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Oncology > 2 - Neoplasia > Flashcards

2 - Neoplasia Flashcards

1
Q

What prevents a benign tumor from becoming malignant?

A

They don’t develop subsequent mutations, or don’t develop the right ones to metastasize.
They retain well-controlled growth, benign histologic features.

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2
Q

What allows malignant tumors to metastasize?

A

They develop subsequent multiple mutations, overexpressions, acquired enzyme pathways (eg telomerases), loss of cell adhesion markers
They develop capacity for invasion & metastasis
They acquire gross & microscopic features of malignancy

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3
Q

Steps in normal physiologic cell proliferation

A 
GF binds TM GF-Receptor
Signal Transduction
2nd messengers & kinase pathway
DNA transcription
Cell Cycling (G1-S-G2-M)
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4
Q

Inactive RAS

A

Bound to GDP

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5
Q

Activated RAS

A

Switched out by GTP

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6
Q

Active RAS inactivates itself by

A

Hydrolyzing GTP to GDP.

Mutation preventing this inactivation leads to cancer.

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7
Q

The most commonly mutated proto-oncogene in human tumors

A

RAS

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8
Q

Steps downstream of RAS

A

PI3K
AKT
mTOR

or

RAF
MAPK

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9
Q

KRAS

A

Human homologue of the Kirsten Rat Sarcoma Oncogene

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10
Q

NRAS

A

Human homologue of the Neuroblastoma RAS Oncogene

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11
Q

Melanoma steps

A 
Benign Nevus
Dysplastic Nevus
Radial Growth Phase
Vertical Growth Phase
Metastatic Melanoma
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12
Q

Melanoma - Benign Nevus

A

BRAF mutation

Benign, limited growth

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13
Q

Melanoma - Dysplastic Nevus

A

Previous: BRAF

CDKN2A loss
PTEN loss

Premalignant, lesions may regress.
Random atypia

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14
Q

Melanoma - Radial Growth Phase

A

Previous:
BRAF mutation
CDKN2A loss
PTEN loss

Increased CD1

Decreased differentiation
Unlimited hyperplasia
Cannot grow in soft agar
Clonal proliferation

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15
Q

Melanoma - Vertical Growth Phase

A 
Previous:
BRAF mutation
CDKN2A loss
PTEN loss
Increased CD1
E-Cadherin Loss
N-Cadherin Expression
αVβ3 Integrin Expression
MMP-2 Expression
Survivin
Reduced TRPM1

Crosses basement membrane
Grows in soft agar
Forms tumor

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16
Q

Melanoma - Metastatic

A 
Previous:
BRAF mutation
CDKN2A loss
PTEN loss
Increased CD1
E-Cadherin Loss
N-Cadherin Expression
αVβ3 Integrin Expression
MMP-2 Expression
Survivin

Absent TRPM1

Dissociates from primary tumor
Grows at distant sites

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17
Q

ERBB1 (EGF receptor)

A

Overexpressed in 80% of squamous cell lung cancer

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18
Q

HER2/NEU (ERBB2)

A

Amplified in 25 - 30% of breast cancers
Bad prognosis

Treat with HER2/NEU antibodies to block the signals of cell division

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19
Q

Benign Tumor - Gross Path

A 
Usually Small (grows to a limited size, then stops)
Well-Circumscribed
Closely resembles tissue of origin
Does not invade or metastasize.
May be encapsulated in fibrous tissue
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20
Q

Malignant Tumor - Gross Path

A 
May be small or may reach large size
Poorly circumscribed
Differentiation may range from well to poorly differentiated.
Cytologic features of malignancy
Capable of invasion and metastasis.
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21
Q

Malignant Tumor - Histo

A 
Increased Nucleus:Cytoplasm ratio
Nuclear hyperchromatism
Prominent Nucleoli
Nuclear Pleomorphism
Increased mitotic rate
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22
Q

Squamous Cell Carcinoma - Where could it come from?

A 
Skin
Esophagus
Lung
Cervix
Anus
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23
Q

Identify squamous cell carcinoma of the skin

A

Look for keratin pearls

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24
Q

Squamous Cell Carcinoma - Identifier

A

Tonofilaments (Intercellular bridges)

Perpendicular between tumor cells

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25
Q

Adenocarcinoma

A

Malignant gland formation
Back-to-back gland growth
Nuclear features of malignancy
Often necrotic (due to outgrowth of blood supply)

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26
Q

Sarcoma

A

Malignant tumor of the mesenchymal tissue (adipose, fibroblasts, muscle)

Ex: Leiomyosarcoma of the uterus

Gross: Hemorrhage, necrosis
Microscopic: Pleomorphic nuclei, mitotic figures

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27
Q

Lymphoma

A

“Fish-Flesh appearance”
Malignant lymphoma in LNs
Sarcomas

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28
Q

Malignant Lymphoma

A

Tumors derived from T cells and B cells

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29
Q

Dysplasia

A

Nuclear atypia
Mild architectural changes
Pre-malignant (at risk for cancer)

30
Q

High Grade Dysplasia

A

In situ carcinoma
Carcinoma in situ

Epithelial cells have cytologic features of malignancy
Still ABOVE basement membrane

Ex: DCIS in breast (Ductal carcinoma in situ)

31
Q

Adenoma of the colon

A

Pencil nuclei neatly arranged, polarized basally, not very atypical, picket fence arrangement.

32
Q

Adenoma with high grade dysplasia

A

Very atypical nuclei
Crowded
In situ carcinoma

33
Q

Most breast carcinomas

A

Arise from duct epithelium

34
Q

Invasive Breast Carcinoma - White

A

Fibrous

35
Q

Invasive Breast Carcinoma - Yellow

A

Necrosis from having outgrown blood supply

36
Q

Invasive Breast Carcinoma - Desmoplasia

A

Reactive fibrous tissue response

Neoplastic cells incite a local fibroblastic response in the primary sites as well as distant ones.

That’s why lymph nodes become hard and fixed!!

37
Q

Paget’s Disease of Bone

A

Hyperproliferative bony disease

38
Q

Paget’s Disease of the Nipple

A

Intraductal breast cancer spreading to skin of nipple

39
Q

3 theories of which malignant cells metastasize

A

Subclone Theory
Cancer Stem Cell Theory
Genetic Signature Theory

40
Q

Subclone Theory

A

A sequence of mutation events lead to one of the cells eventually being able to metastasize

41
Q

Cancer Stem Cell Theory

A

All mutations happen in the stem cells at the beginning of the lineage

42
Q

Genetic Signature Theory

A

Many malignant cells at different stages have the signature genes allowing metastasis

43
Q

Steps to metastasis

A

Invasion of BM & ECM
Intravasation & Vascular Dissemination
Extravasation, Colonization, Growth

44
Q

Invasion of Basement Membrane & Extracellular Matrix

A

Loss of E-Cadherin (loosening of tumor cells)
Inappropriate expression of SNAIL & TWIST, which regulate E-Cadherin expression

Secondarily - Beta-Catenin (proliferator) is no longer sequestered by E-Cadherin, so more tumor cells can proliferate too.

45
Q

Degradation of Basement Membrane & Extracellular Matrix

A 
Increase:
Matrix MetalloProteinase
Cathepsin D
Urokinase plasminogen activator
Type IV Collagenase
46
Q

MMP9

A

Gelatinase

Acts on BM Type IV Collagen

47
Q

Change in attachment of tumor cells to ECM proteins

A

Upregulate laminin integrins, make em sticky for extracellular matrix

48
Q

Locomotion of Tumor Cells

A

Epithelial cells change their appearance to look more like stroma. Express vimentin and smooth muscle actin

Epithelial Mesenchymal Transition

49
Q

Intravasation & Vascular Dissemination

A

Mass squeezes into capillary, shear stress frees some cells.
NK cells induce apoptosis
Macrophages phagocytose
Platelets adhere to tumor cells
TNF-α & IFN-γ change the endothelium to be more permissive.

This means the large majority are killed in transit, but some cells migrate successfully.

50
Q

Extravasation, colonization & growth - Sites

A 
Lungs
Bone
Brain
Lymph Nodes
Liver
51
Q

Extravasation, colonization & growth - Mechanisms

A 
Angiogenesis
EMT
Chemokine expression
Adhesion molecules
Down-regulate "metastasis suppressor proteins"
52
Q

Example: Renal Cell Carcinoma metastasizes to the lungs

A

Tumor cell reaches the alveolar space via blood vessels.
Tumor cell induces vascular sprouting via:

TGF-α, β
PDGF
FGF
EGF
Angiogenin
HIF-1α
VEGF
Angiopoietin 1 & 2
53
Q

Types of VEGF

A 
A
B
C
D
E
54
Q

VEGF-C

A

Lymphangiogenesis

55
Q

VEGF-A
VEGF-B
VEGF-D
VEGF-E

A

Angiogenesis

Endothelial mitosis

56
Q

Why does Breast Cancer with CXCR7 metastasize to the lung and liver?

A

Because there are target chemokine receptors in those organs!

57
Q

Carcinoma Metastasis

A

Typically travels via lmyphatics to regional lymph nodes.

58
Q

Sarcoma Metastasis

A

Typically travels via veins to lungs & bone

59
Q

What metastasizes to the lung?

A

Colorectal Cancer
Breast Cancer
Renal Cell Carcinoma (invades renal veins, moves to IVC, RA, RV & PA)
Hepatocellular Carcinoma

60
Q

What metastasizes to the liver?

A 
Colorectal Cancer
Pancreas Cancer
Other GI (Carcinoid, bile ducts)
Lung Cancer
Breast Cancer
61
Q

What metastasizes to the bone?

A 
Breast Cancer (Osteolytic - often presents with pathologic fracture or osteoblastic)
Prostate Cancer (Osteoblastic - typically causes excess production of bone, when it metastasizes there)
Renal Cell Cancer
62
Q

What metastasizes to the brain neuroaxis?

A

Typically via vertebral veins

Lung Cancer
Breast Cancer
Melanoma
Renal Cell Carcinoma

63
Q

Gastric Carcinoma

A

Signet Ring Carcinoma

Metastasizes to:
Virchow's Node (supraclavicular)
St. Mary Joseph's Nodule (lymph node near the umbilicus)
Krukenberg tumor
(Bilateral ovarian mets)
64
Q

Another place lung cancer metastasizes

A

Adrenal Glands

65
Q

If you’re doing flow cytometry to sort out lymphocytes on a heme specimen

A

Don’t put it in formalin!

Call pathology and find out the best method!

66
Q

Peripheral tumors in the lung

A

More likely to be adenocarcinomas than the central ones.

67
Q

EMT

A

Epithelial - Mesenchymal Transition
Epithelial cells change their surface molecules to change their shape and blend in with nearby spindle cells.

Important in metastasis.

68
Q

Muscle Cell Marker expressed in EMT

A

Vimentin

69
Q

What cell marker makes you slide through tissue better?

A

Smooth Muscle Actin

70
Q

Krukenberg Tumor

A

Bilateral Ovarian metastasis of gastric carcinoma

Oncology (23 decks)

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