Pathoma - Carcinogenesis - Fundamentals Of Pathology

Front 1

A tumor is "driven" by _________________.

Back 1

DNA mutations

Front 2

What are carcinogens?

Back 2

Agents that damage DNA.

Front 3

Important carcinogens include (3)?

Back 3

(1) Chemicals
(2) Oncogenic viruses
(3) Radiation

Front 4

What are aflatoxins?

Back 4

Aspergillus can contaminate stored grains and this fungus can produce aflatoxins. Aflatoxins can increase the risk for hepatocellular carcinoma.

Front 5

Alkylating increase the risk of ______________ and ____________.

Back 5

leukemia; lymphoma

Front 6

When treating cancer patients with alkylating agents (e.g. cisplatin or carboplatin), there is a risk of developing what?

Back 6

secondary cancers like leukemias several years after treatment

Front 7

Alcohol is associated with what types of cancers?

Back 7

(1) SCC of the oropharynx
(2) Upper esophagus
(3) Pancreatic carcinoma (alcohol can cause chronic pancreatitis)
(4) Hepatocellular carcinoma (cirrhosis increases the risk for this CA)

Front 8

At the turn of the prior century, women who used to work out in the fields in England didn't want people to know that they were working in the sun (tanned skin), so they would apply arsenic to their skin to make it pale. They were at increased risk for what?

Back 8

(1) SCC of the skin

Front 9

How would you test for arsenic poisoning?

Back 9

Clip the finger nails or remove the hair. Arsenic can be found in these samples.

Front 10

Exposure to arsenic would make you susceptible to what kinds of cancer?

Back 10

(1) SCC of the skin
(2) Lung cancer (arsenic is in smoke)
(3) Angiosarcoma of liver

Front 11

A source of asbestos would be?

Back 11

(1) Insulation around pipes in naval ships
(2) Roofing material, ceiling tiles (takflis), floor tiles used > 20 years ago
(3) Demolition of old buildings

Front 12

These mineral dusts are very fibrogenic.

Back 12

Silica, asbestos, beryllium.

Front 13

Asbestos come in two geometric forms. What are they? What are their significance?

Back 13

(1) Serpentine
• Curly, flexible fibers.
• Produces interstitial fibrosis, lung cancer
(2) Amphibole
• Straight, rigid fibers
• Produces interstitial fibrosis, lung cancer, mesothelioma

Front 14

Asbestos fibers coated by iron and protein are called __________.

Back 14

ferruginous bodies

Front 15

Exposure to asbestos is more likely to lead to what type of cancer involving the lungs?

Back 15

Lung cancer, not mesothelioma.

Front 16

Exposure to asbestos increases the risk for _________ and ___________.

Back 16

(1) Lung CA
(2) Mesothelioma

Front 17

Cigarette smoke increases the risk for carcinoma what (5)?

Back 17

(1) CA of the oropharynx
(2) Esophagus
(3) Lung
(4) Kidney
(5) Bladder

Front 18

How many people worldwide smoke?

Back 18

1 billion people

Front 19

What is the most common carcinogen worldwide?

Back 19

Cigarette smoke

Front 20

The most important carcinogen in smoke is?

Back 20

Polycyclic hydrocarbons

Front 21

The key risk factor for urothelial carcinoma is ___________.

Back 21

cigarette smoke. Carcinogens are concentrated in the urine, bathing the urothelium in the process. Over a period of years, urothelial CA may ensue.

Front 22

Nitrosamines are highly associated with ___________. It is found in ____________ foods.

Back 22

stomach carcinoma; smoked

Front 23

This carcinogen is responsible for the high rate of stomach cancer in Japan.

Back 23

Nitrosamines

Front 24

What type of stomach carcinoma could you get from ingesting nitrosamines over long time?

Back 24

Intestinal type of stomach carcinoma (most common type of gastric adenocarcinoma)

Front 25

Two patients from Japan come into your office. Patient A on the left and patient B on the right. What could be the underlying cause of this?

Back 25

Front 26

This is the most common benign tumor of the stomach.

Back 26

Leiomyoma

Front 27

There is an increased risk of primary stomach adenocarcinomas in individuals of what blood type?

Back 27

Blood type A

Front 28

The most important risk factor for developing intestinal type gastric carcinoma is?

Back 28

Intestinal metaplasia due to H. pylori

Front 29

What could be a typical presentation of stomach cancer?

Back 29

• Cachexia and weight loss (most common; 60%)
• Epigastric pain (50%)
• Metastasis to left supraclavicular node (Virchow's node)

Front 30

Aside from arsenic and polycyclic hydrocarbons in cigarette smoke, this carcinogen from cigarette smoke may cause urothelial CA of the bladder.

Back 30

Naphthylamine

Front 31

A man in his 50's has been smoking for as long as he can remember. He presents with a painless hematuria, fatigue and malaise. He has lost weight. What could be going on?

Back 31

Transitional cell CA of the bladder. Painless hematuria is the most common sign.

Front 32

Nitrosamines are found in what type of beverage?

Back 32

Beer

Front 33

A group of workers are making plastic pipes. What cancer are the workers at risk for?

Back 33

Angiosarcoma of the liver due to vinyl chloride exposure (PVC is in the pipes)

Front 34

These four chemicals are carcinogens seen in occupational exposure. What are they and what can they predispose to?

Back 34

Nickel, chromium, beryllium, silica

Lung carcinoma

Front 35

EBV is associated with what cancers?

Back 35

(1) Nasopharyngeal carcinoma
• Clasically shows up in a chinese male.
• Clasically it presents as a neck mass because the tumor early metastasizes.

(2) Burkitt lymphoma
• African individual

(3) CNS lymphoma in AIDS

Front 36

Human herpesvirus 8 is associated with what cancer? What people get this cancer?

Back 36

Kaposi's sarcoma. Tumor of endothelial cells.

Three subtypes of patients get this sarcoma:
• Older Eastern European male (is excised)
• AIDS patients (antiretroviral agents)
• Transplants, because of immunosuppression. (reduce immunosuppression slightly)

Front 37

Hepatitis B virus and hepatitis C virus are implicated in the development of what cancer?

Back 37

Hepatocellular carcinoma.

Front 38

HBV is a _________ (DNA/RNA) virus.

Back 38

DNA

Front 39

HCV is a _________ (DNA/RNA) virus.

Back 39

RNA

Front 40

HTLV-1 is associated with what cancer?

Back 40

Adult T-cell leukemia/lymphoma

Front 41

High-risk HPV (e.g., subtypes 16, 18, 31, 33) are associated with what cancers?

Back 41

• SCC of the vulva
• SCC of the vagina
• SCC of the anus
• SCC of the cervix
• Adenocarcinoma of the cervix

Front 42

What type of radiation would be seen in a nuclear reactor accident?

Back 42

Ionizing radiation

Front 43

What type of radiation would be seen in radiotherapy?

Back 43

Ionizing radiation

Front 44

A child has been exposed to radiation in a nuclear reactor accident. What cancers could be seen in this child over time?

Back 44

• Papillary carcinoma of the thyroid
• AML
• CML

Front 45

The most common source of nonionizing radiation is _____.

Back 45

UVB sunlight

Front 46

UVB (nonionizing radiation) can cause what cancers?

Back 46

• SCC of the skin
• Basal cell carcinoma of the skin
• Melanoma of the skin

Front 47

UVB causes damage to DNA by ______________.

Back 47

causing the formation of pyrimidine dimers which are normally excised by restriction endonuclease

Front 48

DNA mutations eventually disrupt what? What is the consequence?

Back 48

Key regulatory systems. This allows for tumor promotion (growth) and progression (spread).

Front 49

The three key regulatory systems that may become disrupted include [...]

Back 49

• Proto-oncogenes
• Tumor suppressor genes
• Regulators of apoptosis

Front 50

What are proto-oncogenes?

Back 50

Genes that are essential for cell growth and differentiation.

Front 51

When a proto-oncogene mutates, it becomes a/an _________, which leads to _______________.

Back 51

oncogene; unregulated cell growth

Front 52

What are the key categories of oncogenes?

Back 52

• Growth factors
• Growth factor receptors
• Signal transducers
• Cell cycle regulators

Front 53

Provide an example of a growth factor proto-oncogene/oncogene and its associated tumor.

Back 53

In astrocytomas, there is a mutation leading to overexpression of PDGF beta. PDGF will stimulate the cells in an autocrine fashion.

Front 54

What are some growth factor receptors that can be mutated and what tumors are they associated with?

Back 54

• HER2/neu. Subset of breast CA.
• RET. MEN2A, MEN2B, sporadic medullary CA of thyroid
• KIT.

Front 55

This growth factor receptor is amplified in a subset of breast cancers. What is it? What drug can be used in the treatment of these subtypes of breast cancer?

Back 55

HER2/neu (encoded by ERBB2). Trastuzumab (herceptin).

Front 56

What should you do in a patient suspected of having MEN2? If it comes out positive, what should be done?

Back 56

RET study. Prophylactically remove the thyroid.

Front 57

HER2/neu is a/an ______________(epidermal-/neural growth factor receptor).

Back 57

epidermal growth factor receptor

Front 58

RET is an _______________ (neural-/stem cell growth factor receptor).

Back 58

neural growth factor receptor

Front 59

A point mutation in what growth factor receptor is associated with GI stromal tumors?

Back 59

KIT

Front 60

What is probably the most important signal transducer gene family to be aware of? What does the gene transcribe?

Back 60

RAS gene family.

GTP-binding proteins.

Front 61

RAS gene family is commonly mutated in ___________ (a few/large number) of cancers.

Back 61

large number

Seen in CA, melanomas and lymphomas.

Front 62

RAS in its "off" state is associated with _______.

Back 62

GDP

Front 63

The moment that a growth factor binds to its receptor, what happens with RAS?

Back 63

It is now associated with GTP. RAS-GTP can now send the signal further to the nucleus.

Front 64

What helps RAS to hydrolyse GTP to GDP?

Back 64

GAP (GTP-Associated Protein)

Front 65

What is another important signal transducer outside of RAS? What type of transducer is it?

Back 65

ABL. It's a tyrosine kinase.

Front 66

When there is a t(__;__) translocation with ____, there is overactivation of this tyrosine kinase, leading to what cancers?

Back 66

t(9;22); BCR

CML and some types of ALL.

Front 67

In what age group of patients with ALL do we see a t(9;22) translocation?

Back 67

Adults. Poor prognosis.

Front 68

The chromosome resulting from t(9;22) is called the ___________ chromosome

Back 68

philadelphia

Front 69

What is the category of proto-oncogenes for the following proteins: c-MYC, N-MYC, L-MYC.

Back 69

Nuclear regulators. They are transcription factors.

Front 70

The mechanism by which N-MYC and L-MYC become overactive and produce cancer is by amplification. However, for c-MYC, this mechanism involves __________.

Back 70

translocation (t[8;14] involving IgH

Front 71

Burkitt's lymphoma is a lymphoma of __________ (B-Cells/T-Cells)

Back 71

B-Cells

Front 72

Immunoglobulin heavy chain locus sits on chromosome ____.

Back 72

14

Front 73

One of the key histologic findings in Burkitt's lymphoma is called ____________. Describe it.

Back 73

Starry sky appearance. Tumor cells represent the "sky", they are blue. Stars are little white areas that are interspersed (strødd inn i) between the tumor areas. White areas represent areas of macrophages eating cells that are dying. The idea is that cells are growing so rapidly (massive overproduction of myc) that they actually grow and die.

Front 74

N-myc and L-myc are associated with what cancers?

Back 74

• Neuroblastoma
• Lung carcinoma (small cell)

Front 75

Fill in the blank. These are categories of proto-oncogenes implicated in causing cancers: Growth factors, growth factor receptors, signaling transducers, nuclear regulators and ____________.

Back 75

cell cycle regulators

Front 76

What is the action of cell cycle regulators?

Back 76

They assist movement through the cell cycle

Front 77

What is the stage of the cell cycle that is the most highly regulated.

Back 77

G1 to S

Front 78

Mantle cell lymphomas are composed of B cells that resemble cells in the mantle zone of ____________.

Back 78

Normal lymphoid follicles

Front 79

The "B-area" of the lymph node is the __________ (cortex/paracortex/medulla)

Back 79

cortex

Front 80

Outside the mantle area surrounding lymphoid follicles, you can develop a region called ____________.

Back 80

margin

Front 81

Draw the cell cycle

Back 81

Front 82

A 55-year old man presents with fatigue and painless lymphadenopathy. The tip of his spleen is felt on palpation. Multifocal submucosal nodules that resemble polyps are found in his GI tract. A biopsy of lymph node shows expansion of the region next to the follicle. What cancer could it be and what is the characteristic immunophenotype for this tumor?

Back 82

Mantle cell lymphoma. The GI involvement is characteristic.

Cyclin D1 protein overexpression due to t(11;14) translocation. Cyclin D1 promotes G1 to S.

Front 83

What neoplasms may arise in the three key B-region area of a lymph node?

Back 83

Front 84

This syndrome is a risk factor for developing malignant melanoma. What is this syndrome? Give three facts.

Back 84

Dysplastic nevus syndrome.

• Majority develop malignant melanoma.
• > 100 nevi on the skin
• AD

Front 85

What are the ABCD signs of melanoma?

Back 85

Front 86

An asian man visits his local physician. He shows him his finger. The physician says that this is related to sun exposure. Is he correct? Give four facts about this condition.

Back 86

No. This is acral lentiginous melanoma.

• 2-8% of cases
• Palms/soles/nail
• Most common in asians and blacks.
• Poor prognosis

Front 87

For melanoma prevention you should use a sunscreen of ____.

Back 87

> 15 SPF

Front 88

What is the most important prognostic indicator in malignant melanoma?

Back 88

Depth of invasion.

Front 89

This type of melanoma is common in the elderly (4-10% of cases). It is least likely to have a vertical phase. What is it?

Back 89

Lentigo maligna melanoma

Front 90

What cell cycle regulator is highly amplified in the tumor represented by the above histograph?

Back 90

This is malignant melanoma. Cells have a radial growth (single and nests of cells in epidermis).

CDK4 is amplified.

Front 91

Compare classical features of benign and malignant tumors. Why are the listed features not sufficient to classify a tumor as benign of malignant.

Back 91

Benign:
• Slow growing
• Well circumscribed
• Distinct
• Mobile

Malignant:
• Rapid growing
• Poorly circumscribed
• Infiltrative
• Fixed to surrounding tissue

Remember, malignant tumors can have benign features and vice versa. That's why these are only screening procedures. The only way to make an absolute diagnosis of CA is biopsy or excision.

Front 92

What is nuclear pleomorphism?

Back 92

It means that some nuclei are small and some are big.

Front 93

What are some nuclear characteristics of malignant tumors?

Back 93

• Nuclear pleomorphism
• Nuclear hyperchromasia (dark blue)
• High N:C ratio (indicates a very active cell)
• High mitotic activity

Front 94

Malignant tumors and benign tumors can share each others properties to some extent. In that case, what is the absolute distinguishing feature between benign and malignant?

Back 94

Metastatic potential

Front 95

One important clinically useful test in the context of neoplasia is _______________.

Back 95

immunohistochemistry

Front 96

You look in the microscope and observe a very poorly differentiated tumor. You generate a long differential in your head (e.g., epithelial origin, sarcoma, mesenchymal origin). How do we narrow down this differential list and how does this technique work?

Back 96

Immunohistochemistry. We take an antibody against a particular antigen and we label it with a brown stain and place the antibody on the cells.

Front 97

What is the function of vimentin and in what type of tumor would you get a positive immunohistochemistry result from?

Back 97

Surrounds nuclear envelope; is associated with cytoplasmic aspect of nuclear pore complex.

Mesenchymal cells have this intermediate filament so it would show up in sarcomas.

Front 98

The intermediate filment that would allow you to distinguish a poorly differentiated tumor as epithelial would be?

Back 98

Keratin

Front 99

The intermediate filment that would allow you to distinguish a poorly differentiated tumor as originating from muscle cells is?

Back 99

Desmin

Front 100

What role to desmin play in muscle?

Back 100

Myofibrils are held in register with one another by the intermediate filament desmin,which secure the periphery of the Z disks of neighboring myofibrils to each other and attach them to the plasma membrane.

Front 101

A neuroglial cell tumor would be positive for what intermediate filament?

Back 101

GFAP

Front 102

A tumor comprised of neurons would be positive for what intermediate filament?

Back 102

Neurofilament

Front 103

You have a carcinoma with glands in your microscope. You are concerned where it might be from. What could you do? Give examples.

Back 103

Immunohistochemical stains:
• PSA --> Prostatic epithelium
• ER (Estrogen receptor) --> Breast
• Thyroglobulin --> Thyroid follicular cells
• Chromogranin --> Neuroendocrine carcinomas (e.g. small cell and carcinoid)

Front 104

True or false: Small cell carcinoma and carcinoid tumor are derived from the same cell type, i.e. neuroendocrine cells.

Back 104

True. Small cell carcinoma is the most poorly differentiated neuroendocrine tumor while carcinoid is the most well differentiated one.

Front 105

This stain is particularly useful for melanoma.

Back 105

S-100

Front 106

What are serum tumor markers?

Back 106

They are proteins released by tumor cells.

Front 107

How can serum tumor markers be useful?

Back 107

• As a screening test, e.g. PSA
• Monitor response to treatment
• Monitoring recurrence

Front 108

You do a screening with PSA. It is severely elevated. You suspect prostate cancer. What is the next appropriate step to confirm cancer?

Back 108

Elevated levels of tumor markers require tissue biopsy for diagnosis of carcinoma.

Front 109

What is done after screening has suggested cancer and biopsy has shown that this is in fact cancer?

Back 109

Grade the cancer, which is important for prognosis.

Front 110

Grading a cancer involves asking the question: "[...]?"

Back 110

Does the tumor look like the tissue in which it is growing?

Front 111

Well differentiated means that a tumor ____________.

Back 111

Resembles parent tissue

Front 112

Poorly differentiated means that the tumor ______________.

Back 112

does not resemble parent tissue

Front 113

Grading takes into account what?

Back 113

The architecture, does it resemble parent tissue?

&

The nuclear features, does it resemble parent tissue?

Front 114

Grading is important for determining the _____________, however, the number one factor determining this is _________.

Back 114

prognosis; staging

Front 115

Staging asks the questions [...]

Back 115

(1) How far has the cancer grown? (Size)
(2) How far has the cancer spread? (Spread)

Front 116

What system do we use for staging?

Back 116

TNM

T - size (solid organs such as breast)/depth of invasion (tubular organs such as bowel)
N - spread to regional lymph nodes (second most important prognostic factor)
M - metastasis (single most important prognostic factor)