Pbd - Week 11

Front 1

What are 5 possible mechanisms by which tumors can evade the immune system?

Back 1

1. Produce cytokines which kill CD8 cells

2. Decrease MHC I expression (this backfires though b/c it increases NK cell affinity)

3. Decrease immungenicity - proteins that CA cells make may mask tumor Ag

4. Immunosuppression d/t TGF-B that tumor makes, or d/t chemo treatment

5. Tumors usually don't provide adaquate co-stimulation

Front 2

Can HPV alone produce invasive CA? If not, how does cervical CA develop?

Back 2

No - intraepithelial changes can be induced by HPV alone, producing SIL, but progression to carcinoma requires loss of E2 function, which requires a break of the viral genome, which presumably requires some environmental carcinogen. Also need the T-zone and other predisposers to develop CA

Front 3

What are the 4 types of HPV contained in the vaccine? Which types mainly cause warts and which types cause CA?

Back 3

HPV vaccine contains the following types:
6 & 11 = major but not exclusive cause of warts
16 & 18 = major but not exclusive cause of cancer

Front 4

What is the difference between high and low grade SIL?

Back 4

High grade = neoplastic cells occupy most of the thickness with ++ nuclear atypia

Low grade = neoplastic cells occupy only a small portion of the cervical thickness and have mild nuclear atypia

Front 5

What is the natural Hx (time to onset & course) of low and high grade SIL of the cervix?

Back 5

Low grade - appears immediately but tends to regress spontaneously

High grade - takes months --> years to appear and has a ++ variable course

Front 6

What are the molecular events that lead to cervical cancer? (ie what is the effect of viral oncoproteins?

Back 6

Viral oncoproteins (E6 &E7) interact with tumor suppressor genes causing either of the following:
- degrading: E6 ----> p53
- inactivation: E7 -----/ RB

Front 7

What 3 host factors contribute to the variability in expression of HPV infection?

Back 7

1. Presence of a co-infection, which will cause inflammation that affects cell proliferation
2. Smoking: thought to be mutagenic and thus increases risk
3. Immune status: greater risk among immuno suppressed (HIV)

Front 8

What are 3 serum tumor markers?

Back 8

1. PSA - prostate
2. CA 125 - ovary
3. Alpha Fetoprotein - testicular

** Not generally useful in establishing intitial Dx but used more for monitoring purposes (ie they may indicate the recurrence of disease)

Front 9

What features (cellular and location) would help distinguish Lung squamous cell carcinoma from adenocarcinoma?

Back 9

SCC: look for inter-cellular bridges & keratinization
Adeno: glandular architecture +- mucin

SCC: central, hilar
Adeno: peripheral

Front 10

Excluding the thyroid and salivary glands, what type of CA are vast majority of Head & Neck tumors?

Back 10

Squamous Cell Carcinomas

Front 11

What are the risk factors for Oral Cavity SCC
(6)
Hint one of them is "bete quid"

Back 11

Risk Factors:
- cigarette smoking
- alcohol
- betel quid (chewed in India)
- Cheweing tobacco & pipes
- HPV
- UV

Front 12

Which is more ominous Leukoplakia or erythroplakia? WHy?

Back 12

Erythroplakia b/c unlike Leukoplakia these are usually dysplastic or CIS or early invasions.

Leukoplakia usually only has thickening of the squamous epithelium --> hyperkeratosis --> early dysplasia

Front 13

Describe the following tumor: Pleomorphic Adenoma
- B or M?
- contains what type(s) of cells?
- Tx?
- Risk of carcinoma?

Back 13

Pleomorphic Adenoma
- Benign
- mix of ductal and myoepitheloid cells (mixoid supporting stroma)
- Tx = Sx (will recur if not fully removed)
- Rarely a risk of carcinoma if left to grow for ++++ time

Painless & slow growing!

Front 14

Describe the following tumor: Warthin's Tumor
- B or M?
- population at risk?
- contains what type(s) of cells?
- Tx?
- Risk of carcinoma?

Back 14

Warthin's Tumor
- Benign
- men > women, 5-->7th decade
- Lymphoid tissue: germinal centre surrounded by a double layer of epithelial cells
- Sx reserction (v. low risk of recurrence)
- Malignant t-formation is VERY rare!

Front 15

Describe the following tumor: Mucoepidermoid Carcinoma
- B or M?
- population at risk?
- contains what type(s) of cells?
- Prognosis depends on what?
- Grade depends on what?

Back 15

Mucoepidermoid Carcinoma
- Malignant
- Women > Men; kids & adolescents
- Mix of: mucin-secreting, clear cells, squamous cells, intermediate cells
- Prognosis depends on tumor location, stage, grade, pt age & sex (better if female)
- Grade depends on amount of mucin-secreting cells, higher the grade the worse the prognosis

Front 16

Describe the following tumor: Adenoid Cystic Carcinoma
- B or M?
- population at risk?
- contains what type(s) of cells?
- Tx?
- Prognosis depends on what 4 things?

Back 16

Adenoid Cystic Carcinoma
- Malignant
- Females > Males, 6th decade (++ common in minor SG's)
- "bland cells" whose architecture is cribiform, tubular or solid
- Tx: Sx resection with radiation
- Prognosis: depends on tumor location, stage, size and architecture (solid = worse)

Front 17

What are 3 requirements of effective CA screening?

Back 17

1. Must be able to identify a population of "at risks"
2. Screening test must be cheap, safe & acceptable (reasonable)
3. Must have an intervention available to increase survival

Front 18

What is the difference between histopathology and cytopathology?

Back 18

Histopathology: looks at biopsied or resected tissues therefore get cells in their architecture (= more informative)

Cytopathology is used for aspirates, don't get architecture (good for Lung & thyroid)

Front 19

Define Leukemia.

Define Lymphoma

Back 19

Leukemia = neoplasms with widespread involvement of the bone marrow and usually peripheral blood

Lymphoma = neoplasms WITHOUT involvement of the blood, usually arising as DISCRETE MASSES

Front 20

Describe, in general terms how blood cancers occur?
(3main steps - hint available)

Back 20

- arise as a result of genetic mutations in the germline
- cause unregulated proliferation of cells of a single type (clonal prolif)
- the abnormal clone intergeres with and overwhelms normal blood cell production & function

Hint 20

- arise as a result of......
- cause unregulated.........
- leading to...............

Front 21

What 3 host factors would predispose a person to getting leukemia?

Back 21

1. Inheritend tendency for Xsome fragility, abnormality or increase #

2. Inherited immunodeficiency

3. Chronic bone marrow dyfunction e.g. aplastic anemia

Front 22

Reed-Sternberg Cells are pathognomic for what disease?

Back 22

Hodgkins lymphoma!

Sa-weeet

Front 23

T-locations in the philadelphia Xsome, (seen in what type of leukemia?) results in variable fusion of what 2 genes?
Kind of a doozy - but good if you can get it!

Back 23

- seen in CML
- result in varibale fusion of ABL and BCR genes

Front 24

For each of the following drugs, list their target:
Gleevac:
Retuximab:
Retinoic Acid:

Back 24

Gleevac: targets a specific type of T-kinases, including BCR

Retuximab: Ab against Bcell receptor CD20 (good for B-cell Lymphomas)

Retinoic acid: used for AP-leukemia where there is a fusion that creates retinoic acid receptorp

Front 25

Compare acute (A) and chronic (C) leukemia in the following ways:
- age of onset
- course if untreated
- anemia/T-cytopenia
- WBC count

Back 25

Age: all (A) adults (C)
Course: <6mo (A) 2-6yrs (C)
anemia/T-penia: prominent (A) mild (C)
WBC: variable (A) increased (C)

Front 26

For each of the following leukemia symptoms, explain the underlying mechanism:
1. Rashes --> tumors
2. Bone marrow failure (2 things)
3. Hemorrhage/infection

Back 26

1. Leukemi proliferation accumulation and invasion of normal tissues
2. Leukemic cells crowd-out other cells in Bmarrow and may also secrete a mediator that inhibits the proliferation of normal cells
3. failure of Bmarrow & hematopoeisis leading to pancytopenia

Front 27

Where do basal cell ca's arise from? How about squamous cell CA? (of the skin)

Back 27

Basal cell = basal cells of epidermis

Squamous cell = abnormal skin or mucous membranes

Front 28

For skin CA's, which is more aggressive, basal cell carcinoma or squamous cell?

Will either one of these metastasize?

Tx?

Back 28

Squamous cell CA is more aggressive,
Both will rarely mets, except for oral squamous CA which are more likely to spread

Tx for both is surgical excision

Front 29

For the following types of Hopigmentation, explain the defect:
- Albinism
- Vitiligo

Back 29

Albinism: defective or absent tyrosine resulting in decreased or absent MELANIN

Vitiligo: autoimmune disorder causing partial or total loss of MELANOCYTES

Front 30

For the following types of H-pigmentation explain the defect:
- Ephelid
- Lentigo

Back 30

Ephelid= "freckles" areas of increased MELANIN production that fade & intesify with the sun

Lentigo = focal areas of increased # of MELANOCYTES, color stable regardless of sun

Front 31

What is a Nevus? How does it's appearance change when it becomes dysplastic?

Back 31

Nevus = uniformly pigmented macules/papules with well defined borders. When it becomes dysplastic, the color is less uniform and the borders are less well defined.

Front 32

What are the 3 main causes of malignant melanoma?

Back 32

1. UV light exposure
2. Previous dysplastic mole
3. Genetics - p16 mutations

Front 33

In malignant melanoma, you have proliferation of large malignant melanocytes where in the skin?

In what direction do these cells migrate?

Back 33

Malignant melanoma = proliferation in basal layer of epidermis

Cells migrate upwards through the epidermis,

** there's variable invasion downwards with no evidence of "maturation"

Front 34

What is the most important prognosis factor for malignant melanoma? What are the 3 criteria of this factor?

Back 34

Stage is the most important prognosis factor.
1. depth of invasion (either by clark's levels or by Breslow thickness)
2. L-node mets
3. distant mets