropathy/myopathy

36

Direct effects of cancer

- pressure atrophy [glands]
- obstruction/occlusion [tract]
- destruction [rupture]
- bleeding
- ulcer [secondary infection]
- infarction

37

Cause of molecular carcinogenesis

- mutations either inherited [germline] or acquired

38

Main targets of mutations

- oncogenes [gain of function, dominant]
- tumor suppressors [LOF, recessive]
- genes that regulated cell death
- genes involved in DNA repair

39

Haploinsufficiency

one allele loss

40

8 steps of malignant transformation

1. self sufficient growth [oncogenes]
2. insensitivity to growth inhibition [tumor suppressor]
3. evasion cell death/apoptosis [p53, BCL2, BAX]
4. Limitless replicative potential [telomerase]
5. sustained growth/angiogenesis [VEGF, bFGF]
6. capacity for invasion/metastasis
7. reprogrammed metabolic pathways
8. ability to evade immune system

41

retinoblastoma mech

- due to point mutation/deletion
- gene = RB1 tumor suppressor

42

chronic myelogenous leukemia mech

- due to chromosome translocation
- gene = BRC-ABL proto-oncogene

43

neuroblastoma mech

- due to gene amplification
- gene = N-myc proto-oncogene

44

breast/ovarian carcinoma

- due to epigenetic mutagenesis
- gene = BRCA1 tumor suppressor

45

Mech and Effect of DNA mismatch repair [MMR] defect?

- due to mismatched base pairs, microsatellite instability
- neoplasm = colon, endometrial
- gene = MSH2, MLH1
- syndrom = Lynch [HNPCC]

46

Mech and Effect of Homologous recombination defect?

- due to double stranded break, ionizing radiation
- neoplasm = leukemia, lymphoma
- gene = FANCA, ATM]
- syndrome = Fanconi anemia, ataxia-telangiectasia

47

Mech and Effect of Nucleotide excision repair [NER] defect?

- due to cross linking, UV radiation
- neoplasm: basal cell melanoma
- gene: XPA, XPB
- syndrome: xeroderma pigementosum [XP]

48

Steps of multi-step carcinogenis in colon

- normal colon
- mucosa at risk
- adenoma
- carcinoma

49

Steps of invasion and metastasis

- loss of cell interactions [E-cadherins]
- ECM degradation [metalloproteinases]
- Attachment and migration [integrins]
- Intravasation [access to vessels]
- Dissemination and homing [chemokines]
- Adhesion and extravasation
- Metastatic deposition
- Interaction with stroma
- Angiogenesis and growth [VEGF]

50

Effect of UV rays

- UVB exposure --> pyrimidine dimers
- can cause melanoma

51

Disease associated with HPV

Cervical squamous cell carcinoma

52

Disease associated with HBV/HCV?

Hepatocellular carcinoma

53

Disease[s] associated with H pylori

gastric lymphoma/adenocarcinoma

54

Venous thrombosis

- trousseau syndrome
- underlying neoplasm: pancreatic carcinoma
- mech: hypercoaguable state

55

sarcoma

maglinant neoplasm of mesenchymal cells

56

carcinoma

– malignant neoplasm of cells differentiating toward epithelial cells

57

What is doubling time

time it takes for a cell to divide

58

What is growth fraction?

percent of neoplastic cells dividing
one of most important factors

59

what grows faster malignant or benign

malignant

60

What is most deadly disease? most prevalent?

most deadly = lung cancer
most prevalent = breast and prostate

61

how can surgery change susceptibility to chemotherapy?

- surgery pushes down growth fraction so can increase susceptibility to chemo

62

What is adenoma?

- benign epithelial neoplasm of glandular tissue

63

Most common early mutation in colorectal adenoma?

APC!