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Pathology > Lec10 Neoplasia > Flashcards

Lec10 Neoplasia Flashcards

1
Q

Is histopathological diagnosis necessary for neoplasia?

A

Yes

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2
Q

What is common etiology of neoplasia?

A

Cacinogens/hereditary

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3
Q

Definition of neoplasm

A

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

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4
Q

6 Characteristics of neoplsam

A
  • autonomous growth
  • monoclonality
  • histology phenotype
  • genetic mutations
  • mutagens/carcingoens [initiating cause]
  • benign or malignant
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5
Q

Benign tumor characteristics

A
  • cohesive, expansile [slow limited growth]
  • well circumscribe, lobulated, encapsulated
  • discrete, mobile [easily removed]
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6
Q

What are two examples of benign tumors than can be lethal

A
  • brain meningioma

- atrial myxoma

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7
Q

Malignant tumor characteristics

A
  • progressive infiltration [limitless growth]
  • invasion/destruction of adjacent structures
  • poorly demarcated [not clear margins]
  • unfavorable prognosis
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8
Q

What is hamartoma?

A

Disorganized growth/mass of indigenous tissue

  • excess of normal tissue in normal place
  • usually benign
    ex. extra bile duct tissue in liver
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9
Q

What is choristoma?

A

Congenital anomaly [heterotropic rest of cells]

  • excess of normal tissue in abnormal place
  • ex. pancreatic tissue in duodenum
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10
Q

Definition of Parenchyma

A

The tumor = transformed neoplastic cells

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11
Q

Definition of stroma

A

The host = surrounding supportive connective tissue

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12
Q

Definition of hyperplasia

A

increase in number of cells

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13
Q

Definition of metaplasia

A

replacement of one mature cell type by another

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14
Q

Definition of Dysplasia

A

loss of cell uniformity/orientation [epithelial]

disordered proliferation, lack of progressiver maturation, differentiation

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15
Q

Definision of Desmoplasia

A

Stromal reactions [fibrosis-collagen] to invasion

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16
Q

Definition of Anaplasia

A

Complete lack of differentiation [malignancy]

Only in malignant tumor

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17
Q

What are 4 histologic criteria of tumor?

A
  1. uniformity of cells
  2. nuclei
  3. mitosis
  4. architecture
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18
Q

Pleomorphism

A

variation in size and shape

Cells and nuclei become less uniform

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19
Q

How do nuclei change in cancer

A

abnormal nuclear morphology

large nuclei, irregular, hyperchromatic

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20
Q

How does proliferative activity change in cancer?

A
  • higher proliferative activity

- more cells undergoing mitosis, atypical shapes

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21
Q

How does architecture change in cancer?

A

Loss of architecture
haphazard growth
irregular glands

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22
Q

How to measure differentiation in tumor cell

A
  • extent of resemblance to normal
  • evaluated on histologic sections
  • morphologically and functionally
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23
Q

Grading of tumors

A
  • quantitative evaluation of differentiation
  • predicts future behavior [prognosis]
    grade from 1-4
    1-2 = low grade
    3-4 = high grade
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24
Q

Benign tumor differentiation

A
  • very well differentiated
  • difficult to distinguish from normal
  • mass may be only sign of neoplasia
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25
Q

Malignant tumor differentiation

A
  • range of differentiation
  • grading: well, moderately, poorly
  • anaplasia: lack of differentiation
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26
Q

How is rate of tumor growth measured

A
  • doubling time
  • growth fraction
  • rate of cell loss

[cell production > cell loss, malignant > benign]

27
Q

At what stage clinically detectable? Incompatible with life?

A

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

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

28
Q

Local growth and invasion in benign vs malignant tumors

A

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
Q

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

A
  • marked dysplasia involving entire thickness of epithelium

- pre-invasive

30
Q

3 forms of metastatic spread

A
  • lymphatic spread: regional lymph nodes
    [carcinomas]
  • hematogenous: liver, lungs
    [carcinomas, sarcomas]
  • seeding of cavities: peritoneum, pleura
    [carcinomas]
31
Q

Tumor staging

A

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
Q

Is staging or grading more important for prognosis?

A

Staging is more important

33
Q

Risk factors for cancer

A
  • 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
Q

cancer cachexia

A
  • loss of body fat, lean muscle
  • weakness, anorexia, anemia
  • high BMR, catabolic rate
35
Q

paraneoplastic syndromes

A
  • 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
Q

Direct effects of cancer

A
  • pressure atrophy [glands]
  • obstruction/occlusion [tract]
  • destruction [rupture]
  • bleeding
  • ulcer [secondary infection]
  • infarction
37
Q

Cause of molecular carcinogenesis

A
  • mutations either inherited [germline] or acquired
38
Q

Main targets of mutations

A
  • oncogenes [gain of function, dominant]
  • tumor suppressors [LOF, recessive]
  • genes that regulated cell death
  • genes involved in DNA repair
39
Q

Haploinsufficiency

A

one allele loss

40
Q

8 steps of malignant transformation

A
  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
Q

retinoblastoma mech

A
  • due to point mutation/deletion

- gene = RB1 tumor suppressor

42
Q

chronic myelogenous leukemia mech

A
  • due to chromosome translocation

- gene = BRC-ABL proto-oncogene

43
Q

neuroblastoma mech

A
  • due to gene amplification

- gene = N-myc proto-oncogene

44
Q

breast/ovarian carcinoma

A
  • due to epigenetic mutagenesis

- gene = BRCA1 tumor suppressor

45
Q

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

A
  • due to mismatched base pairs, microsatellite instability
  • neoplasm = colon, endometrial
  • gene = MSH2, MLH1
  • syndrom = Lynch [HNPCC]
46
Q

Mech and Effect of Homologous recombination defect?

A
  • due to double stranded break, ionizing radiation
  • neoplasm = leukemia, lymphoma
  • gene = FANCA, ATM]
  • syndrome = Fanconi anemia, ataxia-telangiectasia
47
Q

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

A
  • due to cross linking, UV radiation
  • neoplasm: basal cell melanoma
  • gene: XPA, XPB
  • syndrome: xeroderma pigementosum [XP]
48
Q

Steps of multi-step carcinogenis in colon

A
  • normal colon
  • mucosa at risk
  • adenoma
  • carcinoma
49
Q

Steps of invasion and metastasis

A
  • 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
Q

Effect of UV rays

A
  • UVB exposure –> pyrimidine dimers

- can cause melanoma

51
Q

Disease associated with HPV

A

Cervical squamous cell carcinoma

52
Q

Disease associated with HBV/HCV?

A

Hepatocellular carcinoma

53
Q

Disease[s] associated with H pylori

A

gastric lymphoma/adenocarcinoma

54
Q

Venous thrombosis

A
  • trousseau syndrome
  • underlying neoplasm: pancreatic carcinoma
  • mech: hypercoaguable state
55
Q

sarcoma

A

maglinant neoplasm of mesenchymal cells

56
Q

carcinoma

A

– malignant neoplasm of cells differentiating toward epithelial cells

57
Q

What is doubling time

A

time it takes for a cell to divide

58
Q

What is growth fraction?

A

percent of neoplastic cells dividing

one of most important factors

59
Q

what grows faster malignant or benign

A

malignant

60
Q

What is most deadly disease? most prevalent?

A

most deadly = lung cancer

most prevalent = breast and prostate

61
Q

how can surgery change susceptibility to chemotherapy?

A
  • surgery pushes down growth fraction so can increase susceptibility to chemo
62
Q

What is adenoma?

A
  • benign epithelial neoplasm of glandular tissue
63
Q

Most common early mutation in colorectal adenoma?

A

APC!

Pathology (15 decks)

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