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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
Adenocarcinoma
Malignant gland formation Back-to-back gland growth Nuclear features of malignancy Often necrotic (due to outgrowth of blood supply)
26
Sarcoma
Malignant tumor of the mesenchymal tissue (adipose, fibroblasts, muscle) Ex: Leiomyosarcoma of the uterus Gross: Hemorrhage, necrosis Microscopic: Pleomorphic nuclei, mitotic figures
27
Lymphoma
"Fish-Flesh appearance" Malignant lymphoma in LNs Sarcomas
28
Malignant Lymphoma
Tumors derived from T cells and B cells
29
Dysplasia
Nuclear atypia Mild architectural changes Pre-malignant (at risk for cancer)
30
High Grade Dysplasia
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
Adenoma of the colon
Pencil nuclei neatly arranged, polarized basally, not very atypical, picket fence arrangement.
32
Adenoma with high grade dysplasia
Very atypical nuclei Crowded In situ carcinoma
33
Most breast carcinomas
Arise from duct epithelium
34
Invasive Breast Carcinoma - White
Fibrous
35
Invasive Breast Carcinoma - Yellow
Necrosis from having outgrown blood supply
36
Invasive Breast Carcinoma - Desmoplasia
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
Paget's Disease of Bone
Hyperproliferative bony disease
38
Paget's Disease of the Nipple
Intraductal breast cancer spreading to skin of nipple
39
3 theories of which malignant cells metastasize
Subclone Theory Cancer Stem Cell Theory Genetic Signature Theory
40
Subclone Theory
A sequence of mutation events lead to one of the cells eventually being able to metastasize
41
Cancer Stem Cell Theory
All mutations happen in the stem cells at the beginning of the lineage
42
Genetic Signature Theory
Many malignant cells at different stages have the signature genes allowing metastasis
43
Steps to metastasis
Invasion of BM & ECM Intravasation & Vascular Dissemination Extravasation, Colonization, Growth
44
Invasion of Basement Membrane & Extracellular Matrix
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
Degradation of Basement Membrane & Extracellular Matrix
``` Increase: Matrix MetalloProteinase Cathepsin D Urokinase plasminogen activator Type IV Collagenase ```
46
MMP9
Gelatinase | Acts on BM Type IV Collagen
47
Change in attachment of tumor cells to ECM proteins
Upregulate laminin integrins, make em sticky for extracellular matrix
48
Locomotion of Tumor Cells
Epithelial cells change their appearance to look more like stroma. Express vimentin and smooth muscle actin Epithelial Mesenchymal Transition
49
Intravasation & Vascular Dissemination
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
Extravasation, colonization & growth - Sites
``` Lungs Bone Brain Lymph Nodes Liver ```
51
Extravasation, colonization & growth - Mechanisms
``` Angiogenesis EMT Chemokine expression Adhesion molecules Down-regulate "metastasis suppressor proteins" ```
52
Example: Renal Cell Carcinoma metastasizes to the lungs
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
Types of VEGF
``` A B C D E ```
54
VEGF-C
Lymphangiogenesis
55
VEGF-A VEGF-B VEGF-D VEGF-E
Angiogenesis | Endothelial mitosis
56
Why does Breast Cancer with CXCR7 metastasize to the lung and liver?
Because there are target chemokine receptors in those organs!
57
Carcinoma Metastasis
Typically travels via lmyphatics to regional lymph nodes.
58
Sarcoma Metastasis
Typically travels via veins to lungs & bone
59
What metastasizes to the lung?
Colorectal Cancer Breast Cancer Renal Cell Carcinoma (invades renal veins, moves to IVC, RA, RV & PA) Hepatocellular Carcinoma
60
What metastasizes to the liver?
``` Colorectal Cancer Pancreas Cancer Other GI (Carcinoid, bile ducts) Lung Cancer Breast Cancer ```
61
What metastasizes to the bone?
``` 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
What metastasizes to the brain neuroaxis?
Typically via vertebral veins Lung Cancer Breast Cancer Melanoma Renal Cell Carcinoma
63
Gastric Carcinoma
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
Another place lung cancer metastasizes
Adrenal Glands
65
If you're doing flow cytometry to sort out lymphocytes on a heme specimen
Don't put it in formalin! Call pathology and find out the best method!
66
Peripheral tumors in the lung
More likely to be adenocarcinomas than the central ones.
67
EMT
Epithelial - Mesenchymal Transition Epithelial cells change their surface molecules to change their shape and blend in with nearby spindle cells. Important in metastasis.
68
Muscle Cell Marker expressed in EMT
Vimentin
69
What cell marker makes you slide through tissue better?
Smooth Muscle Actin
70
Krukenberg Tumor
Bilateral Ovarian metastasis of gastric carcinoma

Oncology (23 decks)

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