Handout Neoplasia Two

Question 1

Cachexia

Answer 1

catabolic state of severe wasting mediated by TNF

Question 2

Paraneoplastic Syndrome

Answer 2

Symptoms not attributable to direct effects of tumor (or hormones native to the primary tumor organ)

Question 3

Tumor grade

Answer 3

qualitative microscopic assessment of the differentiation of a tumor

Question 4

Tumor stage

Answer 4

anatomic extent of tumor, including primary tumor size, extent of lymph node and distant metastases

Question 5

Biopsy

Answer 5

tissue sample obtained by surgical or endoscopic forceps, incision, or excision

Question 6

Cytology

Answer 6

sample of cells exfoliated or aspirated from the body

Question 7

Follicular B-cell lymphomas have what type of translocation?

Answer 7

t(14;18) trnaslocation that fuses the BCL2 gene from chromosome 18 with the active IgH locus on chromosome 14 resulting in overproduction of anti-apoptotic BCL2.

lymphocytes are subjected to apoptosis at a slow rate –> slow accumulation of excess lymphocytes

Question 8

How do follicular lymphoma patients present?

Answer 8

painless, generalized, very slowly progressive enlargement of lymph nodes at an average age of 60.

equally common in men and women, but twice as common in whites as blacks and asians

Question 9

What is required for tumors to grow over 2mm?

Answer 9

Growth of new blood vessels

Question 10

What is angiogenesis normally inhibited by?

Answer 10

Thrombospondin-1 (induced by p53) and destruction of HIF-1a (by VHL).

Question 11

What happens with tumoral hypoxia

Answer 11

calls off VHL, so that HIF-1a starts VEGF production and growth of irregular leaky blood vessels –> ANGIOGENIC SWITCH

Question 12

What is the angiogenic switch mediated by?

Answer 12

HIF-1a, basic FGF, loss of p53, decreased TSP-1, and overcoming anti-angiogenic factors (angiostatin, endostatin, vasculostatin)

Question 13

Does inhibiting sustained angiogenesis have efficacy in controlling cancer?

Answer 13

NO!

Question 14

What are the four steps involved in local invasion by malignant tumors?

Answer 14

1) detachment of tumor cells from e/o
2) degradation of BM and ECM
3) attachment of tumor cells to BM
4) migration of the escaped malignant cells through the interstitium

Question 15

Detachment of tumor cells from each other is mediated by…

Answer 15

downregulation of E-cadherin or mutated B-catenin

Question 16

What is involved in the degradation of the BM and ECM?

Answer 16

BM is composed of type IV collagen

Degradation is by matrix metalloproteinases (especially MMP-9)

Question 17

Attachment of tumor cells to exposed BM is mediated by…

Answer 17

laminin and fibronectin receptors

Question 18

Migration through BM and ECM is mediated by…

Answer 18

binding to various factors such as autocrine motility factor

Question 19

Characteristic Patterns of Metastasis

Answer 19

Colon cancer –> local lymph nodes and then liver

Prostate and Breast –> local lymph nodes then bone

Question 20

Organ Tropism

Answer 20

the mechanisms of metastatic organ tropism include differential concentration of endothelial cell ligands for adhesion molecules in different organs and chemokines such as CXCR4 and CCR7 receptors in the case of breast cancer

Question 21

Tumor Embolus

Answer 21

Tumor cells that invade veins generally pass through the right heart and go to the lungs, where they stop and elicit formation of blood clot around them. Fibroblasts organize the blood clot part of this. The obstruction of small pulmonary blood vessels can eventually lead to pulmonary HTN and right heart failure

Question 22

Chemicals that cause cancer can be categorized as…

Answer 22

1) Initiators: cause mutations, which become irreversible in the progeny of the mutated cell, if not reversed in it
2) Promoters: cause reversible proliferation of initiated cells
3) Direct: reactive electrophiles
4) Indirect: require metabolic activation of procarcinogens commonly by CYP450

Question 23

Name the 3 most common and important carcinogens

Answer 23

estrogen
alcohol
anti-cancer chemotherapy agents

Question 24

Radiation Carcinogenesis

Answer 24

The cancer-causing effect of radiation has a long latent period (years-decades). UV light cases skin cancer. Radiation therapy causes sarcomas. Nuclear power plant leaks cause thyroid cancer.

Question 25

Microbial Carcinogenesis

Answer 25

HPV –> uterine cervical cancer and cancers of the mouth and upper respiratory tract.
HCV and HBV –> hepatic cancer
EBV –> lymphoma in immunocompromised
Helicobacter pylori –> gastric carcinoma and lymphoma

Question 26

Tumors can resist immune surveillance and response by…

Answer 26

selective outgrowth of Ag-negative cells, decreased expression of MHC molecules, lack of co-stimulation, and antigen masking.

Tumors can also induce TGF-beta which is a potent immunosuppressant, or engage the T cell inhibitory receptor (CTLA-4), or activate Tregs that suppress immune responses. Some tumors express FasL, which can engage Fas on immune cells and induce immune cell to commit apoptosis

Question 27

Paraneoplastic Syndrome Definition

Answer 27

symptoms not attributable to direct effects of tumor (or hormones native to the primary tumor organ) are called paraneoplastic; occur in about 10% of cancer patients

Question 28

Is cachexia a paraneoplastic syndrome?

Answer 28

NO!!!!! CACHEXIA IS A CLASS BY ITSELF

Question 29

Cachexia

Answer 29

catabolic state of severe wasting mediated by tumor necrosis factor.

cancer is the most common cause, but AIDS, end-stage heart disease and end-stage lung disease also cause cachexia

Question 30

Why do you need to watch out for paraneoplastic syndromes?

Answer 30

can be the earliest manifestation of occult tumor

may mimic metastatic disease

Question 31

Paraneoplastic Syndromes Include…

Answer 31

Hypercalcemia = most common
Cushing Syndrome = d/t ACTH production
Syndrome of inappropriate ADH 
Hypoglycemia (d/t tumor insulin)
Carcinoid Syndrome (d/t 5-HT)

Question 32

Hypercalcemia

Answer 32

Frequently occurs in cancer patients
When it is due to lytic bone metastases, however, that is not counted as paraneoplastic. When it is caused by parathyroid hormone-related protein (PTHRP) and other substances released by tumors, it is counted as paraneoplastic

Question 33

What is the most common cancer type to cause hypercalcemia?

Answer 33

squamous cell carcinoma is the most common lung cancer type to cause hypercalcemia

Question 34

What are the symptoms of hypercalcemia?

Answer 34

N/V, constipation, polyuria, disorientation, lethargy, seizures (“altered mental status”)

Question 35

Treatment for hypercalcemia?

Answer 35

hydration and bisphosphates

Question 36

What are the most common source of ACTH causing Cushing Syndrome?

Answer 36

Pituitary adenomas (can also include small cell carcinoma of lung)

Question 37

Signs and symptoms of Cushing Syndrome

Answer 37

weight gain, central obesity, moon face (fat deposition), weakness, hirsutism, HTN, glucose intolerance, depression, psychosis, BUFFALO HUMP DORSAL NECK FAT DEPOSITION, plethora, osteoporosis, menstrual irregularity, muscle wasting

Question 38

Tumor Stage

Answer 38

Anatomic extent of tumor, including primary tumor size, extent of lymph node, and distant metastases. STAGE CARRIES FAR MORE PROGNOSIS

Question 39

Tumor Grade

Answer 39

Qualitative assessment of the differentiation of a tumor (extent to which the microscopic appearance resembles normal tissue at the primary site

Question 40

What are the two stages that take place in the diagnosis of cancer?

Answer 40

1) discovery by symptoms, signs, radiology, or serum markers
2) actionable diagnosis by biopsy or cytology

Question 41

Serum tumor markers include…

Answer 41

PSA, CA-125, CA-19-9, HCG, AFP, CEA, and immunoglobulins

Question 42

Specific diagnosis required to warrant treatment is most commonly, usually best obtained by….

Answer 42

BIOPSY - allows obtaining more tissue for more purposes, and it allows assessment of architecture and local invasion.