Ch 7: neoplasia Flashcards

Question

bone

Answer 1

Osteoma Osteogenic sarcoma

Answer 2

Hemangioma Angiosarcoma

Answer 3

Lymphangioma Lymphangiosarcoma

Answer 4

malignant only | Synovial Sarcoma

Answer 5

only malignant | mesothelioma

Answer 6

Meningioma | Invasive Meningioma

Answer 7

leukemia (malignant)

Answer 8

lymphoma (malignant)

Answer 9

Leiomyoma Leiomyosarcoma

Answer 10

Rhabdomyoma Rhabdomyosarcoma

Answer 11

lack of differentiation • malignant neoplasms that are composed of poorly differentiated cells are anaplastic • lack of differentiation is considered a hallmark of malignancy

Answer 12

variation of size and shape of nuclei

Answer 13

replacement of one type of cell with another | • almost always found in assoc. w/ tissue damage, repair and regeneration

Answer 14

= disordered growth | • often occurs in metaplastic epithelium, but not all metaplasia is dysplastic

Answer 15

when dysplastic changes involve entire thickness of epithelium but the lesion remains confined by the basement membrane and is a preinvasive neoplasm

Answer 16

o doubling time of tumor cells o growth fraction = fraction of tumor cells in the replicative pool- as tumors continue to grow, cells leave the proliferative pool due to shedding, lack of nutreints, necrosis, apoptosis and thus by the time tumor is clinically detectable, most cells are not in the proliferative pool o rate at which cells shed/divide

Answer 17

• Tumor Initiating Cells: cells that allow a human tumor to grow and maintain itself indefinitely when transplanted into an immunodeficient mouse o like “leukemia stem cells” o TIC’s seem to be very common in some types of cancers o Tumors may have a small number of TIC’s that then “differentiate” to form the bulk of the tumor, while others are largely composed of TIC’s

Answer 18

benign tumors grow and expand slowly, thus they usually develop a rim of compressed CT around them o encapsulation doesn’t prevent tumor growth, but it keeps benign neoplasm as a discrete, readily palpable, easily movable mass o not all benign neoplasms are encapsulated – uterine leiomyomas have not capsule, but have well-defined cleavage planes

Answer 19

malignant neoplasms of glial cells in CNS (gliomas) and basal cell carcinomas are considered malignant but they DO NOT metastasize, and are locally invasive

Answer 20

most common in carcinomas • ex. breast in upper quadrant →axillary lymph nodes • ex. inner quadrant of breast → nodes along internal mammary aa. (infraclavicular and supraclavicular nodes) • ex. carcinomas of lung arising in major respiratory passages → perihlar tracheobronchial and mediastinal nodes

Answer 21

***sarcomas – most lethal route! – go to brain, bone, liver and lung! * (liver and lungs are most frequently involved in dissemination) * cancers arising close to vertebral column often embolize through paravertebral plexus * ex. renal cell carcinoma: often invades branches of renal v. to grow in snakelike fashion up IVC * breast carcinoma → bone * bronchogenic carcinoma → adrenals and brain * neuroblastomas → liver and bones

Answer 22

renal V and IVC

Answer 23

portal radicles into vv.

Answer 24

liver via portal system

Answer 25

bone via vascular plexuses

Answer 26

adrenals and brain

Answer 27

CNS/meninges

Answer 28

liver and bones

Answer 29

seen in infancy/childhood – neuroblastoma, Wilms tumor, retinoblastoma, acute leukemias, rhabdomyosarcomas

Answer 30

= breast cancer suscpetilbity • familal cancer = ovarian cancer

Answer 31

familal melanoma

Answer 32

1. Childhood Retinoblastoma: - due to mutation in RB tumor suppressor gene - children develop a retinoblastoma, increased chance of developing osteosarcoma

Answer 33

caused by mutation of adenomatous polyposis coli (APC) tumor suppressor gene. - develop innumerable polypoid ademoas of colon and develop colonic adenocarcinoma by age 50

Answer 34

3. Li-Fraumeni syndrome: results from germiline mutations of p53 gene - not tissue specific

Answer 35

Multiple endocrine Neoplasia types 1 and 2 (MEN-1 and MEN-2): mutation of genes that encode the menin txn factor and the RET tyrosin kinase respectively - MEN-1: pituitary, parathyroid, pancreas - MEN-2: thyroid, parathyroid, adrenals f

Answer 36

Hereditary nonpolyposis colon cancer: caused by inactivation of a DNA mismatch repair gene * most common cancer predisposition syndrome o increases susceptibility to cancer of colon, small intestine, endometrium and ovary

Answer 37

Nevoid basal cell carcinoma syndrome

Answer 38

Neurofibromatosis 1 and 2

Answer 39

o inflammatory GI diseases increase risk of cancer: ulcerative colitis, Helicobacter pylori gastritis, viral hepatitis, chronic pancreatitis o immune response may be maladaptive and may promote tumorigenesis o chronic inflammation may cause fixation of maladaptive mechanisms o ex. COX-2 is induced by inflammatory stimuli and is increased in colon cancers and other tumors

Answer 40

colorectal carcinoma

Answer 41

- seen with alchoholics | - pancreatic carcinoma

Answer 42

esophageal carcinoma

Answer 43

MALT lymphoma

Answer 44

hetpatocellular carcinoma

Answer 45

B-cell non-Hodgkin lymphoma and Hodgkin lymphoma | - b/c of EBV

Answer 46

Non-Hodgkin lymphoma, squamous cell carcinoma, Kaposi sarcoma - Because of Human immunodeficiency virus, human herpesvirus type 8

Answer 47

Malignant Melanoma Squamous Cell Carcinoma Basal Cell Carcinoma

Answer 48

Thyroid Carcinoma-Chernobyl | Leukemia - Hiroshima

Answer 49

lung carcinoma

Answer 50

gatric carcinoma

Answer 51

hepatocellular carcinoma

Answer 52

carcinoma uterine/cervix

Answer 53

endometrial adenocarcinoma

Answer 54

bronchogenic carcinoma

Answer 55

squamous cell carcinoma

Answer 56

prooncogene - overexpression of TGFalpha Astrocytomas, hepatocellular carcinomas

Answer 57

protooncogene ovexpression of HGF Thyroid cancer

Answer 58

overexpression of EGF-receptor family (protooncogene) Squamous cell carcinoma of lung, gliomas

Answer 59

protooncogene | point mutation causes leukemia

Answer 60

PO pointmutation affects GTP-binding *** dyrsregulation of RAS/RAF/MAP pathway is linked with melanomas*** KRAS:Colon, lung, and pancreatic tumors HRAS: Bladder and kidney tumors NRAS: Melanomas, hematologic malignancies

Answer 61

PO | translocation causes chronic myeloid leukemia, acute lymphoblastic leukemia

Answer 62

PO involved in RAS signal transduction | point mutation causes melanomas

Answer 63

PO, transcriptional activator translocation causes burkitt's lymphoma

Answer 64

PO, transcriptional activator amplification causes Neuroblastoma, small-cell carcinoma of lung

Answer 65

PO, txn activator | amplification causes small-cell carcinoma of the lung

Answer 66

PO, translocation causes mantle cell lymphoma amplification causes breast and esophageal cancers

Answer 67

PO overexpression causes breast cancers

Answer 68

PO - amplification of point mutation Forms a complex with cyclin D that phosphorylates RB, allowing the cell to progress through the G 1 restriction point. glioblastoma, melanoma and sarcomas

Answer 69

point mutation of the RAS family genes I sthe single most common abnormality of proto-oncogenes in human tumors • Oncogene • Ras plays role in signaling cascade, resulting in mitogenesis • it is activated by growth factor binding at PM • RAS proteins flip back forth b/w excited and quiescent state o recycling occurs through nucleotide exchange (GDP to GTP) which activates protein • Catalyzed by guanine nucleotide releasing proteins o GTP hydrolysis → GDP to inactivate • Catalysed GTPase activity via GTPase-activating proteins (GAPs): act as “brakes” • inactived RAS = RAS + GDP • Activated RAS = RAS + GTP • Activated RAS stimulates mitogen-activated protein (MAP)

Answer 70

drug that inhibits BCR-ABL kinase

Answer 71

* oncogene * MYC interacts with components of DNA-replication machinery and plays a role in selection of origins of replication. * overexpression may drive activation of more origins than needed for normal cell division, * MYC can act to reprogram somatic cells into pluripotent stem cells * Dysregulation of MYC resulting from translocation of gene results in Burkitt Lymphoma – B cell tumor

Answer 72

* CDK-cyclin complexes phosphorylate crucial target proteins that drive the cell through the cell cycle * mutations result in increased activity of cyclins and CDKs favoring proliferation * cyclincs bind CDKs and intiate cell proliferation

Answer 73

* CIP/WAF family: p21, p27, p57 * INK4 family: p16, p16, p18 * expression of these inhibitors is down-regulated by mitogenic signaling pathways thus promoting the progression of cell cycle

Answer 74

Forms a complex with cyclin E in late G 1, which is involved in G 1/S transition. Forms a complex with cyclin A at the S phase that facilitates G 2/M transition.

Answer 75

Forms a complex with cyclin B that facilitates G 2/M transition.

Answer 76

Block the cell cycle by binding to cyclin-CDK complexes; p21 is induced by the tumor suppressor p53; p27 responds to growth suppressors such as TGF-β.

Answer 77

p16/INK4a binds to cyclin D–CDK4 and promotes the inhibitory effects of RB; p14/ARF increases p53 levels by inhibiting MDM2 activity.

Answer 78

Tumor suppressor gene altered in the majority of cancers; causes cell cycle arrest and apoptosis. Acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX. Levels of p53 are negatively regulated by MDM2 through a feedback loop. p53 is required for the G 1/S checkpoint and is a main component of the G 2/M checkpoint.

Answer 79

TS Growth inhibition somatic mutations: Carcinomas of colon

Answer 80

TS FN; cell adhesion SM: carcinoma of stomach IM: familal gastric cancer

Answer 81

TS FN: Inhibition of RAS signal transduction and of p21 cell cycle inhibitor SM: neuroblastomas IM: Neurofibromatosis type 1 and sarcomas, optic nerve gliomas

Answer 82

TS fn: cytoskeletal stability SM: Schwannomas and meningiomas IM: Neurofibromastosis type 2, acoustic schwannomas, and meningiomas

Answer 83

TS fn: inhibition of signal transdution SM: Carcinomas of stomach, colon, pancreas; melanoma IM: Familial adenomatous polyposis coli/colon cancer

Answer 84

TS: Fn: PI1 kinase signal transduction SM: endometrial and prostate cancers IM: Cowden syndrome

Answer 85

TS Fn:TGF-β signal transduction SM: colon, pancreas tumors

Answer 86

TS Fn: regulation of cell cycle SM: Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung IM: Retinoblastomas, osteosarcoma

Answer 87

TS Fn: Cell cycle arrest and apoptosis in response to DNA damage SM; most human cancers IM: Li-Fraumeni syndrome; multiple carcinomas and sarcomas

Answer 88

TS Fn: nuclear txn SM/IM: Wilm's tumor

Answer 89

TS fn: Regulation of cell cycle by inhibition of cyclin-dependent kinases SM: Pancreatic, breast, and esophageal cancers IM:Malignant melanoma

Answer 90

fn: dna repair IM: Carcinomas of female breast and ovary; carcinomas of male breast

Answer 91

* two mutations are required to eliminate tumor suppressor genes * in familial cases: one gene is inherited, the other spontaneously mutates * in sporadic cases: both genes must mutate * Thus heterozygosity of the RB gene does not affect cell behavior loss of heterozygosity: when the cell loses both of its normal alleles, it results in loss of the gene

Answer 92

• exists in an active hypophosphorylated state in quiescent cells and in an inactive hyperphosphorylated state in G1/S transition (most important checkpoint) - if RB is hypophos. then it remains bound to E2F, and E2F cannot signal txn (RB can be hypophos. via Ggrowth inhibitors stimulated CDKI's) - RB is hyperphsophorylated via Growth factors (EGF, PDGF) stimulated cyclins D/E, resulting in release of E2F and transcriptional activity *note HPV is known to inactivate RB protein

Answer 93

mutation in p53: results in increases in malignant tumors – sarcomas, breast cancer, leukemia, brain tumors, carcinomas of arenal cortex

Answer 94

stimulate the degredation of p53, and are often overexpressed in malignancies where p53 is not mutated

Answer 95

* adenomatous polyposis coli genes represent tumor suppressors that down-regulate growth promotic receptors. * germline mutations result in thousands of adenomatous polyps in colon during teens to 20’s * usually polyps will undergo transformation giving rise to colonic tumors * APC dowregulates B-catenin in the absence of WNT signaling, preventing Beta catenin to accumulate in the cytoplasm * WNT triggered, inhibits APC, allowing B-Catenin build up, resulting in increase in c-myc and cyclinD. * cells with loss of APC behave as if under continuous WNT signaling * Beta-Catenin binds E-Cadherin (cell surface protein that maintains intercellular adhesiveness) – loss of cellular contact allows B-Catenin to stimulate proliferation = contact inhibited

Answer 96

• Beta-Catenin binds E-Cadherin (cell surface protein that maintains intercellular adhesiveness) – loss of cellular contact allows B-Catenin to stimulate proliferation

Answer 97

loss of adhesion to BM, can trigger apoptosis

Answer 98

ovexpression leads to tumors due to loss of apoptosis

Answer 99

• bFGF and VEGF

Answer 100

anti-VEGF Ab used for treatment

Answer 101

** overexpression of MMPs has been implicated in many tumors proteases that have been implicated in tumor invasion. MMP’s regulate tumor invasion not only by remodeling insoluble compnents of BM but also by releasing ECM-sequestered growth factors o breakdown products of collagen have a chemotactic and angiogeneic and growth promoting effects o MMP9 = gelatinase that cleaves collagen type IV

Answer 102

adhesion molecule: expressed on normal T lymph. is used by tumors to migrate to selective sites in lymphoid tissue o overexpression of CD44 may favor metastatic spread

Answer 103

chemokines that are expressed --> in some breast cancers --> allow for metastasis to lymph nodes

Answer 104

Hereditary nonpolyposis colon cancer syndrome: • results from defects in genes involvedin DNA mistmatch repair – results in creation of microsatellites, causing microsatellite instability • familial carcinomas of the colon

Answer 105

* defective DNA excision repair * UV radiation causes crosslinking of pyrimidine residues, and lacks excision repair * increased development of cancers of the skin, especially after exposure to sunlight

Answer 106

• defect in DNA repair by homologous recombination

Answer 107

* breast cancers * cells lacking these genes have been shown to associate with a variety of proteins involved in homologous recombination repair pathway

Answer 108

* cancer cells shift to aerobic glycolysis * aerobic glycolysis allows tumors to need less O2 supplied by blood * HIF1alpha downregulates genes involved in ox phos * decreased demand by tumor cells increases the O2 supply, allowing for increased number of tumor cells that can be supported by the vasculature * halting of breakdown from glucose to pyruvate allows these carbons to be shunted to anabolic pathway and thus used for building blocks for cell division * LKB1: tumor suppressor gene that halts anabolic metabolism

Answer 109

c-MYC overexpression of proto-oncogene due to translocation o MYC is translocated to IGH sequence t(8:14)(q24;q32) and thus loses its regulatory sequence o IGH is highly expressed in B cell precursors

Answer 110

• Philidelphia chromosome: o fusion of genes from 9 and 22 forming BCR-ABL gene o characteristic of CML and acute lymphoblastic leukemias

Answer 111

protooncogene | gene amplification often leading to breast cancer

Answer 112

tumor suppresor - silenced in renal cell carcinomas

Answer 113

* mediate post transcriptional gene silencing through RNA-induced silencing complex * by negatively regulating BCL2 (anti-apoptotic protein), miRNAs behave as tumor suppressor genes

Answer 114

• ex. cigarette smoke: metabolized by the P-450 gene, CYP1A1 – smokers with this genotype are more susceptible to lung cancer

Answer 115

Human T cell Leukemia Virus Type 1: (HTLV-1) - • causes a form of T-cell leukemia/lymphoma (seen in Japan and carribean) • affects CD4+ T cells • contains protein tax that stimulates txn of viral mRNA by acting on 5’ terminal repeat: it inactivates inhibitor p16/INK4a and enhances cyclin D activation. tax also activates NF-kb • HTLV-1 causes expansion of nonmalignant polyclonal cell population through stimulatory effects of Tax – the proliferating T cells are at increased risk of mutations and genomic instability induced by Tax, allowing mutations to accumulate and eventually a monoclonal neoplastic T-cell population emerges

Answer 116

– type 16 and 18 – cause squamous cell carcinoma of cervix and anogenital region • cells in which viral genome is integrated have moregenomic instability, integration interrupts the viral DNA within the E1/E2 open reading frame, leadig to loss of E2 viral repressor, and overexpression E6/E7 oncoproteins.

Answer 117

binds to the Rb protein and displaces E2F txn factor – promoting progression through cell cycle. E7 also inactivates CDKI’s p21 and p27.

Answer 118

has higher affinity for p53 and blocks p53, thus disabling apoptosis

Answer 119

• Burkitt-Lymphoma: B-cell lymphoma, Hodgkin lymphoma, nasopharyngeal and gastric carcinomas, rare forms or T cell lymphomas and NK lymphomas o except for nasopharyngeal carcinoma, all others are B-cell tumors • EBV infects B lymphocytes using the CD21 receptor to attach and infect B cells • LMP-1: latent membrane protein 1, acts as an oncogene and acts on CD40 receptor, activating the NF-kb pathway and JAK/STAT signaling, causing B-cell survival and proliferation o also activates BCL2, prevening apoptosis • Burkitt lymphoma: neoplasm of B lympohcytes that is most common childhood tumor in central Africa and New Guinea o in regions of world where Burkitts is endemic, concomitatnt infections such as malaria impaire immune competence, allowing sustained B cell proliferation.

Answer 120

* close association with HBV infection and liver cancer – Hepatocelluar carcinomas * dominant effect seems to be immunologically mediated chronic inflammation with hepatocyte death leading to regeneration and genomic damage * chronic viral infection leads to compensatory proliferation of hepatocytes * Activation of the NF-kB pathway w/in hepatocytes blocks apoptosis, allowing dividing hepatocytes to incur genotoxic stress and accumulate mutations

Answer 121

• bacterium that causes gastric adenocarcinomas and gastric lymphomas o MALTomas = mucous associated lymphoid tissue • involves increased epithelial cell proliferation in a background of chronic gastric inflammation (similar to viral hep)

Answer 122

DNA viruses: HPV and EBV

Answer 123

• CTL’s are effective against virus-associated neoplasms: important against HPV, EBC ``` • NK cells: capable of destroying tumor cells without prior sensitization – thus may provide first line defense o tumors that don’t express MHC I class Ags cannot be recognized by T cells, these may however trigger NK cells which are normally inhibited by recognition of normal class I molecules ```

Answer 124

non-hodgking lymphoma (50%), primary CNS lymphoma, Kaposi sarcoma, cervical neoplasia

Answer 125

Cushing Syndrome: ** very common** • results from small-cell carcinoma of lung • ACTH is secreted in xs – see elevated corticotropin levels

Answer 126

Hypercalcemia: ** very common** • seen with squamous cell carcinomas of lung • Release of PTH or PTH related proteins: TGFalpha, TNF, IL-1 • may also be seen with osteolytic cancers such as osteosarcomas, multiple myeloma, metastatic bone lesions

Answer 127

Syndrome of Inappropriate ADH secretion: | • seen with small cell carcinoma of lung

Answer 128

Nonbacterial thrombotic endocarditis • seen with advanced cancers – i.e. mucin secreting adenocaricnomas • results in hypercoagulability

Answer 129

gray black patches of hyperkeratosis on the skin • gastric carcinoma, lung carcinoma, uterine carcinoma • immunological causes; results in secretion of EGF

Answer 130

• seen in 1-10% of patients with bronchogenic carcinomas characterized by o periosteal new bone formation, at distal ends of long bones, fingers o arthritis of adjacent joints o clubbing of digits

Answer 131

Grading: based on degree of differentiation, and in some cancers the number of mitoses or architectural features – Typically established by the pathologist – How differentiated is the tumor? Other factors affecting or mitigating? Staging: based on size of primary lesion, extent of spread to reginal lymph nodes, presence or absence of blood-borne metastases – Typically established by the oncologist (although ‘contributed to [depending on the malignancy] by the pathologist’ – How widely spread is the cancer? TNM factors. – T= tumor, N=Lymph node, M=Metastases

Answer 132

Prevalence: Total cases in defined population on a specified date (e.g., Jan 1, 2007); Prevalence represents both new and all pre-existing cases alive on a certain date enumerated by one of these three possible methods of expression: An absolute number (e.g., total cases in US) Expressed as % population (Total cases in population as %) Number cases/100,000 population at the specified date ``` Incidence: New cases diagnosed during specified time (usually a year) for given population (100,000 unit often used) Incidence reflects only new cases during a defined time. # new cases/100,000 population/year ```

Answer 133

gG kappa is seen most commonly in patients with multiple myeloma on electrophoresis

Answer 134

primitive B cell marker

Answer 135

primitive B cell marker | - lymphoid malignancies: B-cell chronic lymphocytic leukemia, non-Hodgkin Leukemia, multiple myeloma

Answer 136

PSA is organ-specific but not cancer-specific, whereas HER2/ neu is cancer-specific but not tissue-specific and is found to be increased in breast cancers, as well as lung and other epithelial cell tumors.

Answer 137

carcinoembryonic Ag - tumor marker for GI cancer: but also elevated in adenocarcinomas of breast, lung, liver cancers - used to only be for colon cancer

Answer 138

gastric cancer, pancreatic cancer, colon cancer

Answer 139

marker for ovraian cancers

Answer 140

breast cancer and squamous cell carcinoma of lung

Answer 141

elevated in trophoblastic tumors and choriocarcinomas of females elvated in seminomatous testicular tumors in males

Answer 142

alpha feto protein | - hepatocellular carcinoma and germ cell tumors of testis

Answer 143

Parathyroid Hormone-Related Peptide Plasma concentrations of parathyroid hormone-related peptide (PTH-RP) are elevated in the majority of patients with cancer-associated hypercalcemia. secreted by tumors associated with hypercalcemia.

Answer 144

medullary carcinoma of thryoid

Answer 145

pheochromocytoma

Answer 146

prostate cancer

Answer 147

breast cancer

Answer 148

gstric carcinoma

Answer 149

breast cancer

Answer 150

colon cancer

Answer 151

pancreatic cancer

Answer 152

lung cancer

Answer 153

bladder cancer